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

StephenW

Spontaneous loss of surface antigen among adults living with chronic hepatitis B virus infection: a systematic review and pooled meta-analyses

    Kali Zhou, MD
    Caitlin Contag, MD
    Evans Whitaker, MD
    Prof Norah Terrault, MD

DOI:https://doi.org/10.1016/S2468-1253(18)30308-X

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.

StephenW

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

DOI：HTTPS：//doi.org/10.1016/S2468-1253（18）30308-X

摘要
背景
慢性乙型肝炎病毒（HBV）感染患者HBsAg的自发丧失（称为功能性治疗）可显着降低肝脏相关并发症。在个别研究中，非流行区域的HBsAg丢失被认为高于流行区域。我们系统地确定了未经治疗的慢性HBV感染的成人每年HBsAg损失的汇总率，并检查了区域流行的影响。
方法
在这项系统评价和荟萃分析中，我们搜索PubMed和Embase进行观察性队列研究和随机对照试验的非治疗组，报告2018年10月1日发表的慢性HBV感染患者自发性HBsAg消失的比例。由于实质性队列差异，从荟萃分析中排除了随机对照试验。两名评审员（KZ和CC）独立从已接受的全文研究中提取数据，与第三名评审员（NT）讨论了差异。我们评估了HBsAg丢失的发生率，并根据潜在的队列是否主要来自流行区（定义为慢性HBV的患病率大于2％）或非流行区来分层结果。本研究在PROSPERO注册，编号为CRD42018074086。
发现
在筛选的5186项研究中，67项（11项随机对照试验，39项前瞻性研究和17项回顾性队列研究）符合纳入标准，56项纳入荟萃分析后排除随机对照试验。 48 972例患者中3837例（7·8％）发生自发性HBsAg丢失，累计352 381人年随访。汇总的HBsAg年死亡率为1.17％（95％CI 0·94-1·41，I2 = 97％）。流行率没有差异：地方性流行率为1·19％（0·88-1·54），非流行性群体为1·29％（0·99-1·62）。
解释
在全球范围内，慢性HBV感染的初治成人中很少发生自发性HBsAg丢失（每年约1％）。 HBsAg损失率低且均匀，突出了针对不同患者群体和地理区域实现功能性治愈的新疗法的需求。
资金
NIH国家糖尿病与消化和肾脏疾病研究所。

StephenW

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