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Le MH, Liu JK, Lee K, Cheung R, Nguyen MH. Late Diagnosis of Chronic Hepatitis B in the United States: A Population-Based, Retrospective Cohort Study From 2007 to 2021. Aliment Pharmacol Ther 2025. [PMID: 40418666 DOI: 10.1111/apt.70193] [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: 03/05/2025] [Revised: 04/10/2025] [Accepted: 05/05/2025] [Indexed: 05/28/2025]
Abstract
BACKGROUND Underdiagnosis of chronic hepatitis B (CHB) remains a major problem in the United States (USA), with > 80% of CHB patients remaining undiagnosed. AIMS To determine the prevalence of late diagnosis of CHB and resultant liver complications. METHODS This retrospective analysis of the Truven MarketScan database (1/2007-12/2021) included more than 250 million privately insured persons. The index date was the date of the first liver complication (cirrhosis, hepatocellular carcinoma [HCC], or liver transplant). Late diagnosis was defined as the diagnosis of CHB 2 years prior to or after the index date. Adults aged ≥ 18 years with a diagnosis of CHB and ≥ 12 months of insurance coverage prior to the index date were included. Exclusion criteria included > 90 days break of insurance coverage within 12 months before the index date and receipt of nonliver transplant within 5 years of the index date. RESULTS 2608 persons met inclusion criteria with a mean age of 54.8 years and 70.3% were male. 1999 (76.6%) had a late diagnosis of CHB, of whom 889 (44.5%) were diagnosed at or within 6 months of the index complication, and 1510 (75.5%) did not have a documented visit with a provider to the index date. Late diagnosis rate remained stable between 2009 (73.8%) and 2017 (74.2%, p-trend = 0.937). In the late diagnosis group, complications included cirrhosis (n = 1820, 91.0%), decompensated cirrhosis (n = 1630, 81.5%), HCC (n = 615, 30.8%) and liver transplant (n = 288, 14.4%). CONCLUSION Approximately three-fourths of patients diagnosed with CHB in the USA had a late diagnosis. Increased screening efforts must be made to prevent poor clinical outcomes.
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Affiliation(s)
- Michael H Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
- The Robert Larner MD College of Medicine at the University of Vermont, Burlington, Vermont, USA
| | - Joanne K Liu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - KeeSeok Lee
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
- Division of Gastroenterology and Hepatology, VA Palo Alto Health Care System, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
- Department of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California, USA
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Chen F, Li Q, Xu X, Wang F. Clinical characteristics and risk factors of hepatitis B virus-related cirrhosis/hepatocellular carcinoma: A single-center retrospective study. LIVER RESEARCH 2023; 7:237-243. [PMID: 39958384 PMCID: PMC11791899 DOI: 10.1016/j.livres.2023.07.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 05/30/2023] [Accepted: 07/20/2023] [Indexed: 02/18/2025]
Abstract
Background and aims Hepatitis B virus (HBV) infection is a major global health problem which progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Early prediction of disease changes and intervention are essential to slow disease progression and protect liver function. This study aimed to analyze the clinical characteristics of patients with HBV-related LC and HCC at different serum alanine aminotransferase (ALT) levels and explore the risk factors of HBV infection progressing to LC/HCC. Methods A total of 379 patients with HBV infection treated in The Third People's Hospital of Shenzhen between January 2014 and December 2016 without any antiviral drug therapy were enrolled. Patients were divided into the LC/HCC and non-LC/HCC groups based on clinical diagnosis, which was determined through imaging and expressions of pathological and laboratory test markers, and patients with LC/HCC were further divided into three groups according to the serum ALT levels. Differences in general information, clinical symptoms, and expression levels of serological indices of the above groups were compared and analyzed, logistic regression was used to analyze the risk factors for LC/HCC development, and the clinical diagnostic efficacy of indicators was judged by the receiver operator characteristic (ROC). Results LC/HCC mainly occurred in the ALT normal and mildly elevated groups, with 70.83% of patients with HCC having an LC background. In the comparison of different ALT level groups, the moderately-severely elevated group had the highest proportion of patients with skin jaundice, abdominal varices, rebound tenderness, higher white blood cell and neutrophil (NEUT) counts; and higher levels of aspartate aminotransferase, glutamyl transpeptidase, total bilirubin, and direct bilirubin. The LC/HCC group was older and had significantly higher proportions of male patients, alcohol consumption, and combined hypertension than the non-LC/HCC group (all P < 0.05). Logistic regression analysis showed that age, combined hypertension, abdominal varicose veins, subcostal palpation, and NEUT count were risk factors for LC/HCC development; and the area under the curve for this model on the ROC analysis was 0.935 (95% confidence interval 0.899-0.972) with specificity and sensitivity of 97.4% and 70.7%, respectively. Conclusions Advanced age, combined hypertension, abdominal varicose veins, subcostal palpation, and high NEUT count are risk factors for LC/HCC development in patients with untreated HBV infection.
