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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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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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3
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COVID-19 as Another Trigger for HBV Reactivation: Clinical Case and Review of Literature. Pathogens 2022; 11:pathogens11070816. [PMID: 35890060 PMCID: PMC9318431 DOI: 10.3390/pathogens11070816] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 07/17/2022] [Accepted: 07/19/2022] [Indexed: 02/07/2023] Open
Abstract
Universal hepatitis B virus (HBV) vaccination has been applied for years in most countries, but HBV infection remains an unresolved public health problem worldwide, with over one-third of the world’s population infected during their lifetime and approximately 248 million hepatitis B surface antigen (HBsAg) chronic carriers. HBV infection may reactivate with symptomatic and sometimes life-threatening clinical manifestations due to a reduction in the immune response of various origins, due to chemotherapy or immunosuppressive therapy, treatments increasingly practiced worldwide. SARS-CoV-2 and its COVID-19 associated disease have introduced new chances for HBV reactivation due to the use of dexamethasone and tocilizumab to counteract the cytokine storm. This could and should be prevented by accurate screening of HBV serologic markers and adequate pharmacologic prophylaxis. This article describes the case of a patient with COVID-19 who developed HBV reactivation and died of liver failure and analyzes published data on this setting to provide useful information to physicians who manage these patients during the SARS-CoV-2 pandemic.
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Çakal B, Çavuş B, Atasoy A, Poda M, Bulakçi M, Güllüoğlu M, Demirci M, Şener LT, Altunok D, Arslan AB, Akyüz F. What is the clinical impact of occult HBV infections and anti-HBc positivity in patients with chronic hepatitis C? Microbiol Immunol 2022; 66:386-393. [PMID: 35661243 DOI: 10.1111/1348-0421.13012] [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: 02/18/2022] [Revised: 05/20/2022] [Accepted: 06/01/2022] [Indexed: 11/29/2022]
Abstract
Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (p<0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (p<0.05). Positive anti-HBc results may predict OBI and also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Bülent Çakal
- Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Bilger Çavuş
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Alp Atasoy
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehveş Poda
- Department of Genetics, Aziz Sancar Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey
| | - Mesut Bulakçi
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehmet Demirci
- Department of Medical Microbiology, Faculty of Medicine, Kirklareli University, Kirklareli, Turkey
| | - Leyla Türker Şener
- Department of Biophysics Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Damla Altunok
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Filiz Akyüz
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Chang Y, Jeong SW, Jang JY. Hepatitis B Virus Reactivation Associated With Therapeutic Interventions. Front Med (Lausanne) 2022; 8:770124. [PMID: 35096867 PMCID: PMC8795508 DOI: 10.3389/fmed.2021.770124] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/20/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is an important cause of morbidity and mortality in patients with current or resolved HBV infection. Because no curative treatment for HBV infection is yet available, there are many individuals at risk for HBV reactivation in the general population. Populations at risk for HBV reactivation include patients who are currently infected with HBV or who have been exposed to HBV in the past. HBV reactivation and its potential consequences is a concern when these populations are exposed to anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for the management of various malignancies, rheumatologic diseases, inflammatory bowel disease, or solid-organ or hematologic stem cell transplantation. Accordingly, it has become important to understand the basics of HBV reactivation and the mechanisms by which certain therapies are more susceptible to HBV reactivation. This review aims to raise the awareness of HBV reactivation and to understand the mechanisms and the risks of HBV reactivation in various clinical settings.
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Affiliation(s)
- Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Jae Young Jang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
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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: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [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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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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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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9
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Japan Society of Hepatology Guidelines for the Management of Hepatitis B Virus Infection: 2019 update. Hepatol Res 2020; 50:892-923. [PMID: 32343469 DOI: 10.1111/hepr.13504] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/16/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology published the first version of the Guidelines for the Management of Hepatitis B in 2013 (first English version in 2014), and has since been publishing updates to the Guidelines as new drugs become available, with the latest original Japanese version being Version 3.1. Herein, the Drafting Committee publishes the second English version that contains all the changes made since the first English version of the guidelines was published in 2014. This 2019 version covers: (i) the nucleos(t)ide analogs, tenofovir disoproxil fumarate and tenofovir alafenamide; (ii) updates to treatment recommendations and management of drug-resistant hepatitis B virus that reflect the new availability of these drugs; and (iii) new information about hepatitis B virus reactivation with each update. This latest update also contains information about treatment goals, indications for treatment and cessation of nucleos(t)ide analog therapy, most of which were covered by the first version.
