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Cornberg M, Sandmann L, Jaroszewicz J, Kennedy P, Lampertico P, Lemoine M, Lens S, Testoni B, Lai-Hung Wong G, Russo FP. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2025:S0168-8278(25)00174-6. [PMID: 40348683 DOI: 10.1016/j.jhep.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.
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Tian C, Ye C, Guo H, Lu K, Yang J, Wang X, Ge X, Yu C, Lu J, Jiang L, Zhang Q, Song C. Liver elastography-based risk score for predicting hepatocellular carcinoma risk. J Natl Cancer Inst 2025; 117:761-771. [PMID: 39576686 DOI: 10.1093/jnci/djae304] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 10/28/2024] [Accepted: 11/18/2024] [Indexed: 04/08/2025] Open
Abstract
BACKGROUND Liver stiffness measurement (LSM) via vibration-controlled transient elastography accurately assesses fibrosis. We aimed to develop a universal risk score for predicting hepatocellular carcinoma (HCC) development in patients with chronic hepatitis. METHODS We systematically selected predictors and developed the risk prediction model (HCC-LSM) in the hepatitis B virus (HBV) training cohort (n = 2251, median follow-up of 3.2 years). The HCC-LSM model was validated in an independent HBV validation cohort (n = 1191, median follow-up of 5.7 years) and a non-viral chronic liver disease (CLD) extrapolation cohort (n = 1189, median follow-up of 3.3 years). An HCC risk score was then constructed based on a nomogram. An online risk evaluation tool Liver Elastography-Based Hepatocellular Carcinoma Risk Score (LEBER) was developed using ChatGPT4.0. RESULTS Eight routinely available predictors were identified, with LSM levels showing a significant dose-response relationship with HCC incidence (P < .001 by log-rank test). The HCC-LSM model exhibited excellent predictive performance in the HBV training cohort (C-index = 0.866) and the HBV validation cohort (C-index = 0.852), with good performance in the extrapolation CLD cohort (C-index = 0.769). The model demonstrated significantly superior discrimination compared to 6 previous models across the 3 cohorts. Cut-off values of 87.2 and 121.1 for the HCC-LSM score categorized participants into low-, medium-, and high-risk groups. An online public risk evaluation tool (LEBER; http://ccra.njmu.edu.cn/LEBER669.html) was developed to facilitate the use of HCC-LSM. CONCLUSION The accessible, reliable risk score based on LSM accurately predicted HCC development in patients with chronic hepatitis, providing an effective risk assessment tool for HCC surveillance strategies.
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Affiliation(s)
- Chan Tian
- Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China
| | - Chunyan Ye
- Department of Liver Diseases, The Third People's Hospital of Changzhou, Changzhou 213000, Jiangsu, China
| | - Haiyan Guo
- Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China
| | - Kun Lu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China
| | - Juan Yang
- Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China
| | - Xiao Wang
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Xinyuan Ge
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China
| | - Chengxiao Yu
- Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China
| | - Jing Lu
- Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China
| | - Longfeng Jiang
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Qun Zhang
- Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Ci Song
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China
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Diao Y, Zeng Y, Huang Z, You C. Efficacy of Antiviral Therapy in Chronic Hepatitis B Patients With Normal Alanine Aminotransferase: A Systematic Review and Meta-Analysis. Can J Gastroenterol Hepatol 2025; 2025:7689981. [PMID: 40225271 PMCID: PMC11991825 DOI: 10.1155/cjgh/7689981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 02/14/2025] [Indexed: 04/15/2025] Open
Abstract
Background and objectives: The efficacy of antiviral therapy in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) is controversial. This study aimed to systematically review and analyze antiviral efficacy in ALT-normal CHB patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Library databases from inception to 17 May 2024 were searched for retrieving relevant studies with antiviral efficacy of ALT-normal CHB patients. Results: Of 4992 records screened, 10 studies met the criteria for inclusion and had a low risk of bias. The pooled proportions of undetectable HBV DNA, HBeAg loss, HBeAg seroconversion, HBsAg loss, and HBsAg seroconversion in ALT-normal CHB patients with antiviral therapy were 87%, 35%, 19%, 16%, and 10%, respectively. Subgroup analysis suggested that the virological and serological responses were better in patients receiving IFN-based therapy or with a longer follow-up time. Compared with no treatment, antiviral therapy was associated with significant higher rates of undetectable HBV DNA (RR: 65.62, 95% CI: 16.65-258.57, and p < 0.01), HBeAg loss (RR: 14.97, 95% CI: 3.31-67.65, and p < 0.01), HBsAg loss (RR: 14.22, 95% CI: 4.10-49.29, and p < 0.01), and HBsAg seroconversion (RR: 24.65, 95% CI: 3.06-198.60, and p < 0.01). The normal ALT group and elevated ALT group had comparable antiviral efficacy including proportions of undetectable HBV DNA, HBeAg loss, and HBeAg seroconversion (p > 0.05). Conclusions: CHB patients with normal ALT could benefit from antiviral therapy, and the virological and serological responses were comparable to that of ALT-elevated ones.
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Affiliation(s)
- Yuting Diao
- Department of Infectious Diseases, Zigong First People's Hospital, 42, Shangyihao Branch Road 1, Zigong 643000, Sichuan, China
| | - Yueying Zeng
- Department of Infectious Diseases, Zigong First People's Hospital, 42, Shangyihao Branch Road 1, Zigong 643000, Sichuan, China
| | - Zhihao Huang
- Department of Infectious Diseases, Zigong First People's Hospital, 42, Shangyihao Branch Road 1, Zigong 643000, Sichuan, China
| | - Chunfang You
- Department of Infectious Diseases, Zigong First People's Hospital, 42, Shangyihao Branch Road 1, Zigong 643000, Sichuan, China
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Roberts LR. Surveillance for Hepatocellular Carcinoma. Clin Liver Dis 2025; 29:17-31. [PMID: 39608955 DOI: 10.1016/j.cld.2024.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
This article reviews surveillance for the detection of early stage hepatocellular carcinoma, covering the rationale for surveillance, optimal selection of persons needing surveillance, methods and frequency of screening, strategies for addressing barriers to surveillance, and trends for future improvement in surveillance leading to more effective cancer control and improved patient outcomes. The importance of integrating liver cancer surveillance as a core component of national public health programs is emphasized. The impact of emerging technologies for identifying persons at risk, stratifying individual risk to improve the cost-effectiveness of surveillance programs, and improving the performance, accessibility, and convenience of surveillance are discussed.
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Affiliation(s)
- Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street Southwest, Rochester, MN 55905, USA.
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Liu J, Chen R, Zhou S, Guo Z, Su L, Cao L, Li Y, Zhang X, Luo F, Xu R, Gao Q, Lin Y, Xu X, Nie S. Acute kidney injury is associated with liver-related outcomes in patients with hepatitis B virus infection: a retrospective cohort study. BMC Nephrol 2025; 26:12. [PMID: 39780049 PMCID: PMC11715857 DOI: 10.1186/s12882-024-03925-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND The effects of acute kidney injury (AKI) on liver-related outcomes in patients with hepatitis B virus (HBV) infection remain unclear. The study aimed to evaluate the association between AKI with liver-related mortality and complications in patients with HBV infection. METHODS The multicenter, retrospective cohort study included Chinese adults with HBV infection from 24 regional central hospitals between January 2000 and December 2022. AKI was defined as a ≥ 26.5 μmol/l increase in serum creatinine concentration within 48 h, or a ≥ 50% increase over the baseline within 7 days. The primary outcome was post-discharge liver-related mortality, while the secondary outcome was a composite of new-onset liver cirrhosis and hepatocellular carcinoma. Cox proportional hazard model was employed for analyses. RESULTS Of the 86,204 inpatients with HBV infection and without liver cancer or cirrhosis at baseline, 4407(5.1%) patients experienced AKI. During a mean follow-up of 4.6 ± 2.4 years, 334 (0.4%) patients died of liver-related events. After adjustment, AKI during hospitalization was significantly associated with a higher risk of liver-related mortality after discharge (adjusted hazard ratio (HR), 1.78; 95% confidence intervals (CI), 1.26-2.51, P = 0.001), especially in those with severe AKI. Similarly, AKI was associated with a higher risk of cirrhosis or new-onset hepatocellular carcinoma (adjusted HR, 1.33; 95%CI, 1.10-1.60, P = 0.004). The association between AKI and liver-related outcomes remained consistent across different subgroups. CONCLUSIONS AKI during hospitalization was associated with substantial increased risk of liver-related mortality and incident liver-related complication. Our findings highlight the importance of monitoring AKI in patients with HBV infection for tailoring personalized treatments.
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Affiliation(s)
- Jiao Liu
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Ruixuan Chen
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Shiyu Zhou
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Zhixin Guo
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Licong Su
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Lisha Cao
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Yanqin Li
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Xiaodong Zhang
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Fan Luo
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Ruqi Xu
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Qi Gao
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Yuxin Lin
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China
| | - Xin Xu
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China.
| | - Sheng Nie
- Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou, 510515, China.
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Cong X, Song S, Li Y, Song K, MacLeod C, Cheng Y, Lv J, Yu C, Sun D, Pei P, Yang L, Chen Y, Millwood I, Wu S, Yang X, Stevens R, Chen J, Chen Z, Li L, Kartsonaki C, Pang Y. Comparison of models to predict incident chronic liver disease: a systematic review and external validation in Chinese adults. BMC Med 2024; 22:601. [PMID: 39736748 DOI: 10.1186/s12916-024-03754-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 11/05/2024] [Indexed: 01/01/2025] Open
Abstract
BACKGROUND Risk prediction models can identify individuals at high risk of chronic liver disease (CLD), but there is limited evidence on the performance of various models in diverse populations. We aimed to systematically review CLD prediction models, meta-analyze their performance, and externally validate them in 0.5 million Chinese adults in the China Kadoorie Biobank (CKB). METHODS Models were identified through a systematic review and categorized by the target population and outcomes (hepatocellular carcinoma [HCC] and CLD). The performance of models to predict 10-year risk of CLD was assessed by discrimination (C-index) and calibration (observed vs predicted probabilies). RESULTS The systematic review identified 57 articles and 114 models (28.4% undergone external validation), including 13 eligible for validation in CKB. Models with high discrimination (C-index ≥ 0.70) in CKB were as follows: (1) general population: Li-2018 and Wen 1-2012 for HCC, CLivD score (non-lab and lab) and dAAR for CLD; (2) hepatitis B virus (HBV) infected individuals: Cao-2021 for HCC and CAP-B for CLD. In CKB, all models tended to overestimate the risk (O:E ratio 0.55-0.94). In meta-analysis, we further identified models with high discrimination: (1) general population (C-index ≥ 0.70): Sinn-2020, Wen 2-2012, and Wen 3-2012 for HCC, and FIB-4 and Forns for CLD; (2) HBV infected individuals (C-index ≥ 0.80): RWS-HCC and REACH-B IIa for HCC and GAG-HCC for HCC and CLD. CONCLUSIONS Several models showed good discrimination and calibration in external validation, indicating their potential feasibility for risk stratification in population-based screening programs for CLD in Chinese adults.
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Affiliation(s)
- Xue Cong
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
| | - Shuyao Song
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
| | - Yingtao Li
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
| | - Kaiyang Song
- Medical Sciences Division, University of Oxford, Oxford, OX3 9DU, UK
| | - Cameron MacLeod
- Medical Sciences Division, University of Oxford, Oxford, OX3 9DU, UK
| | - Yujie Cheng
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
| | - Jun Lv
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
- Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China
| | - Canqing Yu
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
- Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China
| | - Dianjianyi Sun
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
- Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China
| | - Pei Pei
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
- Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China
| | - Ling Yang
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
- Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK
| | - Yiping Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
- Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK
| | - Iona Millwood
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
- Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK
| | - Shukuan Wu
- Meilan Center for Disease Control and Prevention, Haikou, 570100, China
| | - Xiaoming Yang
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
| | - Rebecca Stevens
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
| | - Junshi Chen
- China National Center for Food Safety Risk Assessment, Beijing, 100022, China
| | - Zhengming Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
| | - Liming Li
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
- Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China
| | - Christiana Kartsonaki
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK.
- Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK.
| | - Yuanjie Pang
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China.
- Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China.
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China.
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Wang J, Zhu L, Zhang S, Zhang Z, Fan T, Cao F, Xiong Y, Pan Y, Li Y, Jiang C, Yin S, Tong X, Xiong Y, Xia J, Yan X, Liu Y, Liu X, Chen Y, Li J, Zhu C, Wu C, Huang R. Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA. Emerg Microbes Infect 2024; 13:2339944. [PMID: 38584592 PMCID: PMC11022914 DOI: 10.1080/22221751.2024.2339944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 04/03/2024] [Indexed: 04/09/2024]
Abstract
Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.