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Affiliation(s)
- Feng Chen
- Division of Gastroenterology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
- National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong, China
| | - Qianhui Li
- Division of Gastroenterology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Xiaomin Xu
- Division of Gastroenterology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Fei Wang
- Division of Gastroenterology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
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McMahon B, Cohen C, Brown Jr RS, El-Serag H, Ioannou GN, Lok AS, Roberts LR, Singal AG, Block T. Opportunities to address gaps in early detection and improve outcomes of liver cancer. JNCI Cancer Spectr 2023; 7:pkad034. [PMID: 37144952 PMCID: PMC10212536 DOI: 10.1093/jncics/pkad034] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 04/10/2023] [Indexed: 05/06/2023] Open
Abstract
Death rates from primary liver cancer (hepatocellular carcinoma [HCC]) have continued to rise in the United States over the recent decades despite the availability of an increasing range of treatment modalities, including new systemic therapies. Prognosis is strongly associated with tumor stage at diagnosis; however, most cases of HCC are diagnosed beyond an early stage. This lack of early detection has contributed to low survival rates. Professional society guidelines recommend semiannual ultrasound-based HCC screening for at-risk populations, yet HCC surveillance continues to be underused in clinical practice. On April 28, 2022, the Hepatitis B Foundation convened a workshop to discuss the most pressing challenges and barriers to early HCC detection and the need to better leverage existing and emerging tools and technologies that could improve HCC screening and early detection. In this commentary, we summarize technical, patient-level, provider-level, and system-level challenges and opportunities to improve processes and outcomes across the HCC screening continuum. We highlight promising approaches to HCC risk stratification and screening, including new biomarkers, advanced imaging incorporating artificial intelligence, and algorithms for risk stratification. Workshop participants emphasized that action to improve early detection and reduce HCC mortality is urgently needed, noting concern that many of the challenges we face today are the same or similar to those faced a decade ago and that HCC mortality rates have not meaningfully improved. Increasing the uptake of HCC screening was identified as a short-term priority while developing and validating better screening tests and risk-appropriate surveillance strategies.