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10
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Ekpanyapong S, Reddy KR. Hepatitis B Virus Reactivation: What Is the Issue, and How Should It Be Managed? Clin Liver Dis 2020; 24:317-333. [PMID: 32620274 DOI: 10.1016/j.cld.2020.04.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) reactivation, in the background of cleared and overt chronic HBV infection, can be seen in patients receiving immunosuppressive agents. Risk of reactivation is variably associated with HBV serologic status and types of immunosuppressive therapy. Prevention of HBV reactivation by antiviral prophylaxis is an effective strategy to reduce morbidity and mortality in those with immunocompromised states. This article defines HBV reactivation, discusses risk stratification and common medications that can induce HBV reactivation as well as guideline recommendations for prevention of HBV reactivation, and describes the prognosis and management of patients who experience HBV reactivation.
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Affiliation(s)
- Sirina Ekpanyapong
- Department of Medicine, Division of Gastroenterology and Hepatology, Vejthani Hospital, 1 Soi Lat Phrao 111, Khlong Chan, Bang Kapi District, Bangkok 10240, Thailand
| | - K Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, 3400 Spruce Street, 2 Dulles HUP, Philadelphia, PA 19104, USA.
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Jaroszewicz J, Pawłowska M, Simon K, Zarębska-Michaluk D, Lorenc B, Klapaczyński J, Tudrujek-Zdunek M, Sitko M, Mazur W, Janczewska E, Paluch K, Dybowska D, Buczyńska I, Czauż-Andrzejuk A, Berak H, Krygier R, Piasecki M, Dobracka B, Citko J, Piekarska A, Socha Ł, Deroń Z, Tronina O, Laurans Ł, Białkowska J, Tomasiewicz K, Halota W, Flisiak R. Low risk of HBV reactivation in a large European cohort of HCV/HBV coinfected patients treated with DAA. Expert Rev Anti Infect Ther 2020; 18:1045-1054. [PMID: 32538232 DOI: 10.1080/14787210.2020.1782189] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The aim of the study was to analyze the prevalence and clinical characteristics of HCV/HBV coinfection and to evaluate the rate of HBV-reactivation during anti-HCV therapy in a large real-world study. METHODS Analyzed population consisted of 10,152 chronic hepatitis C patients treated with DAA between 2015 and 2019 in a nationwide study. Prior to the DAA all subjects had HBsAg and 60% anti-HBc testing. RESULTS 111 of 10,152 patients (1.1%) had detectable HBsAg and 1239 of 6139 (20.2%) anti-HBcAb. The prevalence of occult hepatitis B was 0.48%. HCV/HBV patients were younger with a higher proportion of males, HIV-coinfected, and advanced fibrosis. They were less often diagnosed with diabetes but more often with chronic kidney disease. In HBsAg(+) subjects with baseline HBV-DNA available 6/102 (5.9%) HBV-reactivations during or after DAA therapy were observed, and in two (1.9%) significant hepatic flares were noted. In HBsAg(-)/anti-HBc(+) group 2 (0.16%) reactivations were observed only in patients undergoing immunosuppressive therapy. DISCUSSION Data from a large European cohort suggest a relatively low risk of HBV-reactivation during DAA-therapy for HCV infection in HBsAg(+) patients. In HBsAg(-)/anti-HBc(+) HBV-reactivation seems to be limited to subjects with immunodeficiency. Importantly, previous exposure to HBV and occult hepatitis B is present in a significant proportion of HCV-infected.