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Affiliation(s)
- Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Shaoqiu Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
| | - Zhiyi Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Tao Fan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Fei Cao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Ye Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Yifan Pan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Yuanyuan Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Chao Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
| | - Yali Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
| | - Yong Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China
| | - Xingxiang Liu
- Department of Clinical Laboratory, Huai’an No. 4 People’s Hospital, Huai’an, People’s Republic of China
| | - Yuxin Chen
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China
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8
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Ndow G, Shimakawa Y, Leith D, Bah S, Bangura R, Mahmoud I, Bojang L, Ceesay A, Drammeh S, Bola-Lawal Q, Lambert G, Hardy P, Ingiliz P, Haddadin Y, Vo-Quang E, Chevaliez S, Cloherty G, Bittaye SO, Lo G, Toure-Kane C, Mendy M, Njie R, Chemin I, D'Alessandro U, Thursz M, Lemoine M. Clinical outcomes of untreated adults living with chronic hepatitis B in The Gambia: an analysis of data from the prospective PROLIFICA cohort study. Lancet Gastroenterol Hepatol 2024; 9:1133-1146. [PMID: 39521002 DOI: 10.1016/s2468-1253(24)00226-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 06/22/2024] [Accepted: 07/08/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Expanding antiviral therapy to people with chronic hepatitis B virus (HBV) infection who are ineligible to receive treatment under current international criteria has been increasingly debated. Evidence to support this approach is scarce, especially in Africa. We aimed to address this knowledge gap by analysing the clinical outcomes of people with chronic hepatitis B in The Gambia who were untreated and ineligible for antiviral therapy at diagnosis. METHODS Between Dec 7, 2011, and Jan 24, 2014, we implemented the prospective PROLIFICA cohort study in The Gambia. Participants with chronic hepatitis B aged 16 years or older were recruited after large-scale, community-based HBV screening; blood bank-based HBV screening in Edward Francis Small Teaching Hospital, Banjul; and prospective follow-up of HBsAg-positive individuals via historical, population-based HBsAg serosurveys in two rural villages (Keneba and Manduar). Participants underwent HBV serology and other laboratory tests, fasting FibroScan, and abdominal ultrasound. Survival data were collected between Dec 7, 2011, and Aug 17, 2021. Between Oct 9, 2018, and Aug 17, 2021, all HBsAg-positive participants enrolled in the 2011-14 cohort were invited for a reassessment. For this analysis, we included HBsAg-positive people and excluded all participants who were eligible for treatment according to the 2012 European Association for the Study of the Liver (EASL) criteria at baseline and those who were treated irrespective of treatment eligibility. The primary outcome was all-cause mortality, assessed in all treatment-ineligible and treatment-naive participants with follow-up data. The secondary outcome, analysed in those who were reassessed, was disease progression, defined as becoming eligible for antivirals per 2017 EASL criteria; having an increase in liver fibrosis of at least one stage; or having a clinical diagnosis of hepatic decompensation or hepatocellular carcinoma. FINDINGS 943 HBsAg-positive people with chronic hepatitis B were recruited to the PROLIFICA study. Of these 943, 58 (6%) fulfilled 2012 EASL treatment eligibility criteria at baseline, 35 (4%) were ineligible for treatment but received antiviral therapy, and 44 (5%) were immediately lost to follow-up. Thus, 806 (85%) participants were analysed for the primary outcome (486 [60%] were male and 320 [40%] were female). After a median follow-up of 6·11 years (IQR 5·34-6·80), 708 (88%) participants were confirmed to be alive at last surveillance, 71 (9%) were lost to follow-up and were censored, and 27 (3%) died, giving an all-cause mortality rate of 582 per 100 000 person-years (95% CI 399-849). Of the 27 people who died, five (19%) had liver-related deaths. Of 708 participants confirmed to be alive, 544 (77%) attended follow-up and were assessed for the secondary outcome. Disease progression occurred in 36 (7%) participants: five (1%) became newly eligible for antiviral therapy per EASL 2017 criteria without liver fibrosis progression; 18 (3%) had liver fibrosis progression alone; 13 (2%) had liver fibrosis progression and newly fulfilled the treatment criteria; and none had hepatic decompensation or developed hepatocellular carcinoma. In multivariable analysis adjusted for sex and age, only a baseline HBV DNA of 20 000 IU/mL or more, compared with the baseline HBV DNA of 2000 IU/mL or lower as the reference, was significantly associated with liver disease progression (odds ratio 5·39, 95% CI 1·37-21·23). INTERPRETATION Among people with chronic hepatitis B who were ineligible for antiviral therapy in The Gambia, all-cause mortality and liver disease progression were low. The clinical benefit of expanding antiviral therapy in this subgroup of patients remains uncertain. FUNDING European Commission, Medical Research Council UK Research and Innovation, and Gilead Sciences.
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Affiliation(s)
- Gibril Ndow
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia; Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Liver Unit, Imperial College London, St Mary's Hospital, London, UK
| | - Yusuke Shimakawa
- Institut Pasteur, Université Paris Cité, Unité d'Épidémiologie des Maladies Émergentes, Paris, France
| | - Damien Leith
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Sulayman Bah
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Rohey Bangura
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Isatou Mahmoud
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Lamin Bojang
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Amie Ceesay
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Sainabou Drammeh
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Queen Bola-Lawal
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Gabriel Lambert
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia; Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Liver Unit, Imperial College London, St Mary's Hospital, London, UK
| | - Perrine Hardy
- Institut Pasteur, Université Paris Cité, Unité d'Épidémiologie des Maladies Émergentes, Paris, France
| | - Patrick Ingiliz
- Hepatology Department, Henri Mondor University Hospital, L'Institut National de la Santé et de la Recherche Médicale U955, Paris, France
| | - Yazan Haddadin
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Erwan Vo-Quang
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia; Hepatology Department, Henri Mondor University Hospital, L'Institut National de la Santé et de la Recherche Médicale U955, Paris, France
| | - Stéphane Chevaliez
- Virology Department, Henri Mondor University Hospital, L'Institut National de la Santé et de la Recherche Médicale U955, Paris, France
| | - Gavin Cloherty
- Infectious Disease Research Department, Abbott Diagnostics, Abbott Park, IL, USA
| | - Sheikh Omar Bittaye
- Department of Internal Medicine, Edward Francis Small Teaching Hospital, Banjul, The Gambia; School of Medicine and Allied Health Sciences, University of The Gambia, Banjul, The Gambia
| | - Gora Lo
- Institut de Recherche en Santé de Surveillance Épidémiologique et de Formation, Diamniadio, Senegal
| | - Coumba Toure-Kane
- Institut de Recherche en Santé de Surveillance Épidémiologique et de Formation, Diamniadio, Senegal
| | - Maimuna Mendy
- International Agency for Research on Cancer, Lyon, France
| | - Ramou Njie
- Department of Internal Medicine, Edward Francis Small Teaching Hospital, Banjul, The Gambia; School of Medicine and Allied Health Sciences, University of The Gambia, Banjul, The Gambia
| | - Isabelle Chemin
- Cancer Research Centre of Lyon, L'Institut National de la Santé et de la Recherche Médicale U1052, Lyon, France
| | - Umberto D'Alessandro
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia
| | - Mark Thursz
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Liver Unit, Imperial College London, St Mary's Hospital, London, UK
| | - Maud Lemoine
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Bakau, The Gambia; Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Liver Unit, Imperial College London, St Mary's Hospital, London, UK.
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Dong W, Da Roza CC, Cheng D, Zhang D, Xiang Y, Seto WK, Wong WCW. Development and validation of HBV surveillance models using big data and machine learning. Ann Med 2024; 56:2314237. [PMID: 38340309 PMCID: PMC10860422 DOI: 10.1080/07853890.2024.2314237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND The construction of a robust healthcare information system is fundamental to enhancing countries' capabilities in the surveillance and control of hepatitis B virus (HBV). Making use of China's rapidly expanding primary healthcare system, this innovative approach using big data and machine learning (ML) could help towards the World Health Organization's (WHO) HBV infection elimination goals of reaching 90% diagnosis and treatment rates by 2030. We aimed to develop and validate HBV detection models using routine clinical data to improve the detection of HBV and support the development of effective interventions to mitigate the impact of this disease in China. METHODS Relevant data records extracted from the Family Medicine Clinic of the University of Hong Kong-Shenzhen Hospital's Hospital Information System were structuralized using state-of-the-art Natural Language Processing techniques. Several ML models have been used to develop HBV risk assessment models. The performance of the ML model was then interpreted using the Shapley value (SHAP) and validated using cohort data randomly divided at a ratio of 2:1 using a five-fold cross-validation framework. RESULTS The patterns of physical complaints of patients with and without HBV infection were identified by processing 158,988 clinic attendance records. After removing cases without any clinical parameters from the derivation sample (n = 105,992), 27,392 cases were analysed using six modelling methods. A simplified model for HBV using patients' physical complaints and parameters was developed with good discrimination (AUC = 0.78) and calibration (goodness of fit test p-value >0.05). CONCLUSIONS Suspected case detection models of HBV, showing potential for clinical deployment, have been developed to improve HBV surveillance in primary care setting in China. (Word count: 264).
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Affiliation(s)
- Weinan Dong
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Cecilia Clara Da Roza
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Dandan Cheng
- Department of Family Medicine and Primary Care, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Dahao Zhang
- Department of Family Medicine and Primary Care, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Yuling Xiang
- Department of Family Medicine and Primary Care, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Wai Kay Seto
- Department of Medicine and State Key Laboratory of Liver Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - William C. W. Wong
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Family Medicine and Primary Care, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
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Mahajan A, Kharawala S, Desai S, Kendrick S, Das J, Gielen V. Association of Hepatitis B Surface Antigen Levels With Long-Term Complications in Chronic Hepatitis B Virus Infection: A Systematic Literature Review. J Viral Hepat 2024; 31:746-759. [PMID: 39150061 DOI: 10.1111/jvh.13988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 07/09/2024] [Accepted: 07/17/2024] [Indexed: 08/17/2024]
Abstract
Chronic hepatitis B virus (HBV) infection is a global issue and can lead to cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B surface antigen (HBsAg) is an important marker of HBV infection and HBsAg quantification could be a useful tool in clinical practice. This systematic literature review aimed to explore the association between HBsAg titres and long-term disease outcomes and evaluate the relationship between HBsAg titres, or changes in HBsAg titres, and clinical and treatment characteristics in patients with chronic HBV infection. Structured searches were performed in MEDLINE and Embase (January 2000 to 31 March 2023). Eighty-two studies were included, comprising 51% retrospective cohort studies, mostly conducted in Asia (85%). HBsAg levels were shown to predict the long-term development of cirrhosis and HCC in patients who were untreated prior to and during follow-up; however, these data were inconclusive in mixed and treated populations. HBsAg titres were significantly associated with various virological markers including serum HBV DNA, HBcrAg, HBeAg, HBV RNA levels, intrahepatic covalently closed circular DNA (cccDNA) and intrahepatic HBsAg expression. HBsAg titres generally declined over time; this decline was more pronounced in early (HBeAg-positive) than later disease phases (HBeAg-negative). Higher decline in HBsAg levels was consistently associated with subsequent HBsAg seroclearance and a greater decline in total intrahepatic HBV DNA and cccDNA levels. In conclusion, this review showed that HBsAg levels and rates of decline could inform assessment, management and prediction of outcomes in chronic HBV infection. Further studies in broader, more diverse populations and treated patients are needed.
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Affiliation(s)
| | | | | | | | - Joyeta Das
- Research and Development, GSK, Brentford, Middlesex, UK
| | - Vera Gielen
- Research and Development, GSK, Brentford, Middlesex, UK
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11
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Yendewa GA, Salata RA, Olasehinde T, Mulindwa F, Jacobson JM, Mohareb AM. Self-reported hepatitis B testing among noninstitutionalized adults in the United States before the implementation of universal screening, 2013-2017: A nationwide population-based study. J Viral Hepat 2024; 31:657-669. [PMID: 39078109 PMCID: PMC11565436 DOI: 10.1111/jvh.13985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 06/09/2024] [Accepted: 07/16/2024] [Indexed: 07/31/2024]
Abstract
In 2023, the US Centers for Disease Control and Prevention recommended universal screening for hepatitis B virus (HBV); however, the proportion of US adults screened before implementing this recommendation is unknown. We analysed nationally representative data from the National Health Interview Survey (2013-2017) on self-reported HBV testing among noninstitutionalized US adults ≥18 years. We employed Poisson logistic regression to identify factors associated with self-reported testing, using a conceptual framework that included four overarching factors: sociodemographic characteristics, healthcare access, health-seeking behaviours and experiences, and access to internet-based health information. Among 149,628 survey respondents, the self-reported HBV testing rate was 27.2% (95% CI 26.2-28.7) and increased by 1.7% from 2013 to 2017 (p = .006). In adjusted analysis, health-seeking behaviours and experiences had the strongest associations of self-reported testing including a history of hepatitis (AOR 2.68, 95% CI 1.92-3.73), receipt of hepatitis B vaccination (AOR 5.11, 95% CI 4.61-5.68) and prior testing for hepatitis C (AOR 9.14, 95% CI 7.97-10.48) and HIV (AOR 2.69, 95% CI 2.44-2.97). Other factors associated with testing included being male (AOR 1.14, 95% CI 1.03-1.26), ages 30-44 years (AOR 1.37, 95% CI 1.17-1.61), 45-60 years (AOR 1.55, 95% CI 1.30-1.80) and ≥60 years (AOR 1.53, 95% CI 1.28-1.84), residence in the Western US region (AOR 1.23, 95% CI 1.06-1.43), and access to internet-based health information (AOR 1.32, 95% CI 1.18-1.47). Being Hispanic was associated with lower odds of testing (AOR 0.80, 95% CI 0.66-0.97). These findings may help guide optimal HBV screening in the universal testing era.
