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Park YJ, Yi KY, Woo HY, Heo J, Song GA. Risk of HBV reactivation in HBV/HCV-co-infected HCV-treated patients: A single-center study. PLoS One 2025; 20:e0324019. [PMID: 40445953 PMCID: PMC12124557 DOI: 10.1371/journal.pone.0324019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 04/18/2025] [Indexed: 06/02/2025] Open
Abstract
Hepatitis B virus (HBV) reactivation in patients with HBV/hepatitis C virus (HCV) co-infection due to direct-acting antiviral agent (DAA) therapy is a growing concern. This study focused on 47 patients with chronic hepatitis C (CHC) and positivity for HBV surface antigen (HBsAg) who were treated with interferon (IFN)-based therapy, DAA, or DAA after IFN-based therapy failure and followed for a median of 53 months. Here, we aimed to determine HBV reactivation rates and associated factors, the incidence of HBV and liver-related events, and the rate of sustained virologic response (SVR) for HCV. Fifteen (15/47, 31.9%) patients experienced HBV reactivation during or after HCV treatment. This reactivation occurred significantly more frequently in patients who received DAA treatment after IFN-based treatment failure than in those who received IFN-based treatment (IFN-based vs. DAA vs. DAA treatment after IFN-based treatment failure 11.8% vs. 35.3% vs. 53.8%, respectively; p = 0.046). The interval from HCV treatment initiation to HBV reactivation was shortest in the DAA group (4.2 months), followed by the DAA after IFN-based treatment failure group (6.4 months) and the IFN-based treatment group (44.5 months) (p < 0.001). One case of HBV-related hepatitis spontaneously resolved after 4 weeks. The rate of SVR for the entire cohort was 87.2%, with no significant difference in this regard among the IFN-based treated, DAA-treated, and DAA-treated after IFN-based treatment failure arms at 82.4%, 88.2%, and 92.3%, respectively. HBV reactivation in HBsAg-positive CHC patients is more common and occurs earlier in those who receive DAA treatment after IFN-based treatment failure than in those with IFN-based treatment. Therefore, all patients with CHC should be tested for HBV exposure prior to DAA treatment. In addition, HBsAg positive patients, especially those among whom have previously experienced IFN-based treatment failure, should be closely monitored for HBV reactivation during DAA therapy.
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Affiliation(s)
- Young Joo Park
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Ki Youn Yi
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Hyun Young Woo
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Jeong Heo
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Geun Am Song
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
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Ali FS, Nguyen MH, Hernaez R, Huang DQ, Wilder J, Piscoya A, Simon TG, Falck-Ytter Y. AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals. Gastroenterology 2025; 168:267-284. [PMID: 39863345 DOI: 10.1053/j.gastro.2024.11.008] [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: 01/27/2025]
Abstract
BACKGROUND & AIMS Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr. This clinical practice guideline update aims to inform frontline health care practitioners by providing evidence-based practice recommendation for the management of HBVr in at-risk individuals. METHODS The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel conducted a systematic evidence review to identify new studies since publication of the first version of this clinical practice guideline in 2014. The Evidence to Decision framework was used to develop recommendations regarding the role of antiviral prophylaxis and monitoring without antiviral prophylaxis for management of HBVr. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS The panel agreed on 4 recommendations. Based on evidence and baseline risk assessment, the panel made a strong recommendation in favor of antiviral prophylaxis for individuals at high risk of HBVr. For individuals at moderate risk of HBVr, a conditional recommendation was made in favor of antiviral prophylaxis. For individuals at low risk of HBVr, a conditional recommendation was made in favor of monitoring alone without antiviral prophylaxis. Monitoring should be performed at 1- to 3-month intervals, and must include assessment of hepatitis B viral load in addition to assessment of alanine aminotransferase. For individuals deemed to be at-risk of HBVr, the panel agreed on a strong recommendation in favor of testing for HBV; given universal Centers for Disease Control and Prevention screening guidance for hepatitis B for all adults 18 years and older by testing for HBV surface antigen, hepatitis B surface antibody, and total hepatitis B core antibody, stratifying screening practices by magnitude of HBVr risk is no longer needed. CONCLUSIONS This document provides updated guidance for the management of HBVr in at-risk individuals. Limitations and gaps in the evidence are highlighted. This guideline is expected to require updating in 5 years from publication.
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Affiliation(s)
- Faisal S Ali
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California; Stanford Cancer Institute, Stanford University Medical Center, Palo Alto, California
| | - Ruben Hernaez
- Section of Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Julius Wilder
- Division of Gastroenterology, Duke Department of Medicine, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina
| | - Alejandro Piscoya
- School of Medicine, Universidad Tecnológica del Peru (UTP), Lima, Peru
| | - Tracey G Simon
- Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Yngve Falck-Ytter
- Section of Gastroenterology and Hepatology, Veterans Affairs Northeast Ohio Health Care System, Cleveland, Ohio; Division of Gastroenterology and Hepatology, Case Western Reserve University, Cleveland, Ohio
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Poorolajal J, Shadi Y, Heshmati B. Interaction Between Hepatitis B, Hepatitis C and Alcohol in the Development of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. J Viral Hepat 2025; 32:e14042. [PMID: 39716779 DOI: 10.1111/jvh.14042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 11/26/2024] [Indexed: 12/25/2024]
Abstract
The objective of this report is to provide clarification on the interaction among hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol in the development of hepatocellular carcinoma (HCC). A systematic search was performed in PubMed, Web of Science and Scopus databases up to July 18, 2023. The inclusion criteria involved observational studies that examined the relationship between HBV, HCV, alcohol use and the development of HCC. To assess between-study heterogeneity, the I2 statistics were employed. Publication bias was evaluated using the Begg and Egger tests. The effect sizes were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) utilising a random-effects model. Among the initial pool of 31,021 studies identified, 28 studies involving 42,406 participants met the inclusion criteria. Through our meta-analysis, we found that the combined effect of HBV and alcohol was associated with an OR of 14.56 (95% CI: 9.80, 21.65). The combined impact of HCV and alcohol showed an OR of 42.44 (95% CI: 20.11, 89.56). Coinfection with both HBV and HCV was associated with an OR of 32.58 (95% CI: 20.57, 51.60). These results emphasising the importance of reducing alcohol consumption and implementing effective viral hepatitis prevention and treatment.
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Affiliation(s)
- Jalal Poorolajal
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
- Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Yahya Shadi
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Bahram Heshmati
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
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Andaloro S, Mancuso F, Miele L, Addolorato G, Gasbarrini A, Ponziani FR. Effect of Low-Dose Alcohol Consumption on Chronic Liver Disease. Nutrients 2024; 16:613. [PMID: 38474740 DOI: 10.3390/nu16050613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/16/2024] [Accepted: 02/18/2024] [Indexed: 03/14/2024] Open
Abstract
Although alcohol is one of the most important etiologic agents in the development of chronic liver disease worldwide, also recognized as a promoter of carcinogenesis, several studies have shown a beneficial effect of moderate consumption in terms of reduced cardiovascular morbidity and mortality. Whether this benefit is also present in patients with liver disease due to other causes (viral, metabolic, and others) is still debated. Although there is no clear evidence emerging from guidelines and scientific literature, total abstention from drinking is usually prescribed in clinical practice. In this review, we highlight the results of the most recent evidence on this controversial topic, in order to understand the effect of mild alcohol use in this category of individuals. The quantification of alcohol intake, the composition of the tested populations, and the discrepancy between different works in relation to the outcomes represent important limitations emerging from the scientific literature. In patients with NAFLD, a beneficial effect is demonstrated only in a few works. Even if there is limited evidence in patients affected by chronic viral hepatitis, a clear deleterious effect of drinking in determining disease progression in a dose-dependent manner emerges. Poor data are available about more uncommon pathologies such as hemochromatosis. Overall, based on available data, it is not possible to establish a safe threshold for alcohol intake in patients with liver disease.
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Affiliation(s)
- Silvia Andaloro
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Fabrizio Mancuso
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Luca Miele
- Department of Abdominal, Endocrine and Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- CEMAD Unit, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Internal Medicine and Liver Transplant Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Giovanni Addolorato
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- CEMAD Unit, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Internal Medicine and Alcohol Related Disease Unit, Columbus-Gemelli Hospital, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
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Maqsood Q, Sumrin A, Iqbal M, Younas S, Hussain N, Mahnoor M, Wajid A. Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives. Antivir Ther 2023; 28:13596535231189643. [PMID: 37489502 DOI: 10.1177/13596535231189643] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/26/2023]
Abstract
In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.
