Morais Eleonora, Mason Lauren, Dever John, Martin Pam, Chen Jing Voon, Felton Leigh, Kendrick Stuart, Theodore Dickens, Gillespie Iain A
Epidemiology, Value Evidence & Outcomes, GSK, London, UK.
Pallas Health Research and Consultancy, Rotterdam, The Netherlands.
Gastro Hep Adv. 2023 Jun 30;2(7):992-1004. doi: 10.1016/j.gastha.2023.06.004. eCollection 2023.
Functional cure, which requires sustained hepatitis B surface antigen (HBsAg) loss after treatment cessation, is currently the optimal treatment endpoint for chronic hepatitis B virus infection. We performed a systematic literature review (SLR) and meta-analyses to assess the association between HBsAg loss and long-term clinical outcomes.
We performed a SLR of scientific literature published in Medline and Embase reporting the incidence of cirrhosis, hepatic decompensation (HD), hepatocellular carcinoma (HCC), liver-related mortality (LRM), and all-cause mortality (ACM) in relation to HBsAg status. Bayesian hierarchical commensurate prior meta-analyses synthesized evidence on the association between HBsAg loss and each outcome.
Thirty-eight studies, comprising 50,354 patients with 350,734 patient-years of follow-up, were included in the meta-analyses, reporting on cirrhosis (n = 12), HD (n = 12), HCC (n = 36), LRM (n = 12), and ACM (n = 16). Pooled incidence rate ratios (IRRs; vs HBsAg persistence) and respective credible intervals (Crls) were 0.28 (0.060-1.070) for cirrhosis, 0.13 (0.013-0.38) for HD, 0.27 (0.11-0.53) for HCC, 0.17 (0.028-0.61) for LRM, and 0.64 (0.24-1.17) for ACM. Single-predictor-adjusted IRRs remained consistent with those from the primary analyses for all outcomes except cirrhosis and LRM. Outcome incidence rates were modified by selected study, patient and infection characteristics, but trended in the same direction of reduced risk after loss.
Overall, HBsAg loss was associated with a reduced risk of most clinically relevant outcomes. While the magnitude of the effect differed across subgroups, the direction of the association remained similar. Our results validate the need to develop new strategies to achieve HBsAg loss.
功能性治愈要求在停止治疗后持续出现乙肝表面抗原（HBsAg）消失，目前是慢性乙型肝炎病毒感染的最佳治疗终点。我们进行了一项系统文献综述（SLR）和荟萃分析，以评估HBsAg消失与长期临床结局之间的关联。
我们对发表在Medline和Embase上的科学文献进行了SLR，报告了与HBsAg状态相关的肝硬化、肝失代偿（HD）、肝细胞癌（HCC）、肝脏相关死亡率（LRM）和全因死亡率（ACM）的发生率。贝叶斯分层相称先验荟萃分析综合了关于HBsAg消失与每种结局之间关联的证据。
荟萃分析纳入了38项研究，共50354例患者，随访时间达350734患者年，报告了肝硬化（n = 12）、HD（n = 12）、HCC（n = 36）、LRM（n = 12）和ACM（n = 16）。肝硬化的合并发病率比（IRR；与HBsAg持续存在相比）及各自的可信区间（Crl）为0.28（0.060 - 1.070），HD为0.13（0.013 - 0.38），HCC为0.27（0.11 - 0.53），LRM为0.17（0.028 - 0.61），ACM为0.64（0.24 - 1.17）。除肝硬化和LRM外，单预测因素调整后的IRR与主要分析结果一致。结局发生率因所选研究、患者和感染特征而有所改变，但在消失后风险降低的方向上呈相同趋势。
总体而言，HBsAg消失与大多数临床相关结局的风险降低相关。虽然不同亚组的效应大小有所不同，但关联方向保持相似。我们的结果证实了开发实现HBsAg消失新策略的必要性。