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Affiliation(s)
- George A Yendewa
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Robert A Salata
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Temitope Olasehinde
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Frank Mulindwa
- United Health Services Wilson Medical Center, Johnson City, New York, USA
| | - Jeffrey M Jacobson
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Amir M Mohareb
- Center for Global Health, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
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12
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McCoullough LC, Fareh M, Hu W, Sozzi V, Makhlouf C, Droungas Y, Lee CL, Takawy M, Fabb SA, Payne TJ, Pouton CW, Netter HJ, Lewin SR, Purcell DF, Holmes JA, Trapani JA, Littlejohn M, Revill PA. CRISPR-Cas13b-mediated suppression of HBV replication and protein expression. J Hepatol 2024; 81:794-805. [PMID: 38815932 DOI: 10.1016/j.jhep.2024.05.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 04/19/2024] [Accepted: 05/16/2024] [Indexed: 06/01/2024]
Abstract
BACKGROUND & AIMS New antiviral approaches that target multiple aspects of the HBV replication cycle to improve rates of functional cure are urgently required. HBV RNA represents a novel therapeutic target. Here, we programmed CRISPR-Cas13b endonuclease to specifically target the HBV pregenomic RNA and viral mRNAs in a novel approach to reduce HBV replication and protein expression. METHODS Cas13b CRISPR RNAs (crRNAs) were designed to target multiple regions of HBV pregenomic RNA. Mammalian cells transfected with replication competent wild-type HBV DNA of different genotypes, a HBV-expressing stable cell line, a HBV infection model and a hepatitis B surface antigen (HBsAg)-expressing stable cell line were transfected with PspCas13b-BFP (blue fluorescent protein) and crRNA plasmids, and the impact on HBV replication and protein expression was measured. Wild-type HBV DNA, PspCas13b-BFP and crRNA plasmids were simultaneously hydrodynamically injected into mice, and serum HBsAg was measured. PspCas13b mRNA and crRNA were also delivered to a HBsAg-expressing stable cell line via lipid nanoparticles and the impact on secreted HBsAg determined. RESULTS Our HBV-targeting crRNAs strongly suppressed HBV replication and protein expression in mammalian cells by up to 96% (p <0.0001). HBV protein expression was also reduced in a HBV-expressing stable cell line and in the HBV infection model. CRISPR-Cas13b crRNAs reduced HBsAg expression by 50% (p <0.0001) in vivo. Lipid nanoparticle-encapsulated PspCas13b mRNA reduced secreted HBsAg by 87% (p = 0.0168) in a HBsAg-expressing stable cell line. CONCLUSIONS Together, these results show that CRISPR-Cas13b can be programmed to specifically target and degrade HBV RNAs to reduce HBV replication and protein expression, demonstrating its potential as a novel therapeutic option for chronic HBV infection. IMPACT AND IMPLICATIONS Owing to the limitations of current antiviral therapies for hepatitis B, there is an urgent need for new treatments that target multiple aspects of the HBV replication cycle to improve rates of functional cure. Here, we present CRISPR-Cas13b as a novel strategy to target HBV replication and protein expression, paving the way for its development as a potential new treatment option for patients living with chronic hepatitis B.
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Affiliation(s)
- Laura C McCoullough
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Mohamed Fareh
- Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia
| | - Wenxin Hu
- Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia
| | - Vitina Sozzi
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Christina Makhlouf
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Yianni Droungas
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Chee Leng Lee
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Mina Takawy
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Stewart A Fabb
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Thomas J Payne
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Colin W Pouton
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Hans J Netter
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Sharon R Lewin
- Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia
| | - Damian Fj Purcell
- Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Jacinta A Holmes
- Department of Gastroenterology, St. Vincent's Hospital, Melbourne, Victoria, Australia
| | - Joseph A Trapani
- Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia
| | - Margaret Littlejohn
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Peter A Revill
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
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Marrapu S, Kumar R. Chronic hepatitis B: Prevent, diagnose, and treat before the point of no return. World J Hepatol 2024; 16:1151-1157. [PMID: 39474571 PMCID: PMC11514616 DOI: 10.4254/wjh.v16.i10.1151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 09/26/2024] [Accepted: 10/10/2024] [Indexed: 10/21/2024] Open
Abstract
Hepatitis B remains a significant global health challenge, contributing to substantial morbidity and mortality. Approximately 254 million people worldwide live with Chronic hepatitis B (CHB), with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions. Alarmingly, only about 13.4% of the individuals infected with this disease have been diagnosed, and awareness of hepatitis B virus (HBV) infection status is as low as 1% in sub-Saharan Africa. In 2022, CHB led to 1.1 million deaths globally. The World Health Organization (WHO) has set a target of eliminating hepatitis B as a public health concern by 2030; however, this goal appears increasingly unattainable due to multiple challenges. These challenges include low vaccination coverage; a large number of undiagnosed cases; a low proportion of patients eligible for treatment under current guidelines; limited access to healthcare; and the costs associated with lifelong treatment. Treatment of HBV can yield significant clinical benefits within a long window of opportunity. However, the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage. This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.
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Affiliation(s)
- Sudheer Marrapu
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India.
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Marrapu S, Kumar R. Chronic hepatitis B: Prevent, diagnose, and treat before the point of no return. World J Hepatol 2024; 16:1331-1337. [DOI: 10.4254/wjh.v16.i10.1331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 09/26/2024] [Accepted: 10/10/2024] [Indexed: 11/22/2024] Open
Abstract
Hepatitis B remains a significant global health challenge, contributing to substantial morbidity and mortality. Approximately 254 million people worldwide live with Chronic hepatitis B (CHB), with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions. Alarmingly, only about 13.4% of the individuals infected with this disease have been diagnosed, and awareness of hepatitis B virus (HBV) infection status is as low as 1% in sub-Saharan Africa. In 2022, CHB led to 1.1 million deaths globally. The World Health Organization (WHO) has set a target of eliminating hepatitis B as a public health concern by 2030; however, this goal appears increasingly unattainable due to multiple challenges. These challenges include low vaccination coverage; a large number of undiagnosed cases; a low proportion of patients eligible for treatment under current guidelines; limited access to healthcare; and the costs associated with lifelong treatment. Treatment of HBV can yield significant clinical benefits within a long window of opportunity. However, the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage. This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.
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Affiliation(s)
- Sudheer Marrapu
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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15
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Kochaksaraei GS, Yang F, Seow CH, Barkema HW, Coffin CS, Shaheen AA. Epidemiology and natural history of chronic Hepatitis B in the Canadian province of Alberta from 2012 to 2021: A population-based study. Ann Hepatol 2024; 30:101576. [PMID: 39293784 DOI: 10.1016/j.aohep.2024.101576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 07/31/2024] [Accepted: 08/21/2024] [Indexed: 09/20/2024]
Abstract
INTRODUCTION AND OBJECTIVES There are limited recent data on the burden of chronic hepatitis B (CHB) in the North American general population. We aimed to identify the CHB burden from a Canadian population-based perspective. PATIENTS AND METHODS Using a retrospective cohort design, we searched Alberta Analytics administrative databases including the Provincial Laboratory database, to describe CHB epidemiology and natural history in Alberta, Canada between fiscal years 2012-2020. We analyzed incidence and prevalence trends using a Poisson regression model and conducted Kaplan-Meier analyses to examine the incident cohort's survival. RESULTS The age/sex-adjusted incidence of CHB between 2015-2020 was 27.1/100,000 person/years (29.6/100,000 in males and 24.5/100,000 in females) and was highest among individuals aged 45-64 years. Despite a decrease in annual incidence of CHB from 36.4 to 13.4/100,000 between 2015-2020, prevalence increased from 98.9 to 210.3/100,000 in the same period. Of 6,860 incident cases, 2.1% died, and 0.2% underwent liver transplantation during a median follow-up of 3.6 years (interquartile range 2.0-4.9 years). CHB patients had significantly lower survival rates compared to age/sex-matched Canadians, with a standardized mortality ratio of 3.9 (95% confidence interval [CI] 3.3-4.6). Male sex (hazard ratio [HR] 1.7; 95% CI 1.2-2.5), older age at diagnosis (HR, 1.08; 95% CI 1.07-1.09) independently predicted mortality. CONCLUSIONS CHB incidence decreased in Alberta, which is consistent with nationwide trends. Males and individuals aged 45-64 had higher CHB incidence and prevalence. CHB patients' lower survival rates emphasize the need to address barriers to guideline recommended HBV care linkage.
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Affiliation(s)
- Golasa Samadi Kochaksaraei
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Fengjuan Yang
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Cynthia H Seow
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Herman W Barkema
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Carla S Coffin
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Abdel-Aziz Shaheen
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
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Gu S, Tao Y, Fan C, Dai Y, Li F, Conklin JL, Tucker JD, Chou R, Moody MA, Easterbrook P, Tang W. Impact of Hepatitis B Virus Point-of-care DNA Viral Load Testing Compared With Laboratory-based Standard-of-care Approaches on Uptake of HBV Viral Load Testing, Treatment, and Turnaround Times: A Systematic Review and Meta-analysis. Open Forum Infect Dis 2024; 11:ofae483. [PMID: 39296343 PMCID: PMC11409893 DOI: 10.1093/ofid/ofae483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 08/22/2024] [Indexed: 09/21/2024] Open
Abstract
Background Point-of-care (PoC) hepatitis B virus (HBV) DNA viral load (VL) assays represent an alternative to laboratory-based standard-of-care (SoC) VL assays to accelerate diagnosis and treatment. We evaluated the impact of using PoC versus SoC approaches on the uptake of VL testing, treatment, and turnaround times from testing to treatment across the HBV care cascade. Methods We searched 5 databases, 6 conference websites, and contacted manufacturers for unpublished reports, for articles with or without a comparator (SoC VL testing), and had data on the uptake of VL testing, treatment, or turnaround times between hepatitis B surface antigen (HBsAg) testing, VL testing, and treatment in the cascade. We performed a random-effects meta-analysis on rates of VL testing and treatment initiation. Results Six studies, composing 9 arms, were included. Three PoC arms reported less than 1 day between screening for HBsAg positivity and VL testing, and the other one (2 arms) reported it between 7 and 11 days. Five arms reported the time to available VL test results (<1 day). Three studies reported 1-8 days between VL testing results and treatment initiation. Two studies reported the turnaround times between a positive HBsAg screening and treatment initiation (the same day and 27 days). Overall, 84.1% of those with HBsAg positivity were tested for DNA VL and 88.3% of eligible people initiated treatment. Conclusions HBV PoC DNA testing appears to be associated with a turnaround time of <1 day for receipt of VL results and appears associated with high rates of DNA testing and initiation of treatment among those eligible. Clinical Trials Registration PROSPERO CRD42023398440.