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Affiliation(s)
- Brian McMahon
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | | | - Robert S Brown Jr
- Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA
| | - Hashem El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - George N Ioannou
- Department of Medicine, Division of Gastroenterology, VA Puget Sound Health Care System, Seattle, WA, USA
| | - Anna S Lok
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Lewis R Roberts
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Amit G Singal
- Department of Internal Medicine, Division of Digestive and Liver Diseases, UT Southwestern, Dallas, TX, USA
| | - Timothy Block
- Baruch S. Blumberg Institute and Hepatitis B Foundation, Doylestown, PA, USA
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Biondi MJ, Estes C, Razavi-Shearer D, Sahdra K, Lipton N, Shah H, Capraru C, Janssen HLA, Razavi H, Feld JJ. Cost-effectiveness modelling of birth and infant dose vaccination against hepatitis B virus in Ontario from 2020 to 2050. CMAJ Open 2023; 11:E24-E32. [PMID: 36627129 PMCID: PMC9842099 DOI: 10.9778/cmajo.20210284] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The World Health Organization recommends universal birth dose vaccination for hepatitis B virus (HBV), yet only 3 provinces and territories in Canada provide birth dose vaccination, and Canadian-born children in Ontario are acquiring HBV before adolescent vaccination. We sought to determine whether birth and/or infant HBV vaccination is cost-effective. METHODS We used a dynamic HBV model that incorporates population by year, disease stage, sex and the influence of immigration to quantify the disease and economic burden of chronic HBV infection in Ontario from 2020 to 2050. We compared 4 vaccination scenarios, which included a birth dose vaccine and variations of the 2 subsequent doses (either alone or as a part of the hexavalent vaccine) and a hexavalent-only strategy in infancy with the current adolescent vaccination strategy. Our costing estimates were based on values from 2020. RESULTS All 4 infant vaccination approaches prevented an additional 550-560 acute and 160 chronic pediatric HBV infections from 2020 to 2050 compared with adolescent vaccination. Whereas birth dose could be cost-effective, incorporating vaccination into a hexavalent vaccine was cost saving. By 2050, the hexavalent approach led to $428 000 in cost savings per disability-adjusted life years averted. INTERPRETATION At the current prevalence in Ontario, a switch to birth dose or infant dose will be cost-effective or even cost saving. Introducing any form of infant HBV immunization in Ontario will prevent acute and chronic pediatric HBV infections.
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Affiliation(s)
- Mia J Biondi
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Chris Estes
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Devin Razavi-Shearer
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Kanwar Sahdra
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Nechama Lipton
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Hemant Shah
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Camelia Capraru
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Harry L A Janssen
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Homie Razavi
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo
| | - Jordan J Feld
- Viral Hepatitis Care Network (VIRCAN) Study Group (Biondi, Sahdra, Lipton, Shah, Capraru, Janssen, Feld), Toronto Centre for Liver Disease; Institute of Medical Sciences (Feld), University of Toronto; School of Nursing (Biondi), York University, Toronto, Ont.; Arthur Labatt Family School of Nursing (Biondi), Western University, London, Ont.; Center for Disease Analysis Foundation (Estes, Razavi-Shearer, Razavi), Lafayette, Colo.
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Mendlowitz AB, Feld JJ, Biondi MJ. Hepatitis B and C in Pregnancy and Children: A Canadian Perspective. Viruses 2022; 15:91. [PMID: 36680130 PMCID: PMC9863739 DOI: 10.3390/v15010091] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 12/24/2022] [Accepted: 12/27/2022] [Indexed: 12/30/2022] Open
Abstract
In 2016, the World Health Organization released a plan to eliminate viral hepatitis as a public health threat by 2030. For Canada to achieve the recommended decreases in HBV- and HCV-related new diagnoses and deaths, an increase in services is urgently required. Identifying those at risk of, or who have acquired HBV and HCV, remains a challenge, especially with the emergence of new priority populations such as pregnant persons and children. Importantly, prenatal, and pediatric care are times when individuals are often already engaged with the healthcare system, leading to the potential for opportunistic or co-localized care and interventions. At present, Canada may not be maximizing all available virologic tools that could lead to increases in prevention, identification, improved management, or even cure. Here, we describe the continuum of care that includes preconception, prenatal, postpartum, and pediatric stages; and identify current global and Canadian recommendations, findings, and opportunities for improvement.
