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İstemihan Z, Kemeç G, Cebeci T, Çetin O, Genç Uluçeçen S, Rüstemzade A, Nuriyev K, Çavuş B, Çifcibaşi Örmeci A, Akyüz F, Demir K, Beşişik F, Kaymakoğlu S. Results in chronic hepatitis B patients using tenofovir and entecavir for at least 10 years; HBV clearance rare, disease outcomes good: An observational cohort study. Medicine (Baltimore) 2025; 104:e42766. [PMID: 40489803 DOI: 10.1097/md.0000000000042766] [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] [Indexed: 06/11/2025] Open
Abstract
This study aims to investigate antiviral effectiveness, side effects, and disease outcomes in patients who have been using entecavir (ETV) and tenofovir disoproxil fumarate (TDF) for a long-term in chronic hepatitis B. Patients with chronic hepatitis B who had been using TDF or ETV for at least 10 years were included in this retrospective study. Co-infected patients, those receiving immunosuppressive therapy, and transplant patients were excluded. Of the study's total 173 patients (baseline mean age 43.4 ± 11.7 years), 110 (63.6%) were men. Thirty-three (19.1%) patients were cirrhotic, and hepatitis B e-antigen was negative in 131 (75.7%) patients at the baseline. Ninety-two (53.2%) patients used TDF and 81 (46.8%) used ETV for a mean of 156.76 ± 21.60 (120-204) months. Hepatitis B virus (HBV)-DNA negativity (<10 IU/mL) was achieved in 97.7% of all patients. Biochemical remission was achieved in 98.3% of all patients at the last visit. HBsAg became negative in only 5 (2.9%). Hepatocellular carcinoma (HCC) developed in 9 (5.2%) patients. All HCCs occurred after the 5th year of treatment. The age at HBV diagnosis was higher in HCC patients (P = .023), but the most important risk factor for the development of HCC was to have cirrhosis at baseline. Eight (4.6%) patients died in the follow-up, and 2 were due to liver disease and the remaining non-liver disease. At the end of follow-up, HBV-DNA negativity was achieved in almost all patients, and HBsAg sero-clearance was rarely achieved. Very few patients developed HCC and the long-term mortality rate was similar to the general population.
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Affiliation(s)
- Zülal İstemihan
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Gamze Kemeç
- Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Timurhan Cebeci
- Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Okan Çetin
- Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Sezen Genç Uluçeçen
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Aynure Rüstemzade
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Kanan Nuriyev
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Bilger Çavuş
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Asli Çifcibaşi Örmeci
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Filiz Akyüz
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Kadir Demir
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Fatih Beşişik
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Sabahattin Kaymakoğlu
- Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
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He Q, Chen Z, Deng Y, Mao C. Plasma microRNA-30a expression in patients with chronic hepatitis B and its application value in the assessment of the severity of liver fibrosis. Eur J Gastroenterol Hepatol 2025; 37:605-611. [PMID: 39975986 DOI: 10.1097/meg.0000000000002918] [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] [Indexed: 02/21/2025]
Abstract
OBJECTIVE The severity of liver fibrosis (LF) in chronic hepatitis B (CHB) affects the outcome and treatment. We probed plasma miR-30a expression in CHB patients and its value in assessing LF severity. METHODS This retrospective study included 160 CHB patients and another 98 controls. Levels of lipid parameters, liver function parameters, hemoglobin, and alpha-fetoprotein were quantified by ELISA and chemiluminescence immunoassay. White blood cell, platelet, and red blood cell counts were determined using an automatic hematology analyzer. Fibrosis index based on four factors (FIB-4) was calculated. miR-30a level was determined, followed by the analysis of correlations of miR-30a expression with LF classification or with FIB-4 in CHB patients. The diagnostic value of plasma miR-30a for mild-to-moderate and severe LF in CHB patients was analyzed by receiver operating characteristic (ROC) curve. RESULTS Plasma miR-30a was poorly expressed in CHB patients and decreased dependently with LF aggravation. miR-30a was negatively interrelated with LF classification and FIB-4. Plasma miR-30a had high diagnostic value for mild-to-moderate LF in CHB patients [area under the ROC curve (AUC) = 0.775, cutoff value = 0.71, 95% confidence interval (CI) = 0.685-0.849]. Plasma miR-30a had high diagnostic value for severe LF in CHB patients (AUC = 0.873, cutoff value = 0.49, 95% CI = 0.804-0.924). CONCLUSION Plasma miR-30a was weakly expressed in CHB patients. miR-30a expression was negatively correlated with LF severity in CHB patients. miR-30a had high diagnostic value for mild-to-moderate and severe LF in CHB patients. miR-30a might serve as a promising target for LF treatment.
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Affiliation(s)
- Qiufeng He
- Department of Hepatology, Public Health Clinical Center of Chengdu, Chengdu, Sichuan Province, China
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Huang X, Zhang X, Hao X, Wang T, Wu P, Shen L, Yang Y, Wan W, Zhang K. Association of dietary quality and mortality in the non-alcoholic fatty liver disease and advanced fibrosis populations: NHANES 2005-2018. Front Nutr 2025; 12:1507342. [PMID: 39917744 PMCID: PMC11798782 DOI: 10.3389/fnut.2025.1507342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 01/06/2025] [Indexed: 02/09/2025] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) has emerged as a significant global health concern, with advanced fibrosis increasing mortality risks. Despite the abundance of dietary guidelines for managing NAFLD, the precise impact of diet quality on mortality among individuals with advanced fibrosis remains elusive. This study aims to explore the influence of five dietary quality indexes on mortality among NAFLD patients and advanced fibrosis patients. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018 to assess dietary quality based on the Alternate Mediterranean Diet (aMED), Healthy Eating Index-2020 (HEI-2020), Dietary Approach to Stop Hypertension (DASH), Alternate Healthy Eating Index (AHEI), and Dietary Inflammatory Index (DII). Weighted Cox proportional hazard regression models along with restricted cubic splines and subgroup analyses were employed in this study. Results The analysis encompassed 3,634 NAFLD patients. After a median follow-up of 89 months, it was found that higher scores on the aMED (HR 0.814, 95% CI 0.681-0.972), HEI-2020 (HR 0.984, 95% CI 0.972-0.997), DASH (HR 0.930, 95% CI 0.883-0.979), and AHEI (HR 0.980, 95% CI 0.966-0.995) were associated with lower mortality risks, while DII scores (HR 1.280, 95% CI 1.098-1.493) indicated an increased risk of mortality. Additionally, a nonlinear relationship was identified solely between AHEI scores and all-cause mortality in NAFLD patients. Notably, among patients with advanced fibrosis, HEI-2020 as a categorical variable (T3: HR 0.519, 95% CI 0.280-0.964), DASH as a continuous variable (continuous: HR 0.921, 95% CI 0.849-0.999), AHEI (continuous: HR 0.971, 95% CI 0.945-0.997; T2: HR 0.545, 95% CI 0.310-0.960; T3: HR 0.444, 95% CI 0.245-0.804), and DII (continuous: HR 1.311, 95% CI 1.121-1.534; T3: HR 2.772, 95% CI 1.477-5.202) exhibited significant associations with all-cause mortality. Subgroup analyses revealed an interaction between AHEI scores and sex among NAFLD patients, where higher AHEI scores correlated with lower all-cause mortality in females, but no such association was observed in males. For other dietary quality, subgroup analyses indicated that their relationships with mortality were robust. Conclusion Our study suggests that a high-quality diet could potentially mitigate mortality risk in both NAFLD and advanced fibrosis patients.
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Affiliation(s)
- Xingyong Huang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoyue Zhang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xuanyu Hao
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tingting Wang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Peng Wu
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lufan Shen
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yuanyuan Yang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wenyu Wan
- Key Laboratory of Immunodermatology, Ministry of Education, Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Immunodermatology, National Health Commission of the People's Republic of China, The First Hospital of China Medical University, Shenyang, China
- National and Local Joint Engineering Research Center of Immunodermatological Theranostics, The First Hospital of China Medical University, Shenyang, China
| | - Kai Zhang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, Shenyang, China
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Liu HH, Yen CL, Jeng WJ, Hung CC, Hsiao CC, Tian YC, Chen KH. Fibrosis-4 Score Is Associated with Mortality in Hemodialysis Patients with Chronic Viral Hepatitis: A Retrospective Study. Diagnostics (Basel) 2024; 14:2048. [PMID: 39335727 PMCID: PMC11431842 DOI: 10.3390/diagnostics14182048] [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: 08/12/2024] [Revised: 09/03/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Chronic hepatitis B and C infections are major causes of morbidity and mortality in end-stage kidney disease (ESKD) patients on hemodialysis (HD). The Fibrosis-4 (FIB-4) score is a non-invasive method to evaluate chronic liver disease. However, it is unclear whether there is a connection between the FIB-4 score and major adverse cardiovascular events (MACEs) and mortality in patients on HD. This study investigates the relationship between FIB-4 scores, MACEs, and mortality in HD patients. METHODS A 5-year retrospective study included 198 HD patients with chronic hepatitis B and C from Chang Gung Memorial Hospital. FIB-4 scores were categorized into high (>2.071), middle (1.030~2.071), and low (<1.030) tertiles for cross-sectional analyses. MACEs and mortality were tracked longitudinally. RESULTS Patients with high FIB-4 scores had lower hemoglobin and albumin levels. Cox multivariate analysis showed that high FIB-4 scores (aHR: 1.589) and diabetes mellitus (aHR: 5.688) were significant factors for all-cause mortality. The optimal FIB-4 score for 5-year mortality was 2.942. FIB-4 scores were not significant for predicting 5-year MACEs. CONCLUSIONS High FIB-4 scores are associated with increased 5-year all-cause mortality risk in HD patients with chronic hepatitis virus infection.
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Affiliation(s)
- Hao-Hsuan Liu
- Department of Nephrology, New Taipei Municipal TuCheng Hospital, New Taipei City 236043, Taiwan
- Kidney Research Center, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan 333423, Taiwan
| | - Chieh-Li Yen
- Kidney Research Center, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan 333423, Taiwan
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333423, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Cheng-Chieh Hung
- Kidney Research Center, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan 333423, Taiwan
| | - Ching-Chung Hsiao
- Department of Nephrology, New Taipei Municipal TuCheng Hospital, New Taipei City 236043, Taiwan
| | - Ya-Chung Tian
- Kidney Research Center, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan 333423, Taiwan
| | - Kuan-Hsing Chen
- Kidney Research Center, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan 333423, Taiwan
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Akin Belli A, Omarufilo F, Birnbaum J, Emeasoba EU, Sigal SH. The challenges of integrating an immigrant population with chronic hepatitis B into long-term hepatology care: Lessons learned from a Bronx West African screening program. IJID REGIONS 2024; 12:100385. [PMID: 39070138 PMCID: PMC11278613 DOI: 10.1016/j.ijregi.2024.100385] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 06/04/2024] [Accepted: 06/05/2024] [Indexed: 07/30/2024]
Abstract
Objectives Hepatitis B virus (HBV) is endemic in West Africa. Because of immigration to the United States, screening and transition to long-term care is a significant public health concern. We describe the challenges of integrating individuals identified in a screening program into long-term care and the spectrum of disease severity. Methods Between 2019 and 2023, 749 individuals were screened. Beginning 2022, all were offered a free serologic evaluation. Details of the previous diagnosis, HBV care, the serologic evaluation, aspartate aminotransferase to platelet ratio index, and Fibrosis index-4 scores were recorded. The results of transient elastography (TE) were correlated with the serologic evaluation. Results A total of 75 (10%) individuals were hepatitis B surface antigen-positive, including 58 (77.3%) previously and 17 (22.7%) newly diagnosed. Despite attempts at linkage to care, only 14 (37.8%) of those diagnosed before the offer continued and/or entered long-term care. A total of 63 of 75 (84%) returned for the evaluation. Among 56 HBV treatment-naïve individuals, 66.1% had a serologic profile consistent with the carrier state. A total of 10 (18.2%) individuals met the criteria for HBV therapy, and 10 (21.7%) had ≥F2 fibrosis on TE. There was no correlation between aspartate aminotransferase to platelet ratio index and Fibrosis index-4 scores and TE. Eight (29.6%) of 27 patients with a profile of the HBV carrier state had ≥F2 fibrosis. Conclusion Integration of individuals with HBV from West Africa identified in a screening program into long-term care is challenging. Inclusion of a serologic evaluation in programs for immigrant communities should be considered. Up to 30% of individuals with a serologic profile consistent with the HBV carrier state may have ≥F2 fibrosis.
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Affiliation(s)
- Asli Akin Belli
- Albert Einstein College of Medicine, Montefiore Medical Center, Department of Medicine, Division of Hepatology, New York, USA
| | - Fatima Omarufilo
- Albert Einstein College of Medicine, Montefiore Medical Center, Department of Medicine, Division of Hepatology, New York, USA
| | - Jessie Birnbaum
- Albert Einstein College of Medicine, Montefiore Medical Center, Department of Medicine, Division of Hepatology, New York, USA
| | - Emmanuel U. Emeasoba
- Albert Einstein College of Medicine, Montefiore Medical Center, Department of Medicine, Division of Hepatology, New York, USA
| | - Samuel H. Sigal
- Albert Einstein College of Medicine, Montefiore Medical Center, Department of Medicine, Division of Hepatology, New York, USA
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Huynh T, Bui DM, Zhou TX, Hu KQ. Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years. World J Hepatol 2024; 16:1009-1017. [PMID: 39086529 PMCID: PMC11287611 DOI: 10.4254/wjh.v16.i7.1009] [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: 03/11/2024] [Revised: 06/03/2024] [Accepted: 06/27/2024] [Indexed: 07/26/2024] Open
Abstract
BACKGROUND Both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are the first-line treatments for chronic hepatitis B (CHB). We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase (ALT) improvement, but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis. AIM To assess the benefits of TDF switching to TAF for 3 years on ALT, aspartate aminotransferase (AST), and hepatic fibrosis improvement in patients with CHB. METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF, then switched to TAF to determine dynamic patterns of ALT, AST, AST to platelet ratio index (APRI), fibrosis-4 (FIB-4) scores, and shear wave elastography (SWE) reading improvement at switching week 144, and the associated factors. RESULTS The mean age was 55 (28-80); 45.3%, males; 15.1%, clinical cirrhosis; mean baseline ALT, 24.8; AST, 25.7 U/L; APRI, 0.37; and FIB-4, 1.66. After 144 weeks TDF switching to TAF, mean ALT and AST were reduced to 19.7 and 21, respectively. From baseline to switching week 144, the rates of ALT and AST < 35 (male)/25 (female) and < 30 (male)/19 (female) were persistently increased; hepatic fibrosis was also improved by APRI < 0.5, from 79.2% to 96.2%; FIB-4 < 1.45, from 52.8% to 58.5%, respectively; mean APRI was reduced to 0.27; FIB-4, to 1.38; and mean SWE reading, from 7.05 to 6.30 kPa after a mean of 109 weeks switching. The renal function was stable and the frequency of patients with glomerular filtration rate > 60 mL/min was increased from 86.5% at baseline to 88.2% at switching week 144. CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement, but also hepatic fibrosis improvement by APRI, FIB-4 scores, as well as SWE reading, the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.
