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Management of Chronic Hepatitis B
Evidence Reports/Technology Assessments, No. 174
Investigators: Timothy J Wilt, MD, MPH, Tatyana Shamliyan, MD, MS, Aasma Shaukat, MD, Brent C Taylor, PhD, MPH, Roderick MacDonald, MS, Jian-Min Yuan, MD, PhD, James R Johnson, MD, James Tacklind, BS, Indulis Rutks, BS, and Robert L Kane, MD.
Structured Abstract
Objectives:
Synthesize evidence of the natural history of chronic hepatitis B (CHB) and effects and harms of antiviral drugs on clinical, virological, histological, and biochemical outcomes.
Data Sources:
MEDLINE®, electronic databases, and manual searches of systematic reviews.
Review Methods:
We included original observational studies to assess natural history and randomized controlled trials (RCTs) of adults with CHB published in English to assess treatment effects and harms if they reported mortality, incidence of hepato-cellular carcinoma (HCC), cirrhosis or failure, HBeAg or HBsAg, viral load (HBV DNA), alanine aminotransferase (ALT) levels, histological necroinflammatory and fibrosis scores, and adverse events after interferon alfa-2b, pegylated interferon alfa 2-a, lamivudine, adefovir, entecavir, tenovir or telbivudine. We excluded pregnant women, transplant patients, and individuals undergoing cancer chemotherapy. We calculated relative risk or absolute risk differences at end of treatment and post-treatment.
Results:
Observational studies (41 publications) suggested that male gender, coinfection with hepatitis C, D, or HIV, increased HBV DNA, and cirrhosis were associated with increased risk of HCC and death. Drugs did not reduce death, liver failure, or HCC in 16 RCTs not designed to test long-term clinical outcomes. Evidence from 93 publications of 60 RCTs suggested drug effects on viral load or replication, liver enzymes, and histology at end of treatment and lasting from <3 to >6 months off treatment. No one treatment improved all outcomes and there was limited evidence on comparative effects. Two RCTs suggested interferon alfa-2b increased CHB resolution versus placebo. Interferon alfa-2b or lamivudine improved off treatment HBV DNA and HBeAg clearance and seroconversion and ALT normalization. Adefovir improved off treatment ALT normalization and HBV DNA clearance. Pegylated interferon alfa 2-a versus lamivudine improved off-treatment HBV DNA and HBeAg clearance and seroconversion, ALT normalization and liver histology. Lamivudine combined with interferon alfa-2b versus lamivudine improved off treatment HBV DNA clearance and HBeAg seroconversion and reduced HBV DNA mutations. Pegylated interferon alfa 2-a plus lamivudine improved off treatment HBV DNA and HBeAg clearance and seroconversion and ALT normalization compared to lamivudine but not pegylated interferon alfa 2-a monotherapy. Adverse events were common but generally mild and did not result in increased treatment discontinuation. Longer hepatitis duration, male gender, baseline viral load and genotype, HBeAg, and histological status may modify treatment effect on intermediate outcomes. Adefovir and pegylated interferon alfa 2-a with lamivudine improved off treatment viral clearance in HBeAg negative patients. There was insufficient evidence to determine if biochemical, viral, or histological measures are valid surrogates of treatment effect on mortality, liver failure, or cancer.
Conclusion:
Adults with CHB have an increased risk of death, hepatic decompensation, and HCC. Mono or combined drug therapy improves selected virological, biochemical, and histological markers with no consistent effects on all examined outcomes. Patient and disease characteristics may modify treatment-induced intermediate outcomes. Evidence was insufficient to assess treatment effect on clinical outcomes, predict individualized patient response, or determine if intermediate measures are reliable surrogates. Future research should assess long-term drug effects on clinical outcomes and among patient subpopulations.
Contents
- Preface
- Acknowledgments
- Executive Summary
- 1. Introduction
- 2. Methods
- 3. Results
- Consensus Conference Question 1 What is the Natural History of Hepatitis B?
- Consensus Conference Question 2 What are the Benefits and Risks of the Current Therapeutic Options for Hepatitis B with Defined or Continuous Courses of Treatment?
- Consensus Conference Question 3 Which Persons With Hepatitis B Should be Treated?
- Consensus Conference Question 4 What Measures are Appropriate to Monitor Therapy and Assess Outcomes?
- 4. Discussion
- List of Acronyms and Abbreviations
- Appendixes
- References and Included Studies
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-02-0009. Prepared by: Minnesota Evidence-based Practice Center, Minneapolis, Minnesota.
Suggested citation:
Wilt TJ, Shamliyan T, Shaukat A, Taylor BC, MacDonald R, Yuan J-M, Johnson JR, Tacklind J, Rutks I, Kane RL. Management of Chronic Hepatitis B. Evidence Report/Technology Assessment No. 174. (Prepared by the Minnesota Evidence-based Practice Center under Contract No. 290-02-0009.) AHRQ Publication No. 09-E002. Rockville, MD. Agency for Healthcare Research and Quality. October 2008.
This report is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0009). The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.
This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
No investigators have any affiliations or financial involvement (e.g., employment, consultancies, honoraria, stock options, expert testimony, grants or patents received or pending, or royalties) that conflict with material presented in this report.
- 1
540 Gaither Road, Rockville, MD 20850. www
.ahrq.gov
- Review Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic hepatitis B: a systematic review and economic evaluation.[Health Technol Assess. 2006]Review Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic hepatitis B: a systematic review and economic evaluation.Shepherd J, Jones J, Takeda A, Davidson P, Price A. Health Technol Assess. 2006 Aug; 10(28):iii-iv, xi-xiv, 1-183.
- Review Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference.[Ann Intern Med. 2009]Review Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference.Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan JM, Johnson JR, Tacklind J, Rutks I, Kane RL, Wilt TJ. Ann Intern Med. 2009 Jan 20; 150(2):111-24. Epub 2009 Jan 5.
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- [Clinical efficacy of various antiviral-based strategies to treat chronic hepatitis patients with positivity for hepatitis B e antigen and rtN236T mutation].[Zhonghua Gan Zang Bing Za Zhi....][Clinical efficacy of various antiviral-based strategies to treat chronic hepatitis patients with positivity for hepatitis B e antigen and rtN236T mutation].Yue W, Yuan H, Mao XR, Deng YD, Chen L. Zhonghua Gan Zang Bing Za Zhi. 2013 Mar; 21(3):184-8.
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- RecName: Full=Thiosulfate sulfurtransferase/rhodanese-like domain-containing pro...RecName: Full=Thiosulfate sulfurtransferase/rhodanese-like domain-containing protein 3; AltName: Full=Rhodanese domain-containing protein 3gi|408407548|sp|H0UI37.1|TSTD3_HUMAProtein
- RecName: Full=Large ribosomal subunit protein uL13m; AltName: Full=39S ribosomal...RecName: Full=Large ribosomal subunit protein uL13m; AltName: Full=39S ribosomal protein L13, mitochondrial; Short=L13mt; Short=MRP-L13gi|22257023|sp|Q9BYD1.1|RM13_HUMANProtein
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