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Affiliation(s)
- Quratulain Maqsood
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Aleena Sumrin
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Maryam Iqbal
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Saima Younas
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Nazim Hussain
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Muhammada Mahnoor
- Department of Rehabilitation Science, The University of Lahore, Lahore, Pakistan
| | - Abdul Wajid
- Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Science, Quetta, Pakistan
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Suda G, Baba M, Yamamoto Y, Sho T, Ogawa K, Kimura M, Hosoda S, Yoshida S, Kubo A, Fu Q, Yang Z, Tokuchi Y, Kitagataya T, Maehara O, Ohnishi S, Yamada R, Ohara M, Kawagishi N, Natsuizaka M, Nakai M, Morikawa K, Furuya K, Suzuki K, Izumi T, Meguro T, Terashita K, Ito J, Kobayashi T, Tsunematsu I, Sakamoto N. Prophylactic tenofovir alafenamide for hepatitis B virus reactivation and reactivation-related hepatitis. J Med Virol 2023; 95:e28452. [PMID: 36597900 DOI: 10.1002/jmv.28452] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 12/26/2022] [Accepted: 12/29/2022] [Indexed: 01/05/2023]
Abstract
No prospective study on the efficacy of tenofovir alafenamide (TAF), a novel tenofovir prodrug, in preventing hepatitis B virus (HBV) reactivation has yet been reported. This multicenter prospective study enrolled HBV-carriers who received TAF to prevent HBV reactivation before antitumor or immunosuppressive therapy, and patients with resolved HBV infection who experienced HBV-reactivation and received TAF to prevent HBV reactivation-related hepatitis. The efficacy of prophylactic TAF in preventing HBV reactivation and HBV reactivation-related hepatitis was evaluated at 6 and 12 months after initiating TAF. Overall, 110 patients were administered TAF to prevent HBV reactivation or HBV reactivation-related hepatitis. Three patients died owing to primary disease, whereas one patient was transferred to another hospital within 6 months after initiating TAF. Seven patients died due to primary disease, and five patients were transferred to another hospital within 12 months after initiating TAF. Therefore, 106 and 94 (77 patients with HBV infection, 17 with previous-HBV infection) patients were evaluated at 6 and 12 months after initiating TAF, respectively. No patient experienced HBV reactivation, HBV reactivation-related hepatitis, or treatment discontinuation due to HBV reactivation or adverse events of TAF after 6 and 12 months. TAF could effectively prevent HBV reactivation and HBV reactivation-related hepatitis.
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Affiliation(s)
- Goki Suda
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Masaru Baba
- Department of Gastroenterology and Hepatology, Japan Community Health Care Organization (JCHO) Hokkaido Hospital, Hokkaido, Japan
| | - Yoshiya Yamamoto
- Department of Gastroenterology and Hepatology, Hakodate City Hospital, Hokkaido, Japan
| | - Takuya Sho
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Koji Ogawa
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Megumi Kimura
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Shunichi Hosoda
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Sonoe Yoshida
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Akinori Kubo
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Qingjie Fu
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Zijian Yang
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Yoshimasa Tokuchi
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Takashi Kitagataya
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Osamu Maehara
- Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Shunsuke Ohnishi
- Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Ren Yamada
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Masatsugu Ohara
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Naoki Kawagishi
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Mitsuteru Natsuizaka
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Masato Nakai
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Kenichi Morikawa
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Ken Furuya
- Department of Gastroenterology and Hepatology, Japan Community Health Care Organization (JCHO) Hokkaido Hospital, Hokkaido, Japan
| | - Kazuharu Suzuki
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.,Department of Gastroenterology and Hepatology, Hakodate City Hospital, Hokkaido, Japan
| | - Takaaki Izumi
- Department of Gastroenterology and Hepatology, Sapporo City General Hospital, Hokkaido, Japan
| | - Takashi Meguro
- Department of Gastroenterology and Hepatology, Hokkaido Gastroenterology Hospital, Hokkaido, Japan
| | - Katsumi Terashita
- Department of Gastroenterology and Hepatology, Japan Community Health Care Organization (JCHO) Sapporo Hokushin Hospital, Hokkaido, Japan
| | - Jun Ito
- Department of Gastroenterology and Hepatology, The Hokkaido Medical Center, Hokkaido, Japan
| | - Tomoe Kobayashi
- Department of Gastroenterology and Hepatology, Tomakomai City Hospital, Hokkaido, Japan
| | | | - Naoya Sakamoto
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Oh JH, Park DA, Ko MJ, Yoo JJ, Yim SY, Ahn JH, Jun DW, Ahn SB. Direct-Acting Antivirals and the Risk of Hepatitis B Reactivation in Hepatitis B and C Co-Infected Patients: A Systematic Review and Meta-Analysis. J Pers Med 2022; 12:jpm12121957. [PMID: 36556178 PMCID: PMC9781230 DOI: 10.3390/jpm12121957] [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: 10/08/2022] [Revised: 11/08/2022] [Accepted: 11/22/2022] [Indexed: 11/29/2022] Open
Abstract
Hepatitis B (HBV) reactivation was observed to be more than 10% in patients receiving interferon-based therapy for hepatitis C (HCV) co-infection. At present, when direct-acting antiviral (DAA) has become the main treatment for HCV, there are few large-scale studies on the reactivation of HBV in these population. We studied HBV reactivation risk and prophylactic HBV treatment efficacy in HBV/HCV co-infected patients receiving DAA therapy. Relevant studies were selected from the Ovid-Medline, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, KoreaMed, KMbase, and RISS databases through 4 September 2020. Data pooling was carried out using the random-effects method. We identified 39 articles with 119,484 patients with chronic (n = 1673) or resolved (n = 13,497) HBV infection under DAA therapy. When the studies were pooled, the HBV reactivation rate was 12% (95% confidence interval (CI) 6-19, I2 = 87%), indicating that this population needs careful attention. When stratified by baseline HBV DNA, the undetectable HBV DNA group showed a significantly lower risk of reactivation than the detectable HBV DNA group (odds ratio (OR) 0.30, 95% CI 0.11-0.86, I2 = 0%). Prophylactic HBV therapy reduced HBV reactivation risk (OR 0.25, 95% CI 0.07-0.92, I2 = 0%). Patients with a resolved HBV infection showed a negligible rate (0.4%) of HBV reactivation. In conclusion, patients with detectable HBV DNA levels warrant careful monitoring for HBV reactivation and may benefit from preventive anti-HBV treatment.
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Affiliation(s)
- Joo Hyun Oh
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, Republic of Korea
| | - Dong Ah Park
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul 04933, Republic of Korea
| | - Min Jung Ko
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul 04933, Republic of Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University Hospital, Seoul 02841, Republic of Korea
| | - Ji-Hyun Ahn
- Department of Internal Medicine, Hanyang University College of Medicine, Guri 11923, Republic of Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Republic of Korea
- Correspondence: (D.W.J.); (S.B.A.); Tel.: +82-02-2290-8338 (D.W.J.); +82-02-970-8209 (S.B.A.)
| | - Sang Bong Ahn
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, Republic of Korea
- Correspondence: (D.W.J.); (S.B.A.); Tel.: +82-02-2290-8338 (D.W.J.); +82-02-970-8209 (S.B.A.)
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8
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Kawagishi N, Suda G, Sakamori R, Matsui T, Onozawa M, Yang Z, Yoshida S, Ohara M, Kimura M, Kubo A, Maehara O, Fu Q, Hosoda S, Tokuchi Y, Suzuki K, Nakai M, Sho T, Morikawa K, Natsuizaka M, Ogawa K, Sakai H, Ohnishi S, Baba M, Takehara T, Sakamoto N. Serum IL-1β predicts de novo hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C, not during anti-cancer/immunosuppressive therapy. Sci Rep 2022; 12:16800. [PMID: 36207368 PMCID: PMC9546937 DOI: 10.1038/s41598-022-21315-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 09/26/2022] [Indexed: 02/08/2023] Open
Abstract
De novo hepatitis B virus (HBV) reactivation occurs during direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-infected patients with resolved HBV infection. We evaluated the predictive factors, mechanical insight, and differences of cytokine levels during anti-cancer/immunosuppressive and DAA. Eleven, 35, and 19 HCV-infected patients with previous HBV infection with HBV reactivation during DAA treatment, previous HBV infection without HBV reactivation during DAA treatment, and without HBV infection resolution receiving DAA treatment, respectively, were enrolled. Clinical data and baseline cytokine levels were analyzed. Low baseline serum interleukin (IL)-1β levels predicted de novo HBV reactivation during DAA treatment (odds ratio: 47.6, 95% confidence interval: 6.94-333.3). HCV-infected patients with the IL-1β gene single nucleotide polymorphism rs16944 AA allele had significantly higher IL-1β levels; no HCV-infected patient with the IL-1β AA allele experienced HBV reactivation during DAA treatment. Compared to HCV-infected patients with HBV infection resolution, non-HCV infected patients with or without HBV reactivation during anti-cancer/immunosuppressive therapy or bone marrow transplantation had remarkably lower baseline IL-1β levels. Low IL-1β levels were not associated with HBV reactivation. IL-1β levels before DAA for HCV-infected patients with resolved HBV infection could predict HBV reactivation during DAA treatment.