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Affiliation(s)
- Tung Huynh
- Department of Pharmacy, University of California Irvine Medical Center, Orange, CA 92868, United States
| | | | - Tina Xiwen Zhou
- Chicago Medical School at Rosalind Franklin University, North Chicago, IL 60064, United States
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California Irvine, School of Medicine, Orange, CA 92868, United States.
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Xie G, Xiao H, Liu Q, Chen T, Chen F, Zhou K, Wang X, Liu P, Jia Z, Chen L, Deng X, Meng F, Zhang Z, Chi X, Jia W. LiveBoost: A GB-based prediction system for liver fibrosis in chronic hepatitis B patients in China - A multi-center retrospective study. Heliyon 2024; 10:e24161. [PMID: 38293489 PMCID: PMC10825336 DOI: 10.1016/j.heliyon.2024.e24161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 11/24/2023] [Accepted: 01/04/2024] [Indexed: 02/01/2024] Open
Abstract
BACKGROUND The aim of this study was to evaluate the accuracy of LiveBoost™, a gradient boosting (GB)-based prediction system based on standard biochemical values (AST, ALT, platelet count) and age, in Chinese patients with chronic hepatitis B (CHB) and compare its performance with FIB-4 (fibrosis-4 score) and APRI (the aspartate transaminase to platelet ratio index). METHODS This retrospective trial enrolled 454 participants, including 279 CHB patients who underwent liver biopsy and 175 normal controls from 3 centers in China. All participants underwent laboratory blood testing. LiveBoost was constructed using GB and FIB-4 and APRI were calculated from laboratory data. RESULTS LiveBoost outperformed APRI and FIB-4 in predicting hepatic fibrosis and cirrhosis. The GB model had an AUROC of 0.977 for CHB diagnosis, 0.804 for early and advanced fibrosis, and 0.836 for non-cirrhosis and cirrhosis, compared to AUROC of 0.554, 0.673 and 0.720 for FIB-4, AUROC of 0.977, 0.652 and 0.654 for APRI. CONCLUSIONS LiveBoost is a more reliable and cost-effective method than APRI and FIB-4 for assessing liver fibrosis in Chinese patients with CHB.
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Affiliation(s)
- Guoxiang Xie
- Human Metabolomics Institute Inc., Shenzhen, Guangdong, China
| | - Huanming Xiao
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Quan Liu
- Human Metabolomics Institute Inc., Shenzhen, Guangdong, China
| | - Tianlu Chen
- Center for Translational Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fengyan Chen
- Human Metabolomics Institute Inc., Shenzhen, Guangdong, China
| | - Kejun Zhou
- Human Metabolomics Institute Inc., Shenzhen, Guangdong, China
| | - Xiaoning Wang
- Institute of Interdisciplinary Integrative Medicine Research, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ping Liu
- Institute of Interdisciplinary Integrative Medicine Research, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhifeng Jia
- Department of Computer Science and Engineering, Hong Kong University of Science and Technology, Hong Kong, China
| | - Lei Chen
- Department of Computer Science and Engineering, Hong Kong University of Science and Technology, Hong Kong, China
| | - Xin Deng
- Hepatology Department, The Third People's Hospital of Shenzhen, Shenzhen, China
| | - Fankun Meng
- Ultrasound and Functional Diagnosis Center, Beijing Youan Hospital affiliated to Capital Medical University, Beijing, China
| | - Zhenhua Zhang
- Department of Infectious Diseases and Institute of Clinical Virology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xiaoling Chi
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Wei Jia
- Human Metabolomics Institute Inc., Shenzhen, Guangdong, China
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
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Spradling PR, Bocour A, Kuncio DE, Ly KN, Harris AM, Thompson ND. Hepatitis B Care Continuum Models-Data to Inform Public Health Action. Public Health Rep 2024:333549231218277. [PMID: 38205796 PMCID: PMC11569688 DOI: 10.1177/00333549231218277] [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] [Indexed: 01/12/2024] Open
Abstract
The application of a care continuum model (CCM) can identify gaps in diagnosis, care, and treatment of populations with a common condition, but challenges are inherent in developing a CCM for chronic hepatitis B. In contrast with treatment for HIV or hepatitis C, treatment is not indicated for all people with chronic hepatitis B, clinical endpoints are not clear for those receiving treatment, and those for whom treatment is not indicated remain at risk for complications. This topical review examines the data elements necessary to develop and apply chronic hepatitis B CCMs at the jurisdictional health department level. We conducted a nonsystematic review of US-based publications in Ovid MEDLINE (1946-present), Ovid Embase (1974-present), and Scopus (not date limited) databases, which yielded 724 publications for review. Jurisdictional health departments, if properly supported, could develop locale-specific focused CCMs using person-level chronic hepatitis B registries, updated longitudinally using electronic laboratory reporting data and case reporting data. These CCMs could be applied to identify disparities and improve rates in testing and access to care and treatment, which are necessary to reduce liver disease and chronic hepatitis B mortality. Investments in public health surveillance infrastructure, including substantial enhancements in electronic laboratory reporting and case reporting and the use of supplementary data sources, could enable jurisdictional health departments to develop modified CCMs for chronic hepatitis B that focus, at least initially, on "early" CCM steps, which emphasize optimization of hepatitis B diagnosis, linkage to care, and ongoing clinical follow-up of diagnosed people, all of which can lead to improved outcomes.
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Affiliation(s)
- Philip R. Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Angelica Bocour
- Viral Hepatitis Program, New York City Department of Health and Mental Hygiene, New York, NY, USA
| | - Danica E. Kuncio
- Division of Disease Control, Philadelphia Department of Public Health, Philadelphia, PA, USA
| | - Kathleen N. Ly
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Aaron M. Harris
- Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Nicola D. Thompson
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Liu SH, Burgan J, Ling K, Loyst RA, Tantone R, Komatsu DE, Wang ED. Aspartate Aminotransferase-to-Platelet Ratio Index Suggestive of Liver Dysfunction Predicts Early Complications After Open Reduction Internal Fixation of Distal Radius Fractures. JOURNAL OF HAND SURGERY GLOBAL ONLINE 2024; 6:1-5. [PMID: 38313624 PMCID: PMC10837168 DOI: 10.1016/j.jhsg.2023.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 06/24/2023] [Indexed: 02/06/2024] Open
Abstract
Purpose Aspartate aminotransferase-to-platelet ratio index (APRI) is a cost-effective and noninvasive measure of liver function, an alternative to the gold standard liver biopsy, which is resource-intensive and invasive. The purpose of this study was to investigate the association between preoperative APRI and 30-day postoperative complications after isolated open reduction internal fixation (ORIF) of distal radius fractures (DRFs). Methods The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent isolated ORIF of DRFs between 2015 and 2021. The study population was divided into two groups on the basis of preoperative APRI: normal/reference (APRI, <0.5) and liver dysfunction (APRI, ≥0.5). Information on patient demographics, comorbidities, and 30-day postoperative complications after isolated ORIF of DRFs was collected. Multivariate logistic regression analysis was performed to investigate the relationship between preoperative APRI and postoperative complications. Results Compared to patients with normal APRI, patients with preoperative APRI associated with liver dysfunction were significant for male sex (P < .001), younger age (P < .001), American Society of Anesthesiologists classification grade ≥3 (P < .001), being smokers (P < .001), and having comorbid diabetes (P = .002) and bleeding disorders (P < .001). Preoperative APRI associated with liver dysfunction was independently associated with a greater likelihood of any complications (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.19-1.87; P < .001), nonhome discharge (OR, 1.62; 95% CI, 1.15-2.27; P = .005), and a length of stay of >2 days (OR, 1.70; 95% CI, 1.32-2.20; P < .001). Conclusions Aspartate aminotransferase-to-platelet ratio index values associated with liver dysfunction were associated with an increased rate of early postoperative complications after DRF ORIF. Clinical relevance This study suggests APRI's utility as a cost-effective, noninvasive measure of liver function that physicians can use before surgery to better identify surgical candidates with DRFs and suspicion of liver dysfunction. Type of study/level of evidence Prognostic III.
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Affiliation(s)
- Steven H. Liu
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - Jane Burgan
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - Kenny Ling
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - Rachel A. Loyst
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - Ryan Tantone
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - David E. Komatsu
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - Edward D. Wang
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
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10
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Ajuwon BI, Roper K, Richardson A, Lidbury BA. Routine blood test markers for predicting liver disease post HBV infection: precision pathology and pattern recognition. Diagnosis (Berl) 2023; 10:337-347. [PMID: 37725092 DOI: 10.1515/dx-2023-0078] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 08/25/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND Early stages of hepatitis B virus (HBV) infection usually involve inflammation of the liver. Patients with chronic infection have an increased risk of progressive liver fibrosis, cirrhosis, and life-threatening clinical complications of end-stage hepatocellular carcinoma (HCC). CONTENT Early diagnosis of hepatic fibrosis and timely clinical management are critical to controlling disease progression and decreasing the burden of end-stage liver cancer. Fibrosis staging, through its current gold standard, liver biopsy, improves patient outcomes, but the clinical procedure is invasive with unpleasant post-procedural complications. Routine blood test markers offer promising diagnostic potential for early detection of liver disease without biopsy. There is a plethora of candidate routine blood test markers that have gone through phases of biomarker validation and have shown great promise, but their current limitations include a predictive ability that is limited to only a few stages of fibrosis. However, the advent of machine learning, notably pattern recognition, presents an opportunity to refine blood-based non-invasive models of hepatic fibrosis in the future. SUMMARY In this review, we highlight the current landscape of routine blood-based non-invasive models of hepatic fibrosis, and appraise the potential application of machine learning (pattern recognition) algorithms to refining these models and optimising clinical predictions of HBV-associated liver disease. OUTLOOK Machine learning via pattern recognition algorithms takes data analytics to a new realm, and offers the opportunity for enhanced multi-marker fibrosis stage prediction using pathology profile that leverages information across patient routine blood tests.
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Affiliation(s)
- Busayo I Ajuwon
- National Centre for Epidemiology and Population Health, ANU College of Health and Medicine, The Australian National University, Acton, Australian Capital Territory, Australia
- Department of Microbiology, Faculty of Pure and Applied Sciences, Kwara State University, Malete, Nigeria
| | - Katrina Roper
- National Centre for Epidemiology and Population Health, ANU College of Health and Medicine, The Australian National University, Acton, Australian Capital Territory, Australia
| | - Alice Richardson
- Statistical Support Network, The Australian National University, Acton, Australian Capital Territory, Australia
| | - Brett A Lidbury
- National Centre for Epidemiology and Population Health, ANU College of Health and Medicine, The Australian National University, Acton, Australian Capital Territory, Australia
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11
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Majeed NA, Hitawala AA, Heller T, Koh C. Diagnosis of HDV: From virology to non-invasive markers of fibrosis. Liver Int 2023; 43 Suppl 1:31-46. [PMID: 36621853 PMCID: PMC10329733 DOI: 10.1111/liv.15515] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 11/25/2022] [Accepted: 01/04/2023] [Indexed: 01/10/2023]
Abstract
Hepatitis D viral infection in humans is a disease that requires the establishment of hepatitis B, relying on hepatitis B surface Ag and host cellular machinery to replicate and propagate the infection. Since its discovery in 1977, substantial progress has been made to better understand the hepatitis D viral life cycle, pathogenesis and modes of transmission along with expanding on clinical knowledge related to prevention, diagnosis, monitoring and treatment. The availability of serologic diagnostic assays for hepatitis D infection has evolved over time with current widespread availability, improved detection and standardized reporting. With human migration, the epidemiology of hepatitis D infection has changed over time. Thus, the ability to use diagnostic assays remains essential to monitor the global impact of hepatitis D infection. Separately, while liver biopsy remains the gold standard for the staging of this rapidly progressive and severe form of chronic viral hepatitis, there is an unmet need for clinical monitoring of chronic hepatitis D infection for management of progressive disease. Thus, exploration of the utility of non-invasive fibrosis markers in hepatitis D is ongoing. In this review, we discuss the virology, the evolution of diagnostics and the development of non-invasive markers for the detection and monitoring of fibrosis in patients with hepatitis D infection.