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Affiliation(s)
- Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia , Katowice, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University , Poland
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Wrocław Medical University , Wrocław, Poland
| | | | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Department of Infectious Diseases, Medical University of Gdańsk , Gdańsk, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration , Warsaw, Poland
| | | | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum , Kraków, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases in Chorzów, Medical University of Silesia , Katowice, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences in Bytom, Medical University of Silesia , Katowice, Poland
| | - Katarzyna Paluch
- Department of Infectious Diseases, Provincial Hospital , Kielce, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University , Poland
| | - Iwona Buczyńska
- Department of Infectious Diseases and Hepatology, Wrocław Medical University , Wrocław, Poland
| | - Agnieszka Czauż-Andrzejuk
- Department of Infectious Diseases and Hepatology, Medical University of Białystok , Białystok, Poland
| | - Hanna Berak
- Outpatient Clinic, Hospital of Infectious Diseases in Warsaw , Warsaw, Poland
| | - Rafał Krygier
- Outpatient Clinic, State University of Applied Sciences in Konin , Poland
| | - Maciej Piasecki
- Department of Infectious Diseases and Hepatology, Medical University of Silesia , Katowice, Poland
| | - Beata Dobracka
- Outpatient Clinic, Medical Center MedicalSpec , Wroclaw, Poland
| | - Jolanta Citko
- Outpatient Clinic, Regional Hospital, Medical Practice of Infections , Olsztyn, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź , Łódź, Poland
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University , Szczecin, Poland
| | - Zbigniew Deroń
- Ward of Infectious Diseases and Hepatology, Biegański Regional Specialist Hospital , Łódź, Poland
| | - Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw , Warszawa, Poland
| | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University , Szczecin, Poland.,Outpatient Department, Multidisciplinary Regional Hospital , Gorzów, Poland
| | - Jolanta Białkowska
- Department of Infectious and Liver Diseases, Medical University , Łódź, Poland
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases and Hepatology, Medical University of Lublin , Lublin, Poland
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University , Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok , Białystok, Poland
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Zarębska-Michaluk D, Flisiak R, Flisiak-Jackiewicz M. Management of hepatitis B and hepatitis C coinfection: an expert review. Expert Rev Anti Infect Ther 2020; 18:1033-1044. [PMID: 32579414 DOI: 10.1080/14787210.2020.1776112] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections share common routes of transmission. HBV/HCV coinfection can lead to interactions affecting mechanisms of infection and therapy. AREAS COVERED In the review, we present epidemiology of HBV/HCV coinfection and current therapeutic options for both viruses. The possibility of drug-drug interactions during the treatment of coinfected patients is discussed. However, the major part of the review is dedicated to interactions between viruses and risk of HBV reactivation during HCV treatment with direct-acting antivirals (DAA). Finally, we analyze available international and national guidelines for the management of HBV reactivations related to DAA administration. EXPERT OPINION The most important international societies' guidelines include comments on HBV/HCV coinfection, but due to their inconsistency we present a proposal of management for HBV/HCV coinfected patients focusing mostly on HBV reactivation in patients treated for HCV. We provide some advice that should be considered in future guidelines for the management of HBV/HCV coinfection.
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Affiliation(s)
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok , 15-540, Białystok, Poland
| | - Marta Flisiak-Jackiewicz
- Department of Pediatrics, Gastroenterology, Hepatology, Nutrition and Allergology, Medical University of Bialystok , 15-247, Bialystok, Poland
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13
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Musolino C, Cacciola I, Tripodi G, Lombardo D, Raffa G, Alibrandi A, Squadrito G, Raimondo G, Pollicino T. Behaviour of occult HBV infection in HCV-infected patients under treatment with direct-acting antivirals. Antivir Ther 2020; 24:187-192. [PMID: 30628893 DOI: 10.3851/imp3288] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/28/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND There is controversial data on possible occult HBV reactivation in HCV patients successfully treated with direct-acting antivirals (DAA). However, diagnosis of occult HBV infection (OBI) was not performed by gold standard procedures in any study. METHODS By using several highly sensitive assays, we examined serially collected serum samples from 40 HBV-surface-negative DAA-treated HCV patients with OBI identified by testing liver biopsy specimens through nested-PCR technique. Serum samples were obtained at four time points from each patient (at baseline, at 4 weeks after starting, at the end and 12 weeks after stopping therapy) and tested for HBV DNA by nested-PCR and real-time PCR techniques. RESULTS All tested serum samples were negative by both quantitative HBV surface antigen (HBsAg) and HBV core-related antigen assays. 26/40 patients were anti-HBs-positive and in all of them, the amount of this antibody was stable at the four time points evaluated. Serum HBV DNA was detected in 10 samples at baseline, in 6 samples 4 weeks after starting therapy, in 11 samples at the end of therapy and in 21 samples 12 weeks after stopping treatment (P=0.001). Aminotransferase values dropped within the normal levels at week 4 of therapy and persisted normal over time in all cases. CONCLUSIONS A slight increase in the amount of HBV DNA 3 months after stopping DAA therapy was the only parameter showing a possible reappearance of HBV activity in OBI patients cured for a concomitant HCV infection, but it was insufficient to lead toward a virological reactivation capable of inducing liver injury.