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Affiliation(s)
- Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takeshi Matsui
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan
| | - Masahiro Onozawa
- Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Zijian Yang
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Sonoe Yoshida
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Akinori Kubo
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Osamu Maehara
- Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Qingjie Fu
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Shunichi Hosoda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Yoshimasa Tokuchi
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Kazuharu Suzuki
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Hajime Sakai
- Department of Hematology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Shunsuke Ohnishi
- Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Masaru Baba
- Department of Gastroenterology and Hepatology, Japan Community Health Care Organization Hokkaido Hospital, Hokkaido, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
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9
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Abdelbary MS, Samir R, El-Nahaas SM, Shahin RM, El-Sayed M, Gaber Y, Tantawi O, Zayed NA, Yosry A. Hepatitis B Reactivation Following Eradication of HCV with Direct-Acting Antiviral Drugs (DAAs) in a Cohort of Patients from Different Institutions in Egypt. J Clin Exp Hepatol 2022; 12:1276-1284. [PMID: 36157140 PMCID: PMC9499996 DOI: 10.1016/j.jceh.2022.04.020] [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: 01/10/2022] [Accepted: 04/27/2022] [Indexed: 12/12/2022] Open
Abstract
Background Concerns about HBV reactivation (HBVr) have been raised with the introduction of DAA for HCV treatment. The aim of the study was to assess the risk of HBVr in chronic HCV patients during or after DAA. Methods A cohort of 166 chronic HCV patients who were treated with SOF-based DAA regimens and initially positive for HBcAb total were evaluated; 10 HBsAg-positive, 156 had past HBV exposure (HBsAg-negative/HBcAb-positive). Laboratory investigations, including liver functions tests, HBV-DNA, LSM by Transient elastography, and ARFI together with serum markers of fibrosis; APRI and FIB-4 were done at baseline and after 12 weeks of DAAs therapy. HBV-DNA levels and liver functions were monitored for assessment of HBVr. Results Virological HBVr was diagnosed by ≥ 1 log10 IU/ml HBV-DNA levels in 2/166 patients (1.2%) among the whole HCV cohort, who were initially positive for HBsAg; 20%. Clinical HBVr (>3 folds liver enzyme elevation) was detected in one patient with virological HBVr. Conversely, none of past HBV-infected patients experienced HBVr. All patients achieved SVR12 and had a significant decline in serum transaminases, bilirubin, APRI, and LSM measurements after HCV eradication. Conclusion HBVr might be considered after successful eradication of HCV following DAAs therapy, especially among patients who are positive for HBsAg, while past HBV infection does not seem to be a predisposing condition to HBVr.
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Key Words
- ALT, Alanine Aminotransferase
- APASL, Asian Pacific Association for the Study of the Liver
- APRI, Aspartate-aminotransferase-to-platelet-ratio index
- ARFI, Acoustic Radiation Forced Impulse
- AST, Aspartate Aminotransferase
- CUC-HF, Cairo University Center for Hepatic Fibrosis
- DAA, Direct-acting antivirals
- DAAs
- DNA, Deoxyribonucleic acid
- EASL, European Association for the Study of the Liver
- FIB-4, Fibrosis-4
- HBV reactivation
- HBV, Hepatitis B virus
- HBV-DNA
- HBVr, Hepatitis B virus reactivation
- HBcAb, Hepatitis B core antibody total
- HBsAg, Hepatitis B surface antigen
- HCV
- HCV, Hepatitis C virus
- LSM, Liver stiffness measurement
- MOHP, Ministry of Health and Population
- PCR, Polymerase chain reaction
- PegINF, Pegylated Interferon
- ULN, upper limit of normal
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Affiliation(s)
- Mohamed S. Abdelbary
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Egypt
| | - Reham Samir
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Egypt
| | - Saeed M. El-Nahaas
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Egypt
| | - Rasha M.H. Shahin
- Department of Clinical Pathology, Faculty of Medicine, Cairo University, Egypt
| | - Mohammad El-Sayed
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Egypt
| | - Yasmine Gaber
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Egypt
| | - Omnia Tantawi
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Egypt
| | - Naglaa A. Zayed
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Egypt
| | - Ayman Yosry
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Egypt
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10
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Nagra N, Kozarek RA, Burman BE. Therapeutic Advances in Viral Hepatitis A-E. Adv Ther 2022; 39:1524-1552. [PMID: 35220557 DOI: 10.1007/s12325-022-02070-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 01/31/2022] [Indexed: 11/25/2022]
Abstract
Viral hepatitis remains a significant global health problem. All forms of viral hepatitis A through E (A-E) can lead to acute symptomatic infection, while hepatitis B and C can lead to chronic infection associated with significant morbidity and mortality related to progression to cirrhosis, end-stage-liver disease, and liver cancer. Viral hepatitis occurs worldwide, though certain regions are disproportionately affected. We now, remarkably, have highly effective curative regimens for hepatitis C, and safe and tolerable medications to suppress hepatitis B activity, and to prevent liver damage and slow disease progression. We have effective vaccines for hepatitis A and B which provide long-lasting immunity, while improved sanitation and awareness can curb outbreaks of hepatitis A and E. However, more effective and available preventive and curative strategies are needed to achieve global eradication of viral hepatitis. This review provides an overview of the epidemiology, transmission, diagnosis, and clinical features of each viral hepatitis with a primary focus on current and future therapeutic and curative options.
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Affiliation(s)
- Navroop Nagra
- Department of Gastroenterology, University of Louisville, Louisville, KY, 40202, USA
| | - Richard A Kozarek
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA
| | - Blaire E Burman
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA.
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11
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Xu HQ, Wang CG, Zhou Q, Gao YH. Effects of alcohol consumption on viral hepatitis B and C. World J Clin Cases 2021; 9:10052-10063. [PMID: 34904075 PMCID: PMC8638036 DOI: 10.12998/wjcc.v9.i33.10052] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/15/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the main target organ for hepatitis viruses and the vital organ for alcohol metabolism. These two factors of viral hepatitis and alcohol abuse in combination can exert dual harmful actions, leading to enhanced damage to the liver. Epidemiological studies have revealed a higher prevalence of hepatitis C virus (HCV) infection among alcoholics than the general population. The interaction of alcohol with viral hepatitis [e.g., hepatitis B virus (HBV), HCV] and the underlying mechanisms are not fully understood. The effects of alcohol on viral hepatitis include promoted viral replication, weakened immune response, and increased oxidative stress. Clinically, alcohol abuse is correlated with an increased risk of developing end-stage liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B and C, suggesting that the combination of alcohol and HBV/HCV lead to more severe liver damage. The influence of mild to moderate alcohol drinking on the HBV-induced liver fibrosis, cirrhosis, and hepatocellular carcinoma among patients infected with HBV remains unclear. Unlike HBV infected patients, no safe level of alcohol intake has been established for patients with HCV. Even light to moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease. Furthermore, interferon-based therapy is less effective in alcohol drinkers than in control patients, even after abstinence from alcohol for a period of time. Therefore, abstaining from alcohol is highly recommended to protect the liver, especially in individuals with HBV/HCV infection, to improve the clinical efficacy of antiviral treatment and prevent the rapid progression of chronic viral hepatitis.
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Affiliation(s)
- Hong-Qin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Chun-Guang Wang
- Department of Surgery, The Second Hospital of Jilin University, Jilin University, Changchun 130041, Jilin Province, China
| | - Qiang Zhou
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Yan-Hang Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
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12
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Lau G, Yu ML, Wong G, Thompson A, Ghazinian H, Hou JL, Piratvisuth T, Jia JD, Mizokami M, Cheng G, Chen GF, Liu ZW, Baatarkhuu O, Cheng AL, Ng WL, Lau P, Mok T, Chang JM, Hamid S, Dokmeci AK, Gani RA, Payawal DA, Chow P, Park JW, Strasser SI, Mohamed R, Win KM, Tawesak T, Sarin SK, Omata M. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int 2021; 15:1031-1048. [PMID: 34427860 PMCID: PMC8382940 DOI: 10.1007/s12072-021-10239-x] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 07/20/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIM Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. METHODS All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. RECOMMENDATIONS We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.