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Affiliation(s)
- Nehna Abdul Majeed
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Asif Ali Hitawala
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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12
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Liu Y, Zhang P, Li J, Li H, Zhou C, Zhang Y, Ming Y. Association between serum lipid profile and liver fibrosis in patients infected with Schistosoma japonicum. Parasit Vectors 2022; 15:268. [PMID: 35906693 PMCID: PMC9336000 DOI: 10.1186/s13071-022-05359-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 06/10/2022] [Indexed: 12/15/2022] Open
Abstract
Background Liver fibrosis is thought to have a close relationship with lipid profile. The possible association between lipids and liver fibrosis of different etiologies has been widely explored. However, the association between lipids and liver fibrosis in patients infected with Schistosoma japonicum remains unclear. In the present study we undertook a preliminary exploration of the association between lipid profile and liver fibrosis, and developed a new predictive index for liver fibrosis in S. japonicum-infected patients. Methods A total of 1503 patients diagnosed with S. japonicum at Xiangyue Hospital, China were enrolled in this retrospective study. The patients were divided into two groups, i.e., those with and those without liver fibrosis, by two experienced schistosomiasis specialists, according to the results of liver ultrasound examination. Demographic, clinical, and laboratory data were collected. Multivariable logistic models were used to estimate the independent associations between lipid profile and liver fibrosis. Receiver operating characteristic (ROC) curves were used to assess the discriminative ability of the new index in predicting liver fibrosis in patients with schistosomiasis. Results Logistic regression analysis showed that high-density lipoprotein (HDL) [adjusted odds ratio (aOR), 95% confidence interval (CI) 7.334, 5.051–10.649; P < 0.001], low-density lipoprotein (LDL) (aOR, 95% CI 0.434, 0.370–0.509; P < 0.001), hemoglobin (HB) (aOR, 95% CI 0.979, 0.971–0.987; P < 0.001) and platelets (PLT) (aOR, 95% CI 0.996, 0.994–0.999; P < 0.001) were independently associated with liver fibrosis in patients with schistosomiasis. ROC analysis indicated that the combination of HDL, LDL and HB levels [(HDL × 100)/(LDL × HB)] had a higher area under the ROC curve (AUC = 0.773), and thus may better predict liver fibrosis than the aspartate transaminase-to-platelet ratio index (AUC = 0.608) and fibrosis index based on four factors (AUC = 0.624). Conclusions To the best of our knowledge, this is the first study to report that HDL, LDL, HB and PLT levels are independently associated with liver fibrosis in patients with schistosomiasis. (HDL × 100)/(LDL × HB) outperformed the aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors in terms of ROC, and thus could be a new predictive index for liver fibrosis. These findings may help clinicians to more easily and effectively diagnose liver fibrosis in patients with schistosomiasis. Graphical abstract ![]()
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Affiliation(s)
- Yang Liu
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China
| | - PengPeng Zhang
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China.,Engineering and Technology Research Center for Transplantation Medicine, National Health Commission, Changsha, 410013, China
| | - JunHui Li
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China.,Engineering and Technology Research Center for Transplantation Medicine, National Health Commission, Changsha, 410013, China
| | - Hao Li
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China
| | - Chen Zhou
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China
| | - Yu Zhang
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China
| | - YingZi Ming
- Transplantation Center, Third Xiangya Hospital, Central South University, Changsha, China. .,Engineering and Technology Research Center for Transplantation Medicine, National Health Commission, Changsha, 410013, China.
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13
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Okdemir S, Cakmak E. A novel non-invasive score for the prediction of advanced fibrosis in patients with chronic hepatitis B. Ann Hepatol 2022; 27:100544. [PMID: 34571267 DOI: 10.1016/j.aohep.2021.100544] [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: 01/28/2021] [Revised: 04/05/2021] [Accepted: 04/17/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Evaluation of liver fibrosis is important for treatment decisions, complications and to predict prognosis in patients with chronic hepatitis B (CHB). Our aim was to develop a new non-invasive fibrosis scoring method and prove its accuracy in the differentiation of no/low grade and advanced fibrosis in patients with CHB. PATIENTS AND METHODS Our study included 273 chronic hepatitis B patients who underwent liver biopsy from February, 2007 to February, 2019 with medical records retrospectively reviewed. Preparations of these patients were divided into two groups as ≤ 3 no-low grade fibrosis (n=236) and ≥ 4 advanced fibrosis (n=37) according to histological ISHAK fibrosis scoring system. RESULTS The newly developed AGAP score and other non-invasive fibrosis scores; Fibrosis-4 index, Aspartate aminotransferase to platelets ratio, Gamma glutamyl transpeptidase to platelet ratio, Goteborg University Cirrhosis Index, King's score, Albumin-bilirubin index, Fibrosis cirrhosis index, Fibrosis index, Fibrosis quotient, Lok score and mean and/or median values of Fibroindex were significantly higher in the advanced fibrosis group compared to the no/low grade fibrosis group (p<0.001). However, there was no significant difference in AAR score among the groups (p=0.265). With cut-off value of 4.038, AUROC value of 0.803, sensitivity of 75.7%, specificity of 73.7% and accuracy of 0.740, AGAP score showed the best performance in advanced fibrosis differentiation compared to 12 other non-invasive fibrosis scoring methods. CONCLUSIONS The newly developed AGAP score showed better performance in patients with CHB compared to 12 other non-invasive fibrosis scores in differentiation of no/low grade fibrosis and advanced fibrosis.
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Affiliation(s)
- Sannur Okdemir
- Department of Internal Medicine, Sarkikaraagac State Hospital, Isparta 32800, Turkey
| | - Erol Cakmak
- Department of Gastroenterology, Cumhuriyet University Faculty of Medicine, Sivas 58140, Turkey.
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14
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Luo H, Peng S, Ouyang W, Tan Y, Jiang T, Tang L, Li S, Qiu J, Zhou C. Assessment of liver fibrosis by transient elastography and multi-parameters model in young children with chronic hepatitis B virus infection. BMC Infect Dis 2022; 22:160. [PMID: 35180839 PMCID: PMC8857795 DOI: 10.1186/s12879-022-07142-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 02/08/2022] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE This study aimed to compare the diagnostic value of the single or combined applications of transient elastography (TE) and multivariate indicators with biopsy for the detection of liver fibrosis in children caused by chronic hepatitis B (CHB). METHODS This study included 148 CHB children treated at Hunan Children's Hospital from January 1st 2015 to December 31st 2018, aged from 0.83 to 14.58 years old. All patients underwent liver biopsy (LB), of which 43 patients underwent TE. Multiple clinical data, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), Platelet (PLT), and HBV-deoxyribonucleic acid (HBV DNA) of all patients were collected. The diagnostic values for CHB of TE and its combinations with these indicators were measured. The patients were classified in two ways: no hepatic fibrosis group (F0) versus fibrosis group (F ≥ 1), and no significant hepatic fibrosis group (F < 2) versus significant hepatic fibrosis group (F ≥ 2). The statistical assessment was performed between groups within each classification to compare the diagnostic value of different parameters. RESULTS The operating characteristic area under curve (AUC) of liver fibrosis diagnosed by liver stiffness measurement (LSM) which obtained by TE, AST-to-PLT ratio index (APRI), and fibrosis-4 index (FIB-4) were 0.740, 0.701, and 0.651, while the corresponding cut-off values were 5.9 kPa, 0.50, and 0.10, respectively. The AUC of significant liver fibrosis diagnosed by LSM, APRI and FIB-4 were 0.849, 0.701, and 0.509, while the corresponding cut-off values were 8.4 kPa, 0.76, and 0.08, respectively. While with the combinations of LSM and APRI, LSM and FIB-4, LSM and APRI and FIB-4, APRI and FIB-4, the AUC of significant liver fibrosis were 0.866, 0.855, 0.869, and 0.684, respectively. The AUC of significant liver fibrosis diagnosed by the LSM was significantly higher than APRI and FIB-4. CONCLUSIONS The diagnostic value of transient elastography was better than that of APRI and FIB-4 for CHB children with significant liver fibrosis. In addition, TE also has relatively high application values on the diagnosis of patients with different degrees of liver fibrosis caused by CHB.
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Affiliation(s)
- Haiyan Luo
- Department of Hepatology, Hunan Children's Hospital, Changsha, 410007, China
| | - Songxu Peng
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, 410078, China
| | - Wenxian Ouyang
- Department of Hepatology, Hunan Children's Hospital, Changsha, 410007, China
| | - Yanfang Tan
- Department of Hepatology, Hunan Children's Hospital, Changsha, 410007, China
| | - Tao Jiang
- Department of Hepatology, Hunan Children's Hospital, Changsha, 410007, China
| | - Lian Tang
- Department of Hepatology, Hunan Children's Hospital, Changsha, 410007, China
| | - Shuangjie Li
- Department of Hepatology, Hunan Children's Hospital, Changsha, 410007, China.
| | - Jun Qiu
- Pediatrics Research Institute of Hunan Province, Hunan Children's Hospital, Changsha, 410007, China.
| | - Changci Zhou
- Academy of Pediatrics of University of South China, Hengyang, 421001, China
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15
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Yim HJ, Kim W, Ahn SH, Jung YK, Um SH, Sohn JH, Jang JY, Kim DJ, Park ES, Jin SY, Kim KH. Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients. J Gastroenterol Hepatol 2022; 37:378-386. [PMID: 34653281 DOI: 10.1111/jgh.15710] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 09/15/2021] [Accepted: 10/04/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. METHODS This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. RESULTS A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). CONCLUSIONS The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.
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Affiliation(s)
- Hyung Joon Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Won Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Joo Hyun Sohn
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Jae Young Jang
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Eun-Sook Park
- Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - So-Young Jin
- Department of Pathology, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
| | - Kyun-Hwan Kim
- Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon, Republic of Korea
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16
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Chon YE, Kim SU, Seo YS, Lee HW, Lee HA, Kim MN, Roh YH, Park JY, Kim DY, Ahn SH, Tak WY, Park SY, Kim BK. Long-term effects of entecavir and tenofovir treatment on the fibrotic burden in patients with chronic hepatitis B. J Gastroenterol Hepatol 2022; 37:200-207. [PMID: 34478195 DOI: 10.1111/jgh.15678] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 08/29/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Antiviral therapy (AVT) induces fibrosis regression in patients with chronic hepatitis B. We investigated long-term effects of entecavir (ETV) versus tenofovir (TDF) on fibrotic burden. METHODS Treatment-naïve chronic hepatitis B patients who had begun ETV or TDF were recruited from four tertiary hospitals. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) were used to determine fibrotic burden. RESULTS In the entire population (n = 3277), although patients treated with ETV had higher baseline APRI (1.71 vs 1.07, P < 0.001) and FIB-4 (3.60 vs 2.80, P < 0.001) than those treated with TDF, significant fibrosis regression was identified during 6 years of AVT in both ETV (APRI, mean 1.71 → 0.48, P < 0.001; FIB-4, mean 3.60 → 2.21, P < 0.001) and TDF groups (APRI, mean 1.07 → 0.43, P < 0.001; FIB-4, mean 2.80 → 2.19, P < 0.001). In patients without cirrhosis (n = 2366), baseline APRI was significantly higher in ETV group than in TDF group (1.72 vs 0.97, P < 0.001); however, they became similar after 6 months. Similarly, baseline FIB-4 was significantly higher in ETV group than in TDF group (3.25 vs 2.35, P < 0.001), but became similar from 4 to 6 years. In patients with cirrhosis (n = 911), baseline APRI (1.70 vs 1.34, P < 0.001) and FIB-4 (4.62 vs 3.91, P = 0.005) were higher in ETV group than in TDF, however, both parameters became statistically similar from 6 months to 6 years. CONCLUSION Significant regression of APRI and FIB-4 was observed during long-term ETV and TDF treatment. Despite higher baseline fibrotic burden in ETV group, fibrotic burden between the groups eventually converged through significant fibrosis regression after 1 to 4 years of AVT.
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Affiliation(s)
- Young Eun Chon
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Mi Na Kim
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Republic of Korea
| | - Yun Ho Roh
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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17
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Huyen PTM, Dung DTN, Weiß PJ, Hoan PQ, Giang DP, Uyen NT, Van Tuan N, Trung NT, Velavan TP, Song LH, Hoan NX. Circulating levels of sPD-1 and PD-1 genetic variants are associated with hepatitis B infection and related liver disease progression. Int J Infect Dis 2021; 115:229-236. [PMID: 34910956 DOI: 10.1016/j.ijid.2021.12.325] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/07/2021] [Accepted: 12/09/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Programmed cell death-1 (PD-1) variants and circulating levels of soluble PD-1 are associated with susceptibility to malignant and infectious disease. This study aimed to examine the association of PD-1.5 and PD-1.9 variants, and plasma sPD-1 levels with HBV infection and disease progression. METHODS The study cohort consists of HBV-infected adults (n=513) stratified by clinical course, including chronic hepatitis B (CHB, n=173), liver cirrhosis (LC, n=134), hepatocellular carcinoma (HCC, n=206), and matched healthy controls (HC, n=196). The PD-1.5 (rs2227981 C/T) and PD-1.9 (rs2227982 C/T) genetic variants were genotyped by Sanger sequencing, and plasma sPD-1 levels were quantified by enzyme immunoassay. RESULTS The plasma sPD-1 levels were significantly high among HBV patients. The highest plasma sPD-1 levels were observed in CHB patients, followed by the LC and HCC groups. In addition, the plasma sPD-1 levels correlated positively with liver inflammation (aspartate transaminase, AST: rho=0.57, P<0.0001 and alanine aminotransferase, ALT: rho=0.57, P<0.0001) and were positively correlated with liver fibrosis (AST to Platelet Ratio Index, APRI score: rho=0.53, P<0.0001). The PD-1.9 TT genotype was less frequent in CHB patients compared to LC, HCC and HCC+LC patients in both codominant and recessive models (P<0.01) and was found to be a risk factor for HCC predisposition [HCC vs. non-HCC: OR=2.0 (95% CI: 1.13-3.7), Padj=0.017]. The PD-1.5 CT genotype was associated with a reduced risk of acquiring HCC [OR=0.6 (95%CI: 0.4-0.9), Padj=0.031]. CONCLUSION Our study concludes that sPD-1 levels are associated with liver inflammation and progression of liver fibrosis and the PD-1.5 and PD-1.9 variants are associated with HBV infection and progression of liver disease.