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Affiliation(s)
- Shuqin Gu
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Yusha Tao
- Dermatology Hospital of South Medical University, Guangzhou, China
- University of North Carolina Project-China, Guangzhou, China
| | - Chengxin Fan
- University of North Carolina Project-China, Guangzhou, China
- School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yifan Dai
- Dermatology Hospital of South Medical University, Guangzhou, China
| | - Feifei Li
- Dermatology Hospital of South Medical University, Guangzhou, China
| | - Jamie L Conklin
- Health Sciences Library, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Joseph D Tucker
- University of North Carolina Project-China, Guangzhou, China
- Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Roger Chou
- Departments of Medicine and Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, USA
| | - M Anthony Moody
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA
- Division of Infectious Diseases, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA
| | - Philippa Easterbrook
- Department of Global HIV, Hepatitis and STI Programmes, World Health Organization, Geneva, Switzerland
| | - Weiming Tang
- Dermatology Hospital of South Medical University, Guangzhou, China
- University of North Carolina Project-China, Guangzhou, China
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Anolli MP, Renteria SU, Degasperi E, Borghi M, Facchetti F, Sambarino D, Perbellini R, Monico S, Ceriotti F, Lampertico P. Quantification of serum HDV RNA by Robogene 2.0 in HDV patients is significantly influenced by the extraction methods. Liver Int 2024; 44:831-837. [PMID: 38247385 DOI: 10.1111/liv.15795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 10/25/2023] [Accepted: 11/07/2023] [Indexed: 01/23/2024]
Abstract
BACKGROUND AND AIM Management of chronic hepatitis delta (CHD) requires reliable tests for HDV RNA quantification. The aim of the study was to compare two extraction methods for the quantification of HDV RNA in untreated and bulevirtide (BLV)-treated CHD patients. METHODS Frozen sera from untreated and BLV-treated CHD patients were tested in a single-centre study for HDV RNA levels (Robogene 2.0, Roboscreen GmbH, Leipzig, Germany; LOD 6 IU/mL) with two extraction methods: manual (INSTANT Virus RNA/DNA kit; Roboscreen GmbH, Leipzig, Germany) versus automated (EZ1 DSP Virus Kit; Qiagen, Hilden, Germany). BLV-treated patients were sampled at baseline and during therapy. RESULTS Two hundred sixty-four sera collected from 157 CHD (139 untreated, 18 BLV-treated) patients were analysed: age 51 (28-78), 59% males, 90% of European origin, 60% cirrhotics, ALT 85 (17-889) U/L, HBsAg 3.8 (1.7-4.6) Log IU/mL, 81% HBV DNA undetectable, 98% HDV genotype 1. Median HDV RNA was 4.53 (.70-8.10) versus 3.77 (.70-6.93) Log IU/mL by manual versus automated extraction (p < .0001). Manual extraction reported similar HDV RNA levels in 31 (20%) patients, higher in 119 (76%) [+.5 and +1 log10 in 60; > +1 log10 in 59] and lower in 7 (4%). Among 18 BLV-treated patients, rates of HDV RNA < LOD significantly differed between the two assays at Weeks 16 and 24 (0% vs. 22%, p = .02; 11% vs. 44%, p = .03), but not at later timepoints. By contrast, virological response rates were similar. CONCLUSIONS Quantification of HDV RNA by Robogene 2.0 is influenced by the extraction method, the manual extraction being 1 Log more sensitive.
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Affiliation(s)
- Maria Paola Anolli
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Uceda Renteria
- Virology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Elisabetta Degasperi
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marta Borghi
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Floriana Facchetti
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Dana Sambarino
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Riccardo Perbellini
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Monico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Ferruccio Ceriotti
- Virology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, CRC "A. M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
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Lin CL, Kao JH. Precision Management of Patients with HBV Infection. CURRENT HEPATOLOGY REPORTS 2024; 23:22-31. [DOI: 10.1007/s11901-024-00632-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/02/2024] [Indexed: 01/03/2025]
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19
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Cheng B, Wu D, Zhang M, Chen S, Wu X, Zhong J, Wu M, Huo M. High immunocompetence in chronic hepatitis patients with normal alanine transaminase levels and and negative hepatitis B e-antigen for the progression of liver fibrosis. Immun Inflamm Dis 2024; 12:e1134. [PMID: 38270318 PMCID: PMC10793183 DOI: 10.1002/iid3.1134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 10/13/2023] [Accepted: 12/17/2023] [Indexed: 01/26/2024] Open
Abstract
INTRODUCTION This study aimed to investigate the role of immunocompetence in chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) levels and negative hepatitis B e antigen (HBeAg) in the risk assessments of the progression of liver fibrosis. METHODS We collected the clinical data of 57 patients with CHB, with normal ALT levels and negative HBeAg from December 2020 to December 2022. With hepatitis B virus (HBV) DNA > 20 IU/mL and ALT ≤ 40 U/L, these patients had never undergone antiviral therapy. The levels of CD4+ , CD4+ CD25+ , CD8+ , and CD4+ CD25+ CD127LOW regulatory T cells (Tregs) in the patients were detected using flow cytometry; the liver stiffness measurement (LSM) values of the patients were detected using Fibroscan. RESULTS There was a statistically significant difference between the levels of fibrosis-4 (FIB-4) and hepatitis B surface antigen (HBsAg) when the cutoff point was HBsAg ≥ 1500 (p < .001). FIB-4 was negatively correlated with HBsAg (R = -0.291, p = .028) and positively correlated with age (R = 0.787, p < .001). LSM was negatively correlated with Treg but this correlation was not statistically significant (p > .05). Findings based on the analysis using logistic regression were as follows: (i) age was the independent risk factor when FIB-4 was used as the indicator for assessing liver fibrosis; (ii) Treg was the independent risk factor when LSM was used as the indicator for assessing liver fibrosis. When Treg was used to predict liver fibrosis, the cutoff value, diagnostic efficacy, area under the receiver operating characteristic (ROC) curve, and p value of the ROC curve were 6.875, 0.641, 0.84, and .027, respectively. CONCLUSION Age and Treg are independent risk factors for progressive liver fibrosis. The cutoff value of Treg > 6.81 indicates the need for timely antiviral treatment and can serve as an indicator for evaluating liver fibrosis.
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Affiliation(s)
- Bianqiao Cheng
- Department of GastroenterologyFuzhou Second HospitalFujianChina
- Department of Clinical MedicineFujian Medical UniversityFujianChina
| | - Dandan Wu
- Department of Clinical MedicineFujian Medical UniversityFujianChina
| | - Ming Zhang
- Department of Clinical MedicineFujian Medical UniversityFujianChina
| | - Shiming Chen
- Department of Clinical MedicineFujian Medical UniversityFujianChina
| | - Xunyuan Wu
- Department of Clinical MedicineFujian Medical UniversityFujianChina
| | - Jingjing Zhong
- Department of Clinical MedicineFujian Medical UniversityFujianChina
| | - Meimei Wu
- Department of Infection ManagementFuzhou Second HospitalFujianChina
| | - Miaomiao Huo
- Department of GastroenterologyFuzhou Second HospitalFujianChina
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Zhang Y, Wan G, Li H, Gao L, Liu N, Gao P, Liu Y, Gao X, Duan X. A prediction nomogram for hepatitis B virus-associated hepatocellular carcinoma. Scand J Gastroenterol 2024; 59:70-77. [PMID: 37647217 DOI: 10.1080/00365521.2023.2252546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 08/16/2023] [Accepted: 08/23/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND The present study aimed to develop and validate a new nomogram for predicting the incidence of hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients receiving antiviral therapy from real-world data. METHODS The nomogram was established based on a real-world retrospective study of 764 patients with HBV from October 2008 to July 2020. A predictive model for the incidence of HCC was developed by multivariable Cox regression, and a nomogram was constructed. The predictive accuracy and discriminative ability of the nomogram were assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Risk group stratification was performed to assess the predictive capacity of the nomogram. The nomogram was compared to three current commonly used predictive models. RESULTS A total of 764 patients with HBV were recruited for this study. Age, family history of HCC, alcohol consumption, and Aspartate aminotransferase-to-Platelet Ratio Index (APRI) were all independent risk predictors of HCC in CHB patients. The constructed nomogram had good discrimination with a C-index of 0.811. The calibration curve and DCA also proved the reliability and accuracy of the nomogram. Three risk groups (low, moderate, and high) with significantly different prognoses were identified (p < 0.001). The model's performance was significantly better than that of other risk models. CONCLUSIONS The nomogram was superior in predicting HCC risk among CHB patients who received antiviral treatment. The model can be utilized in clinical practice to aid decision-making on the strategy of long-term HCC surveillance, especially for moderate- and high-risk patients.
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Affiliation(s)
- Yijin Zhang
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Gang Wan
- Department of Medical Record, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongjie Li
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lili Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Nan Liu
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ping Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yaping Liu
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xuesong Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xuefei Duan
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Campbell C, Wang T, Gillespie I, Barnes E, Matthews PC. Analysis of primary care electronic health record data of people living with hepatitis B virus: infection and hepatocellular carcinoma risk associated with socio-economic deprivation. Public Health 2024; 226:215-227. [PMID: 38091810 PMCID: PMC7615551 DOI: 10.1016/j.puhe.2023.10.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 08/28/2023] [Accepted: 10/18/2023] [Indexed: 01/15/2024]
Abstract
OBJECTIVES We set out to characterise chronic hepatitis B (CHB) in the primary care population in England and investigate risk factors for progression to hepatocellular carcinoma (HCC). STUDY DESIGN Retrospective cohort study. METHODS We identified 8039 individuals with CHB in individuals aged ≥18 years between 1999 and 2019 in the English primary care database QResearch. HCC risk factors were investigated using Cox proportional hazards modelling. RESULTS Most of those with a record of CHB were males (60%) of non-White ethnicity (>70%), and a high proportion were in the most deprived Townsend deprivation quintile (44%). Among 7029 individuals with longitudinal data, 161 HCC cases occurred. Increased HCC hazards were significantly associated with male sex (adjusted hazards ratio [aHR] 3.17, 95% confidence interval [95% CI] 1.92-5.23), in the fifth deprivation quintile as compared to the third quintile (aHR 1.69, 95% CI 1.01-2.84), with older age (for age groups 56-65 and ≥66 years, compared to 26-35 years, aHRs 2.82 [95% CI 1.45-5.46] and 3.76 [95% CI 1.79-7.9], respectively), Caribbean ethnicity (aHR 3.32, 95% CI 1.43-7.71, compared to White ethnicity), ascites (aHR 3.15, 95% CI 1.30-7.67), cirrhosis (aHR 6.55, 95% CI 4.57-9.38) and peptic ulcer disease (aHR 2.26, 95% CI 1.45-3.51). CONCLUSIONS Targeting interventions and HCC surveillance at vulnerable groups is essential to improve CHB outcomes and to support progress towards international goals for the elimination of hepatitis infection as a public health threat.
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Affiliation(s)
- C Campbell
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
| | - T Wang
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
| | | | - E Barnes
- NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Hepatology, Oxford University Hospitals, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK
| | - P C Matthews
- NIHR Oxford Biomedical Research Centre, Oxford, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK; Department of Infectious Diseases, University College London Hospital, Euston Road, London NW1 2BU, UK.
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22
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Chun HS, Papatheodoridis GV, Lee M, Lee HA, Kim YH, Kim SH, Oh YS, Park SJ, Kim J, Lee HA, Kim HY, Kim TH, Yoon EL, Jun DW, Ahn SH, Sypsa V, Yurdaydin C, Lampertico P, Calleja JL, Janssen HLA, Dalekos GN, Goulis J, Berg T, Buti M, Kim SU, Kim YJ. PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B. J Hepatol 2024; 80:20-30. [PMID: 37734683 DOI: 10.1016/j.jhep.2023.09.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 07/31/2023] [Accepted: 09/05/2023] [Indexed: 09/23/2023]
Abstract
BACKGROUND & AIMS Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.
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Affiliation(s)
- Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea; Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea; Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea.
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Yeong Hwa Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Seo Hyun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Yun-Seo Oh
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Su Jin Park
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Jihye Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea; Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea
| | - Hwi Young Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea; Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea
| | - Tae Hun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea; Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Vana Sypsa
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Cihan Yurdaydin
- Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Harry LA Janssen
- Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - John Goulis
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Maria Buti
- Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Yonsei Liver Center, Severance Hospital, Seoul, Korea.
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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Hao X, Fan R, Zeng HM, Hou JL. Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection. J Clin Transl Hepatol 2023; 11:1508-1519. [PMID: 38161501 PMCID: PMC10752803 DOI: 10.14218/jcth.2023.00087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/04/2023] [Accepted: 06/02/2023] [Indexed: 01/03/2024] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and represents a global health challenge. Liver cancer ranks third in cancer-related mortality with 830,000 deaths and sixth in incidence with 906,000 new cases annually worldwide. HCC most commonly occurs in patients with underlying liver disease, especially chronic hepatitis B virus (HBV) infection in highly endemic areas. Predicting HCC risk based on scoring models for patients with chronic liver disease is a simple, effective strategy for identifying and stratifying patients to improve the early diagnosis rate and prognosis of HCC. We examined 23 HCC risk scores published worldwide in CHB patients with (n=10) or without (n=13) antiviral treatment. We also described the characteristics of the risk score's predictive performance and application status. In the future, higher predictive accuracy could be achieved by combining novel technologies and machine learning algorithms to develop and update HCC risk score models and integrated early warning and diagnosis systems for HCC in hospitals and communities.