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Affiliation(s)
- George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China.
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China.
| | - Ming-Lung Yu
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tz-You 1st Rd, Chinese Taipei, Kaohsiung, Taiwan.
| | - Grace Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | | | - Hasmik Ghazinian
- Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia
| | - Jin-Lin Hou
- Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Teerha Piratvisuth
- Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Ji-Dong Jia
- Liver Research Center, Beijing Friendship Hospital, Beijing, China
| | - Masashi Mizokami
- Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Gregory Cheng
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
- Faculty of Health Science, Macau University, Macau SAR, China
| | - Guo-Feng Chen
- Department of Liver Diseases, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Zhen-Wen Liu
- Research Center for Liver Transplantation, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Oidov Baatarkhuu
- Department of Infectious Diseases, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Ann Lii Cheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Woon Leung Ng
- Department of Medicine, United Christian Hospital, Hong Kong SAR, China
| | - Patrick Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China
| | - Tony Mok
- Department of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jer-Ming Chang
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Saeed Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Rino A Gani
- Liver Transplantation Team, Ciptomangunkusumo Hospital, Jakarta, Indonesia
| | - Diana A Payawal
- Department of Medicine, Cardinal Santos Medical Center, Mandaluyong, Metro, Manila, Philippines
| | - Pierce Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia
| | - Rosmawaiti Mohamed
- Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - Khin Maung Win
- Yangon Gastroenterology and Liver Centre, Yangon, Myanmar
| | - Tanwandee Tawesak
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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13
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Suda G, Sakamoto N. Recent advances in the treatment of hepatitis C virus infection for special populations and remaining problems. J Gastroenterol Hepatol 2021; 36:1152-1158. [PMID: 32667068 DOI: 10.1111/jgh.15189] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/02/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy.
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Affiliation(s)
- Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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14
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Lu MY, Chen CT, Shih YL, Tsai PC, Hsieh MH, Huang CF, Yeh ML, Huang CI, Wang SC, Tsai YS, Ko YM, Lin CC, Chen KY, Wei YJ, Hsu PY, Hsu CT, Jang TY, Liu TW, Liang PC, Hsieh MY, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Yu ML, Chang WY. Changing epidemiology and viral interplay of hepatitis B, C and D among injecting drug user-dominant prisoners in Taiwan. Sci Rep 2021; 11:8554. [PMID: 33879825 PMCID: PMC8058093 DOI: 10.1038/s41598-021-87975-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 04/06/2021] [Indexed: 02/07/2023] Open
Abstract
The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10-0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13-0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04-40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.
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Affiliation(s)
- Ming-Ying Lu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Chun-Ting Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Yu-Lueng Shih
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Health Management Center and Department of Community Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Shu-Chi Wang
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Yu-Min Ko
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ching-Chih Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Kuan-Yu Chen
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Yu-Ju Wei
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Cheng-Ting Hsu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ta-Wei Liu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Health Management Center and Department of Community Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
| | - Wen-Yu Chang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Taiwan Liver Research Foundation, Kaohsiung, Taiwan, ROC
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15
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Otoguro T, Tanaka T, Kasai H, Kobayashi N, Yamashita A, Fukuhara T, Ryo A, Fukai M, Taketomi A, Matsuura Y, Moriishi K. Establishment of a Cell Culture Model Permissive for Infection by Hepatitis B and C Viruses. Hepatol Commun 2021; 5:634-649. [PMID: 33860122 PMCID: PMC8034569 DOI: 10.1002/hep4.1653] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 11/19/2020] [Accepted: 11/22/2020] [Indexed: 12/18/2022] Open
Abstract
Compared with each monoinfection, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is well known to increase the risks of developing liver cirrhosis and hepatocellular carcinoma. However, the mechanism by which HBV/HCV coinfection is established in hepatocytes is not well understood. Common cell culture models for coinfection are required to examine viral propagation. In this study, we aimed to establish a cell line permissive for both HBV and HCV infection. We first prepared a HepG2 cell line expressing sodium taurocholate cotransporting polypeptide, an HBV receptor, and then selected a cell line highly permissive for HBV infection, G2/NT18-B. After transduction with a lentivirus-encoding microRNA-122, the cell line harboring the highest level of replicon RNA was selected and then treated with anti-HCV compounds to eliminate the replicon RNA. The resulting cured cell line was transduced with a plasmid-encoding CD81. The cell line permissive for HCV infection was cloned and then designated the G2BC-C2 cell line, which exhibited permissiveness for HBV and HCV propagation. JAK inhibitor I potentiated the HCV superinfection of HBV-infected cells, and fluorescence-activated cell-sorting analysis indicated that HBV/HCV double-positive cells accounted for approximately 30% of the coinfected cells. Among several host genes tested, cyclooxygenase-2 showed synergistic induction by coinfection compared with each monoinfection. Conclusion: These data indicate that our in vitro HBV/HCV coinfection system provides an easy-to-use platform for the study of host and viral responses against coinfection and the development of antiviral agents targeting HBV and HCV.
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Affiliation(s)
- Teruhime Otoguro
- Department of MicrobiologyGraduate School of Medical ScienceUniversity of YamanashiYamanashiJapan
| | - Tomohisa Tanaka
- Department of MicrobiologyGraduate School of Medical ScienceUniversity of YamanashiYamanashiJapan
| | - Hirotake Kasai
- Department of MicrobiologyGraduate School of Medical ScienceUniversity of YamanashiYamanashiJapan
| | - Nobuhiro Kobayashi
- Department of Gastroenterological Surgery IGraduate School of MedicineHokkaido UniversityHokkaidoJapan
| | - Atsuya Yamashita
- Department of MicrobiologyGraduate School of Medical ScienceUniversity of YamanashiYamanashiJapan
| | - Takasuke Fukuhara
- Department of Molecular VirologyResearch Institute for Microbial DiseasesOsaka UniversityOsakaJapan.,Department of Microbiology and ImmunologyGraduate School of MedicineHokkaido UniversityHokkaidoJapan
| | - Akihide Ryo
- Department of MicrobiologyYokohama City University Graduate School of MedicineKanagawaJapan
| | - Moto Fukai
- Department of Gastroenterological Surgery IGraduate School of MedicineHokkaido UniversityHokkaidoJapan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery IGraduate School of MedicineHokkaido UniversityHokkaidoJapan
| | - Yoshiharu Matsuura
- Department of Molecular VirologyResearch Institute for Microbial DiseasesOsaka UniversityOsakaJapan
| | - Kohji Moriishi
- Department of MicrobiologyGraduate School of Medical ScienceUniversity of YamanashiYamanashiJapan
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16
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Poola S, Sanaka S, Sewell K, Tillmann HL. Hepatitis B surface antibody titres and hepatitis B reactivation with direct-acting antiviral therapy for hepatitis C. J Viral Hepat 2021; 28:373-382. [PMID: 33047433 DOI: 10.1111/jvh.13421] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 08/12/2020] [Accepted: 09/20/2020] [Indexed: 02/06/2023]
Abstract
HBV reactivation can occur while undergoing direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV). The role of hepatitis B surface antibody (HBsAb) has not been systematically explored. Therefore, the purpose of this systematic review was to explore the role of the presence of HBsAb on the risk of HBV reactivation related to DAA therapy. We reviewed MEDLINE, CINAHL, EMBASE and Cochrane Central for studies on DAA therapy and data on HBsAb in patients with resolved hepatitis B (hepatitis B surface antigen-negative and hepatitis B core antibody-positive). We identified twenty-nine reports: thirteen case reports with HBV reactivation (10 HBsAb-negative and 3 HBsAb-positive patients) and sixteen cohort studies totalling 2528 patients with resolved HBV infection (1429 HBsAb negative, 1099 HBsAb positive). Reactivation was found in 12 (0.8%) HBsAb-negative and 7 (0.6%) HBsAb-positive individuals of cohort studies. All but two HBV reactivation occurred in patients with HBsAb titre <30 iU/L. The presence of HBsAb showed a trend towards delayed reactivation (median 12 weeks vs 9.5 weeks; P = .07). Importantly, with the exception of a patient with escape variant and an HIV-infected individual, no HBsAb-positive individual demonstrated clinical reactivation. HBsAb presence seems to protect from clinical HBV reactivation related to DAA therapy. The most pronounced prevention for reactivation may require titres greater than 30 iU/L.