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Affiliation(s)
- Pham Thi Minh Huyen
- Department of Biochemistry, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam; Faculty of Biochemistry, Hanoi Medical University, Hanoi, Vietnam; Faculty of Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Dang Thi Ngoc Dung
- Faculty of Biochemistry, Hanoi Medical University, Hanoi, Vietnam; Faculty of Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Peter Johann Weiß
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Phan Quoc Hoan
- Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Dao Phuong Giang
- Centre for Genetic Consultation and Cancer Screening, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam; Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
| | - Ngo Thi Uyen
- Faculty of Biochemistry, Hanoi Medical University, Hanoi, Vietnam
| | | | - Ngo Tat Trung
- Centre for Genetic Consultation and Cancer Screening, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam; Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Centre for Genetic Consultation and Cancer Screening, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Le Huu Song
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam; Faculty of Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Nghiem Xuan Hoan
- Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam; Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
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18
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Jeong J, Shin JW, Jung SW, Lee SB, Park EJ, Park NH. Clinical usefulness of noninvasive fibrosis indices for predicting hepatocellular carcinoma in treatment-naïve patients with chronic hepatitis B following entecavir therapy. Hepatol Res 2021; 51:923-932. [PMID: 34224182 DOI: 10.1111/hepr.13690] [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: 02/05/2021] [Revised: 05/10/2021] [Accepted: 05/30/2021] [Indexed: 02/08/2023]
Abstract
AIMS This study aimed to evaluate the clinical usefulness of the aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), and modified FIB-4 (mFIB-4) indices in predicting hepatocellular carcinoma (HCC) in patients receiving entecavir (ETV) treatment. METHODS Among 1955 patients treated with ETV, a total of 857 treatment-naive chronic hepatitis B patients (424 with liver cirrhosis [LC], 433 without cirrhosis) treated with ETV for more than 1 year were analyzed. RESULTS Of the 857 patients, 85 (9.9%) patients (77 in the LC group and 8 in the non-LC group) developed HCC during the follow-up period. The median observation period was 6.9 years. Multivariate regression analysis of HCC incidence revealed that the initial mFIB-4 index (hazard ratio [HR] 1.058; 95% confidence interval [CI], 1.007-1.112; p = 0.027) and improvement in the FIB-4 index after 1 year of ETV treatment (HR 0.531; 95% CI, 0.339-0.831; p = 0.006) were independent prognostic factors in the entire cohort. In the LC group, the improvement of the FIB-4 index following ETV treatment (HR 0.491; 95% CI, 0.280-0.861; p = 0.013) was negatively correlated with incidence of HCC. However, the area under the receiver operating characteristic curve of specific cut-off values of the FIB-4 index at baseline and 1 year after ETV treatment were 0.572 (95% CI, 0.504-0.640) and 0.615 (95% CI, 0.546-0.684), respectively. In the non-LC group, none of the invasive fibrosis indices could predict HCC incidence. CONCLUSIONS The specific cut-off value of the FIB-4 index was not suitable for predicting HCC. However, the improvement in the FIB-4 index after 1 year of ETV therapy could be a predictor of HCC development in cirrhotic patients.
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Affiliation(s)
- Joonho Jeong
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
| | - Jung Woo Shin
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
| | - Seok Won Jung
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
| | - Seung Bum Lee
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
| | - Eun Ji Park
- Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
| | - Neung Hwa Park
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea.,Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
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Ding R, Zhou X, Huang D, Wang Y, Li X, Yan L, Lu W, Yang Z, Zhang Z. Nomogram for predicting advanced liver fibrosis and cirrhosis in patients with chronic liver disease. BMC Gastroenterol 2021; 21:190. [PMID: 33906623 PMCID: PMC8077956 DOI: 10.1186/s12876-021-01774-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 04/20/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND We aimed to formulate a novel predictive nomogram to discriminate liver fibrosis stage in patients with chronic liver disease. METHODS Nomograms were established based on the results of multivariate analysis. The predictive accuracy of the nomograms was assessed by ROC analysis and calibration. Decision curve analysis (DCA) was used to determine the clinical benefit of the nomograms. RESULTS INR, platelets, and N-terminal propeptide type III collagen (PIIINP) were independent predictors for advanced liver fibrosis (≥ S3) and cirrhosis (S4) in patients with chronic liver disease in the training cohort. In the training set, the areas under the ROCs (AUROCs) of nomogram S3S4, APRI, FIB-4, and GPR for stage ≥ S3 were 0.83, 0.71, 0.68, and 0.74, respectively; the AUROCs of nomogram S4, APRI, FIB-4, and GPR for stage S4 were 0.88, 0.74, 0.78, and 0.79, respectively. The calibrations showed optimal agreement between the prediction by the established nomograms and actual observation. In the validation set, the AUROCs of nomogram S3S4, APRI, FIB-4, and GPR for stage ≥ S3 were 0.86, 0.79, 0.78, and 0.81, respectively; the AUROCs of nomogram S4, APRI, FIB-4, and GPR for stage S4 were 0.88, 0.77, 0.81, and 0.83, respectively. Furthermore, the decision curve analysis suggested that the nomograms represent better clinical benefits in both independent cohorts than APRI, FIB-4, and GPR. CONCLUSION The constructed nomograms could be a superior tool for discriminating advanced fibrosis and cirrhosis in chronic liver disease.
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Affiliation(s)
- Rongrong Ding
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
| | - Xinlan Zhou
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
| | - Dan Huang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
| | - Yanbing Wang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
| | - Xiufen Li
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
| | - Li Yan
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
| | - Wei Lu
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
| | - Zongguo Yang
- Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
| | - Zhanqing Zhang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai, 201508 China
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Ding R, Zheng J, Huang D, Wang Y, Li X, Zhou X, Yan L, Lu W, Yang Z, Zhang Z. INR-to-platelet ratio (INPR) as a novel noninvasive index for predicting liver fibrosis in chronic hepatitis B. Int J Med Sci 2021; 18:1159-1166. [PMID: 33526976 PMCID: PMC7847629 DOI: 10.7150/ijms.51799] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/18/2020] [Indexed: 02/05/2023] Open
Abstract
Objective: We aimed to investigate whether a novel noninvasive index, i.e., the international normalized ratio-to-platelet ratio (INPR), was a variable in determining liver fibrosis stage in patients with chronic hepatitis B (CHB). Methods: A total of 543 treatment-naïve CHB patients were retrospectively enrolled. Liver histology was assessed according to the Metavir scoring scheme. All common demographic and clinical parameters were analyzed. Results: Based on routine clinical parameters (age, sex, HBeAg status, HBV DNA, hematological parameters, coagulation index, and liver biochemical indicators), a novel index, i.e., the INR-to-platelet ratio (INPR), was developed to magnify the unfavorable effects of liver fibrosis on INR and platelets. The AUCs of INPR for predicting significant fibrosis, advanced fibrosis, and cirrhosis were 0.74, 0.76 and 0.86, respectively. Compared with APRI, FIB-4, and GPR, the INPR had comparable predictive efficacy for significant fibrosis and better predictive performance for advanced fibrosis and cirrhosis. Conclusion: INPR could be an accurate, easily calculated and inexpensive index to assess liver fibrosis in patients with CHB. Further studies are needed to verify this indicator and compare it with other noninvasive methods for predicting liver fibrosis in CHB patients.
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Affiliation(s)
- Rongrong Ding
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Jianming Zheng
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Dan Huang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Yanbing Wang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Xiufen Li
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Xinlan Zhou
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Li Yan
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Wei Lu
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Zongguo Yang
- Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Zhanqing Zhang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
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21
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A Novel Prediction Model for Significant Liver Fibrosis in Patients with Chronic Hepatitis B. BIOMED RESEARCH INTERNATIONAL 2020; 2020:6839137. [PMID: 32695818 PMCID: PMC7368191 DOI: 10.1155/2020/6839137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 05/19/2020] [Indexed: 12/07/2022]
Abstract
Background Preventing liver fibrosis from progressing to cirrhosis and even liver cancer is a key step in the treatment of chronic hepatitis B (CHB). This study is aimed at constructing and validating a new nomogram for predicting significant liver fibrosis (S ≥ 2) in CHB patients. Methods The nomogram was based on a retrospective study of 252 CHB patients. The predictive accuracy and discriminative ability of the nomogram were evaluated by the area under receiver operating characteristic curve (AUROC), decision curves, and calibration curve compared with the fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI). The results were validated using bootstrap resampling and an external set of 168 CHB patients. Results A total of 420 CHB patients were enrolled based on liver biopsy results. Independent factors predicting significant liver fibrosis were laminin (LN), procollagen type III N-terminal peptide (PIIINP), and blood platelet count (PLT) in a multivariate analysis, and these factors were selected to construct the nomogram. The calibration curve for the probability of significant liver fibrosis showed optimal agreement between the prediction from the nomogram and actual observation. The prediction from the nomogram was more consistent with the results of liver biopsy than FIB-4 and APRI. The AUROC of the nomogram was higher than that of FIB-4 and APRI for predicting significant liver fibrosis. These results were confirmed in the validation set. Furthermore, the decision curve analysis suggested that the most net benefits were provided by the nomogram. Conclusions We found the proposed nomogram resulted in a more accurate prediction of significant liver fibrosis in CHB patients and could provide the most net benefits. We recommend this noninvasive assessment for patients with liver fibrosis to avoid the risk of liver biopsy and earlier intervention to prevent the development of cirrhosis or liver cancer.
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Khare S, Arora A, Sharma P, Dhawan S, Bansal N, Singla V, Kumar A. Performance of Non-invasive Blood Parameters for Ruling Out Significant Liver Fibrosis in Patients with Chronic Hepatitis B. J Clin Transl Hepatol 2020; 8:143-149. [PMID: 32832394 PMCID: PMC7438358 DOI: 10.14218/jcth.2020.00002] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 05/06/2020] [Accepted: 05/10/2020] [Indexed: 12/12/2022] Open
Abstract
Background and Aims: Evaluation of significant liver fibrosis is important for treatment decision and treatment response evaluation in patients with chronic hepatitis B. Since liver biopsy is invasive and transient elastography (TE) has limited availability, various non-invasive blood parameters need evaluation for their capabilities for detection of significant fibrosis. Methods: In this retrospective study, records of patients who had undergone liver biopsy for treatment-naïve chronic hepatitis B were evaluated to obtain various non-invasive blood parameters (aspartate aminotransferase-to-platelet ratio index [referred to as APRI], Fibrosis-4 score [referred to as FIB-4], gamma-glutamyl transpeptidase-to-platelet ratio [referred to as GPR], and gamma-glutamyl transpeptidase-to-albumin ratio [referred to as GAR]), in addition to TE, to assess significant liver fibrosis and compare these to fibrosis stage in liver biopsy. Results: A total of 113 patients were included in the study (median age 33 [interquartile range: 11-82 years], 74% males). Most (75%) patients were HBeAg-negative. The liver biopsy revealed significant fibrosis (Ishak ≥3) in 13% of the patients and nil or mild fibrosis (Ishak <3) in 87% of the patients. TE findings were available for 85 patients, APRI and FIB-4 for 95 patients, GPR for 79 patients, and GAR for 78 patients. The median values of all the parameters were significantly higher in patients with significant fibrosis, as compared to patients with non-significant fibrosis, and all the blood parameters as well as TE were able to identify patients with significant fibrosis significantly well (p<0.05). All non-invasive parameters had low positive predictive value but negative predictive value above 92%. Compared to TE, all the non-invasive blood parameters had similar area under the curve for detecting significant fibrosis, with excellent negative predictive value (≥93%). Conclusions: Non-invasive blood parameters (APRI, FIB-4, GPR, and GAR) with negative predictive values above 93% are excellent parameters for ruling-out significant fibrosis in patients with chronic hepatitis B. These can be used at bedside in place of TE.
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Affiliation(s)
- Shivam Khare
- Institute of Liver, Gastroenterology & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Institute of Liver, Gastroenterology & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Shashi Dhawan
- Department of Histopathology, Sir Ganga Ram Hospital, New Delhi, India
| | - Naresh Bansal
- Institute of Liver, Gastroenterology & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Vikas Singla
- Institute of Liver, Gastroenterology & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
- Correspondence to: Ashish Kumar, Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110060, India. Tel: +91-9312792573, E-mail:
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Jiang M, Yan X, Song X, Yan Q, Zhao Y, Wang L, Gao P. Total bile acid to platelet ratio: A noninvasive index for predicting liver fibrosis in primary biliary cholangitis. Medicine (Baltimore) 2020; 99:e20502. [PMID: 32481469 DOI: 10.1097/md.0000000000020502] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The aim of the study was to develop a new early noninvasive diagnostic model for primary biliary cholangitis (PBC).A total of 118 PBC patients who had undergone a liver biopsy were enrolled in the study, and were randomized into a model group (78 patients) and a validation group (40 patients). The patients' histological stages were based on the classifications of the Scheuer's stage. All common parameters and liver pathological results were analyzed. And total bile acid to platelet ratio, aspartate aminotransferase to platelet ratio index, fibrosis index based on 4 factors and red cell distribution width to platelet ratio were calculated.There were 106 (89.8%) women and 12 men in this study, and the number of patients in Scheuer stage I, II, III, and IV hepatic fibrosis was 52 (44.1%), 36 (30.5%), 26 (22.0%), and 4 (3.4%), respectively. The areas under the receiver operating characteristic curves of the total bile acid to platelet ratio (TPR), the aspartate aminotransferase to platelet ratio index, the fibrosis index based on 4 factors , and the red cell distribution width to platelet ratio for predicting advanced liver fibrosis were 0.771, 0.715, 0.618, and 0.517 respectively. The areas under the receiver operating characteristic curves of the TPR was higher than other non-invasive serological models.As a simple, inexpensive and easily accessible non-invasive liver fibrosis diagnostic model, the TPR may be a new noninvasive marker for predicting histologic severity of PBC.
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Affiliation(s)
- Minjie Jiang
- Department of Hepatology, the First Hospital of Jilin University, Changchun, Jilin Province, China
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Nguyen DT, Tran TTT, Nghiem NM, Le PT, Vo QM, Day J, Rahman M, Le HM. Effectiveness of sofosbuvir based direct-acting antiviral regimens for chronic hepatitis C virus genotype 6 patients: Real-world experience in Vietnam. PLoS One 2020; 15:e0233446. [PMID: 32433676 PMCID: PMC7239434 DOI: 10.1371/journal.pone.0233446] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 05/05/2020] [Indexed: 12/22/2022] Open
Abstract
Background Hepatitis C virus (HCV) genotype 6 is the commonest cause of chronic hepatitis C infection in much of southeast Asia, but data on the effectiveness of direct-acting antiviral agents (DAAs) against this genotype are limited. We conducted a retrospective cohort study of patients attending the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam, to define the effectiveness of DAAs in the treatment of chronic HCV genotype 6 in actual practice. Methods We included all patients with genotype 6 infections attending our hospital between March 2016 and October 2017 who received treatment with sofosbuvir-based DAA treatment regimens, and compared their responses with those with genotype 1 infections. Results 1758 patients (1148 genotype 6, 65.4%; 610 genotype 1, 34.6%) were analyzed. The majority of patients (1480, 84.2%) received sofosbuvir/ledipasvir (SOF/LDV) ± ribavirin (RBV); 278 (15.8%) received sofosbuvir/Daclatasvir (SOF/DCV) ± RBV. The median age of the patients was 57 years, (interquartile range (IQR) 46–64 years) The baseline HCV viral load (log IU/ml) was significantly higher in patients infected with genotype 6 compared with those infected with genotype 1 (6.8, 5.3–6.6 versus 6.3, 5.3–6.5 log10 IU/ml, p = <0.001, Mann Whitney U test). A sustained virological response (SVR), defined as an undetectable viral load measured between 12 and 24 weeks after completing treatment, and indicating cure, was seen in 97.3% (1711/1758) of patients. Treatment failure, defined as HCV viral load ≥15 IU/ml ≥12 weeks after completing treatment appeared to be more frequent in patients infected with genotype 6 virus (3.2%, 37/1148) than in those infected with genotype 1 (1.7%, 10/610), p = 0.050 chi-squared test). We found no evidence that patient’s age, gender, liver cirrhosis, diabetes, HBV or HIV coinfection, prior treatment failure with pegylated interferon therapy, body mass index (BMI), aspartate aminotransferase to platelet ratio index (APRI), or fibrosis 4 (FIB-4) index were associated with treatment failure. Conclusions Our study suggests that patients with HCV genotype 6 infection in Vietnam may respond less well to treatment with sofosbuvir based DAAs than patients with genotype 1 infections. Further studies are needed to confirm this observation and to define whether it is driven by genotype-specific mutations.