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Affiliation(s)
- Andrew B. Mendlowitz
- Viral Hepatitis Care Network, Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada
| | - Jordan J. Feld
- Viral Hepatitis Care Network, Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada
| | - Mia J. Biondi
- Viral Hepatitis Care Network, Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada
- School of Nursing, York University, Toronto, ON M3J 1P3, Canada
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6
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Zhang C, Zhang W, Shui Y, Li P, Tian Z, Duan S, Wei Q. Implications of m6A-associated snRNAs in the prognosis and immunotherapeutic responses of hepatocellular carcinoma. Front Immunol 2022; 13:1001506. [PMID: 36405741 PMCID: PMC9667552 DOI: 10.3389/fimmu.2022.1001506] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 10/18/2022] [Indexed: 11/07/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the most prevalent pathological type of liver cancer worldwide with high mortality and poor prognosis. N6-methyladenosine (m6A) can modify RNAs such as mRNA, lncRNA, miRNA, and tRNA, thereby playing a critical role in the pathogenesis of HCC. However, the role of m6A-associated small nuclear RNA (snRNA) in the prognostic value and immunotherapeutic response in HCC remains unclear. Materials and methods In this study, snRNA expression data, gene mutation data, and clinical data of HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. We used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify significant prognostic m6A-associated snRNAs, and then developed a multivariate Cox model based on the selected snRNAs. HCC patients were split into low- and high-risk groups based on the median risk score. We subsequently performed Kaplan-Meier curve analysis to estimate overall survival (OS) by clinicopathological characteristics and tumor mutational burden (TMB) status in low- and high-risk HCC patients. Finally, we compared the immunotherapeutic response as represented by tumor immune dysfunction and exclusion (TIDE) scores between the two risk groups. Results Eight m6A-associated snRNAs were selected as independent predictors to develop the risk model. Our results revealed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group on clinicopathologic characteristics, including age (≤65 years and >65 years), gender (male), grade (G I-II and G III-IV) and TNM staging (Stage I-II and Stage III-IV). In addition, the OS of low-TMB and low-risk group was longer than that of high-TMB and high-risk group. The TIDE score indicated that HCC patients in the high-risk group were more susceptible to immunotherapy. Conclusion Our study suggests that m6A-associated snRNAs may be useful biomarkers for the prognosis of HCC and that m6A-associated snRNA models can predict the effect of immunotherapy in HCC patients.
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Affiliation(s)
- Cheng Zhang
- Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wangjian Zhang
- School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yongjie Shui
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Ping Li
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhifeng Tian
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Shiwei Duan
- School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China
- *Correspondence: Qichun Wei, ; Shiwei Duan,
| | - Qichun Wei
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- *Correspondence: Qichun Wei, ; Shiwei Duan,
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Zhang C, Zhang W, Yuan Z, Yang W, Hu X, Duan S, Wei Q. Contribution of DNA methylation to the risk of hepatitis C virus-associated hepatocellular carcinoma: A meta-analysis. Pathol Res Pract 2022; 238:154136. [PMID: 36155324 DOI: 10.1016/j.prp.2022.154136] [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: 04/21/2022] [Revised: 09/07/2022] [Accepted: 09/16/2022] [Indexed: 10/14/2022]
Abstract
DNA methylation is a crucial epigenetic modification in hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) can induce hepatocarcinogenesis. Nevertheless, the interaction mechanism between DNA methylation and HCV infection in HCC is still ambiguous. In this study, we performed a comprehensive meta-analysis to assess the contribution of DNA methylation in HCV-associated HCC. After four steps of literature screening, we finally obtained 33 qualified case-control studies for this meta-analysis. These studies consisted of 587 HCV-positive cancer tissues and 326 HCV-negative cancer tissues. Our results revealed that four genes (p16, GSTP1, APC, and RUNX3) were more hypermethylated in the HCV-positive liver cancer tissues than in the HCV-negative liver cancer tissues. In addition, the p16 gene was more hypermethylated in the HCV-positive paracancerous tissues than in the HCV-negative paracancerous tissues. Subgroup meta-analysis by geographical populations showed that p16 methylation was significantly higher in HCV-positive cancerous tissues from Japanese and Chinese. Besides, p16 methylation was significantly higher among patients (> 60 years) but not among the others (≤ 60 years). However, there was no obvious association between DNA methylation and other clinicopathological characteristics, including gender, tumor size, differentiation, and clinical stage. Our study suggested that DNA methylation could become potential biomarkers for HCV-associated HCC. DNA methylation contributed to the risk of HCV-associated HCC.