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Affiliation(s)
- Xin Hao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Rong Fan
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Hong-Mei Zeng
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin-Lin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
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Zhang L, Yang L, Gao Y, Bi X, Lin Y, Deng W, Jiang T, Lu Y, Hao H, Wan G, Yi W, Xie Y, Li M. Nomogram for evaluating obvious liver inflammation in treatment-naïve HBeAg positive chronic hepatitis B virus infection patients with normal ALT. Virulence 2023; 14:2158710. [PMID: 36600180 PMCID: PMC9828634 DOI: 10.1080/21505594.2022.2158710] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 12/11/2022] [Indexed: 01/06/2023] Open
Abstract
The purpose of this study was to develop an effective and non-invasive nomogram for evaluating liver obvious inflammation in untreated HBeAg positive patients with chronic hepatitis B virus (HBV) infection. A nomogram was established on a model cohort of 292 treatment-naïve HBeAg positive patients with normal alanine aminotransferase (ALT ≤40 U/L) at Beijing Ditan Hospital from January 2008 to March 2018. Then the nomogram was prospectively validated in a cohort of 88 patients from July 2019 to May 2021. Calibration curves and Concordance index were used to evaluate the accuracy of prediction and identification performance of the model. In untreated HBeAg positive chronic hepatitis B virus infection patients with normal ALT, the formula for predicting liver inflammation was Logit (P) =-0.91-0.41×log10 (qHBeAg)+0.11×AST-0.01×PLT. The nomogram had C-index of 0.751 (95% CI, 0.688-0.815), indicating a good consistency between prediction and real observation on the model cohort. The validation cohort confirmed its good performance. In this study, liver inflammation nomograms based on HBeAg, AST, and PLT were established and verified in treatment-naïve HBeAg positive chronic HBV patients with normal ALT.
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Affiliation(s)
- Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Gang Wan
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Yi
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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25
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You H, Wang F, Li T, Xu X, Sun Y, Nan Y, Wang G, Hou J, Duan Z, Wei L, Jia J, Zhuang H. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022). J Clin Transl Hepatol 2023; 11:1425-1442. [PMID: 37719965 PMCID: PMC10500285 DOI: 10.14218/jcth.2023.00320] [Citation(s) in RCA: 77] [Impact Index Per Article: 38.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 09/19/2023] Open
Abstract
To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
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Affiliation(s)
- Hong You
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fusheng Wang
- The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Taisheng Li
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyuan Xu
- Peking University First Hospital, Beijing, China
| | - Yameng Sun
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuemin Nan
- Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | | | - Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhongping Duan
- Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- Peking University Health Science Center, Beijing, China
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Ghany MG, Buti M, Lampertico P, Lee HM. Guidance on treatment endpoints and study design for clinical trials aiming to achieve cure in chronic hepatitis B and D: Report from the 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference. J Hepatol 2023; 79:1254-1269. [PMID: 37377088 DOI: 10.1016/j.jhep.2023.06.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 04/14/2023] [Indexed: 06/29/2023]
Abstract
Representatives from academia, industry, regulatory agencies, and patient advocacy groups convened under the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) in June 2022 with the primary goal of achieving consensus on chronic HBV and HDV treatment endpoints to guide clinical trials aiming to "cure" HBV and HDV. Conference participants reached an agreement on some key points. The preferred primary endpoint for phase II/III trials evaluating finite treatments for chronic hepatitis B (CHB) is a "functional" cure, defined as sustained HBsAg loss and HBV DNA less than the lower limit of quantitation (LLOQ) 24 weeks off-treatment. An alternate endpoint would be "partial cure" defined as sustained HBsAg level <100 IU/mL and HBV DNA
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Affiliation(s)
- Marc G Ghany
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
| | - Maria Buti
- Liver Unit, Vall d'Hebron University Hospital and CIBEREHD del Instituto Carlos III, Barcelona, Spain
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy
| | - Hannah M Lee
- Department of Gastroenterology, Hepatology and Nutrition, Stravitz Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia, USA
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27
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Yu HS, Jiang H, Li MK, Yang BL, Smayi A, Chen JN, Wu B, Yang YD. Lowering the threshold of alanine aminotransferase for enhanced identification of significant hepatic injury in chronic hepatitis B patients. World J Gastroenterol 2023; 29:5166-5177. [PMID: 37744292 PMCID: PMC10514758 DOI: 10.3748/wjg.v29.i35.5166] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 07/22/2023] [Accepted: 08/31/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND The clinical and histological features of chronic hepatitis B (CHB) patients who fall into the "grey zone (GZ)" and do not fit into conventional natural phases are unclear. AIM To explore the impact of varying the threshold of alanine aminotransferase (ALT) levels in identifying significant liver injury among GZ patients. METHODS This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy. The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines. GZ CHB patients were classified into four groups: GZ-A (HBeAg positive, normal ALT levels, and HBV DNA ≤ 107 IU/mL), GZ-B (HBeAg positive, elevated ALT levels, and HBV DNA < 104 or > 107 IU/mL), GZ-C (HBeAg negative, normal ALT levels, and HBV DNA ≥ 2000 IU/mL), and GZ-D (HBeAg negative, elevated ALT levels, and HBV DNA ≤ 2000 IU/mL). Significant hepatic injury (SHI) was defined as the presence of notable liver inflammation (≥ G2) and/or significant fibrosis (≥ S2). RESULTS The results showed that 50.22% of patients were classified as GZ, and 63.7% of GZ patients developed SHI. The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria (35 U/L for men and 25 U/L for women) can more accurately identify patients with significant liver damage in the GZ phases. In total, the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 64.86% [(221 + 294)/794]. When we lowered the ALT treatment threshold to the new criteria (30 U/L for men and 19 U/L for women), the same outcome was revealed, and the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 75.44% [(401 + 198)/794]. Additionally, the proportion of SHI was 49.1% in patients under 30 years old and increased to 55.3% in patients over 30 years old (P = 0.136). CONCLUSION These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.
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Affiliation(s)
- Hong-Sheng Yu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
- Department of Liver Disease, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
| | - Hao Jiang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
- Department of Liver Disease, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
| | - Ming-Kai Li
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
- Department of Liver Disease, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
| | - Bi-Lan Yang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
- Department of Liver Disease, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
| | - Abdukyamu Smayi
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
- Department of Liver Disease, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
| | - Jian-Ning Chen
- Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
| | - Bin Wu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
- Department of Liver Disease, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
| | - Yi-Dong Yang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
- Department of Liver Disease, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
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28
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Duan Z, Dong J, Liu Y, Zhou H, Duan S, Liu W, Liang R, Ding Y. Awareness of HBV Functional Cure and Attitude Toward Related Clinical Trials Among Patients with Chronic Hepatitis B in China. Patient Prefer Adherence 2023; 17:2063-2072. [PMID: 37636489 PMCID: PMC10460183 DOI: 10.2147/ppa.s422916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 08/11/2023] [Indexed: 08/29/2023] Open
Abstract
Purpose HBV functional cure is an optimal treatment goal for chronic hepatitis B (CHB) at present and numerous new drugs aiming for HBV functional cure are in development. We carried out an internet-based survey to understand the treatment status, unmet needs, awareness of HBV functional cure and attitude toward related clinical trials among CHB patients in China. Patients and Methods An internet-based anonymous survey was conducted on CHB patients who reside in mainland China. Determinants of awareness and attitude were identified by logistic regression models. Results Of the 1220 CHB patients who completed the survey questionnaire, 11.1% (135/1220) were aware of HBV functional cure and 50.2% (612/1220) answered "definitely will" to participate in related clinical trials. Participants who knew their HBsAg level (HBsAg<1500 IU/mL: OR=3.03, 95% CI: 1.87-4.92; HBsAg≥1500 IU/mL: OR=2.57, 95% CI: 1.35-4.88), who expected to achieve HBsAg loss with treatment (OR=1.63, 95% CI: 1.07-2.50) and who were dissatisfied with current treatment due to the failure of achieving HBsAg loss (OR=1.67, 95% CI: 1.10-2.53) had better awareness of HBV functional cure. Participants who had HBsAg level less than 1500 IU/mL (OR=1.45, 95% CI: 1.05-1.99), treatment with pegylated interferon alpha with or without nucleos(t)ide (OR=1.68, 95% CI: 1.11-2.53) and better awareness of HBV functional cure (OR=1.62, 95% CI: 1.01-2.61) were more likely to say "definitely will" to participate in related clinical trials. Conclusion Chinese CHB patients reported a low awareness of HBV functional cure. Although CHB patients in China reported a low rate of HBV functional cure awareness, they had a high acceptance of related clinical trials.
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Affiliation(s)
- Zhongping Duan
- Fourth Department of Hepatology Center, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Jinling Dong
- Fourth Department of Hepatology Center, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Ying Liu
- iGandan, the Portal for All Liver Disease Caring, Beijing, People’s Republic of China
| | - Haiyang Zhou
- iGandan, the Portal for All Liver Disease Caring, Beijing, People’s Republic of China
| | - Shuli Duan
- iGandan, the Portal for All Liver Disease Caring, Beijing, People’s Republic of China
| | - Weihong Liu
- Brii Biosciences Inc., Beijing, People’s Republic of China
| | - Rico Liang
- Brii Biosciences Inc., Beijing, People’s Republic of China
| | - Yue Ding
- Brii Biosciences Inc., Beijing, People’s Republic of China
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29
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Combination treatment of pegylated interferon and tenofovir versus tenofovir for people with chronic hepatitis B. Cochrane Database Syst Rev 2023; 2023:CD015730. [PMCID: PMC10401907 DOI: 10.1002/14651858.cd015730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2024]
Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of pegylated interferon combined with tenofovir versus tenofovir monotherapy in adults with chronic hepatitis B.
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30
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Lee YT, Fujiwara N, Yang JD, Hoshida Y. Risk stratification and early detection biomarkers for precision HCC screening. Hepatology 2023; 78:319-362. [PMID: 36082510 PMCID: PMC9995677 DOI: 10.1002/hep.32779] [Citation(s) in RCA: 61] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/25/2022] [Accepted: 08/28/2022] [Indexed: 12/08/2022]
Abstract
Hepatocellular carcinoma (HCC) mortality remains high primarily due to late diagnosis as a consequence of failed early detection. Professional societies recommend semi-annual HCC screening in at-risk patients with chronic liver disease to increase the likelihood of curative treatment receipt and improve survival. However, recent dynamic shift of HCC etiologies from viral to metabolic liver diseases has significantly increased the potential target population for the screening, whereas annual incidence rate has become substantially lower. Thus, with the contemporary HCC etiologies, the traditional screening approach might not be practical and cost-effective. HCC screening consists of (i) definition of rational at-risk population, and subsequent (ii) repeated application of early detection tests to the population at regular intervals. The suboptimal performance of the currently available HCC screening tests highlights an urgent need for new modalities and strategies to improve early HCC detection. In this review, we overview recent developments of clinical, molecular, and imaging-based tools to address the current challenge, and discuss conceptual framework and approaches of their clinical translation and implementation. These encouraging progresses are expected to transform the current "one-size-fits-all" HCC screening into individualized precision approaches to early HCC detection and ultimately improve the poor HCC prognosis in the foreseeable future.
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Affiliation(s)
- Yi-Te Lee
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California
| | - Naoto Fujiwara
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California; Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, California; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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31
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Wu TW, Chou CL, Chen CF, Wang LY. Common Genetic Variants of Response to Hepatitis B Vaccines Correlate with Risks of Chronic Infection of Hepatitis B Virus: A Community-Based Case-Control Study. Int J Mol Sci 2023; 24:ijms24119741. [PMID: 37298692 DOI: 10.3390/ijms24119741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 05/26/2023] [Accepted: 06/02/2023] [Indexed: 06/12/2023] Open
Abstract
Hepatitis B (HB) vaccination effectively reduces the risks of chronic infection with the hepatitis B virus (HBV). It is unknown whether there is a common genetic determinant for response to the HB vaccine and susceptibility to chronic HBV infection. This case-control study, which included 193 chronic HBV carriers and 495 non-carriers, aimed to explore the effects of the most significant single nucleotide polymorphisms (SNPs) in response to the HB vaccine on the risks of chronic HBV infection. Out of 13 tested SNPs, the genotype distributions of four SNPs at the human leukocyte antigen (HLA) class II region, including rs34039593, rs614348, rs7770370, and rs9277535, were significantly different between HBV carriers and non-carriers. The age-sex-adjusted odds ratios (OR) of chronic HBV infection for rs34039593 TG, rs614348 TC, rs7770370 AA, and rs9277535 AA genotypes were 0.51 (95% confidence interval [CI], 0.33-0.79; p = 0.0028), 0.49 (95% CI, 0.32-0.75; p = 6.5 × 10-4), 0.33 (95% CI, 0.18-0.63; p = 7.4 × 10-4), and 0.31 (95% CI, 0.14-0.70; p = 0.0043), respectively. Multivariable analyses showed that rs614348 TC and rs7770370 AA genotypes were significantly independent protectors against chronic HBV infection. The multivariable-adjusted ORs for subjects with none, either one, or both of the protective genotypes were 1.00 (referent), 0.47 (95% CI: 0.32-0.71; p = 3.0 × 10-4), and 0.16 (95% CI: 0.05-0.54; p = 0.0032), respectively. Among eight HBeAg-positive carriers, only one of them carried a protective genotype. This study shows that response to the HB vaccine and susceptibility to chronic HBV infection share common genetic determinants and indicates that HLA class II members are the main responsible host genetic factors.