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Affiliation(s)
| | - Thanh Thi Thanh Tran
- Oxford University Clinical Research Unit, Wellcome Trust Asia Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
| | - Ngoc My Nghiem
- The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
| | - Phuong Thanh Le
- The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
| | - Quang Minh Vo
- The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
| | - Jeremy Day
- Oxford University Clinical Research Unit, Wellcome Trust Asia Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom
| | - Motiur Rahman
- Oxford University Clinical Research Unit, Wellcome Trust Asia Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom
- * E-mail:
| | - Hung Mạnh Le
- The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
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Yan LT, Wang LL, Yao J, Yang YT, Mao XR, Yue W, Mao YW, Zhou W, Chen QF, Chen Y, Duan ZP, Li JF. Total bile acid-to-cholesterol ratio as a novel noninvasive marker for significant liver fibrosis and cirrhosis in patients with non-cholestatic chronic hepatitis B virus infection. Medicine (Baltimore) 2020; 99:e19248. [PMID: 32080129 PMCID: PMC7034726 DOI: 10.1097/md.0000000000019248] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 01/04/2020] [Accepted: 01/17/2020] [Indexed: 12/22/2022] Open
Abstract
Although serum bile acids and total cholesterol (TC) are closely related to liver cirrhosis, the potential diagnostic value of total bile acid-to-cholesterol ratio (TBA/TC) for liver fibrosis is unclear. The present study aimed to evaluate the value of TBA/TC in the diagnosis of cirrhosis and the relationship between TBA/TC and significant liver fibrosis in chronic hepatitis B virus (HBV) infected patients without cholestasis.667 patients with alkaline phosphatase (ALP) ≤ 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) ≤ 3 ULN were rigorously included in this cross-sectional study. Liver biopsy was performed in 32 patients and METAVIR scoring system was used to evaluate liver fibrosis stage. Liver ultrasound elastography was performed in 138 patients, significant fibrosis was defined as fibrosis ≥ F2. Multiple logistic regression as well as receiver operating characteristic (ROC) curves analyses were performed.Compared to patients with non-cirrhosis, TBA and TBA/TC were significantly higher in cirrhosis while TC was significantly lower (all P < .001). In multivariate analysis, TBA/TC was also independently associated with cirrhosis [odds ratio (OR) = 1.102, 95% confidence interval (CI): 1.085-1.166]. The area under the curve (AUC) of TBA/TC (0.87) was almost equivalent to the aspartate aminotransferase to platelet ratio index (APRI, AUC = 0.84) and fibrosis 4 score (FIB-4, AUC = 0.80), and the optimal cut-off value for TBA/TC to diagnose cirrhosis was 2.70. Among the patients performed liver biopsy, TBA/TC were significantly higher both in significant fibrosis and cirrhosis as well as significantly correlated with fibrosis stage (all P < .001). Furthermore, In patients performed liver ultrasound elastography, TBA/TC was also independently associated with significant fibrosis (OR = 1.040, 95% CI: 1.001-1.078).Assessment of TBA/TC could serve as an additional marker of significant liver fibrosis and cirrhosis in non-cholestatic chronic HBV infection.
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Affiliation(s)
- Li-Ting Yan
- Department of Infectious Diseases
- Institute of Infectious Diseases
| | - Li-Li Wang
- Department of Medical Image, The First Hospital of Lanzhou University, Lanzhou
| | - Jia Yao
- Department of Gastroenterology, Shanxi Baiqiuen Hospital
- Department of Shanxi Medical University, Taiyuan
| | - Ya-Ting Yang
- Department of Infectious Diseases
- Institute of Infectious Diseases
| | | | - Wei Yue
- Department of Infectious Diseases
| | | | - Wei Zhou
- Department of Infectious Diseases
| | | | - Yu Chen
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Zhong-Ping Duan
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Jun-Feng Li
- Department of Infectious Diseases
- Institute of Infectious Diseases
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Wei L, Ye Z, Bao Z, Xu X, Lin X, Chen L. Application of acoustic radiation force impulse elastography combined with serum markers in Child-Pugh grading. Clinics (Sao Paulo) 2020; 75:e1670. [PMID: 32935822 PMCID: PMC7470432 DOI: 10.6061/clinics/2020/e1670] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 05/04/2020] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVES Acoustic radiation force impulse (ARFI) elastography, the aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), and the fibrosis-4 (FIB-4) index are widely used to assess liver fibrosis. However, efficacies of these methods in the evaluation of hepatic functional reserve remain unclear. In this study, we investigated the relationship between ARFI elastography combined with either AAR, APRI, or FIB-4 index and Child-Pugh (CP) class for the evaluation of hepatic functional reserve in patients with chronic hepatitis B (CHB)-related cirrhosis. METHODS The shear wave velocities of 104 patients with clinically confirmed CHB-related cirrhosis were determined using the ARFI; and clinical serum markers (e.g. ALT, AST, PLT) were used to calculate the AAR, APRI, and FIB-4 index. Cirrhosis patients were scored according to their CP class. The ARFI, AAR, APRI, and FIB-4 index were compared with the CP class. The efficacy of each indicator in diagnosis was analyzed using the receiver operating characteristic (ROC) curve and the ARFI combined with either the AAR, APRI, or FIB-4 index, which is used to predict decompensated cirrhosis. RESULTS No significant differences were observed in gender and age among CP classes A, B, and C patients (p>0.05). The ARFI values and the AAR, APRI, and FIB-4 index of patients with CP classes A, B, and C were significantly different (p<0.05). With an increasing CP class, the ARFI, AAR, APRI, and FIB-4 values increased. The correlation between the ARFI and the CP class was stronger than that between the AAR, APRI, and FIB-4 index and the CP class. The area under the ROC curve for the diagnosis of decompensated cirrhosis using the ARFI was 0.841, which was higher than that for the AAR, APRI, and FIB-4 index. According to the area under the curve results, no significant differences were found when the ARFI was combined with either the AAR, APRI, or FIB-4 index and when the ARFI alone was used. CONCLUSIONS The ARFI value has a strong correlation with the CP class. Therefore, ARFI elastography complements CP class in the assessment of the hepatic functional reserve in patients with CHB-related cirrhosis.
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Affiliation(s)
- Linglin Wei
- Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- *Corresponding authors. E-mails: /
| | - Zhen Ye
- Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Zhongtao Bao
- Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xiang Xu
- Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xiaoyu Lin
- Liver Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ling Chen
- Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- *Corresponding authors. E-mails: /
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Alsebaey A, Badr R, Abdelsameea E, Amer MO, Eljaky MA, El-Azab G, Salama M. King’s Fibrosis, Fibrosis Index, GPR, and ALBI Score Are Useful Models for Liver Fibrosis in Chronic Hepatitis B Patients Pre- and Post-Treatment. HEPATITIS MONTHLY 2019; 19. [DOI: 10.5812/hepatmon.96081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Yuan X, Duan SZ, Cao J, Gao N, Xu J, Zhang L. Noninvasive inflammatory markers for assessing liver fibrosis stage in autoimmune hepatitis patients. Eur J Gastroenterol Hepatol 2019; 31:1467-1474. [PMID: 31107735 PMCID: PMC7333545 DOI: 10.1097/meg.0000000000001437] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To examine the accuracy of noninvasive inflammatory markers in predicting liver fibrosis stage in patients with autoimmune hepatitis (AIH). PATIENTS AND METHODS We enrolled 55 patients with AIH and 60 healthy controls in this study, and divided them into three groups: F0 (control); F1-F3 (noncirrhotic fibrosis); and F4 (cirrhosis). The following markers were analyzed for all participants: lymphocyte-to-neutrophil ratio (LNR); lymphocyte-to-platelet ratio (LPR); lymphocyte-to-monocyte ratio (LMR); immunoglobulin-to-platelet ratio (IGPR); aminotransferase-to-platelet ratio index (APRI); aspartate aminotransferase-to-alanine aminotransferase ratio (AAR); and fibrosis-4 score (FIB-4). The predictive accuracy of these noninvasive markers was assessed using area under the receiver operating characteristic curve. Multivariate ordinal logistic regression models were used to analyze associations between the noninvasive markers and liver fibrosis stage. RESULTS AAR, LPR, LMR, IGPR, APRI, and FIB-4 were linked to liver fibrosis-stage (P < 0.05), with correlation indices of - 0.219, 0.258, - 0.149, 0.647, 0.841, and 0.704, respectively, but not LNR (P = 0.093). area under the receiver operating characteristic curves of LPR, IGPR, AAR, LMR, APRI, and FIB-4 for detecting cirrhosis (F4 vs. F0-F3) were 0.936 (95% confidence interval: 0.870-1.000, P < 0.001), 0.939 (0.875-1.000, P < 0.001), 0.528 (0.319-0.738, P = 0.768), 0.555 (0.409-0.700, P = 0.568), 0.798 (0.694-0.902, P = 0.002), and 0.881 (0.796-0.967, P < 0.001). Our multivariate ordinal regression analysis showed that LPR and IGPR were associated independently with liver fibrosis stage, with a coefficient of 0.385 (95% confidence interval: 0.103-0.667, P = 0.007) and 14.903 (2.091-27.786, P = 0.023), respectively. CONCLUSION LPR and IGPR were associated independently with liver fibrosis stage in treatment-naive AIH, and were superior to APRI and FIB-4 in detecting cirrhosis.
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Affiliation(s)
- Xiaoling Yuan
- Department of Infectious Disease, Ninth People’s Hospital
- Department of Pathology, Princeton Medical Center, Plainsboro
| | - Sheng-Zhong Duan
- Laboratory of Oral Microbiota and Systemic Diseases, School of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
- National Clinical Research Center for Oral Diseases
- Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
| | - Junying Cao
- Department of Infectious Disease, Ninth People’s Hospital
| | - Nan Gao
- Department of Biological Sciences, Rutgers University, Newark
| | - Jie Xu
- Department of Infectious Disease, Ninth People’s Hospital
| | - Lanjing Zhang
- Department of Pathology, Princeton Medical Center, Plainsboro
- Department of Biological Sciences, Rutgers University, Newark
- Rutgers Cancer Institute of New Jersey, New Brunswick
- Department of Chemical Biology, Rutgers Ernest Mario School of Pharmacy, Piscataway, New Jersey, USA
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Mansour A, Mohajeri-Tehrani MR, Samadi M, Gerami H, Qorbani M, Bellissimo N, Poustchi H, Hekmatdoost A. Risk factors for non-alcoholic fatty liver disease-associated hepatic fibrosis in type 2 diabetes patients. Acta Diabetol 2019; 56:1199-1207. [PMID: 31197470 DOI: 10.1007/s00592-019-01374-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 05/30/2019] [Indexed: 02/07/2023]
Abstract
AIMS In patients with type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and liver fibrosis is frequent and presumably associated with increased cardiovascular disease risk and mortality. The objective was to investigate risk factors associated with hepatic fibrosis in patients with type 2 diabetes and NAFLD to provide a basis for the prevention and treatment. METHODS Liver stiffness measurements (LSM) expressed in kilopascals (kPa) and controlled attenuation parameter (CAP) expressed in dB/m were diagnosed by transient elastography. Hepatic steatosis and significant fibrosis were defined as having a CAP score ≥ 260 dB/m and an LSM score ≥ 8 kPa, respectively. Associations between fibrosis categories with anthropometric and metabolic variables were determined; then, variables with statistical significance in the univariate analysis were included in multivariate model. RESULTS A total of 108 participant with type 2 diabetes and NAFLD (mean age: 44.69 ± 5.57 years; mean duration of diabetes 4.68 ± 4.24 years) were recruited. In these patients, body mass index, obesity, fat mass, waist circumferences, resting energy expenditure, CAP score, fasting insulin, C-peptide, HbA1C, hs-CRP as well as liver enzymes and systolic blood pressure and diastolic blood pressure were positively associated with fibrosis (all p < 0.05). Using multivariate logistic regression, serum aspartate aminotransferase (OR 1.12; 95% CI 1.06-1.19), waist circumferences (odds ratio [OR] 1.15; 95% CI 1.05-1.25) and C-peptide (OR 3.81; 95% CI 1.5-9.7) remained as independently associated with liver fibrosis. CONCLUSION For participants with type 2 diabetes with coexisting NAFLD, stratification by independent risk factors for fibrosis could have important prognostic value.
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Affiliation(s)
- Asieh Mansour
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, 46, West Arghavan St., Farahzadi Blvd., Shahrak Gharb, Tehran, Iran
| | - Mohammad Reza Mohajeri-Tehrani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Majid Samadi
- Radiology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hadis Gerami
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Qorbani
- Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Nick Bellissimo
- School of Nutrition, Faculty of Community Services, Ryerson University, Toronto, Canada
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, 46, West Arghavan St., Farahzadi Blvd., Shahrak Gharb, Tehran, Iran.