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Affiliation(s)
- Cristina Musolino
- Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Irene Cacciola
- Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Gianluca Tripodi
- Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Daniele Lombardo
- Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Giuseppina Raffa
- Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | | | - Giovanni Squadrito
- Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Teresa Pollicino
- Department of Human Pathology, University Hospital of Messina, Messina, Italy
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14
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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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15
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Butt AA, Yan P, Aslam S, Sherman KE, Siraj D, Safdar N, Hameed B. Hepatitis C virologic response in hepatitis B and C coinfected persons treated with directly acting antiviral agents: Results from ERCHIVES. Int J Infect Dis 2020; 92:184-188. [PMID: 31978574 DOI: 10.1016/j.ijid.2020.01.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 12/29/2019] [Accepted: 01/14/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND There are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. METHODS All HCV infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. Logistic regression model was used to determine factors associated with SVR. RESULTS Among 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pre-treatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). CONCLUSION HBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. Though not statistically significant, the virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores.
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Affiliation(s)
- Adeel A Butt
- VA Pittsburgh Healthcare System, Pittsburgh, PA, United States; Weill Cornell Medical College, New York, NY, United States; Weill Cornell Medical College, Doha, Qatar; Hamad Medical Corporation, Doha, Qatar.
| | - Peng Yan
- VA Pittsburgh Healthcare System, Pittsburgh, PA, United States
| | - Samia Aslam
- VA Pittsburgh Healthcare System, Pittsburgh, PA, United States
| | - Kenneth E Sherman
- University of Cincinnati School of Medicine, Cincinnati, OH, United States
| | - Dawd Siraj
- University of Wisconsin School of Medicine, Madison, WI, United States
| | - Nasia Safdar
- University of Wisconsin School of Medicine, Madison, WI, United States
| | - Bilal Hameed
- University of California at San Francisco, San Francisco, CA, United States
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16
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Wu J, Guo N, Zhang X, Xiong C, Liu J, Xu Y, Fan J, Yu J, Zhao X, Liu B, Wang W, Zhang J, Cao H, Li L. HEV-LF S : A novel scoring model for patients with hepatitis E virus-related liver failure. J Viral Hepat 2019; 26:1334-1343. [PMID: 31294523 DOI: 10.1111/jvh.13174] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Revised: 06/01/2019] [Accepted: 06/10/2019] [Indexed: 12/27/2022]
Abstract
A noninvasive assessment method for acute or acute-on-chronic liver failure in patients with hepatitis E virus (HEV) infection is urgently needed. We aimed to develop a scoring model for diagnosing HEV patients who developed liver failure (HEV-LF) at different stages. A cross-sectional set of 350 HEV-LF patients were identified and enrolled, and the Guidelines for Diagnosis and Treatment of Liver Failure in China and the Asian Pacific Association for the Study of the Liver were adopted as references. HEV-LFS , a novel scoring model that incorporates data on cholinesterase (CHE), urea nitrogen (UREA), platelets and international normalized ratio was developed using a derived dataset. For diagnosing HEV-LF stages F1 to F3, the HEV-LFS scoring model (F1: 0.87; F2: 0.90; F3: 0.92) had a significantly higher AUROC than did the CLIF-C-ACLFs (F1: 0.65; F2: 0.56; F3: 0.51) and iMELD (F1: 0.70; F2: 0.57; F3: 0.51) scoring models, of which the HEV-LFS scoring model had the best sensitivity and specificity. In addition, the HEV-LFS scoring model was correlated with mortality, length of hospitalization and ICU stay. As the GDTLF score increased, the CHE level decreased and the UREA increased gradually. Encouragingly, a calibration curve showed good agreement between the derivation and validation sets. Notably, we also established a nomogram to facilitate the practical operability of the HEV-LFS scoring model in clinical settings. In conclusion, both CHE and UREA may be indicators for HEV-LF patients. The HEV-LFS scoring model is an efficient and accessible model for classifying HEV-LF at different stages.