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Affiliation(s)
- Tzu-Wei Wu
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
| | - Chao-Liang Chou
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
- Department of Neurology, MacKay Memorial Hospital, New Taipei City 251, Taiwan
| | - Chuen-Fei Chen
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
| | - Li-Yu Wang
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
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32
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Xu X, Wang H, Shan S, Sun Y, Xu X, You H, Jia J, Zhuang H, Kong Y, on behalf of the China Registry of Hepatitis B (CR-HepB) Group. The Impact of the Definitions of Clinical Phases on the Profiles of Grey-Zone Patients with Chronic Hepatitis B Virus Infection. Viruses 2023; 15:1212. [PMID: 37243297 PMCID: PMC10222301 DOI: 10.3390/v15051212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 04/26/2023] [Accepted: 04/30/2023] [Indexed: 05/28/2023] Open
Abstract
We aim to investigate the impact of different clinical phases' definitions of chronic hepatitis B (CHB) infection on the profiles of grey zone, based on HBV guidelines set by the Chinese Society of Hepatology and Chinese Society of Infectious Diseases (CSH/CSID, 2022 version) and guidelines set by the American Association for the Study of Liver Diseases (AASLD, 2018 version). We retrospectively examined untreated CHB patients enrolled in the China Registry of Hepatitis B database. Patients' clinical phases were determined as per CSH/CSID and AASLD. Liver fibrosis was estimated by FIB-4 and/or APRI. Among 3462 CHB patients, 56.9% and 41.7% fell into the grey zone based on AASLD and CSH/CSID. Compared with grey zone patients as per AASLD, those under CSH/CSID guidelines showed lower levels of median ALT (26.0 vs. 37.0 U/L, p < 0.001), AST (25.0 vs. 29.4 U/L, p < 0.001) and APRI (0.3 vs. 0.4, p < 0.001), and lower rates of advanced fibrosis estimated by APRI (7.9% vs. 11.4% p = 0.001), but comparable rates by FIB-4 (13.0% vs. 14.1%, p = 0.389). With the stepwise lowering of ALT upper limits of normal (ULN) values from 50/40 U/L for males/females to 40/40 U/L, 35/25 U/L and 30/19 U/L, the proportions of grey zone patients as per CSH/CSID declined from 46.7% to 41.7%, 34.3% and 28.8%, respectively, whereas they remained stable (55.7%, 56.2%, 56.9% and 57.0%) as per AASLD. Compared with the AASLD guidelines, CSH/CSID guidelines leave fewer and less severe patients in the grey zone. Lowering ALT ULN values reduces the number of grey zone patients as per CSH/CSID, but not under AASLD guidelines.
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Affiliation(s)
- Xiaoqian Xu
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing 100050, China
| | - Hao Wang
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing 100050, China
| | - Shan Shan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Yameng Sun
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Xiaoyuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing 100191, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing 100050, China
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Murata K, Mizokami M. Possible biological mechanisms of entecavir versus tenofovir disoproxil fumarate on reducing the risk of hepatocellular carcinoma. J Gastroenterol Hepatol 2023; 38:683-691. [PMID: 36918402 DOI: 10.1111/jgh.16178] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/08/2023] [Indexed: 03/16/2023]
Abstract
Hepatitis B virus (HBV) is a life-threatening infectious virus associated with the risk of liver failure and hepatocellular carcinoma (HCC). Regarding HBV treatment, the recent development of nucleoside/nucleotide analogs (NUC), HBV reverse transcriptase inhibitors, enabled favorable viral control as well as improved prognosis in patients with chronic hepatitis B. However, NUC fails to clear HBV because the formation of covalently closed circular DNA or HBV surface antigen occurs upstream of the point of action of NUC. Recently, we found that acyclic nucleoside phosphonates (ANP) such as adefovir or tenofovir, but not lamivudine or entecavir, induced IFN-λ3 productions in the gastrointestinal tract and modulated lipopolysaccharide (LPS)-mediated cytokine profiles in peripheral blood mononuclear cells, such as interleukin (IL)-12p70 induction and IL-10 inhibition, which are immunologically favorable cytokine profiles for HBV elimination. Furthermore, IFN-α, in combination with ANP, showed additional and synergistic effects on IFN-λ3 and IL-12p70 production, respectively, while not affecting IL-10 levels. Mechanistic analyses of the cytokine modulation by ANP revealed that ANP blocked the mammalian target of the rapamycin (mTOR) pathway by inhibiting Akt translocation to the plasma membrane, thereby inhibiting Akt phosphorylation. As it has been reported that IFN-λ inhibits tumor growth directly or indirectly and the mTOR pathway is generally activated in most cancer cells, ANP might have potential anti-HCC effects. Our in vitro and ex vivo findings might stir the debate on whether types of NUC affect the risk of HBV-related HCC incidence.
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Affiliation(s)
- Kazumoto Murata
- Division of Virology, Department of Infection and Immunity, Jichi Medical University, Shimotsuke, Japan
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Masashi Mizokami
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan
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Genetic Susceptibility to Hepatocellular Carcinoma in Patients with Chronic Hepatitis Virus Infection. Viruses 2023; 15:v15020559. [PMID: 36851773 PMCID: PMC9964813 DOI: 10.3390/v15020559] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies.
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Affiliation(s)
- Geoffrey Dusheiko
- From University College London (G.D.), Kings College Hospital London (G.D., K.A.), Kings College London (K.A.), and the Institute of Immunity and Transplantation, University College London (M.K.M.) - all in London
| | - Kosh Agarwal
- From University College London (G.D.), Kings College Hospital London (G.D., K.A.), Kings College London (K.A.), and the Institute of Immunity and Transplantation, University College London (M.K.M.) - all in London
| | - Mala K Maini
- From University College London (G.D.), Kings College Hospital London (G.D., K.A.), Kings College London (K.A.), and the Institute of Immunity and Transplantation, University College London (M.K.M.) - all in London
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Lee JS, Lim TS, Lee HW, Kim SU, Park JY, Kim DY, Ahn SH, Lee HW, Lee JI, Kim JK, Min IK, Kim BK. Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis. Diagnostics (Basel) 2022; 13:3. [PMID: 36611295 PMCID: PMC9818663 DOI: 10.3390/diagnostics13010003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/14/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
This study aimed to evaluate the predictive performance of pre-existing well-validated hepatocellular carcinoma (HCC) prediction models, established in patients with HBV-related cirrhosis who started potent antiviral therapy (AVT). We retrospectively reviewed the cases of 1339 treatment-naïve patients with HBV-related cirrhosis who started AVT (median period, 56.8 months). The scores of the pre-existing HCC risk prediction models were calculated at the time of AVT initiation. HCC developed in 211 patients (15.1%), and the cumulative probability of HCC development at 5 years was 14.6%. Multivariate Cox regression analysis revealed that older age (adjusted hazard ratio [aHR], 1.023), lower platelet count (aHR, 0.997), lower serum albumin level (aHR, 0.578), and greater LS value (aHR, 1.012) were associated with HCC development. Harrell’s c-indices of the PAGE-B, modified PAGE-B, modified REACH-B, CAMD, aMAP, HCC-RESCUE, AASL-HCC, Toronto HCC Risk Index, PLAN-B, APA-B, CAGE-B, and SAGE-B models were suboptimal in patients with HBV-related cirrhosis, ranging from 0.565 to 0.667. Nevertheless, almost all patients were well stratified into low-, intermediate-, or high-risk groups according to each model (all log-rank p < 0.05), except for HCC-RESCUE (p = 0.080). Since all low-risk patients had cirrhosis at baseline, they had unneglectable cumulative incidence of HCC development (5-year incidence, 4.9−7.5%). Pre-existing risk prediction models for patients with chronic hepatitis B showed suboptimal predictive performances for the assessment of HCC development in patients with HBV-related cirrhosis.
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Affiliation(s)
- Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University Health System, Gyeonggi-do, Seoul 03722, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Seoul 06273, Republic of Korea
| | - Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Seoul 06273, Republic of Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University Health System, Gyeonggi-do, Seoul 03722, Republic of Korea
| | - In Kyung Min
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
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Allaire M, Bruix J, Korenjak M, Manes S, Maravic Z, Reeves H, Salem R, Sangro B, Sherman M. What to do about hepatocellular carcinoma: Recommendations for health authorities from the International Liver Cancer Association. JHEP Rep 2022; 4:100578. [PMID: 36352896 PMCID: PMC9638834 DOI: 10.1016/j.jhepr.2022.100578] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a major public health problem worldwide for which the incidence and mortality are similar, pointing to the lack of effective treatment options. Knowing the different issues involved in the management of HCC, from risk factors to screening and management, is essential to improve the prognosis and quality of life of affected individuals. This document summarises the current state of knowledge and the unmet needs for all the different stakeholders in the care of liver cancer, meaning patients, relatives, physicians, regulatory agencies and health authorities so that optimal care can be delivered to patients. The document was commissioned by the International Liver Cancer Association and was reviewed by senior members, including two ex-presidents of the Association. This document lays out the recommended approaches to the societal management of HCC based on the economic status of a given region.
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Key Words
- AASLD, American Association for the Study of Liver Disease
- AFP, alpha-fetoprotein
- ALT, alanine aminotransferase
- APRI, aspartate aminotransferase-to-platelet ratio index
- Alcohol consumption
- BCLC, Barcelona clinic liver cancer
- DCP, des-gammacarboxy prothrombin
- DEB-TACE, TACE with drug-eluting beads
- EASL, European Association for the study of the Liver
- EBRT, external beam radiation therapy
- ELF, enhanced liver fibrosis
- GGT, gamma-glutamyltransferase
- HCC, hepatocellular carcinoma
- Hepatocellular carcinoma
- Hepatocellular carcinoma surveillance
- Hepatocellular carcinoma treatment
- Li-RADS, Liver Imaging Reporting and Data System
- NAFLD, non-alcoholic fatty liver disease
- Obesity
- RFA, radiofrequency ablation
- TACE, transarterial chemoembolisation
- TARE, transarterial radioembolisation
- TKI, tyrosine kinase inhibitor
- Viral hepatitis
- cTACE, conventional TACE
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Affiliation(s)
- Manon Allaire
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d’Hépato-gastroentérologie, Paris, France
| | - Jordi Bruix
- University Hospital Clinic IDIBAPS, Barcelona, Spain
| | - Marko Korenjak
- European Liver Patients' Association (ELPA), Brussels, Belgium
| | - Sarah Manes
- Global Liver Institute Washington District of Columbia, USA
| | | | - Helen Reeves
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, IL 60611, USA
| | - Bruno Sangro
- Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain
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Spearman CW, Dusheiko G, Jonas E, Abdo A, Afihene M, Cunha L, Desalegn H, Kassianides C, Katsidzira L, Kramvis A, Lam P, Lesi OA, Micah EA, Musabeyezu E, Ndow G, Nnabuchi CV, Ocama P, Okeke E, Rwegasha J, Shewaye AB, Some FF, Tzeuton C, Sonderup MW. Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa. Lancet Gastroenterol Hepatol 2022; 7:1036-1048. [PMID: 35810766 DOI: 10.1016/s2468-1253(22)00041-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 01/26/2022] [Accepted: 02/02/2022] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.