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30
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Huang D, Lin T, Wang S, Cheng L, Xie L, Lu Y, Chen M, Zhu L, Shi J. The liver fibrosis index is superior to the APRI and FIB-4 for predicting liver fibrosis in chronic hepatitis B patients in China. BMC Infect Dis 2019; 19:878. [PMID: 31640590 PMCID: PMC6805580 DOI: 10.1186/s12879-019-4459-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Accepted: 09/10/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters. METHODS Liver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF. RESULTS The mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity. CONCLUSIONS The LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4.
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Affiliation(s)
- Dedong Huang
- Department of Infectious Diseases, the 903rd Hospital of PLA, Hangzhou, China
| | - Taofa Lin
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Shaoyang Wang
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China. .,Clinical educational Institute of the 900th Hospital of PLA affiliated Fujian Medical University, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China.
| | - Lieyun Cheng
- Department of ultrasound, the 900th Hospital of PLA, Fuzhou, China
| | - Liping Xie
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Youguang Lu
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Muxing Chen
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Lingling Zhu
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Jie Shi
- Department of Infectious Diseases, the 903rd Hospital of PLA, Hangzhou, China
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Zhou L, Li X, Huang X, Chen L, Gu L, Huang Y. Soluble programmed death-1 is a useful indicator for inflammatory and fibrosis severity in chronic hepatitis B. J Viral Hepat 2019; 26:795-802. [PMID: 30578715 PMCID: PMC6849537 DOI: 10.1111/jvh.13055] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Revised: 10/17/2018] [Accepted: 11/15/2018] [Indexed: 02/06/2023]
Abstract
Elevated programmed death-1 (PD-1) has been found in immune cells in viral infections and plays an important role in infection persistence. The soluble form of PD-1 (sPD-1) is involved in tumours and viral infections. The aim of this study was to investigate the role of sPD-1 in chronic hepatitis B (CHB). A total of two hundred and eighteen CHB patients and sixty healthy controls (HC) were enrolled. Demographic data and clinical parameters were collected. An ELISA assay was used to measure serum sPD-1 levels, and the relationships between sPD-1 and clinical/virological characteristics was analysed. sPD-1 levels in CHB patients were higher (median 4.409 IQR 3.435-5.306 pg/mL) than those of HC individuals (median 0.3665 IQR 0.2425-0.5010 pg/mL). Among patients at various disease stages, patients with immune activity showed the highest sPD-1 levels (median 5.138 IQR 4.329-5.406 pg/mL). sPD-1 concentration was associated with HBV markers (HBsAg, HBV DNA and HBeAg) and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBil] and gamma glutamyl transferase [γ-GT] levels) (all P < 0.05). sPD-1 levels were higher in CHB patients with moderate-to-severe inflammation or fibrosis than in those with mild inflammation or fibrosis, regardless of ALT levels. The association between sPD-1 and disease progression of CHB suggests that sPD-1 could serve as a new indicator in assessing liver fibrosis. These findings may further aid in determining the initiation of antiviral treatment in patients with normal ALT levels.
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Affiliation(s)
- Liang Zhou
- Department of Infectious Diseasethe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina,Department of Critical Care MedicineThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
| | - Xiaoyan Li
- Department of Infectious Diseasethe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Xiaohui Huang
- Guangdong Provincial Key Laboratory of Liver Researchthe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Lubiao Chen
- Department of Infectious Diseasethe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Lin Gu
- Guangdong Provincial Key Laboratory of Liver Researchthe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Yuehua Huang
- Department of Infectious Diseasethe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina,Guangdong Provincial Key Laboratory of Liver Researchthe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
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32
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Wang A, Lazo M, Carter HB, Groopman JD, Nelson WG, Platz EA. Association between Liver Fibrosis and Serum PSA among U.S. Men: National Health and Nutrition Examination Survey (NHANES), 2001-2010. Cancer Epidemiol Biomarkers Prev 2019; 28:1331-1338. [PMID: 31160348 DOI: 10.1158/1055-9965.epi-19-0145] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 04/09/2019] [Accepted: 05/28/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND To evaluate the association of liver fibrosis scores with PSA level among U.S. adult men overall and by race/ethnicity. METHODS Data from the National Health and Nutrition Examination Survey (NHANES), 2001-2010, were used. Males ages ≥40 years without a prostate cancer diagnosis and who had serum PSA, liver enzymes, albumin, and platelet counts measured as part of NHANES protocol were included. Liver fibrosis was measured using three scores: aspartate aminotransferase to platelet ratio index (APRI), fibrosis 4 index (FIB-4), and NAFLD fibrosis score (NFS). We assessed overall and race/ethnicity-stratified geometric mean PSA by fibrosis score using predictive margins by linear regression, and the association of abnormal fibrosis scores (APRI > 1, FIB-4 > 2.67, NFS > 0.676) and elevated PSA (>4 ng/mL) by logistic regression. RESULTS A total of 6,705 men were included. Abnormal liver fibrosis scores were present in 2.1% (APRI), 3.6% (FIB-4), and 5.6% (NFS). Men with higher fibrosis scores had lower geometric mean PSA (all P trend < 0.02). Men with abnormal APRI had a lower odds of PSA > 4 ng/mL [adjusted OR (aOR) = 0.33; 95% confidence interval (CI), 0.11-0.96]. Compared with men with 0 abnormal scores, those with 2 or 3 abnormal fibrosis scores had a lower odds of PSA > 4 ng/mL (aOR = 0.55; 95% CI, 0.33-0.91). The patterns were similar by race/ethnicity. CONCLUSIONS Men of all race/ethnicities with higher liver fibrosis scores had lower serum PSA, and men with advanced fibrosis scores had a lower odds of an elevated PSA. IMPACT These findings support further research to inform the likelihood of delay in prostate cancer detection in men with abnormal liver function.
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Affiliation(s)
- Anqi Wang
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. .,Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Mariana Lazo
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.,Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland
| | - H Ballentine Carter
- Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland
| | - John D Groopman
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.,Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - William G Nelson
- Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.,Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Elizabeth A Platz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.,Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland.,Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland
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Cai Y, Liu D, Cui J, Sha Y, Zhou H, Tang N, Wang N, Huang A, Xia J. Diagnostic accuracy of red blood cell distribution width to platelet ratio for predicting staging liver fibrosis in chronic liver disease patients: A systematic review and meta-analysis. Medicine (Baltimore) 2019; 98:e15096. [PMID: 30946368 PMCID: PMC6455720 DOI: 10.1097/md.0000000000015096] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Red cell volume distribution width to platelet ratio (RPR), as a novel noninvasive assessment, is frequently investigated. However, the utility of RPR to evaluate the diagnostic accuracy of liver fibrosis remains controversial. We performed a meta-analysis to determine the diagnostic performance of RPR for detecting staging liver fibrosis in patients with chronic liver disease. METHODS MEDLINE, EMBASE, and Cochrane Library databases were systematically searched. Summary receiver operating characteristic curves (SROC), diagnostic odds ratios (DOR), pooled estimates of sensitivity, specificity, and likelihood ratios were used to assess the diagnostic accuracy of RPR. Meta-regression and subgroup analyses were also performed to identify factors that contributed to heterogeneity. The Quality Assessment for Studies of Diagnostic Accuracy Studies-2 tool was applied to assess the quality. RESULTS Fifteen studies with a total of 3346 patients were included in the meta-analysis. The area under the curve for SROC to summarize diagnostic accuracy of RPR for prediction of significant fibrosis, advanced fibrosis, and cirrhosis was 0.73 (standard error [SE] = 0.02), 0.83 (SE = 0.03), and 0.85 (SE = 0.04), respectively. Pooled DOR with corresponding 95% confidence interval (CI) was 4.93 (95% CI: 3.78-6.43), 10.27 (95% CI: 6.26-16.84), and 12.16 (95% CI: 5.85-25.28), respectively, using a random effects model. Meta-regression showed that length of liver biopsy specimen potentially contributed to heterogeneity. There was no significant publication bias observed across the eligible studies. CONCLUSIONS In chronic liver disease patients, RPR presented a good performance for prediction of significant fibrosis, advanced fibrosis, and cirrhosis. More future trials are required for prospective validation.
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Affiliation(s)
- Ying Cai
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
- Department of Intensive Care Medicine, The Second Affiliated Hospital of Chongqing Medical University
| | - Dina Liu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Jing Cui
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Yu Sha
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Hengyu Zhou
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
- College of Nursing, Chongqing Medical University, Chongqing
| | - Ni Tang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Na Wang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Ailong Huang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
| | - Jie Xia
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
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Wang HQ, Jin KP, Zeng MS, Chen CZ, Rao SX, Ji Y, Fu CX, Sheng RF. Assessing liver fibrosis in chronic hepatitis B using MR extracellular volume measurements: Comparison with serum fibrosis indices. Magn Reson Imaging 2019; 59:39-45. [PMID: 30849483 DOI: 10.1016/j.mri.2019.03.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 01/07/2019] [Accepted: 03/04/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To evaluate the diagnostic value of liver extracellular volume (ECVliver) measurement by equilibrium MR in staging liver fibrosis in chronic hepatitis B (CHB) patients, and to compare its performance with serum fibrosis indices. MATERIALS AND METHODS 91 CHB patients were included and underwent gadopentetate dimeglumine-enhanced MRI with T1 mapping sequence before and 15-min after contrast. ECVliver, aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (FIB-4) were calculated and compared between fibrosis subgroups, and the correlations between the three indices and fibrosis stage or inflammatory activity were measured by Spearman correlation analysis and stepwise multiple regression analysis. Diagnostic performance in evaluating liver fibrosis stage was assessed and compared using receiver operating characteristic analysis. RESULTS Interobserver agreement showed an excellent interclass correlation coefficient of 0.895 for ECVliver. ECVliver, APRI and FIB-4 were different between fibrosis stages as a whole (F/H = 18.44-24.36, P ≤ 0.001). ECVliver had the strongest correlation with fibrosis stage (r = 0.727, P < 0.001), while APRI and FIB-4 had weak correlations (r = 0.466 and 0.440, P < 0.001). Multivariate analysis showed that only ECVliver was independently correlated with fibrosis stage (P < 0.001). The fibrosis stage was the only independent factor correlated with ECVliver comparing to inflammatory activity (P < 0.001). AUCs of ECVliver were larger than both APRI and FIB-4 in fibrosis staging, with significant differences in the diagnosis of advanced fibrosis (≥F3) and cirrhosis (F4) (P = 0.0024 to 0.0049). CONCLUSION MR ECVliver provides a promising noninvasive tool in staging liver fibrosis for CHB patients, superior to the fibrosis indices of APRI and FIB-4.
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Affiliation(s)
- He-Qing Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 20032, China
| | - Kai-Pu Jin
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 20032, China
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 20032, China
| | - Cai-Zhong Chen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 20032, China
| | - Sheng-Xiang Rao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 20032, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 20032, China
| | | | - Ruo-Fan Sheng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 20032, China.
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Nan Y, Niu X, Wang R, Zhao S, Fu N, Du J, Wang Y, Wang B, Zhang Y. microRNA-1273g-3p is a useful non-invasive test for the prediction of liver fibrosis in patients with chronic hepatitis C. Exp Ther Med 2019; 17:1817-1824. [PMID: 30783454 PMCID: PMC6364236 DOI: 10.3892/etm.2018.7114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 07/07/2017] [Indexed: 12/12/2022] Open
Abstract
Previous studies using microRNA (miRNA or miR) microarrays have demonstrated that miR-1273g-3p is upregulated in patients with hepatitis C virus (HCV)-associated fibrosis. As miRNAs have been suggested to be promising non-invasive biomarkers, the aim of the present study was to assess whether miR-1273g-3p may be useful as a potential indicator of fibrosis progression in patients with HCV. Liver biopsies were performed on 112 patients with chronic hepatitis C (CHC) and liver stiffness measurements (LSM) were performed using FibroTouch. Liver fibrosis was determined based on Meta-analysis of Histological Data in Viral Hepatitis classification, and the aspartate aminotransferase (AST)-to-platelet count (PLT) ratio index (APRI) and Fibrosis-4 score (FIB-4) were calculated. The diagnostic performance of miR-1273g-3p, LSM, APRI and FIB-4 in predicting fibrosis stage were evaluated and compared by receiver operating characteristic (ROC) analysis. It was demonstrated that miR-1273g-3p levels were significantly positively correlated with the liver fibrosis stage (r=0.657, P<0.001). The results of LSM, APRI and FIB-4, the three non-invasive diagnostic methods, had good consistency with liver biopsy results, and their correlation coefficients with fibrosis staging were 0.815, 0.417 and 0.522, respectively. The areas under the ROC curves of miR-1273g-3p for F≥2 and F=4 stage samples were 0.841 and 0.933, respectively, which were lower than LSM (0.890 and 0.937), and higher than FIB-4 (0.791 and 0.766) and APRI (0.719 and 0.760). Spearman analysis demonstrated that serum miR-1273g-3p levels were significantly positively correlated with age, body mass index, alanine aminotransferase, AST and total bilirubin (all P<0.05), and negatively correlated with PLT (P<0.05). However, no significant correlation was observed between miR-1273g-3p levels, baseline HCV RNA loads and genotype. Therefore, the results demonstrated that miR-1273g-3p levels, as a novel non-invasive test, may be a useful and easy method for predicting the stage of liver fibrosis in patients with CHC, and has a better diagnostic performance than FIB-4 and APRI. Further prospective studies are required to validate the efficacy of miR-1273g-3p as a predictor of liver fibrosis.