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Affiliation(s)
- Cheng Zhang
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Wangjian Zhang
- Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhijun Yuan
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wenjun Yang
- Department of Pathology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Xiangrong Hu
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Shiwei Duan
- School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China.
| | - Qichun Wei
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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Sonneveld MJ, Veldhuijzen IK, van de Laar TJW, Op de Coul ELM, van der Meer AJ. Decrease in viral hepatitis diagnoses during the COVID-19 pandemic in the Netherlands. J Hepatol 2022; 77:896-897. [PMID: 33887356 PMCID: PMC9377202 DOI: 10.1016/j.jhep.2021.04.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/09/2021] [Accepted: 04/12/2021] [Indexed: 12/04/2022]
Affiliation(s)
- Milan J Sonneveld
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
| | - Irene K Veldhuijzen
- National Institute for Public Health and the Environment, Centre for Infectious Disease Control, Epidemiology and Surveillance, Bilthoven, the Netherlands
| | - Thijs J W van de Laar
- Department of Donor Medicine Research, Laboratory of Blood Borne Infections, Sanquin Research, Amsterdam, the Netherlands
| | - Eline L M Op de Coul
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Trends in decompensated cirrhosis and hepatocellular carcinoma among people with a hepatitis B notification in New South Wales. JHEP Rep 2022; 4:100552. [PMID: 36119722 PMCID: PMC9478454 DOI: 10.1016/j.jhepr.2022.100552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 07/01/2022] [Accepted: 07/19/2022] [Indexed: 01/27/2023] Open
Abstract
Background & Aims Population-level trends and factors associated with HBV-related decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality are crucial to evaluate the impacts of therapeutic interventions. Methods Trends in HBV-DC and -HCC diagnoses and liver-related mortality in New South Wales, Australia, were determined through linkage of HBV notifications (1993-2017) to hospital admissions (2001-2018), mortality (1993-2018), and cancer registry (1994-2014) databases. Late HBV notification was defined as notification at or within 2 years of a DC or HCC diagnosis. Cox proportional-hazards regression and multivariable logistic regression analyses were performed to evaluate associated factors. Results Among 60,660 people with a HBV notification, 1,276 (2.0%) DC and 1,087 (1.8%) HCC diagnoses, and 1,219 (2.0%) liver-related deaths were documented. Since the early 2000s, the number of DC and HCC diagnoses increased; however, age-standardised incidence decreased from 2.64 and 1.95 in 2003 to 1.14 and 1.09 per 1,000 person-years in 2017, respectively. Similarly, age-standardised liver mortality decreased from 2.60 in 2003 to 1.14 per 1,000 person-years in 2017. Among people with DC and HCC diagnoses, late HBV notification declined from 41% and 40% between 2001-2009 to 29% and 25% in 2010-2018, respectively. Predictors of DC diagnosis included older age (birth <1944, adjusted hazard ratio [aHR] 2.06, 95% CI 1.57–2.69), alcohol use disorder (aHR 4.82, 95% CI 3.96–5.87) and HCV co-infection (aHR 1.88, 95% CI 1.53–2.31). Predictors of HCC diagnosis included older age (birth <1944, aHR 3.94, 95% CI 2.91–5.32) and male sex (aHR 3.79, 95% CI 3.05–4.71). Conclusion In an era of improved antiviral therapies, the risk of HBV-related liver morbidity and mortality has declined. HCV co-infection and alcohol use disorder are key modifiable risk factors associated with the burden of HBV. Lay summary Rising hepatitis B-related morbidity and mortality is a major public health concern. However, the development of highly effective medicines against hepatitis B virus (HBV) has brought renewed optimism for its elimination by 2030. This study shows a steady decline in HBV-related liver morbidity and mortality in New South Wales, Australia. Moreover, late hepatitis notification has also declined, allowing individuals with HBV to have access to timely antiviral treatment. Despite this, hepatitis C co-infection and alcohol use disorder are key modifiable risk factors associated with HBV disease burden. To attain the desired benefits from highly effective antiviral treatment, managing comorbidities, including hepatitis C and high alcohol use, must improve among individuals with hepatitis B.