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Affiliation(s)
- C Wendy Spearman
- Division of Hepatology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
| | - Geoffrey Dusheiko
- University College London Medical School, London, UK; Kings College Hospital, London, UK
| | - Eduard Jonas
- Surgical Gastroenterology Unit, Division of General Surgery, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Abdelmounem Abdo
- National Centre for Gastrointestinal and Liver Disease, Ibn Sina Hospital, Alamarat, Khartoum, Sudan
| | - Mary Afihene
- Department of Medicine, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Lina Cunha
- Gastroenterology Unit, Maputo Private Hospital, Maputo, Mozambique
| | - Hailemichael Desalegn
- Department of Internal Medicine, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Chris Kassianides
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Leolin Katsidzira
- Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Olufunmilayo A Lesi
- Gastroenterology and Hepatology Unit, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Eileen A Micah
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | | | - Gibril Ndow
- Disease Control and Elimination Theme, MRC Unit The Gambia at the London School of Tropical Medicine, London, UK; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Chidi V Nnabuchi
- Asokoro District Hospital, Nile University Teaching Hospital, Abuja, Nigeria
| | - Ponsiano Ocama
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Edith Okeke
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, College of Health Sciences, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - John Rwegasha
- Gastroenterology Training Centre, Department of Internal Medicine, Muhimbili National Hospital, Dar Es Salaam, Tanzania
| | - Abate B Shewaye
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Fatuma F Some
- Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
| | - Mark W Sonderup
- Division of Hepatology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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Teng YX, Xie S, Guo PP, Deng ZJ, Zhang ZY, Gao W, Zhang WG, Zhong JH. Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: Current Progresses and Challenges. J Clin Transl Hepatol 2022; 10:955-964. [PMID: 36304509 PMCID: PMC9547250 DOI: 10.14218/jcth.2021.00586] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 01/24/2022] [Accepted: 04/18/2022] [Indexed: 01/27/2023] Open
Abstract
The rising global prevalence of metabolic diseases has increased the prevalence of non-alcoholic fatty liver disease (NAFLD), leading to an increase in cases of NAFLD-related hepatocellular carcinoma (HCC). To provide an updated literature review detailing epidemiology, risk factors, pathogenic pathways, and treatment strategies linked to NAFLD-related HCC, we conducted a literature search on PubMed from its inception to December 31, 2021. About 25% of the global population suffers from NAFLD. The annual incidence of HCC among NAFLD patients is approximately 1.8 per 1,000 person-years. Older age, male sex, metabolic comorbidities, unhealthy lifestyle habits (such as smoking and alcohol consumption), physical inactivity, genetic susceptibility, liver fibrosis, and degree of cirrhosis in NAFLD patients are important risk factors for NAFLD-related HCC. Therefore, low-calorie diet, moderate-intensity exercise, treatment of metabolic comorbidities, and cessation of smoking and alcohol are the main measures to prevent NAFLD-related HCC. In addition, all patients with advanced NAFLD-related fibrosis or cirrhosis should be screened for HCC. Immune suppression disorders and changes in the liver microenvironment may be the main pathogenesis of NAFLD-related HCC. Hepatic resection, liver transplantation, ablation, transarterial chemoembolization, radiotherapy, targeted drugs, and immune checkpoint inhibitors are used to treat NAFLD-related HCC. Lenvatinib treatment may lead to better overall survival, while immune checkpoint inhibitors may lead to worse overall survival. Given the specific risk factors for NAFLD-related HCC, primary prevention is key. Moreover, the same treatment may differ substantially in efficacy against NAFLD-related HCC than against HCC of other etiologies.
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Affiliation(s)
- Yu-Xian Teng
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Si Xie
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Ping-Ping Guo
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Zhu-Jian Deng
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Zi-Yi Zhang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Wei Gao
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Wan-Guang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi, China
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Sheng Q, Wang N, Zhang C, Fan Y, Li Y, Han C, Wang Z, Wei S, Dou X, Ding Y. HBeAg-negative Patients with Chronic Hepatitis B Virus Infection and Normal Alanine Aminotransferase: Wait or Treat? J Clin Transl Hepatol 2022; 10:972-978. [PMID: 36304490 PMCID: PMC9547271 DOI: 10.14218/jcth.2021.00443] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/25/2021] [Accepted: 02/27/2022] [Indexed: 12/04/2022] Open
Abstract
Alanine aminotransferase (ALT) is a common clinical indicator of liver inflammation. The current Chinese guidelines for the management of chronic hepatitis B (CHB) recommend antiviral treatment for patients with detectable hepatitis B virus (HBV) DNA and persistent ALT levels (ALTs) exceeding the upper limit of normal. However, it has been recently reported that patients with chronic HBV infection, especially HBeAg-negative patients with persistently normal ALTs, may have liver biopsy findings of significant inflammation and fibrosis. For HBeAg-negative patients with chronic HBV infection and normal ALTs, many controversial questions have been asked. To treat or not? When to initiate the treatment? Which drug is appropriate? In this review, we summarize the available data on the management of HBeAg-negative patients with chronic HBV infection and normal ALTs with the aim of improving the current clinical management.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiaoguang Dou
- Correspondence to: Xiaoguang Dou and Yang Ding, Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 HuaXiang Road, TieXi District,Shenyang, Liaoning 110022, China. ORCID: https://orcid.org/0000-0003-1856-7331 (XGD), https://orcid.org/0000-0002-7066-2865 (YD). Tel: +86-18940251121 (XGD), +86-13332434847 (YD), Fax: +86-24-25998744, E-mail: (XGD), (YD)
| | - Yang Ding
- Correspondence to: Xiaoguang Dou and Yang Ding, Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 HuaXiang Road, TieXi District,Shenyang, Liaoning 110022, China. ORCID: https://orcid.org/0000-0003-1856-7331 (XGD), https://orcid.org/0000-0002-7066-2865 (YD). Tel: +86-18940251121 (XGD), +86-13332434847 (YD), Fax: +86-24-25998744, E-mail: (XGD), (YD)
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Santos CMDL, Brito MD, Castro PASVD, Vries TPD, Viana NL, Coelho MPP, Malheiro OB, Bering T, Gonzalez MC, Teixeira R, Cambraia RD, Rocha GA, Silva LD. Metabolic-associated fatty liver disease is associated with low muscle mass and strength in patients with chronic hepatitis B. World J Hepatol 2022; 14:1652-1666. [PMID: 36157867 PMCID: PMC9453457 DOI: 10.4254/wjh.v14.i8.1652] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 07/04/2022] [Accepted: 08/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although the prognostic relevance of sarcopenia has been increasingly recognised in the context of liver disease, there is a paucity of data evaluating body composition in patients with chronic hepatitis B (CHB). Beyond virus-related factors, nutritional and metabolic aspects can be associated with skeletal muscle abnormalities in these patients and should not be disregarded.
AIM To evaluate the association between components of sarcopenia and demographic, clinical, lifestyle, nutritional, and biochemical variables in CHB patients.
METHODS Dual-energy X-ray absorptiometry (DXA) was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for body mass index (ALMBMI). Muscle function was evaluated by hand grip strength (HGS) and the timed up and go test. Metabolic-associated fatty liver disease (MAFLD) was defined according to the criteria proposed by an international expert panel. A body shape index and the International Physical Activity Questionnaire were used to assess central obesity and physical activity level, respectively.
RESULTS This cross-sectional study included 105 CHB outpatients followed at the tertiary care ambulatory centre (mean age, 48.5 ± 12.0 years; 58.1% males; 76.2% without cirrhosis; 23.8% with compensated cirrhosis). The DXA-derived fat mass percentage was inversely correlated with the ALMBMI (r = - 0.87) and HGS (r = - 0.63). In the multivariable analysis, MAFLD, sedentarism and central obesity were positively and independently associated with low ALMBMI. MAFLD and central obesity were independently associated with low HGS.
CONCLUSION MAFLD and central obesity were associated with low muscle mass and strength in patients with chronic hepatitis B, independent of the liver disease stage.
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Affiliation(s)
- Cecy Maria de Lima Santos
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Matheus Duarte Brito
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Pedro Alves Soares Vaz de Castro
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Thais Pontello de Vries
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Nataly Lopes Viana
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Marta Paula Pereira Coelho
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Olívio Brito Malheiro
- Department of Locomotor System, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Tatiana Bering
- Department of Food and Nutrition, Universidade Federal de Mato Grosso, Cuiabá 78060-900, Mato Grosso, Brazil
| | - Maria Cristina Gonzalez
- Postgraduate Program in Health and Behaviour, Catholic University of Pelotas, Pelotas 96015-560, Rio Grande do Sul, Brazil
| | - Rosângela Teixeira
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Rodrigo Dias Cambraia
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Luciana Diniz Silva
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
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Abstract
Hepatitis B and hepatitis C are a global burden and underscore the impact of preventable acute and chronic diseases on personal as well as population level health. Caring for pediatric patients with hepatitis B and C requires a deep understanding of the pathophysiology of viral processes. Insight into the epidemiology, transmission, and surveillance of these infections is critical to prevention and therapy. Extensive research in recent years has created a growing number of treatments, changing the landscape of the medical field's approach to the viral hepatitis pandemic.
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Wang J, Ding W, Liu J, Liu Y, Yan X, Xia J, Wu W, Jia B, Chen Y, Gao D, Hong S, Wang X, Wang L, Tong X, Yin S, Zhang Z, Li J, Huang R, Wu C. Association of Coexistent Hepatitis B Surface Antigen and Antibody With Severe Liver Fibrosis and Cirrhosis in Treatment-Naive Patients With Chronic Hepatitis B. JAMA Netw Open 2022; 5:e2216485. [PMID: 35696167 PMCID: PMC9194671 DOI: 10.1001/jamanetworkopen.2022.16485] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
IMPORTANCE Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) constitutes an atypical serological profile in chronic hepatitis B virus infection, and the association between coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic hepatitis B (CHB) remains unclear. OBJECTIVE To investigate the association of coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with CHB. DESIGN, SETTING, AND PARTICIPANTS Consecutive treatment-naive patients with CHB from 2 medical institutions in China were enrolled between January 10, 2015, and March 31, 2021. Severe liver fibrosis and cirrhosis were identified using the aspartate transaminase (AST) to platelet ratio index (APRI), the fibrosis index based on 4 factors (FIB-4; factors comprise age, AST level, alanine aminotransferase [ALT] level, and platelet count), transient elastography, or ultrasonography. Data were analyzed from August 1, 2021, to April 15, 2022. MAIN OUTCOMES AND MEASURES The primary outcomes were rates of severe liver fibrosis and cirrhosis among patients with vs patients without coexistant HBsAg and anti-HBs. Severe liver fibrosis was defined as an APRI score of 1.5 or higher, a FIB-4 score of 3.25 or higher, or a liver stiffness measurement of 8 kPa or higher; cirrhosis was defined as an APRI score of 2.0 or higher, a FIB-4 score of 6.5 or higher, a liver stiffness measurement of 11 kPa or higher, or ultrasonographic findings suggestive of cirrhosis. RESULTS Of 6534 enrolled patients, 4033 patients (61.7%) were male, and the median (IQR) age was 41.0 (33.0-52.0) years. A total of 277 patients (4.2%) had coexistent HBsAg and anti-HBs. Patients with vs without anti-HBs were older (median [IQR], 46.0 [33.0-55.5] years vs 41.0 [33.0-52.0] years) and had a higher proportion of hepatitis B e antigen (HBeAg) positivity (123 of 277 patients [44.4%] vs 2115 of 6257 patients [33.8%]; P < .001), higher ALT levels (median [IQR], 45.1 [24.6-119.0] U/L vs 36.7 [22.0-77.0] U/L; P = .001) and AST levels (median [IQR], 35.0 [23.5-68.4] U/L vs 28.3 [21.6-51.0] U/L; P < .001), and lower platelet counts (median [IQR], 173.0 × 103/μL [129.0-212.5 × 103/μL] vs 185.0 × 103/μL [141.0-224.0 × 103/μL]; P = .004), albumin levels (median [IQR], 4.37 [4.11-4.56] g/dL vs 4.43 [4.17-4.61] g/dL; P = .02), and HBsAg levels (median [IQR], 2.8 log10 [1.6-3.4 log10] IU/mL vs 3.3 log10 [2.6-3.9 log10] IU/mL; P < .001). Compared with patients without anti-HBs, those with anti-HBs had higher APRI scores (median [IQR], 0.5 [0.3-1.4] vs 0.4 [0.3-0.9]; P < .001), FIB-4 scores (median [IQR], 1.4 [0.9-2.6] vs 1.1 [0.7-2.1]; P < .001), and liver stiffness values (median [IQR], 7.5 [6.2-9.8] kPa vs 6.3 [5.2-8.1] kPa; P = .003). Patients with anti-HBs also had higher proportions of severe liver fibrosis (102 of 277 patients [36.8%] vs 1397 of 6207 patients [22.5%]; P < .001) and cirrhosis (87 of 277 patients [31.4%] vs 1194 of 6213 patients [19.2%]; P < .001) compared with patients without anti-HBs. The coexistence of HBsAg and anti-HBs was independently associated with severe liver fibrosis (odds ratio [OR], 2.29; 95% CI, 1.56-3.38; P < .001) and cirrhosis (OR, 1.73; 95% CI, 1.12-2.68; P = .01) in the multivariate analysis. However, the association of coexistent HBsAg and anti-HBs with cirrhosis was only observed in patients with HBeAg negativity (OR, 1.66; 95% CI, 1.05-2.62; P = .03) and not in patients with HBeAg positivity (OR, 1.45; 95% CI, 0.87-2.43; P = .16). CONCLUSIONS AND RELEVANCE In this cross-sectional study, the coexistence of HBsAg and anti-HBs was unusual in hepatitis B virus infection and was associated with more advanced liver diseases, such as severe liver fibrosis and cirrhosis, especially among patients with HBeAg negativity. These results suggest that close monitoring for liver fibrosis and cirrhosis is warranted in patients with CHB who have this serological profile.