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Affiliation(s)
- Yuemin Nan
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
- Correspondence to: Professor Yuemin Nan, Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei 050051, P.R. China, E-mail:
| | - Xuemin Niu
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Rongqi Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Suxian Zhao
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Na Fu
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Jinghua Du
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Yang Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Baoyu Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Yuguo Zhang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
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Sha FR, Pk MU, Abuelezz NZ, Pervin R, Talukder RI, Begum M, Rahman M. Investigating the Efficiency of APRI, FIB-4, AAR and AARPRI as Noninvasive Markers for Predicting Hepatic Fibrosis in Chronic Hepatitis B Patients in Bangladesh. Open Microbiol J 2019. [DOI: 10.2174/1874285801913010034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background and Aims:Accurate, affordable non-invasive markers are highly needed for efficient diagnosis and management of liver fibrosis caused by chronic hepatitis B. This is the first study to investigate the diagnostic efficiency of Aspartate Transaminase to Platelet Ratio (APRI), Fibrosis Index (FIB-4), Aspartate transaminase to Alanine Transaminase Ratio (AAR) and AAR/Platelet ratio index (AARPRI) as non-invasive markers to predict hepatic fibrosis caused by Chronic Hepatitis B (CHB) in Bangladesh.Methods:In this study, a training cohort of 1041 CHB patients were recruited, whereas 104 and 109 CHB patients of matched ages were recruited as internal and external validation cohort groups respectively. Histological and hematological data were analyzed. METAVIR scoring system was used to classify liver fibrosis stages. Area Under Receiver Operating Curve (AUROC), correlations and cutoff values for the four diagnostic markers were calculated and assessed.Results:92%, 81% and 84% of the patients had liver fibrosis in the training cohort, internal and external cohort groups respectively. Among the four noninvasive panels, APRI showed the best area under ROC; (0.767, CI: 0.780-0.914; 0.775) for the training cohort, (0.775, CI: 0.693-0.857), and (0.847, CI: 0.780-0.914) for the internal and external cohorts respectively. Cut-off value of APRI was 0.512 with sensitivity/specificity of 84%/67% in training cohort, 81% / 66% in the internal cohort, and 88% / 66% in an external cohort. The odds ratio for APRI was 32.95 (95%CI: 4.746-228.862,p<0.001).Conclusion:Among all the four tested markers, APRI is the most accurate non-invasive test to predict major liver fibrosis (F2-3) in Bangladeshi CHB patients.
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Abstract
GOALS To determine the impact of geography and patient characteristics on hepatitis C virus (HCV) genotype and subtype distribution in a large sample of patients under routine clinical care BACKGROUND:: HCV genotype impacts disease course and response to treatment. Although several studies have reported genotype distribution within specific US populations, there are no comprehensive descriptions in large, geographically diverse cohorts. STUDY Using data from the Chronic Hepatitis Cohort Study, we present the distribution of HCV genotypes (GT) and subtypes (ST) among a racially diverse cohort of over 8000 HCV-infected patients from four large US health systems. RESULTS Genotype distribution varied significantly by geographic and demographic factors. In age-adjusted analyses, African American patients had significantly higher prevalence of GT1 (85%) than other racial categories, largely driven by a markedly higher proportion of GT1 subtype b (∼34%) than in Asian/other (24%) and white (21%) patients. GT3 represented an increasing proportion of infections as birth decade progressed, from 4% in patients born before 1946 to 18% of those born after 1976. Within the cohort of "living/uncured" patients, highly elevated alanine aminotransferase (>2 times the upper limit of normal) was significantly more common in GT3 patients, whereas Fibrosis-4 Index scores indicative of cirrhosis were most common in the combined group of GT4&6 patients. CONCLUSION Distribution of HCV genotypes and subtypes in the United States is more variable than suggested by previous national-level estimates and single-center studies. "Real-world" prevalence data may improve targeting of prevention, screening, and treatment efforts for hepatitis C.
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Ji SS, Jiang HD, Jiang JC, Li J, Lin ST, Chen B, Xu SH. Applicability of liver stiffness measurement based nomograms to the assessments of hepatitis B related significant fibrosis and cirrhosis. Clin Chim Acta 2018; 489:75-82. [PMID: 30471249 DOI: 10.1016/j.cca.2018.11.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 11/07/2018] [Accepted: 11/20/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND We evaluated liver fibrosis in patients with chronic hepatitis B (CHB) and mildly raised alanine transaminase (ALT) activities between 1-2 times the upper limit of normal (ULN) which was near the threshold for initiating treatment. METHODS Nomogram-Fibrosis and Nomogram-Cirrhosis were elaborated with variables independently associated with significant fibrosis and cirrhosis determined by multivariate logistic regression. Calibration, receiver operator characteristic (ROC) and decision curves were applied to comparing nomograms with aspartate aminotransferase (AST) to platelet count (PLT) ratio index (APRI), age-AST-PLT-ALT index (FIB-4) and liver stiffness measurement (LSM). RESULTS The Nomogram-Fibrosis was constructed with LSM, PLT, and gamma-glutamyl transpeptidase (GGT). Nomogram-Cirrhosis contained one more variable of age other than Nomogram-Fibrosis. The calibration demonstrated that the assessments of significant fibrosis or cirrhosis by nomograms were in line with liver biopsy. The AUROC of Nomogram-Fibrosis was 0.788, lager than APRI (0.586), FIB-4 (0.656) and LSM (0.735). The AUROC of Nomogram-Cirrhosis was 0.889, larger than APRI (0.642), FIB-4 (0.725) and LSM (0.837). Furthermore, the decision curve analysis suggested the most net benefits were provided by the nomograms. CONCLUSIONS Nomogram-Fibrosis and Nomogram-Cirrhosis could be promising tools for recognizing significant fibrosis and cirrhosis for CHB patients with mild raised ALT activities.
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Affiliation(s)
- Si-Si Ji
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Hai-Dan Jiang
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Jia-Chun Jiang
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Jia Li
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Shu-Ting Lin
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Bin Chen
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China.
| | - Shi-Hao Xu
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China.
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Wang L, Fan YX, Dou XG. Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B. World J Clin Cases 2018; 6:521-530. [PMID: 30397608 PMCID: PMC6212603 DOI: 10.12998/wjcc.v6.i12.521] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 08/17/2018] [Accepted: 10/09/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To explore the effect of alanine aminotransferase (ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B (CHB) patients.
METHODS A total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT (ALT ≤ 40), slightly elevated ALT (40 < ALT ≤ 80) and elevated ALT (ALT > 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis (stages S2-4), including the aspartate aminotransferase (AST)-to-platelet (PLT) ratio index (APRI), fibrosis index based on 4 factors (FIB-4), King’s score, Forns index and gamma-glutamyl transpeptidase (GGT)-to-PLT ratio (GPR), were evaluated for each group.
RESULTS Higher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher non-invasive test scores. The areas under the receiver operating characteristics curves (AUROCs) of the non-invasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L (range 0.705-0.755) and 40 < ALT ≤ 80 U/L (range 0.726-0.79) than for patients with ALT > 80 U/L (range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L (range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 < ALT ≤ 80 U/L (range 0.732-0.754 for ≥ S3, range 0.626-0.723 for S4) and ALT > 80 U/L (range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in ALT.
CONCLUSION ALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these non-invasive tests.
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Affiliation(s)
- Lin Wang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Yao-Xin Fan
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Xiao-Guang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
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Day J, Patel P, Parkes J, Rosenberg W. Derivation and Performance of Standardized Enhanced Liver Fibrosis (ELF) Test Thresholds for the Detection and Prognosis of Liver Fibrosis. J Appl Lab Med 2018; 3:815-826. [PMID: 31639756 DOI: 10.1373/jalm.2018.027359] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Accepted: 08/15/2018] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Noninvasive tests are increasingly used to assess liver fibrosis and determine prognosis but suggested test thresholds vary. We describe the selection of standardized thresholds for the Enhanced Liver Fibrosis (ELF) test for the detection of liver fibrosis and for prognostication in chronic liver disease. METHODS A Delphi method was used to identify thresholds for the ELF test to predict histological liver fibrosis stages, including cirrhosis, using data derived from 921 patients in the EUROGOLF cohort. These thresholds were then used to determine the prognostic performance of ELF in a subset of 457 patients followed for a mean of 5 years. RESULTS The Delphi panel selected sensitivity of 85% for the detection of fibrosis and >95% specificity for cirrhosis. The corresponding thresholds were 7.7, 9.8, and 11.3. Eighty-five percent of patients with mild or worse fibrosis had an ELF score ≥7.7. The sensitivity for cirrhosis of ELF ≥9.8 was 76%. ELF ≥11.3 was 97% specific for cirrhosis. ELF scores show a near-linear relationship with Ishak fibrosis stages. Relative to the <7.7 group, the hazard ratios for a liver-related outcome at 5 years were 21.00 (95% CI, 2.68-164.65) and 71.04 (95% CI, 9.4-536.7) in the 9.8 to <11.3 and ≥11.3 subgroups, respectively. CONCLUSION The selection of standard thresholds for detection and prognosis of liver fibrosis is described and their performance reported. These thresholds should prove useful in both interpreting and explaining test results and when considering the relationship of ELF score to Ishak stage in the context of monitoring.
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Affiliation(s)
- James Day
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK
| | - Preya Patel
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK
| | - Julie Parkes
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK.,The Department of Public Health Sciences and Medical Statistics, University of Southampton, Southampton, UK
| | - William Rosenberg
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK;
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Fibrosis Staging Using Direct Serum Biomarkers is Influenced by Hepatitis Activity Grading in Hepatitis C Virus Infection. J Clin Med 2018; 7:jcm7090267. [PMID: 30208564 PMCID: PMC6162836 DOI: 10.3390/jcm7090267] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 09/07/2018] [Accepted: 09/09/2018] [Indexed: 12/17/2022] Open
Abstract
Background: Chronic liver diseases (CLDs) generally progress from inflammation to fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is inevitable for the management of CLD patients. The purpose of this study was to compare the diagnostic abilities of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP), Enhanced liver fibrosis (ELF) score, Fibrosis-4 index, and AST to platelet ratio index (APRI) based on histopathological analysis of liver biopsy samples, from patients with positive Hepatitis C Virus (HCV) infection. Methods: Japanese patients with HCV infection who underwent liver biopsy examinations were enrolled in this study. WFA-M2BP levels and ELF scores were calculated using preserved serum samples. The fibrosis staging and activity grading were assessed using a modified METAVIR score. Results: A total of 122 patients were enrolled; the cohort included 27 patients with stage 1, 66 with stage 2, 20 with stage 3, and nine with stage 4 fibrosis. All four biomarkers distinguished stage 3 and stage 2 fibrosis. ROC curves revealed that all four fibrosis biomarkers presented AUC values greater than 0.8. Each of the four biomarkers in stage 2 was significantly different between the activity grade 1 and 2 groups. Conclusion: Fib-4 index and APRI were comparable with WFA-M2BP and ELF score in the diagnosis of advanced liver fibrosis in Japanese patients with HCV infection. All four biomarkers of liver fibrosis were influenced by histopathological activity grading, which implies that liver biopsy should be the gold standard to evaluate liver fibrosis staging even though several noninvasive biomarkers have been investigated well.
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Dong M, Wu J, Yu X, Li J, Yang S, Qi X, Mao R, Zhang Y, Yu J, Zhu H, Yang F, Qin Y, Zhang J. Validation and comparison of seventeen noninvasive models for evaluating liver fibrosis in Chinese hepatitis B patients. Liver Int 2018; 38:1562-1570. [PMID: 29314613 DOI: 10.1111/liv.13688] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 12/25/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS To avoid liver biopsy, many noninvasive models comprised of serum markers for liver fibrosis assessment have been developed. Given that most of them were developed in hepatitis C cohorts and few of them have been validated in Chinese hepatitis B patients, we aim to conduct this validation and compare their diagnostic accuracies in such a population. METHODS A total of 937 HBV-infected patients who underwent liver biopsy were included in this single-centre retrospective study. The diagnostic accuracies of the 17 noninvasive models were assessed by areas under the receiver-operating characteristic curves (AUROCs), using histologically evaluated fibrotic stages of the biopsy specimens as standards. To compare efficiencies of the models, a grading system based on AUROC levels was developed. RESULTS For discriminating significant fibrosis in all patients, the best three noninvasive models were King's score (AUROC = 0.756), Virahep-C model (AUROC = 0.756) and GPR (AUROC = 0.744); and for diagnosing cirrhosis, Lok index (AUROC = 0.832), FI (AUROC = 0.820) and FIB-4 (AUROC = 0.818) got the first three places. AUROCs in HBeAg-positive group were generally higher than those in HBeAg-negative group. In addition, based on the grading system, Virahep-C and GPR outstood others in evaluating liver fibrosis in all patients. CONCLUSIONS In Chinese HBV-infected patients, Virahep-C models and GPR had high accuracies in diagnosing liver fibrosis and cirrhosis, while the most discussed models like APRI and FIB-4 did not outstand. Assessment should take into account the HBeAg sero-status, since these noninvasive models were more appropriate for HBeAg-positive patients than HBeAg-negative ones.
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Affiliation(s)
- Minhui Dong
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jingwen Wu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xueping Yu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jing Li
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Sisi Yang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xun Qi
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Richeng Mao
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yongmei Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jie Yu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Haoxiang Zhu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Feifei Yang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yanli Qin
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiming Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
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Tseng CH, Chang CY, Mo LR, Lin JT, Tai CM, Perng DS, Lin CW, Hsu YC. Acoustic Radiation Force Impulse Elastography with APRI and FIB-4 to Identify Significant Liver Fibrosis in Chronic Hepatitis B Patients. Ann Hepatol 2018; 17:789-794. [PMID: 30145564 DOI: 10.5604/01.3001.0012.3137] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM In chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy, therapeutic decision currently depends on histopathology of the liver. We aimed to evaluate if acoustic radiation force impulse (ARFI) in conjunction with aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) score could replace liver biopsy to indicate treatment for CHB. MATERIAL AND METHODS We prospectively enrolled 101 clinically non-cirrhotic patients whose serum alanine aminotransferase was mildly elevated (1-2 folds above the upper normal limit) despite a high viral load (HBV DNA > 2,000 IU/mL). All participants underwent liver biopsy, and measurement of ARFI, APRI and FIB-4. The ability of the markers to distinguish fibrosis ≥ METAVIR F2 was evaluated. RESULTS According to histopathology, liver fibrosis was METAVIR F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients, and was correlated with ARFI (p = 0.0001), APRI (p = 0.012), and FIB-4 (p = 0.004). The six patients with cirrhosis were included for analysis, and received antiviral therapy. The C statistics of ARFI, APRI, and FIB-4 for fibrosis ≥ F2 were 0.70 (95% confidence interval [CI], 0.59-0.80), 0.62 (95% CI, 0.51-0.73), and 0.64 (0.53- 0.75), respectively. The cut-off values for 95% sensitivity and 95% specificity to identify significant fibrosis were 0.97 m/sec and 1.36 m/sec for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. Using a combination of these 3 indices, 44 patients (43.6%) could be spared a liver biopsy procedure. CONCLUSIONS A combination of ARFI, APRI, and FIB-4 may spare some CHB patients with equivocal indication for antiviral treatment a liver biopsy.
