Hospital DivinaProvidência, Porto Alegre, Brazil.
Hospital Moinhos de Vento, Porto Alegre, Brazil.
J Viral Hepat. 2020 Jul;27(7):650-662. doi: 10.1111/jvh.13283. Epub 2020 Mar 23.
Current therapies for chronic hepatitis B (CHB) include nucleos(t)ide analogues (NAs) and interferon (IFN), but their relative efficacy as monotherapy or in combination has not been examined systematically for HBsAg loss (functional cure). Hence, we systematically reviewed the evidence for HBsAg loss in CHB patients treated with IFN, NA or the combination. We searched PubMed, EMBASE and abstracts from EASL, Asia Pacific Association for study of the Liver and American Association for the Study of Liver Disease for randomized controlled trials of CHB patients, comparing NA, IFN or the combination. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by NA genetic barrier, cirrhosis, type of combination therapy, HBeAg, treatment naivety, IFN dosage/duration and outcome duration. Sensitivity analysis was performed for selected strata, and HBsAg loss was measured at the end-of-study (EOS), end-of-treatment (EOT) or end-of-follow-up (EOF). Effects were reported as risk differences (RD) with 95% confidence intervals (CI) using a random-effects model. Forty-five studies were included, all with low risk of bias. For HBsAg loss at EOS, when comparing combination vs IFN, RD = 1%, 95%CI-1%, 2%; combination vs NA, RD = 5%, 95%CI 3%,7%; IFN vs NA, RD = 3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose vs nonstandard; IFN duration ≥48 weeks vs <48 weeks, and loss of efficacy >2 years of follow-up. Similar findings were seen in HBsAg seroconversion, but only three studies reported HBsAg seroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48 weeks of therapy, although this effect faded over time.
目前治疗慢性乙型肝炎（CHB）的方法包括核苷（酸）类似物（NAs）和干扰素（IFN），但它们作为单药或联合治疗的相对疗效尚未系统地评估过 HBsAg 丢失（功能性治愈）。因此，我们系统地回顾了 IFN、NA 或联合治疗 CHB 患者的 HBsAg 丢失的证据。我们检索了 PubMed、EMBASE 和 EASL、亚太肝病研究协会和美国肝病研究协会的会议摘要，以查找比较 NA、IFN 或联合治疗的 CHB 患者的随机对照试验。使用 Cochrane 偏倚风险工具 v2.0 和 GRADE 方法。分析按 NA 遗传屏障、肝硬化、联合治疗类型、HBeAg、治疗初治、IFN 剂量/持续时间和结局持续时间进行分层。对选定的分层进行了敏感性分析，并在研究结束时（EOS）、治疗结束时（EOT）或随访结束时（EOF）测量 HBsAg 丢失。使用随机效应模型，以风险差异（RD）和 95%置信区间（CI）报告效应。纳入了 45 项研究，所有研究的偏倚风险均较低。在 EOS 时比较联合治疗与 IFN，RD=1%，95%CI-1%，2%；联合治疗与 NA，RD=5%，95%CI 3%，7%；IFN 与 NA，RD=3%，95%CI 2%，5%。亚组分析显示标准 IFN 剂量与非标准 IFN 剂量、IFN 持续时间≥48 周与<48 周以及疗效丧失>2 年随访之间存在显著差异。HBsAg 血清学转换也有类似发现，但只有三项研究报告了 HBsAg 血清学转换。总之，与 NA 相比，IFN 单药/联合治疗可使 HBsAg 丢失率略有增加，但有统计学意义，与 IFN 标准剂量和≥48 周的治疗有关，尽管这种效果随时间推移而减弱。