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Affiliation(s)
- Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yong Liu
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Weihua Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Bei Jia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Dongmei Gao
- Community Work Office, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Shuqin Hong
- Hospital Grade Creation Office, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Xiaohong Wang
- Department of Surgery, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Li Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Zhaoping Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Rattananukrom C, Kitiyakara T. Comparison between using hepatocellular carcinoma (
HCC
) risk scores and the
HCC
national guideline to identify high‐risk chronic hepatitis B patients for
HCC
surveillance in Thailand. JGH Open 2022; 6:408-420. [PMID: 35774347 PMCID: PMC9218522 DOI: 10.1002/jgh3.12753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/20/2022] [Accepted: 04/25/2022] [Indexed: 11/08/2022]
Affiliation(s)
- Chitchai Rattananukrom
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Srinagarind Hospital Khon Kaen University Khon Kaen Thailand
| | - Taya Kitiyakara
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital Mahidol University Bangkok Thailand
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Hepatitis B Virus-Associated Hepatocellular Carcinoma. Viruses 2022; 14:v14050986. [PMID: 35632728 PMCID: PMC9146458 DOI: 10.3390/v14050986] [Citation(s) in RCA: 95] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.
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Verification of hepatitis B-related hepatocellular carcinoma predictive models to evaluate the risk of HCC in patients with liver cirrhosis under antiviral treatment. Eur J Gastroenterol Hepatol 2022; 34:546-552. [PMID: 35170528 DOI: 10.1097/meg.0000000000002302] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The development of chronic hepatitis B (CHB)-related HCC can be attributed to continuous hepatitis B virus (HBV) infection. It is crucial to identify and monitor patients with CHB at high risk of HCC occurrence so that HCC can be detected early and the patients are able to receive effective treatment promptly to increase the survival rate and improve prognosis. AIM This study aimed to verify hepatitis B-related hepatocellular carcinoma predictive models to evaluate the risk of HCC in patients with liver cirrhosis under antiviral treatment. METHODS Patients with HBV-related compensated cirrhosis were treated with lamivudine and adefovir randomly, and then with a combination of two drugs at different time points based on the virologic response. Patients with HCC occurrence during follow-up were categorized as HCC group, whereas others as control group. They were further divided into 2-year HCC, 2-year control, 5-year HCC, and 5-year control groups according to the observation time. The operating curves of the patients were used to verify models before and after antiviral treatment. RESULTS Using the baseline as a parameter, the area under the curve (AUC) of risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B) after 2 and 5 years was 0.863 and 0.797, respectively. The AUC after 2 and 5 years was 0.839 and 0.747, respectively, for guide with age, gender, HBV DNA, core promoter mutations and cirrhosis (GAG-HCC) and 0.741 and 0.748, respectively, for Taiwanese HBV cohort (TW1). Using 48 weeks as the parameter, it has an optimal critical value of 8 points. The AUC of REACH-B after 2 and 5 years was 0.738 and 0.721, respectively. CONCLUSION REACH-B can predict the risk of HCC occurrence in patients with compensated liver cirrhosis before and after antiviral treatment. GAG-HCC and TW1 could predict the risk before antiviral treatment.
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Huang WC, Lin YC, Chen PJ, Hsu NT, Tu CL, Chang TS, Hung CH, Kee KM, Chao WH, Lu SN. Community-Based Screening for Hepatitis B and C Infectivity Using Two Quantitative Antigens to Identify Endemic Townships. Viruses 2022; 14:v14020304. [PMID: 35215896 PMCID: PMC8879708 DOI: 10.3390/v14020304] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/25/2022] [Accepted: 01/30/2022] [Indexed: 02/01/2023] Open
Abstract
Screening and linkage to care are essential to achieve viral hepatitis elimination before 2030. The accurate identification of endemic areas is important for controlling diseases with geographic aggregation. Viral activity drives prognosis of chronic hepatitis B and hepatitis C virus infection. This screening was conducted in Chiayi County from 2018–2019. All residents aged 30 years or older were invited to participate in quantitative HBsAg (qHBsAg) and HCV Ag screening. Among the 4010 participants (male:female = 1630:2380), the prevalence of qHBsAg and HCV Ag was 9.9% (396/4010) and 4.1% (163/4010), respectively. High-prevalence townships were identified, three for qHBsAg > 15% and two for HCV Ag > 10%. The age-specific prevalence of qHBsAg was distributed in an inverse U-shape with a peak (16.0%, 68/424) for subjects in their 40 s; for HCV, prevalence increased with age. Concentrations of qHBsAg < 200 IU/mL were found in 54% (214/396) of carriers. The rate of oral antiviral treatment for HCV was 75.5% (114/151), with subjects younger than 75 years tending to undergo treatment (85.6% vs. 57.4%, p < 0.001). QHBsAg and HCV Ag core antigens can reflect the concentration of the viral load, which serves as a feasible screening tool. Using quantitative antigen screening for hepatitis B and C in community-based screening, two hyperendemic townships were identified from an endemic county.
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Affiliation(s)
- Wei-Cheng Huang
- Department of Geriatric, Chang Gung Memorial Hospital Chiayi Branch, Puzi 61363, Taiwan;
- Department of Family Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833253, Taiwan;
| | - Yu-Chen Lin
- Chiayi County Health Bureau, Taibao 60044, Taiwan; (Y.-C.L.); (W.-H.C.)
| | - Po-Ju Chen
- Department of Family Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833253, Taiwan;
| | - Nien-Tzu Hsu
- Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833253, Taiwan;
| | - Chia-Ling Tu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Chiayi Branch, Puzi 61363, Taiwan; (C.-L.T.); (T.-S.C.)
| | - Te-Sheng Chang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Chiayi Branch, Puzi 61363, Taiwan; (C.-L.T.); (T.-S.C.)
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (C.-H.H.); (K.-M.K.)
| | - Chao-Hung Hung
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (C.-H.H.); (K.-M.K.)
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833253, Taiwan
| | - Kwong-Ming Kee
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (C.-H.H.); (K.-M.K.)
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833253, Taiwan
| | - Wen-Hua Chao
- Chiayi County Health Bureau, Taibao 60044, Taiwan; (Y.-C.L.); (W.-H.C.)
| | - Sheng-Nan Lu
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (C.-H.H.); (K.-M.K.)
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833253, Taiwan
- Taiwan National Hepatitis C Program Office, Ministry of Health and Welfare, Taipei 115204, Taiwan
- Correspondence: ; Tel.: +886-7-731-7123 (ext. 8301); Fax: +866-7-732-2402
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Jo AJ, Choi WM, Kim HJ, Choi SH, Han S, Ko MJ, Lim YS. A risk scoring system to predict clinical events in chronic hepatitis B virus infection: A nationwide cohort study. J Viral Hepat 2022; 29:115-123. [PMID: 34762757 DOI: 10.1111/jvh.13631] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/19/2021] [Accepted: 11/02/2021] [Indexed: 02/06/2023]
Abstract
Many patients with chronic hepatitis B do not receive adequate follow-up. This study aimed to develop a risk score to predict clinical events in patients with chronic hepatitis B virus (HBV) infection at the population level for identifying patients at high risk to warrant regular follow-up. This study analysed population-based data from the nationwide claims database of South Korea obtained between 2005 and 2015. We identified 507,239 non-cirrhotic patients with chronic HBV infection who are not under antiviral treatment. A risk score for predicting clinical events (hepatocellular carcinoma, death or liver transplantation) was developed based on multivariable Cox proportional hazard model in a development cohort (n = 401,745) and validated in a validation cohort (n = 105,494). The cumulative incidence rates of clinical events at 5 years were 2.56% and 2.44% in the development and validation cohorts, respectively. Clinical events in asymptomatic patients with chronic HBV infection (CAP-B) score ranging from 0 to 7.5 points based on age, sex, socioeconomic status, chronic hepatitis C co-infection, diabetes mellitus, statin or antiplatelet exposure, smoking, alcohol consumption, alanine aminotransferase and gamma-glutamyltransferase had good discriminatory accuracy in both the development and validation cohorts (c-indices for 3-, 5- and 10-year risk prediction: all 0.786). The predicted and observed probabilities of clinical events were calibrated in both cohorts. A score of >3.5 points identified subjects at distinctly high risk. The CAP-B score using easily accessible variables can predict clinical events and may allow selection of patients with chronic HBV infection for priority of regular follow-up.
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Affiliation(s)
- Ae Jeong Jo
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyo Jeong Kim
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - So Hyun Choi
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea.,Department of Statistics, Kyungpook National University, Daegu, Republic of Korea
| | - Seungbong Han
- Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Min Jung Ko
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Kim HY, Lampertico P, Nam JY, Lee HC, Kim SU, Sinn DH, Seo YS, Lee HA, Park SY, Lim YS, Jang ES, Yoon EL, Kim HS, Kim SE, Ahn SB, Shim JJ, Jeong SW, Jung YJ, Sohn JH, Cho YK, Jun DW, Dalekos GN, Idilman R, Sypsa V, Berg T, Buti M, Calleja JL, Goulis J, Manolakopoulos S, Janssen HLA, Jang MJ, Lee YB, Kim YJ, Yoon JH, Papatheodoridis GV, Lee JH. An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B. J Hepatol 2022; 76:311-318. [PMID: 34606915 DOI: 10.1016/j.jhep.2021.09.025] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 09/13/2021] [Accepted: 09/15/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk. METHODS Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development. RESULTS In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up. CONCLUSIONS This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir. LAY SUMMARY Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance.
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Affiliation(s)
- Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Joon Yeul Nam
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyung-Chul Lee
- Department of Anesthesiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College, Republic of Korea; Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Young-Suk Lim
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea
| | - Eun Sun Jang
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Hyoung Su Kim
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Republic of Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Republic of Korea
| | - Jae-Jun Shim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
| | - Yong Jin Jung
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Republic of Korea
| | - Joo Hyun Sohn
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri-si, Republic of Korea
| | - Yong Kyun Cho
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Ramazan Idilman
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Vana Sypsa
- Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Maria Buti
- Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain
| | | | - John Goulis
- 4th Department of Internal Medicine, Aristotle University of Thessaloniki Medical School, General Hospital of Thessaloniki "Hippokratio", Thessaloniki, Greece
| | - Spilios Manolakopoulos
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Hippokratio", Athens, Greece
| | - Harry L A Janssen
- Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada
| | - Myoung-Jin Jang
- Medical Research Collaboration Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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50
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Schemmer P, Burra P, Hu R, Hüber CM, Loinaz C, Machida K, Vogel A, Samuel D. State of the art treatment of hepatitis B virus hepatocellular carcinoma and the role of hepatitis B surface antigen post-liver transplantation and resection. Liver Int 2022; 42:288-298. [PMID: 34846790 PMCID: PMC9300017 DOI: 10.1111/liv.15124] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 11/17/2021] [Accepted: 11/28/2021] [Indexed: 01/27/2023]
Abstract
Chronic hepatitis B virus (HBV) infection is the major aetiology of hepatocellular carcinoma (HCC). The optimal goal of therapy, hepatitis B surface antigen (HBsAg) loss and anti-HBs production, is achieved rarely and HBsAg-associated HCC risk is well recognized. Here we review the role of HBsAg in HCC, the link between HBsAg and HCC recurrence post-liver transplantation or resection, and the implications for therapy. HBV-associated carcinogenesis is a multifactorial process. The observation that HBV-related HCC can occur in the absence of cirrhosis is compatible with a direct oncogenic effect of the virus, which may occur via multiple mechanisms, including those mediated by both mutated and unmutated HBsAg. HCC recurrence in HBsAg-positive patients post-liver transplantation has been reported in 10%-15% of patients and is likely to be because of expansion of residual HCC tumour cell populations containing integrated HBV DNA, which expand and independently replicate HBV, leading to the recurrence of both HCC and HBV. The direct role of HBsAg in HCC recurrence post-liver resection is less clear. Cirrhosis is the most important risk factor for HCC development, and precancerous cirrhotic liver remains after resection, with the potential to undergo malignant transformation regardless of the existence of HBV-derived oncogenic drivers. The role of HBsAg in the development of HCC and its recurrence post-surgical intervention has multiple implications for therapy and suggests a potential role for immunotherapy in the future management of HCC, in particular post-liver transplantation. Use of hepatitis B immunoglobulins that target HBsAg directly, alongside immune-oncology therapies, may be relevant in this setting.
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Affiliation(s)
- Peter Schemmer
- General, Visceral and Transplant SurgeryDepartment of SurgeryMedical University of GrazGrazAustria
| | - Patrizia Burra
- Department of Surgery, Oncology, and GastroenterologyPadua University HospitalPaduaItaly
| | - Rey‐Heng Hu
- Department of SurgeryNational Taiwan University HospitalTaipeiTaiwan
| | | | - Carmelo Loinaz
- Department of General and Digestive SurgeryUniversity Hospital 12 de OctubreMadridSpain
| | - Keigo Machida
- Keck Hospital of University of Southern CaliforniaLos AngelesCaliforniaUSA
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and EndocrinologyMedizinische Hochschule HannoverHannoverGermany
| | - Didier Samuel
- Centre HepatobiliaireUniversity Hospital Paul BrousseUniversity Paris‐Saclay and Inserm‐Paris Saclay Research Unit 1193VillejuifFrance
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