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Affiliation(s)
- Cheng-Hao Tseng
- Division of Gastroenterology and Hepatology, E-DA cancer hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chi-Yang Chang
- Division of Gastroenterology and Hepatology, E-DA hospital/I-Shou University, Kaohsiung, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology and Hepatology, E-DA hospital/I-Shou University, Kaohsiung, Taiwan
| | - Jaw-Town Lin
- Division of Gastroenterology and Hepatology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, E-DA hospital/I-Shou University, Kaohsiung, Taiwan
| | - Daw-Shyong Perng
- Division of Gastroenterology and Hepatology, E-DA hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-DA hospital/I-Shou University, Kaohsiung, Taiwan
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Coghill S, McNamara J, Woods M, Hajkowicz K. Epidemiology and clinical outcomes of hepatitis delta (D) virus infection in Queensland, Australia. Int J Infect Dis 2018; 74:123-127. [PMID: 30003953 DOI: 10.1016/j.ijid.2018.07.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 07/03/2018] [Accepted: 07/04/2018] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES To investigate the epidemiology, clinical characteristics and outcomes of those with hepatitis delta virus (HDV) infection in Queensland, Australia. DESIGN Retrospective cohort study of individuals tested for HDV between 1997 and 2016 in the public healthcare system in Queensland. RESULTS 179 individuals recorded positive HDV serology between 1997 and 2016, with a total of 4407 individuals undergoing testing (seroprevalence 4.1%). The majority of HDV positive individuals were male and were born overseas. Those born in Africa had a higher risk ratio (RR) for HDV infection (RR, 1.55; 95% CI, 1.14-2.09); being born in Asia was associated with a relatively lower risk of HDV infection (RR, 0.36; 95% CI, 0.27-0.58). Positive hepatitis C virus (HCV) serology was significantly associated with positive HDV serology (RR, 2.98; 95% CI, 2.36-3.78). Of the HDV positive individuals born in Australia, the majority were HCV positive (69.8%). HDV positive individuals were less likely to be Hepatitis B e antigen (HBeAg) positive (RR, 0.64; 95% CI, 0.45-0.93) and recorded lower hepatitis B virus (HBV) viral loads. Positive HDV serology was associated with increased risk of liver cirrhosis (RR, 2.3; 95% CI 1.73-3.07) and liver transplantation (RR, 1.93; CI 1.31-2.85). Only 8% of HDV positive individuals underwent HDV treatment. CONCLUSIONS In Queensland, HDV seropositivity is associated with overseas birth, particularly in Africa. HDV infection is associated with decreased HBV viraemia and more advanced liver disease.
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Affiliation(s)
- Sarah Coghill
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia.
| | - John McNamara
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia
| | - Marion Woods
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia
| | - Krispin Hajkowicz
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia
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Primary biliary cholangitis is more severe in previous hepatitis B virus infection patients. Eur J Gastroenterol Hepatol 2018; 30:682-686. [PMID: 29462025 DOI: 10.1097/meg.0000000000001100] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The aim of this study was to evaluate the association between previous hepatitis B virus (HBV) infection and the severity of primary biliary cholangitis (PBC). PATIENTS AND METHODS A total of 379 HBsAg-negative PBC patients were investigated between 2012 and 2017 in this study. Fifty-two of these patients underwent liver biopsy. The enrolled patients were divided into an anti-HBc-positive group and an anti-HBc-negative group; the patients with liver biopsy were further divided into early stage (stage I) and advanced stage (stages II, III, and IV) according to histological assessment. Liver fibrosis was also assessed by noninvasive prognosis scores including the Mayo Risk Score, the Newcastle model, the aspartate aminotransferase-to-platelet ratio index, the fibrosis index based on the four factors (FIB-4), and the albumin-bilirubin score. The difference in disease stage between the two groups was assessed by histological stage and noninvasive scores predicting fibrosis. RESULTS The histology showed that more patients in the anti-HBc-positive group had advanced stage compared with anti-HBc-negative patients (P<0.05). Higher Mayo Risk Score, the Newcastle model, aminotransferase-to-platelet ratio index, and fibrosis index based on the four factors (all P<0.05) were obtained in all patients except for the albumin-bilirubin score (P=0.096). CONCLUSION Previous HBV infection was associated with a worse histological stage and advanced fibrosis score of PBC. It appears that the previous HBV infection may have aggravated the PBC severity, potentially leading to poorer outcomes.
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Li J, Mao RC, Li XL, Zheng JW, Qi X, Yuan Q, Zhang J, Zhang JM, Xia NS. A novel noninvasive index for the prediction of moderate to severe fibrosis in chronic hepatitis B patients. Dig Liver Dis 2018; 50:482-489. [PMID: 29396134 DOI: 10.1016/j.dld.2017.12.028] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 11/25/2017] [Accepted: 12/24/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUNDS The evaluation of liver fibrosis stages is essential for the clinical management of chronic hepatitis B (CHB). AIMS To develop and validate a novel noninvasive index for moderate to severe fibrosis (≥S2) in CHB patients. METHODS A total of 401 CHB patients who underwent liver biopsy were divided into the training (n = 300) and validation (n = 101) cohort. Histological severity was scored using a modified Scheuer system. Clinical and laboratory assessments were collected. RESULTS In the training cohort, PACG, a novel index combining the quantitative hepatitis B core antibody (qAnti-HBc), platelet count (PLT), and albumin globulin ratio (A/G), presented better diagnostic performance (AUROC = 0.814) than that of APRI (0.735, p = 0.007) and FIB-4 (0.749, p = 0.014). In the validation cohort, the AUROC of the PACG, APRI, FIB-4 and Fibroscan were 0.834, 0.806, 0.791 and 0.810, respectively. More importantly, a higher and lower cutoff of PACG for predicting ≥S2 fibrosis or not had a >90% sensitivity and specificity, with a diagnostic accuracy of 85.9%. CONCLUSION PACG is a promising noninvasive alternative to liver biopsy in CHB patients for the evaluation of moderate to severe fibrosis.
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Affiliation(s)
- Jing Li
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Ri-Cheng Mao
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiao-Ling Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China
| | - Jin-Wei Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China
| | - Xun Qi
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Quan Yuan
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
| | - Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China
| | - Ji-Ming Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
| | - Ning-Shao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China
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47
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Wong GLH. Non-invasive assessments for liver fibrosis: The crystal ball we long for. J Gastroenterol Hepatol 2018; 33:1009-1015. [PMID: 29380413 DOI: 10.1111/jgh.14103] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 12/26/2017] [Accepted: 01/20/2018] [Indexed: 12/14/2022]
Abstract
Non-invasive assessment of liver fibrosis has been one of the most rapidly advancing fields in hepatology in the last decade. Progressive liver fibrosis results in cirrhosis, hepatocellular carcinoma (HCC), and various liver-related complications in essentially all chronic liver diseases. Assessment of liver fibrosis allows clinicians to determine the prognosis, need of treatment, disease progression, and response to treatment in patients with chronic liver disease. Liver biopsy has been the gold standard in last few decades and most adopted diagnostic tool in clinical trials. Nonetheless, it is impractical to apply the test in a large number of patients or to do it serially. Hence, various non-invasive assessments have been developed and adopted in some international management guidelines. Liver stiffness measurement (LSM) with transient elastography is one of the most widely validated non-invasive assessments for liver fibrosis. It is an accurate and reproducible method to predict advanced fibrosis in chronic hepatitis B. Using transient elastography, it is possible to perform repeated liver fibrosis assessments on a large number of asymptomatic patients. The key challenge of his tool is the confounding effect of alanine aminotransferase (ALT) level, such that decrease in LSM may only reflect ALT normalization, hence not accurate enough to indicate regression of liver fibrosis. This may be partially handled by combining LSM with a serum-based formula, which is independent of ALT such as the Forns index and enhanced liver fibrosis test. An LSM-based HCC risk score is useful to prioritize patients for HCC surveillance.
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Affiliation(s)
- Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Sha Tin, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong
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48
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Zhang W, Zhang X, Zou K, Xie J, Zhao S, Liu J, Liu H, Wang J, Wang Y. Seabuckthorn berry polysaccharide protects against carbon tetrachloride-induced hepatotoxicity in mice via anti-oxidative and anti-inflammatory activities. Food Funct 2018; 8:3130-3138. [PMID: 28766672 DOI: 10.1039/c7fo00399d] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The berries of Seabuckthorn (Hippophae rhamnoides L.) are traditional medicinal foods that have been used by Tibetans and Mongolians for thousands of years. The polysaccharides are the main components of Seabuckthorn berries, possessing immune stimulating, anti-cancer and anti-fatigue activities. The present study focused on evaluating the protective effects and mechanisms of Seabuckthorn berry polysaccharide (SP) against carbon tetrachloride (CCl4)-induced hepatotoxicity. Mice were orally administrated with 50, 100 and 200 mg kg-1 of SP once daily for 14 consecutive days prior to CCl4 challenge. Pretreatment with SP significantly decreased alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels, while increasing the levels of prealbumin (PALB) in the CCl4-challenged mice, which were accompanied by diminished liver injuries, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, increased GSH levels, and reduced malondialdehyde (MDA) content. The pretreatment with SP also markedly reduced the CCl4-induced expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Furthermore, the pretreatment with SP decreased hepatic Toll-like receptor 4 (TLR4) expression and inhibited the phosphorylation of p38 MAPK, extracellular signal-regulated kinase (p-ERK), c-Jun N-terminal kinase (p-JNK) and nuclear factor-kappa B (NF-κB) in the CCl4-challenged mice. These results suggest that the pretreatment with SP protected against CCl4-induced liver damage via its anti-oxidative and anti-inflammatory activities. SP might be suitable for functional foods and natural drugs in preventing CCl4-induced hepatotoxicity.
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Affiliation(s)
- Wei Zhang
- College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
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49
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Li Q, Lu C, Li W, Huang Y, Chen L. The gamma-glutamyl transpeptidase-to-albumin ratio predicts significant fibrosis and cirrhosis in chronic hepatitis B patients. J Viral Hepat 2017; 24:1143-1150. [PMID: 28685907 DOI: 10.1111/jvh.12751] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 05/31/2017] [Indexed: 12/20/2022]
Abstract
Background/Aim Simple, inexpensive and clinically available noninvasive liver fibrosis tests are highly needed. We aimed to develop a novel noninvasive index for predicting significant fibrosis and cirrhosis in chronic hepatitis B (CHB) patients. Methods Using liver histology as gold standard, we developed a novel index to predict significant fibrosis and cirrhosis in CHB patients and then compared the diagnostic accuracy of the novel index, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) in a training set (606 patients) and a validation set (216 patients) from the same patient catchment area. Results Of 606 CHB patients in the training set, 33.2% had significant fibrosis and 11.4% had cirrhosis. In multivariable analysis, gamma-glutamyl transpeptidase (GGT) (OR=1.032, p<0.001) and albumin (OR=0.953, p=0.048) were independent predictors of significant fibrosis. Consequently, a GGT-to-albumin ratio (GAR) was developed. In the training set, the area under the receiver operating characteristic curve (AUROC) of GAR was significantly higher than that of APRI and FIB-4 to predict ≥F2 (0.82, 0.70, and 0.68, respectively), ≥F3 (0.86, 0.76, and 0.75, respectively), and F4 (0.88, 0.75, and 0.73, respectively), respectively. In the validation set, the AUROC of GAR was also better than APRI and FIB-4 for predicting ≥F2 (0.81, 0.63 and 0.61, respectively), ≥F3 (0.88, 0.78, and 0.76, respectively) and F4 (0.92, 0.85, and 0.78, respectively), respectively. Conclusions GAR is a more accurate noninvasive index than APRI and FIB-4 to stage significant fibrosis and cirrhosis in CHB patients and represents a novel noninvasive alternative to liver biopsy.
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Affiliation(s)
- Q Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.,Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - C Lu
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - W Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Y Huang
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.,Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - L Chen
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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50
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Wang H, Zhou Y, Yan R, Ru GQ, Yu LL, Wang MS, Chen MJ. Development and validation of a model for staging hepatic fibrosis for chronic hepatitis B patients with E antigen-positive. Oncotarget 2017; 8:98812-98822. [PMID: 29228729 PMCID: PMC5716769 DOI: 10.18632/oncotarget.22003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 10/05/2017] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Interest is growing in the use of non-invasive techniques for complementing liver biopsy for liver fibrosis assessment. We aimed to prospectively evaluate liver histology in chronic hepatitis B (CHB) patients with e-antigen positivity, and develop and validate a novel scoring system-e-antigen-positive CHB liver fibrosis (EPLF) score-for noninvasively predicting the fibrosis stages. METHODS We identified the baseline variables associated with fibrosis stage (MATAVIR score, F0-F4) in 212 CHB patients with e-antigen positivity. These significant variables were used to develop the EPLF scoring system. The EPLF score equation was developed based on the prediction of fibrosis stages via multivariate ordered logistic regression analysis. The diagnostic powers of the EPLF score and several non-invasive markers were assessed through an area under the receiver operating characteristic curve (AUROC) analyses. This EPLF score model was validated in another set of 208 similar patients. RESULTS The natural logarithms of serum albumin, HBeAg, and HBsAg levels were selected as significant independent variables for the EPLF score equation. The EPLF score had good diagnostic power (AUROC, 0.72-0.90, p<0.001) and good diagnostic accuracy (72-85%), with a high positive predictive value (80.8-92.8%) for each fibrosis stage in the test group. Similar results were observed in the validation group (AUROC, 0.73-0.89, p<0.001). The EPLF score exhibited a strong correlation with fibrosis stage (r=0.67, p<0.001), and was the preferable non-invasive marker for staging liver fibrosis. CONCLUSION In e-antigen-positive patients with CHB, the EPLF score could serve as a potential non-invasive marker of liver fibrosis stage.
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Affiliation(s)
- Hong Wang
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Ying Zhou
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Rong Yan
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Guo Qing Ru
- Department of Pathology, Zhejiang Provincial People's Hospital, Zhejiang, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Li Li Yu
- Department of Pathology, Zhejiang Provincial People's Hospital, Zhejiang, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Ming Shan Wang
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Mei Juan Chen
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang, People's Hospital of Hangzhou Medical College, Zhejiang, China
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