Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic HBV Infection: Systematic Review and Meta-analysis
Ryan T. Anderson, MS, MPH
Senior Research Associate, The Forum for Collaborative Research, University of California, Berkeley, School of Public Health, Washington, District of Columbia
Hannah S.J. Choi, MS
Graduate Student, Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
Oliver Lenz, PhD
Scientific Director, Janssen Research and Development, Antwerp, Belgium
Marion G. Peters, MD
AIDS Clinical Trial Group, Chicago Illinois
Harry L.A. Janssen, MD, PhD
Program Director, Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
Poonam Mishra, MD, MPH
Deputy Division Director for Safety, US Food and Drug Administration, Silver Spring, Maryland
Eric Donaldson, PhD
Clinical Virology Reviewer, US Food and Drug Administration, Silver Spring, Maryland
Gabriel Westman, MD, PhD
Senior Clinical Assessor, Swedish Medical Products Agency, Uppsala, Sweden; Researcher, Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden
Stephanie Buchholz, Dr rer nat
Clinical Assessor, Federal Institute for Drugs and Medical Devices, Bonn, Germany
Veronica Miller, PhD
Executive Director, The Forum for Collaborative Research, University of California, Berkeley, School of Public Health, Washington, District of Columbia
Bettina E. Hansen, PhD, MSc∗,'Correspondence information about the author PhD, MSc Bettina E. HansenEmail the author PhD, MSc Bettina E. Hansen
Senior Biostatistician, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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Abstract
Abstract
Background & Aims
Seroclearance of hepatitis B surface antigen (HBsAg) is the desired endpoint of treatment for chronic hepatitis B virus (HBV) infection, according to guidelines. We performed a systematic review and meta-analysis to evaluate the strength of association between HBsAg seroclearance and long-term clinical outcomes.
Methods
We performed a systematic review of the PubMed, EMBASE, and Cochrane Library databases for articles that assessed HBsAg status and reported the incidence of hepatocellular carcinoma (HCC), liver decompensation, liver transplantation, and/or all-cause mortality during follow up. We performed a meta-analysis of rate ratios (RR) using a random effects model independently for each endpoint and for a composite endpoint.
Results
We analyzed data from 28 studies, comprising a total of 188,316 patients with chronic HBV infection (treated and untreated), and 1,486,081 person-years (P-Y) of follow up; 26 reported data on HCC, 7 on liver decompensation, and 13 on liver transplantation and/or death. The composite event rates were 0.19/1000 P-Y for the HBsAg seroclearance group and 2.45/1000 P-Y for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 for liver decompensation for liver decompensation (95% CI, 0.13–0.59; P=.001), 0.30 for HCC (95% CI, 0.20–0.44; P<.001), 0.22 for liver transplantation and/or death (95% CI, 0.13–0.39; P<.001), and 0.31 for the composite endpoint (95% CI, 0.23–0.43; 95% CI, .023–0.43; P<.001). No differences in RR estimates were observed among subgroups of different study or patient characteristics.
Conclusions
In a systematic review and meta-analysis, we found seroclearance of HBsAg to be significantly associated with improved patient outcomes. The results are consistent among different types of studies, in all patient subpopulations examined, and support the use of HBsAg seroclearance as a primary endpoint of trials of patients with chronic HBV infection.
Keywords:
viral hepatitis, long-term outcomes, primary endpoint, HBsAg作者: StephenW 时间: 2020-5-29 10:32