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Affiliation(s)
- Shiva Poola
- Department of Medicine, East Carolina University, Greenville, NC, USA.,Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, East Carolina University, Greenville, NC, USA.,Vidant Medical Center, Greenville, NC, USA
| | - Sirish Sanaka
- Department of Medicine, East Carolina University, Greenville, NC, USA.,Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, East Carolina University, Greenville, NC, USA.,Vidant Medical Center, Greenville, NC, USA
| | - Kerry Sewell
- Research Librarian for the Health Sciences, East Carolina University, Greenville, NC, USA
| | - Hans L Tillmann
- Department of Medicine, East Carolina University, Greenville, NC, USA.,Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, East Carolina University, Greenville, NC, USA.,Vidant Medical Center, Greenville, NC, USA
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17
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Miyasaka A, Yoshida Y, Suzuki A, Masuda T, Okamoto H, Takikawa Y. Hepatitis B virus reactivation after successful treatment of hepatitis C virus with sofosbuvir and ribavirin: A case report and literature review. Medicine (Baltimore) 2020; 99:e22650. [PMID: 33031326 PMCID: PMC7544429 DOI: 10.1097/md.0000000000022650] [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] [Indexed: 12/27/2022] Open
Abstract
RATIONALE Hepatitis B virus (HBV) reactivation caused by immunosuppressive therapy or chemotherapy is well known. The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has also been reported to cause HBV reactivation. We report a rare case of HBV reactivation in a patient with HCV infection after DAA therapy. PATIENT CONCERNS In 1996, a 53-year-old female was identified as infected with HCV at a medical check-up, following which she visited our hospital. She was infected with HCV genotype 2b, and at follow up in 1997, was found to be hepatitis B surface antigen (HBsAg) and antibody against HBsAg negative, antibody against HBV core positive. She then experienced malignant lymphoma in 2001 at 58 years of age. Complete remission was achieved following chemotherapy and autologous peripheral blood stem cell transplantation. In 2014, she remained negative for HBsAg and antibody against HBsAg but positive for antibody against HBV core. In 2015, 12 weeks of sofosbuvir and ribavirin treatment for HCV was started. Serum HCV RNA levels rapidly decreased, and HCV elimination was confirmed at 24 weeks after cessation of DAA treatment. Acute hepatitis B developed at 15 weeks post- sustained virological response without any symptoms and physical examination findings. DIAGNOSES This case is speculated to represent HBV reactivation induced by DAA treatment in a patient with previously resolved HBV, based on virologic and clinical status. Genome sequencing revealed the HBV genotype as A2. INTERVENTIONS The patient was treated with nucleotide analog for HBV reactivation once a day. OUTCOMES Serum HBV-DNA levels decreased, and serum liver enzymes improved following initiation of nucleotide analog treatment. Also, adverse events of nucleotide analog treatment were not observed. LESSONS Although the risk may be very low, DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. Thus, those patients must be closely monitored for serum HBV DNA levels during and after DAA treatment.
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Affiliation(s)
- Akio Miyasaka
- Division of Hepatology, Department of Internal Medicine
| | | | - Akiko Suzuki
- Division of Hepatology, Department of Internal Medicine
| | - Tomoyuki Masuda
- Department of Pathology, Iwate Medical University School of Medicine, Yahaba-cho, Shiwa-gun, Iwate
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimozuke, Tochigi, Japan
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18
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Shih YF, Liu CJ. Hepatitis C Virus and Hepatitis B Virus Co-Infection. Viruses 2020; 12:E741. [PMID: 32664198 PMCID: PMC7412310 DOI: 10.3390/v12070741] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 06/28/2020] [Accepted: 07/08/2020] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C virus (HCV) and hepatitis B virus (HBV) co-infection can be encountered in either virus endemic countries. Co-infection can also be found in populations at risk of parenteral transmission. Previous studies demonstrated a high risk of liver disease progression in patients with HCV/HBV co-infection; thus, they should be treated aggressively. Previous evidence recommended therapy combining peginterferon (pegIFN) alfa and ribavirin for co-infected patients with positive HCV RNA. Recent trials further advise using direct-acting antivirals (DAAs) for the clearance of HCV in the co-infected patients. Reactivation of HBV has been observed in patients post-intervention, with higher risks and earlier onset in those having had HCV cured by DAA- versus pegIFN-based therapy. The mechanism of HBV reactivation is an interesting but unsolved puzzle. Our recent study revealed that in vitro HBV replication was suppressed by HCV co-infection; HBV suppression was attenuated when interferon signaling was blocked. In vivo, the HBV viremia, initially suppressed by the presence of HCV super-infection, rebounded following HCV clearance by DAA treatment and was accompanied by a reduced hepatic interferon response. In summary, major achievements in the treatment of HCV/HBV co-infection have been accomplished over the past 20 years. Future clinical trials should address measures to reduce or prevent HBV reactivation post HCV cure.
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Affiliation(s)
- Yi-Fen Shih
- Department of Physical Therapy and Assistive Technology, National Yang-Ming University, Taipei 112, Taiwan;
| | - Chun-Jen Liu
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan
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19
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Joko K, Mashiba T, Ochi H, Yano R, Sato K, Okujima Y, Aono M, Azemoto N, Takechi S, Yokota T, Jinoka R, Moriyama Y, Nishiyama M. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepatogastroenterol 2020; 9:78-83. [PMID: 32117695 PMCID: PMC7047307 DOI: 10.5005/jp-journals-10018-1305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background A possible interaction of hepatitis viruses at cellular and molecular levels has been suggested. Eradication of hepatitis C virus (HCV) has been reported to induce activation of hepatitis B virus (HBV)-related liver diseases. Materials and methods The present study examined association of HBV markers with recurrence of hepatocellular carcinoma (HCC) in patients with resolved HCV infection by direct-acting antiviral (DAA) therapy. In a patient pool of 378 patients with sustained virologic response (SVR) by DAA, the antibody to the hepatitis B surface antigen (anti-HBs), the antibody to the hepatitis B core antigen (anti-HBc), and HBV-DNA levels were estimated before and at the end of DAA therapy. These patients were HBsAg negative. Eighty-nine patients had a history of curative treatment of HCC by resection or radiofrequency ablation. A Cox proportional hazards model was used to identify risk factors for HCC recurrence, including the change ratio of the antibody against HBV proteins. Results Although 188 patients had resolved HBV infection, no patient showed HBV reactivation, but anti-HBs and anti-HBc levels decreased significantly. No significant difference in the HCC recurrence rate was evident between patients with and without resolved HBV infection. Changes of immune responses to HBV proteins did not affect HCC recurrence after DAA therapy for HCV infection in this cohort. Conclusion The mechanisms underlying diverse roles of DAA-induced SVR of HCV on HBV kinetics need to be resolved in future. How to cite this article Joko K, Mashiba T, Ochi H, et al. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepato-Gastroenterol 2019;9(2):78–83.
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Affiliation(s)
- Kouji Joko
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan; Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Toshie Mashiba
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Hironori Ochi
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Ryo Yano
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Kaori Sato
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yusuke Okujima
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Michiko Aono
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Nobuaki Azemoto
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Shunji Takechi
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Tomoyuki Yokota
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Ryosuke Jinoka
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yasunori Moriyama
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Masataka Nishiyama
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
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20
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Kanda T, Lau GKK, Wei L, Moriyama M, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Kadir Dokmeci A, Mamun-Al-Mahtab, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Ooka Y, Yokosuka O, Sarin SK, Omata M. APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation. Hepatol Int 2019; 13:649-661. [PMID: 31541423 PMCID: PMC6861433 DOI: 10.1007/s12072-019-09988-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 08/30/2019] [Indexed: 12/13/2022]
Abstract
In the direct-acting antiviral (DAA) era for hepatitis C virus (HCV) infection, sustained virological response (SVR) is very high, but close attention must be paid to the possible occurrence of hepatocellular carcinoma (HCC) and reactivation of hepatitis B virus (HBV) in patients with co-infection who achieved SVR in short term. HCC occurrence was more often observed in patients with previous HCC history. We found occurrence of HCC in 178 (29.6%) of 602 patients with previous HCC history (15.4 months mean follow-up post-DAA initiation) but, in contrast, in only 604 (1.3%) of 45,870 patients without previous HCC history (18.2 months mean follow-up). Thus, in these guidelines, we recommend the following: in patients with previous HCC history, surveillance at 4-month intervals for HCC by ultrasonography (US) and tumor markers should be performed. In patients without previous HCC history, surveillance at 6- to 12-month intervals for HCC including US is recommended until the long-term DAA treatment effects, especially for the resolution of liver fibrosis, are confirmed. This guideline also includes recommendations on how to follow-up patients who have been infected with both HCV and HBV. When HCV was eradicated in these HBsAg-positive patients or patients with previous HBV infection (anti-HBc and/or anti-HBs-positive), it was shown that HBV reactivation or HBV DNA reappearance was observed in 67 (41.4%) of 162 or 12 (0.9%) of 1317, respectively. For these co-infected patients, careful attention should be paid to HBV reactivation for 24 weeks post-treatment.