The World Health Organization has set a 65% HBV mortality reduction target by 2030. Since the early 2000s, diagnoses of decompensated cirrhosis and HCC increased, but age-standardised incidence rates decreased. Age-standardised liver mortality rates decreased from 2.64 in 2003 to 0.97 per 1,000 person-years in 2017. Late HBV notification declined from 41% and 40% during 2001-2009 to 28% and 26% in 2010-2018, respectively. Hepatitis C co-infection and alcohol-use disorder are key modifiable risk factors associated with HBV disease burden.
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Mandel E, Peci A, Cronin K, Capraru CI, Shah H, Janssen HLA, Tran V, Biondi MJ, Feld JJ. The impact of the first, second and third waves of covid-19 on hepatitis B and C testing in Ontario, Canada. J Viral Hepat 2022; 29:205-208. [PMID: 34820967 DOI: 10.1111/jvh.13637] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 10/05/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022]
Abstract
The COVID-19 pandemic interrupted routine healthcare services. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are often asymptomatic, and therefore, screening and on/post-treatment monitoring are required. Our aim was to determine the effect of the first, second and third waves of the pandemic on HBV and HCV testing in Ontario, Canada. We extracted data from Public Health Ontario for HBV and HCV specimens from 1 January 2019 to 31 May 2021. Testing volumes were evaluated and stratified by age, sex and region. Changes in testing volumes were analysed by per cent and absolute change. Testing volumes decreased in April 2020 with the first wave of the pandemic and recovered to 72%-75% of prepandemic volumes by the end of the first wave. HBsAg testing decreased by 33%, 18% and 15%, and HBV DNA testing decreased by 37%, 27% and 20%, in each consecutive wave. Anti-HCV testing decreased by 35%, 21% and 19%, and HCV RNA testing decreased by 44%, 30% and 36% in each consecutive wave. These trends were consistent by age, region and sex. Prenatal HBV testing volumes were stable. In conclusion, significant decreases in HBV and HCV testing occurred during the first three waves of the pandemic and have not recovered. In addition to direct consequences on viral hepatitis elimination efforts, these data provide insight into the impacts of the pandemic on chronic disease screening and management. Strategies to make up for missed testing will be critical to avoid additional consequences of COVID-19 long after the pandemic has resolved.
