Summary
Background
Spontaneous loss of HBsAg (known as functional cure) in patients with chronic hepatitis B virus (HBV) infection significantly reduces liver-related complications. HBsAg loss has been suggested to be higher in non-endemic regions than in endemic regions in individual studies. We systematically determined a pooled annual rate of HBsAg loss in adults with untreated chronic HBV infection and examined the effect of regional endemicity.
Methods
In this systematic review and meta-analysis, we searched PubMed and Embase for observational cohort studies and non-treatment arms of randomised controlled trials reporting proportions of patients with chronic HBV infection that achieved spontaneous HBsAg loss, published up to Oct 1, 2018. We excluded randomised controlled trials from meta-analyses because of substantial cohort differences. Two reviewers (KZ and CC) independently extracted data from accepted full-text studies, with discrepancies discussed with a third reviewer (NT). We assessed rate of HBsAg loss, and stratified results by whether the underlying cohort arose primarily from an endemic region (defined as having prevalence of chronic HBV greater than 2%) or non-endemic region. This study is registered with PROSPERO, number CRD42018074086.
Findings
Of 5186 studies screened, 67 (11 randomised controlled trials, 39 prospective and 17 retrospective cohort studies) met the inclusion criteria and 56 were included in meta-analyses after exclusion of randomised controlled trials. Spontaneous HBsAg loss occurred in 3837 (7·8%) of 48 972 patients, with cumulative 352 381 person-years of follow-up. The pooled annual incidence of HBsAg loss was 1·17% (95% CI 0·94–1·41, I2=97%). Rates did not differ by endemicity: 1·19% (0·88–1·54) in endemic versus 1·29% (0·99–1·62) in non-endemic cohorts.
Interpretation
Globally, spontaneous HBsAg loss occurs infrequently (about 1% per year) in treatment-naive adults with chronic HBV infection. The low and homogeneous rate of HBsAg loss highlights the need for new therapeutics aimed at achieving functional cure across different patient groups and geographical regions.
Funding
NIH National Institute of Diabetes and Digestive and Kidney Diseases.作者: StephenW 时间: 2019-2-5 15:39
慢性乙型肝炎病毒感染成人中表面抗原的自发丧失:系统评价和汇总的荟萃分析
Kali Zhou,医学博士
Caitlin Contag,MD
医学博士Evans Whitaker
医学博士Norah Terrault教授