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Affiliation(s)
- Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - George K K Lau
- Humanity and Health Medical Center, Hong Kong SAR, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Ming-Lung Yu
- College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Banha, Egypt
| | - Cosmas Rinaldi Adithya Lesmana
- Digestive Disease and GI Oncology Centre, Medistra Hospital, Jakarta, Indonesia
- Hepatobiliary Division, Department of Internal Medicine, Dr. Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun-Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geoffrey W McCaughan
- Royal Prince Alfred Hospital, Centenary Institute, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- University of Queensland, School of Medicine, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine, and National Taiwan University Hospital, Taipei, Taiwan
| | - Yoshihiko Ooka
- Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Osamu Yokosuka
- Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
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21
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Sasadeusz J, Grigg A, Hughes PD, Lee Lim S, Lucas M, McColl G, McLachlan SA, Peters MG, Shackel N, Slavin M, Sundararajan V, Thompson A, Doyle J, Rickard J, De Cruz P, Gish RG, Visvanathan K. Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Other Populations and Newer Agents. Clin Liver Dis 2019; 23:521-534. [PMID: 31266625 DOI: 10.1016/j.cld.2019.04.012] [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] [Indexed: 02/07/2023]
Abstract
Because of the relatively high prevalence of both hepatitis B infection and various forms of autoimmune inflammatory diseases treated with aggressive immunotherapy, reactivation of hepatitis B occurs in a substantial number of patients. The risk of reactivation depends on the degree and duration of immunosuppression. A large number of drug treatments have resulted in reactivation of hepatitis B virus infection and, based on the mechanisms and extent of immunosuppression, recommendations for some of the newer classes of immunosuppressive drugs are provided.
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Affiliation(s)
- Joe Sasadeusz
- Peter Doherty Institute for Infection and Immunity, Elizabeth Street, Melbourne, Victoria 3000, Australia; University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.
| | - Andrew Grigg
- Olivia Newton John Cancer Research Institute, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Peter D Hughes
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; Royal Melbourne Hospital, 300 Grattan Street, Parkville, Victoria 3050, Australia
| | - Seng Lee Lim
- National University of Singapore, 21 Lower Kent Ridge Road, Singapore 119077, Singapore
| | - Michaela Lucas
- University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia
| | - Geoff McColl
- University of Queensland Oral Health Centre, 288 Herston Road, Queensland 4006, Australia
| | - Sue Anne McLachlan
- St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
| | - Marion G Peters
- University of California, San Francisco, S357 Parnassus Avenue, San Francisco, CA 94143, USA
| | - Nicholas Shackel
- Ingham Institute, 1 Campbell Street, Liverpool, Sydney, North South Wales 2170, Australia
| | - Monica Slavin
- Royal Melbourne Hospital, 300 Grattan Street, Parkville, Victoria 3050, Australia; Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia
| | - Vijaya Sundararajan
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia; Department of Public Health, La Trobe University, Plenty Road, Bundoora, Victoria 3086, Australia
| | - Alexander Thompson
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
| | - Joseph Doyle
- The Alfred and Monash University, 85 Commercial Road, Melbourne, Victoria 3004, Australia; Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia
| | - James Rickard
- Olivia Newton John Cancer Research Institute, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Peter De Cruz
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia
| | - Robert G Gish
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA
| | - Kumar Visvanathan
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
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22
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Abstract
Epidemiologic studies suggest that 10% to 15% of patients infected with hepatitis C virus (HCV) are coinfected with hepatitis B virus (HBV) in the United States as a result of the shared modality of transmission, but the true prevalence is not known. The progression of liver disease to cirrhosis and hepatocellular carcinoma is generally faster in patients who are coinfected, and HCV is usually more predominant. Immunosuppression of the host or eradication of hepatitis C can change this paradigm, causing hepatitis B reactivation. This review describes HCV-HBV viral interactions, risks for reactivation, screening, and society guidelines for surveillance and treatment.
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Affiliation(s)
- Rashed Abdelaal
- Department of Surgery, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA; Department of Transplant Hepatology, University of California at Los Angeles, Los Angeles, CA, USA
| | - Beshoy Yanny
- Department of Surgery, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA; Department of Transplant Hepatology, University of California at Los Angeles, Los Angeles, CA, USA; Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Mohamed El Kabany
- Department of Surgery, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA; Department of Transplant Hepatology, University of California at Los Angeles, Los Angeles, CA, USA; Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
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23
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Sanaka S, Kasarala GR, Tillmann HL. A Downside to Hepatitis C Virus Cure? Vigilance Is Needed Regarding Hepatitis B Virus Reactivation, Organ Rejection, or Hepatocellular Carcinoma Progression. J Infect Dis 2019; 217:857-860. [PMID: 29365131 DOI: 10.1093/infdis/jix659] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 12/19/2017] [Indexed: 02/06/2023] Open
Abstract
Cure of hepatitis C virus has become feasible in almost all patients. However, vigilance is needed in 3 scenarios: previous exposure to hepatitis B virus (HBV), history of organ transplantation, and history of cured hepatocellular carcinoma (HCC). The current data suggest that HBV reactivation occurs in about 10% of hepatitis B surface antigen (HBsAg)-positive patients and approximately 1% of hepatitis B core antibody-positive but HBsAg-negative patients. The risk of organ rejection is also around 1%, but can be fatal if not acted on immediately. Finally, the risk of early HCC recurrence may be increased but should not delay initiation of antiviral therapy in the setting of cured HCC; however, increased surveillance may be warranted.
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Affiliation(s)
- Sirish Sanaka
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, North Carolina
| | - George R Kasarala
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, North Carolina
- Vidant Medical Center, Greenville, North Carolina
| | - Hans L Tillmann
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, North Carolina
- Vidant Medical Center, Greenville, North Carolina
- Greenville Veterans Affairs Health Care Center, Greenville, North Carolina
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24
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Sanaka S, Tillmann HL. Hindsight is 20/20 - the importance of knowing! Know your patients' HBV status. Antivir Ther 2019; 23:471-473. [PMID: 30538213 DOI: 10.3851/imp3260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2018] [Indexed: 02/07/2023]
Affiliation(s)
- Sirish Sanaka
- Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, East Carolina University, Greenville, NC, USA
| | - Hans L Tillmann
- Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, East Carolina University, Greenville, NC, USA.,Vidant Medical Center, Greenville, NC, USA.,Greenville VA Health Care Center, Greenville, NC, USA
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25
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Whitsett M, Feldman DM, Pan CQ. Risk assessment and management of hepatitis B reactivation from direct-acting antivirals for hepatitis C. LIVER RESEARCH 2019. [DOI: 10.1016/j.livres.2019.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Chang JJ, Mohtashemi N, Bhattacharya D. Significance and Management of Isolated Hepatitis B Core Antibody (Anti-HBc) in HIV and HCV: Strategies in the DAA Era. Curr HIV/AIDS Rep 2019; 15:172-181. [PMID: 29572624 DOI: 10.1007/s11904-018-0379-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize the prevalence and clinical implications of the isolated anti-HBc serologic profile in HIV-infected individuals. We highlight the rare but important issue of HBV reactivation in the setting of HCV therapy and describe an approach to management. RECENT FINDINGS The isolated anti-HBc pattern, a profile that most often indicates past exposure to HBV with waning anti-HBs immunity, is found commonly in HIV-infected individuals, particularly those with HCV. Some large cohort studies demonstrate an association with advanced liver disease, while others do not. Conversely, meta-analyses have found an association between occult HBV infection (a component of the isolated anti-HBc pattern) and advanced liver disease and hepatocellular carcinoma in HIV-uninfected individuals. In HIV-uninfected individuals with anti-HBc positivity, HBV reactivation has been reported in patients receiving HCV therapy. This phenomenon is likely the result of disinhibition of HBV with HCV eradication. In HIV-infected patients, the long-term liver outcomes associated with the isolated anti-HBc pattern remain to be fully elucidated, supporting the need for large cohort studies with longitudinal follow-up. HBV reactivation during HCV DAA therapy has been well-described in HIV-uninfected cohorts and can inform algorithms for the screening and management of the isolated anti-HBc pattern in this population.