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Affiliation(s)
- Erin Mandel
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| | - Adriana Peci
- Public Health Ontario Laboratory, Toronto, Ontario, Canada
| | - Kirby Cronin
- Public Health Ontario Laboratory, Toronto, Ontario, Canada
| | - Camelia I Capraru
- Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, Ontario, Canada
| | - Hemant Shah
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.,Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, Ontario, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.,Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, Ontario, Canada
| | - Vanessa Tran
- Public Health Ontario Laboratory, Toronto, Ontario, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Mia J Biondi
- Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, Ontario, Canada.,Arthur Labatt Family School of Nursing, Western University, London, Ontario, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.,Viral Hepatitis Care Network (VIRCAN) Study Group, Toronto Centre for Liver Disease, Toronto, Ontario, Canada.,Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
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11
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Yasseen AS, Kwong JC, Feld JJ, Kustra R, MacDonald L, Greenaway CC, Janjua NZ, Mazzulli T, Sherman M, Lapointe-Shaw L, Sander B, Crowcroft NS. The viral hepatitis B care cascade: A population-based comparison of immigrant groups. Hepatology 2022; 75:673-689. [PMID: 34537985 DOI: 10.1002/hep.32162] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 06/28/2021] [Accepted: 08/09/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIMS The global burden of viral hepatitis B is substantial, and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status, and we aimed to quantify disease burden among immigrant subgroups. APPROACH AND RESULTS In this population-based, retrospective cohort study, we used linked laboratory and health administrative records to describe the HBV care cascade in five distinct stages: (1) lifetime prevalence; (2) diagnosis; (3) engagement with care; (4) treatment initiation; and (5) treatment continuation. Infections were identified based on at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Care cascades were compared between long-term residents and immigrant groups, including subgroups born in hepatitis B endemic countries. Stratified analyses and multivariable Poisson regression were used to identify drivers for cascade progression. Between January 1997 and December 2014, 2,014,470 persons were included, 50,475 with infections, of whom 30,118 were engaged with care, 11,450 initiated treatment, and 6554 continued treatment >1 year. Lifetime prevalence was estimated as 163,309 (1.34%) overall, 115,722 (3.42%) among all immigrants, and 50,876 (9.37%) among those from highly endemic countries. Compared to long-term residents, immigrants were more likely to be diagnosed (adjusted rate ratio [aRR], 4.55; 95% CI, 4.46, 4.63), engaged with care (aRR, 1.07; 95% CI, 1.04, 1.09), and initiate treatment (aRR, 1.09; 95% CI, 1.03, 1.16). CONCLUSIONS In conclusion, immigrants fared well compared to long-term residents along the care cascade, having higher rates of diagnosis and slightly better measures in subsequent cascade stages, although intensified screening efforts and better strategies to facilitate linkage to care are still needed.
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Affiliation(s)
- Abdool S Yasseen
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,Public Health Ontario, Toronto, Ontario, Canada
| | - Jeffrey C Kwong
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,Public Health Ontario, Toronto, Ontario, Canada.,University Health Network, Toronto, Ontario, Canada.,Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Jordan J Feld
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,University Health Network, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Rafal Kustra
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Liane MacDonald
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Public Health Ontario, Toronto, Ontario, Canada
| | - Christina C Greenaway
- Division of Infectious Diseases, Jewish General Hospital, Montreal, Quebec, Canada.,Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada.,Department of Medicine, McGill University, Montreal, Quebec, Canada
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Tony Mazzulli
- Public Health Ontario, Toronto, Ontario, Canada.,University Health Network, Toronto, Ontario, Canada
| | | | - Lauren Lapointe-Shaw
- ICES, Toronto, Ontario, Canada.,University Health Network, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Beate Sander
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,Public Health Ontario, Toronto, Ontario, Canada.,University Health Network, Toronto, Ontario, Canada
| | - Natasha S Crowcroft
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,Public Health Ontario, Toronto, Ontario, Canada
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12
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Castaneda D, Gonzalez AJ, Alomari M, Tandon K, Zervos XB. From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol 2021; 27:1691-1715. [PMID: 33967551 PMCID: PMC8072198 DOI: 10.3748/wjg.v27.i16.1691] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 02/06/2023] Open
Abstract
Viral infections affecting the liver have had an important impact on humanity, as they have led to significant morbidity and mortality in patients with acute and chronic infections. Once an unknown etiology, the discovery of the viral agents triggered interest of the scientific community to establish the pathogenesis and diagnostic modalities to identify the affected population. With the rapid scientific and technological advances in the last centuries, controlling and even curing the infections became a possibility, with a large focus on preventive medicine through vaccination. Hence, a comprehensive understanding of hepatitis A, B, C, D and E is required by primary care physicians and gastroenterologists to provide care to these patients. The review article describes the epidemiology, pathogenesis, clinical presentation, diagnostic tools and current medication regimens, with a focus on upcoming treatment options and the role of liver transplantation.
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Affiliation(s)
- Daniel Castaneda
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | | | - Mohammad Alomari
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Kanwarpreet Tandon
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
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