Anderson Ryan T, Choi Hannah S J, Lenz Oliver, Peters Marion G, Janssen Harry L A, Mishra Poonam, Donaldson Eric, Westman Gabriel, Buchholz Stephanie, Miller Veronica, Hansen Bettina E
The Forum for Collaborative Research, University of California, Berkeley, California, School of Public Health, Washington, District of Columbia.
Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.
Clin Gastroenterol Hepatol. 2021 Mar;19(3):463-472. doi: 10.1016/j.cgh.2020.05.041. Epub 2020 May 27.
BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is the desired end point 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 the association between HBsAg seroclearance and long-term clinical outcomes.
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 evaluation. We performed a meta-analysis of rate ratios (RR) using a random-effects model independently for each end point and for a composite end point.
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 (PY) of follow-up evaluation; 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 PY for the HBsAg seroclearance group and 2.45/1000 PY for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 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 end point (95% CI, 0.23-0.43; P < .001). No differences in RR estimates were observed among subgroups of different study or patient characteristics.
In a systematic review and meta-analysis, we found seroclearance of HBsAg to be associated significantly 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 end point of trials of patients with chronic HBV infection.
根据指南，乙肝表面抗原（HBsAg）血清学清除是慢性乙型肝炎病毒（HBV）感染治疗的理想终点。我们进行了一项系统评价和荟萃分析，以评估HBsAg血清学清除与长期临床结局之间关联的强度。
我们对PubMed、EMBASE和Cochrane图书馆数据库进行了系统评价，查找评估HBsAg状态并报告随访评估期间肝细胞癌（HCC）、肝失代偿、肝移植和/或全因死亡率发生率的文章。我们对每个终点和一个复合终点分别使用随机效应模型对率比（RR）进行荟萃分析。
我们分析了28项研究的数据，这些研究共纳入188,316例慢性HBV感染患者（包括接受治疗和未接受治疗的患者），随访评估时间总计1,486,081人年（PY）；26项研究报告了HCC数据，7项报告了肝失代偿数据，13项报告了肝移植和/或死亡数据。HBsAg血清学清除组的复合事件发生率为0.19/1000 PY，HBsAg持续存在组为2.45/1000 PY。HBsAg血清学清除组肝失代偿的合并RR为0.28（95%CI，0.13 - 0.59；P = 0.001），HCC为0.30（合95%CI，0.20 - 0.44；P < 0.001），肝移植和/或死亡为0.22（95%CI，0.13 - 0.39；P < 0.001），复合终点为0.31（95%CI，0.23 - 0.43；P < 0.001）。在不同研究或患者特征的亚组中，RR估计值未观察到差异。
在一项系统评价和荟萃分析中，我们发现HBsAg血清学清除与患者预后改善显著相关。在所有检查的患者亚组中，不同类型研究的结果一致，支持将HBsAg血清学清除作为慢性HBV感染患者试验的主要终点。