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Affiliation(s)
- Jennifer J Chang
- UCLA CARE Center, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, 37-121 CHS, Los Angeles, CA, 90095, USA.,Department of Infectious Diseases, Kaiser Permanente at Los Angeles Medical Center, 1505 N. Edgemont St., 2nd Floor, Los Angeles, CA, 90027, USA
| | - Neaka Mohtashemi
- UCLA CARE Center, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, 37-121 CHS, Los Angeles, CA, 90095, USA
| | - Debika Bhattacharya
- UCLA CARE Center, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, 37-121 CHS, Los Angeles, CA, 90095, USA.
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Wang J, Hu C, Chen Y, Liu Z, Yu Q, Yang S, Dong J, Yang Y, Wu Y, Ren D, Yao N, Guo D, Tian Z, Zhao Y, Chen T, He Y, Liu J. HBV reactivation during direct-acting antiviral therapy in hepatitis B and C coinfected patients undergoing haemodialysis. Antivir Ther 2019; 24:77-84. [PMID: 30833515 DOI: 10.3851/imp3292] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND There have been increasing reports of HBV reactivation in HBV and HCV coinfected patients with direct-acting antiviral (DAA) treatment. The potential risk of HBV reactivation in patients undergoing haemodialysis has also been noted. There is a lack of data pertaining to the reactivation risk during DAA treatment in those coinfected patients with end-stage renal disease who are undergoing haemodialysis. METHODS HBV-HCV-coinfected patients were screened from 178 persons at two blood purification centres in China and received sofosbuvir (200 mg) combined with daclatasvir (60 mg) daily. The risk and pattern of HBV reactivation during DAA treatment was retrospectively analysed. RESULTS HBV reactivation occurred in 45.5% (5/11) of the HBV-HCV-coinfected patients undergoing haemodialysis during DAA treatment, which was much higher than the reported rates in the general population of coinfected patients. Five patients with HBV reactivation were all positive for hepatitis B surface antigen (HBsAg) before DAA treatment. Three patients (27.3%) had mild hepatitis flares due to HBV reactivation, but no patients had severe hepatitis or hepatic failure. Compared with the four patients who were HBsAg- at the baseline, the risk of HBV reactivation in HBsAg+ patients was greater (71.4% versus 0; χ2=5.238; P=0.061), although the difference was not statistically significant. CONCLUSIONS A significant proportion of HBV-HCV-coinfected patients undergoing haemodialysis developed HBV reactivation after DAA therapy. The risk of HBV reactivation was greater in HBsAg+ patients than in those patients who were HBsAg- but anti-HBc+ or HBV DNA+.
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Affiliation(s)
- Jing Wang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
- Department of Rheumatology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Chunhua Hu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yi Chen
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Zhengwen Liu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Qiang Yu
- Department of Pediatric Surgery, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Shujuan Yang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
- Department of Infectious Diseases, The Eight Hospital of Xi'an, Xi'an City, China
| | - Jun Dong
- Department of Haemodialysis, Zhen'An County Hospital, Shangluo City, China
| | - Yuan Yang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yuchao Wu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Danfeng Ren
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Naijuan Yao
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Dandan Guo
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Zhen Tian
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yingren Zhao
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Tianyan Chen
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yingli He
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Jinfeng Liu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
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28
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El Kassas M, Shimakawa Y, Ali-Eldin Z, Funk AL, Wifi MN, Zaky S, El-Raey F, Esmat G, Fontanet A. Risk of hepatitis B virus reactivation with direct-acting antivirals against hepatitis C virus: A cohort study from Egypt and meta-analysis of published data. Liver Int 2018; 38:2159-2169. [PMID: 29738637 DOI: 10.1111/liv.13874] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 04/26/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Hepatitis B virus (HBV) reactivation in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAAs) became an issue. However, its frequency has been poorly estimated, because of the varying definitions used and evaluation of heterogeneous study populations, including those concurrently treated for HBV. METHODS We prospectively followed HBV surface antigen (HBsAg)-positive Egyptians undergoing interferon-free DAAs, to estimate the risk of HBV reactivation and HBV-related hepatitis. We also conducted a meta-analysis to estimate the reactivation risk using published data obtained from a systematic review of PubMed/Embase, in addition to our Egyptian data. We applied a standard definition of HBV reactivation proposed by the international liver associations (APASL and AASLD). RESULTS Of 4471 CHC patients, 35 HBsAg-positive patients started interferon-free DAAs without HBV nucleos(t)ide analogues in our Egyptian cohort. Ten experienced HBV reactivation (28.6%), of whom 1 developed hepatitis (10.0%). Our systematic review identified 18 papers. The pooled reactivation risk in HBsAg-positive patients was 18.2% (95% CI: 7.9%-30.7%) without HBV therapy and 0.0% (95% CI: 0.0%-0.0%) with HBV nucleos(t)ide analogue. The pooled risk of hepatitis in those with HBV reactivation was 12.6% (95% CI: 0.0%-34.7%). The pooled reactivation risk in HBsAg-negative, antibody to HBV core antigen-positive (anti-HBc-positive) patients was negligible (0.1%, 95% CI: 0.0%-0.3%), irrespective of the presence of antibody to HBsAg (anti-HBs). CONCLUSIONS We confirmed high HBV reactivation risk in HBsAg-positive patients undergoing DAAs, with only a minority developing clinically important hepatitis. The risk is negligible for HBsAg-negative anti-HBc-positive patients.
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Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Yusuke Shimakawa
- Unité d'Epidémiolotie des Maladies Emergentes, Institut Pasteur, Paris, France
| | - Zainab Ali-Eldin
- Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Anna-Louise Funk
- Unité d'Epidémiolotie des Maladies Emergentes, Institut Pasteur, Paris, France
| | - Mohamed Naguib Wifi
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Samy Zaky
- Department of Tropical Medicine, Faculty of Medicine, Al-Azhar University, Damietta, Egypt
| | - Fathiya El-Raey
- Department of Tropical Medicine, Faculty of Medicine, Al-Azhar University, Damietta, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Arnaud Fontanet
- Unité d'Epidémiolotie des Maladies Emergentes, Institut Pasteur, Paris, France
- PACRI Unit, Conservatoire National des Arts et Métiers, Paris, France
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Teegen EM, Maurer MM, Globke B, Pratschke J, Eurich D. Liver transplantation for Hepatitis-B-associated liver disease - Three decades of experience. Transpl Infect Dis 2018; 21:e12997. [PMID: 30203903 DOI: 10.1111/tid.12997] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 08/24/2018] [Accepted: 09/02/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hepatitis B (HBV)-associated end-stage liver disease used to be a relevant indication for liver transplantation (LT). After transplantation, HBV-reinfection remains a serious issue. Different strategies to prevent HBV-reinfection range from the single application of immunoglobulins (HBIG), to the use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG, followed by HBIG-discontinuation. The aim of this analysis was to compare different strategies and to sum up the results of 30 years at a high-volume transplant center and deliver additional information on the histopathological level. METHODS Data of 372 liver transplantations performed for the HBV-induced liver disease in 352 patients were extracted from a prospectively organized database. HBV-reinfection was determined in the entire cohort, according to the mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients with successful prophylaxis, untreated and controlled HBV-reinfection. Histopathological results were obtained from protocol biopsies in 151 patients. RESULTS HBV-reinfection was significantly associated with the type of prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and influencing the overall survival before 2005. After the introduction of modern NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and survival. Controlled HBV-infection prevents from HBV-associated transplant hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs. CONCLUSIONS Uncontrolled HBV-reinfection does not occur any more. Even in the presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable mode to prevent HBV-recurrence remains the combination of NUCs with a high genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.
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Affiliation(s)
- Eva Maria Teegen
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Max Magnus Maurer
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Brigitta Globke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Dennis Eurich
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
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30
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Mavilia MG, Wu GY. HBV-HCV Coinfection: Viral Interactions, Management, and Viral Reactivation. J Clin Transl Hepatol 2018; 6:296-305. [PMID: 30271742 PMCID: PMC6160312 DOI: 10.14218/jcth.2018.00016] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 04/25/2018] [Accepted: 05/01/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is a complex clinical entity that has an estimated worldwide prevalence of 1-15%. Most clinical studies have shown that progression of disease is faster in HBV-HCV coinfected patients compared to those with monoinfection. Hepatocellular carcinoma development appears to have higher rate in coinfections. Viral replication in coinfected cells is characterized by a dominance of HCV over HBV replication. There are no established guidelines for treatment of HBV-HCV coinfection. Studies on interferon-based therapies and direct-acting antivirals have shown varying levels of efficacy. Clinical reports have indicated that treatment of HCV without suppression of HBV increases the risk for HBV reactivation. In this review, we appraise studies on both direct-acting antivirals and interferon-based therapies to evaluate the efficacy and rates of reactivation with each regimen. Screening for and prevention of coinfection are important to prevent serious HBV reactivations.