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Affiliation(s)
- Jian Wu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Department of Laboratory Medicine, The First People's Hospital of Yancheng City, Yancheng, China
| | - Naizhou Guo
- Department of Laboratory Medicine, The First People's Hospital of Yancheng City, Yancheng, China
| | - Xueyan Zhang
- Department of Public Health, Jiangsu Vocational College of Medicine, Yancheng, China
| | - Cunquan Xiong
- Department of Public Health, Jiangsu Vocational College of Medicine, Yancheng, China
| | - Jun Liu
- Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, Affiliated to Jiangnan University, Wuxi, China
| | - Yanping Xu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jun Fan
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jiong Yu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xinguo Zhao
- Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, Affiliated to Jiangnan University, Wuxi, China
| | - Bin Liu
- Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, Affiliated to Jiangnan University, Wuxi, China
| | - Wei Wang
- Department of Laboratory Medicine, The First People's Hospital of Yancheng City, Yancheng, China
| | - Jinrong Zhang
- Department of Laboratory Medicine, The People's Hospital of Dafeng City, Yancheng, China
| | - Hongcui Cao
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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17
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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] [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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18
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Aghemo A, Piroth L, Bhagani S. What do clinicians need to watch for with direct-acting antiviral therapy? J Int AIDS Soc 2019; 21 Suppl 2:e25076. [PMID: 29633552 PMCID: PMC5978638 DOI: 10.1002/jia2.25076] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 01/18/2018] [Indexed: 12/15/2022] Open
Abstract
Introduction The introduction of drugs targeting the virus replication cycle has revolutionized treatment of chronic hepatitis C virus. These drugs, called direct‐acting antivirals, have brought about extremely high rates of virological cure and have increased the number of patients who can receive treatment due to the lack of absolute contraindications. A combination of different classes of direct‐acting antivirals is the current standard of care. Although treatment administration and monitoring has been simplified in recent years, it is still relatively complex and mostly in the hands of specialists. Several factors must be assessed before starting treatment to maximize efficacy and minimize side effects of treatment. In this review, we describe the factors that impact on the efficacy and safety of antiviral treatment for hepatitis C and provide clear recommendations for clinicians prescribing direct‐acting antivirals. Methods We reviewed literature to define best practice, based on factors associated with treatment efficacy and safety data to recommend treatment options, baseline and on‐treatment assessments. The review included searches in PubMed, and the abstracts presented at the International Liver Congress TM and The Liver Meeting TM between January 2013 and September 2017. Results Clinical features that must be assessed before starting treatment include virological factors, such as hepatitis C virus genotype, HIV and hepatitis B coinfection and host factors, such as concomitant medications, liver disease stage and renal function. Conclusions Patients who start antiviral treatment for chronic hepatitis C require a thorough clinical evaluation. There is a need for assessing factors that impact on the treatment schedule and duration or affect the pharmacokinetics of direct‐acting antivirals.
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Affiliation(s)
- Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Division of Internal Medicine and Hepatology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Lionel Piroth
- Infectious Diseases Department, University Hospital, INSERM, Dijon, France
| | - Sanjay Bhagani
- Department of Infectious Diseases/HIV Medicine, Royal Free London Foundation Trust, Research Department of Infection, UCL, London, UK
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19
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Colombo MG, Musabaev EI, Ismailov UY, Zaytsev IA, Nersesov AV, Anastasiy IA, Karpov IA, Golubovska OA, Kaliaskarova KS, AC R, Hadigal S. Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions. World J Gastroenterol 2019; 25:3897-3919. [PMID: 31413526 PMCID: PMC6689802 DOI: 10.3748/wjg.v25.i29.3897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 06/04/2019] [Accepted: 06/08/2019] [Indexed: 02/06/2023] Open
Abstract
Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of region-specific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.
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Affiliation(s)
- Massimo Giuseppe Colombo
- Research and Clinical Center, Department of Medicine, Humanitas Hospital, Rozzano 20089, MI, Italy
| | - Erkin Isakovich Musabaev
- Research Institute of Virology, Scientific Research Institute of Virology, Tashkent 100194, Uzbekistan
| | - Umed Yusupovich Ismailov
- Hepatoсenter, Research Institute of Virology, Scientific Research Institute of Virology, Tashkent 100194, Uzbekistan
| | - Igor A Zaytsev
- Department of Therapy, Infectious Diseases and Dermatology, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | - Alexander V Nersesov
- Department of Gastroenterology and Hepatology, National Research Institute of Cardiology and Internal Diseases, Almaty 050000, Kazakhstan
| | | | | | - Olga A Golubovska
- Department Infectious Diseases, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | | | - Ravishankar AC
- Medical Affairs, Mylan Pharmaceuticals Private Limited, Kadubeesanahalli, Bengaluru 560103, India
| | - Sanjay Hadigal
- Medical Affairs, Mylan Pharmaceuticals Private Limited, Kadubeesanahalli, Bengaluru 560103, India
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20
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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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21
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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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22
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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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23
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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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24
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Coffin CS, Fung SK, Alvarez F, Cooper CL, Doucette KE, Fournier C, Kelly E, Ko HH, Ma MM, Martin SR, Osiowy C, Ramji A, Tam E, Villeneuve JP. Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada. CANADIAN LIVER JOURNAL 2018; 1:156-217. [PMID: 35992619 PMCID: PMC9202759 DOI: 10.3138/canlivj.2018-0008] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 08/01/2023]
Abstract
Hepatitis B virus (HBV) infection is an important public health problem in Canada. In keeping with evolving evidence and understanding of HBV pathogenesis, the Canadian Association for the Study of Liver Disease periodically publishes HBV management guidelines. The goals of the 2018 guidelines are to (1) highlight the public health impact of HBV infection in Canada and the need to improve diagnosis and linkage to care, (2) recommend current best-practice guidelines for treatment of HBV, (3) summarize the key HBV laboratory diagnostic tests, and (4) review evidence on HBV management in special patient populations and include more detail on management of HBV in pediatric populations. An overview of novel HBV tests and therapies for HBV in development is provided to highlight the recent advances in HBV clinical research. The aim and scope of these guidelines are to serve as an up-to-date, comprehensive resource for Canadian health care providers in the management of HBV infection.
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Affiliation(s)
- Carla S. Coffin
- Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - Scott K. Fung
- Faculty of Medicine, University of Toronto, Toronto, Ontario
| | - Fernando Alvarez
- Centre hospitalier de l’université de Montréal (CHUM)—CHU Sainte-Justine, Montreal, Québec
| | - Curtis L. Cooper
- Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Karen E. Doucette
- Division of Infectious Diseases, University of Alberta, Edmonton, Alberta
| | - Claire Fournier
- Department of Medicine, Université de Montréal, Montreal, Québec
| | - Erin Kelly
- Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Hin Hin Ko
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia
| | - Mang M Ma
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta
| | | | - Carla Osiowy
- Viral Hepatitis and Bloodborne Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba
| | - Alnoor Ramji
- St. Paul’s Hospital, Vancouver, British Columbia
| | - Edward Tam
- LAIR Centre, Vancouver, British Columbia
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25
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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] [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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26
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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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27
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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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28
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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: 25] [Impact Index Per Article: 3.6] [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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29
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Blackard JT, Sherman KE. Hepatitis B virus (HBV) reactivation-The potential role of direct-acting agents for hepatitis C virus (HCV). Rev Med Virol 2018; 28:e1984. [PMID: 29761585 PMCID: PMC6233878 DOI: 10.1002/rmv.1984] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 04/04/2018] [Accepted: 04/05/2018] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus (HCV) is known to inhibit hepatitis B virus (HBV) replication in patients with HBV/HCV coinfection. Reactivation of HBV in patients treated for HCV with direct-acting agents (DAAs) has emerged recently as an important clinical consideration. A growing number of case reports and case series support the association between new HCV treatments and HBV reactivation. Yet, very little is known about the specific viral characteristics that facilitate reactivation as functional characterization of the reactivated HBV has been conducted only rarely. This review provides the most recent data on HBV reactivation in the context of DAA initiation and highlights the existing viral genomic data from reactivating viruses. Current functional studies of HBV reactivation are largely limited by the retrospective identification of cases, no standardization of genomic regions that are studied with respect to HBV reactivation, and the lack of inclusion of nonreactivating controls to establish specific viral mutations that are associated with HBV reactivation. Importantly, none of these sequencing studies included cases of HBV reactivation after initiation of DAAs. While new HCV treatments have revolutionized care for HCV infected patients, HBV reactivation will likely increase in frequency, as DAAs are more commonly prescribed. Pretreatment determination of HBV status and thoughtful management of HBV coinfections will be necessary and lead to improved patient safety and yield optimal treatment results.
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Affiliation(s)
- Jason T Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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30
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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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