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Affiliation(s)
- Marianna G. Mavilia
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- *Correspondence to: Marianna G. Mavilia, Department of Medicine, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06032, USA. Tel: +1-860-679-2509, Fax: +1-860-679-6582, E-mail:
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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31
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Bath RM, Doering BE, Nailor MD, Goodlet KJ. Pharmacotherapy-Induced Hepatitis B Reactivation Among Patients With Prior Functional Cure: A Systematic Review. Ann Pharmacother 2018; 53:294-310. [PMID: 30203666 DOI: 10.1177/1060028018800501] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE To describe and quantify the incidence and morbidity of hepatitis B reactivation (HBVr) secondary to pharmaceutical agents (eg, rituximab, tumor necrosis factor inhibitors, direct-acting antivirals [DAAs] for hepatitis C) among patients with previously resolved hepatitis B infection. DATA SOURCES The MEDLINE database was searched from inception through July 2018 using the terms hepatitis B + ( reactivation OR [drug or drug class linked to HBVr]). STUDY SELECTION AND DATA EXTRACTION Relevant English-language cohort studies or randomized trials quantifying the incidence of HBVr secondary to pharmacotherapy among patients negative for hepatitis B surface antigen and DNA and positive for hepatitis B core antibody were included. DATA SYNTHESIS Among 2045 articles, 102 met inclusion criteria. Receipt of rituximab was associated with the highest risk of HBVr (for oncological indication: 6.2% rate [225/3601 patients]) and subsequent hepatitis (up to 52.4% of all HBVr cases). Biologic agents for autoimmune disease were uncommonly associated with HBVr (2.4%, 56/2338), with only 4 cases of hepatitis, all attributable to rituximab. Reactivation caused by DAAs was rare (0.3%, 28/8398), with no cases of hepatitis. Relevance to Patient Care/Clinical Practice: This review compares and contrasts the incidence and clinical relevance of HBVr for various pharmacotherapies among patients with functionally cured hepatitis B, with discussion of appropriate risk mitigation strategies. CONCLUSIONS Among patients with prior functional cure of hepatitis B, prophylactic antiviral therapy is recommended with rituximab administration irrespective of indication because of a high risk for HBVr-associated morbidity. Enhanced monitoring alone is reasonable for patients receiving nonrituximab biologics or DAAs.
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Affiliation(s)
- Rhiannon M Bath
- 1 Midwestern University College of Pharmacy, Glendale, AZ, USA
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32
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Jiang XW, Ye JZ, Li YT, Li LJ. Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C: A systematic review and meta-analysis. World J Gastroenterol 2018; 24:3181-3191. [PMID: 30065564 PMCID: PMC6064961 DOI: 10.3748/wjg.v24.i28.3181] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 06/02/2018] [Accepted: 06/22/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the incidence of hepatitis B virus (HBV) reactivation in patients receiving direct-acting antiviral agent (DAA)-based therapy or interferon (IFN)-based therapy for hepatitis C and the effectiveness of preemptive anti-HBV therapy for preventing HBV reactivation. METHODS The PubMed, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAA-based therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis B surface antigen (HBsAg)-positive patients receiving DAA-based therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBsAg-positive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy (RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBsAg-positive patients undergoing DAA-based therapy (RR = 0.31, 95%CI: 0.1-0.96, P = 0.042). CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBsAg-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.
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Affiliation(s)
- Xian-Wan Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Jian-Zhong Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Ya-Ting Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Lan-Juan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
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Preda CM, Popescu CP, Baicus C, Constantinescu I, Oproiu A, Voiosu T, Diculescu M, Negreanu L, Gheorghe L, Sporea I, Trifan A, Ceausu E, Proca D, Manuc M. Risk of hepatitis B virus reactivation in hepatitis B virus + hepatitis C virus-co-infected patients with compensated liver cirrhosis treated with ombitasvir, paritaprevir/r + dasabuvir + ribavirin. J Viral Hepat 2018; 25:834-841. [PMID: 29397016 DOI: 10.1111/jvh.12872] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Accepted: 01/10/2018] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus may reactivate in patients with chronic hepatitis C treated with direct-acting antivirals. The aim of this study was to investigate the risk of hepatitis B virus (HBV) reactivation in HBV + hepatitis C virus (HCV)-co-infected patients with compensated liver cirrhosis treated with paritaprevir/ombitasvir/ritonavir, dasabuvir with ribavirin. We reviewed prospectively gathered data from a national cohort of 2070 hepatitis C virus patients with compensated liver cirrhosis who received reimbursed paritaprevir/ombitasvir/r, dasabuvir with ribavirin for 12 weeks from the Romanian National Health Agency during 2015-2016. Twenty-five patients in this cohort were HBs antigen positive (1.2%); 15 untreated with nucleotide analogues agreed to enter the study. These patients were followed up: ALT monthly, serology for HBV and DNA viral load at baseline, EOT and SVR at 12 weeks. Hepatitis B virus (HBV)-co-infected patients were all genotype 1b and 52% females, with a median age of 60 years (51 ÷ 74); 76% were pretreated with peginterferon + ribavirin; 72% were with severe necroinflammatory activity on FibroMax assessment; 40% presented comorbidities; and all were HBe antigen negative. Hepatitis C virus (HCV) SVR response rate was 100%. Hepatitis B virus (HBV)-DNA viral load was undetectable in 7/15 (47%) before therapy, and for the other 8 patients, it varied between below 20 and 867 IU/mL. Five patients (33%) presented virological reactivation (>2 log increase in HBV-DNA levels) during therapy. One patient presented with hepatitis associated with HBV reactivation, and two started anti-HBV therapy with entecavir. Hepatitis B virus (HBV) virological reactivation was present in 33% in our patients. Generally, HBV-DNA elevations were mild (<20 000 IU/mL); however, we report one case of hepatitis associated with HBV reactivation.
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Affiliation(s)
- C M Preda
- UMF "Carol Davila" Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - C P Popescu
- UMF "Carol Davila" Virology Department, Victor Babes Hospital, Bucharest, Romania
| | - C Baicus
- UMF "Carol Davila" Internal Medicine Department, Colentina Hospital, Bucharest, Romania
| | - I Constantinescu
- UMF "Carol Davila" Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - A Oproiu
- UMF "Carol Davila" Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - T Voiosu
- UMF "Carol Davila" Internal Medicine Department, Colentina Hospital, Bucharest, Romania
| | - M Diculescu
- UMF "Carol Davila" Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - L Negreanu
- UMF "Carol Davila" Gastroenterology Department, Emergency Universitary Hospital, Bucharest, Romania
| | - L Gheorghe
- UMF "Carol Davila" Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - I Sporea
- UMF Timisoara, Gastroenterology & Hepatology Department, Timisoara Emergency Hospital, Timisoara, Romania
| | - A Trifan
- UMF Gr T Popa Iasi, Gastroenterology & Hepatology Department, Gastroenterology & Hepatology Institute, Iasi, Romania
| | - E Ceausu
- UMF "Carol Davila" Virology Department, Victor Babes Hospital, Bucharest, Romania
| | - D Proca
- UMF "Carol Davila" Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - M Manuc
- UMF "Carol Davila" Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
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34
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Tucci A, Rizza S, Cocchis D, Martini S, Romagnoli R, Marzano A. Early and Late Hepatitis B Reactivation After IFN- or DAA-based Therapy of Recurrent Hepatitis C in Anti-HBc-positive Liver Transplant Recipients. Transplantation 2018; 102:e354-e355. [PMID: 29757904 DOI: 10.1097/tp.0000000000002241] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Alessandra Tucci
- 1 Division of Gastroenterology, San Giovanni Battista Hospital, University of Turin, Turin, Italy. 2 Liver Transplant Center, San Giovanni Battista Hospital, University of Turin, Turin, Italy
| | - Stefano Rizza
- Division of Gastroenterology, San Giovanni Battista Hospital, University of Turin, Turin, Italy
| | - Donatella Cocchis
- Liver Transplant Center, San Giovanni Battista Hospital, University of Turin, Turin, Italy
| | - Silvia Martini
- Liver Transplant Center, San Giovanni Battista Hospital, University of Turin, Turin, Italy
| | - Renato Romagnoli
- Liver Transplant Center, San Giovanni Battista Hospital, University of Turin, Turin, Italy
| | - Alfredo Marzano
- Division of Gastroenterology, San Giovanni Battista Hospital, University of Turin, Turin, Italy
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