乙型肝炎治疗在实现HBsAg血清清除方面的功效：系统评价和荟

StephenW

J Viral Hepat. 2020 Mar 14. doi: 10.1111/jvh.13283. [Epub ahead of print]
The efficacy of hepatitis B treatments in achieving HBsAgseroclearance: a systematic review and meta-analysis.
Fonseca MA1,2, Ling Zhi Jie J3, Al-Siyabi O4, Co-Tanko V5, Chan E6,7, Lim SG8,9.
Author information

1
    Hospital DivinaProvidência, Porto Alegre/RS, Brazil.
2
    Hospital Moinhos de Vento, PortoAlegre/RS, Brazil.
3
    Royal Melbourne Institute of Technology, Melbourne, Victoria, Australia.
4
    Division of Gastroenterology and Hepatology, Dept of Medicine, Royal Hospital, Oman, Oman Muscat.
5
    Division of Gastroenterology and Hepatology, Department of Medicine, UP-Philippine General Hospital, Manila, Philippines.
6
    Singapore Clinical Research Institute, Singapore, Singapore.
7
    Duke-NUS Medical School, Singapore.
8
    Division of Gastroenterology and Hepatology, Dept of Medicine, National University Health System, Singapore, Singapore.
9
    Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Abstract

Current therapies for Chronic Hepatitis B (CHB) include nucleos(t)ide analogues (NA) 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, APASL and AASLD forrandomized 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, interferon 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-followup(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 versus IFN, RD=1%, 95%CI-1%,2%; combination versus NA, RD=5%, 95%CI 3%,7%; IFN versus NA, RD=3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose versus non-standard; IFN duration≥48weeks versus <48 weeks, and loss of efficacy>2years of followup. Similar findings were seen in HBsAgseroconversion but only 3 studies reported HBsAgseroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48weeks of therapy, although this effect faded over time.

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KEYWORDS:

Chronic Hepatitis B; HBsAg loss; combination therapy; functional cure; interferon; nucleoside analogues

PMID:
    32170983
DOI:
    10.1111/jvh.13283

StephenW

J病毒性肝炎。 2020年3月14日。doi：10.1111 / jvh.13283。 [Epub提前发行]
乙型肝炎治疗在实现HBsAg血清清除方面的功效：系统评价和荟萃分析。
丰塞卡（Fonseca）MA1,2，凌志杰J3，Al-Siyabi O4，联合坦科V5，Chan E6,7，林SG8,9。
作者信息

1个
    巴西阿雷格里港/ RSDivinaProvidência医院。
2
    巴西PortoAlegre / RS的Moinhos de Vento医院。
3
    澳大利亚维多利亚州墨尔本皇家墨尔本理工学院。
4
    阿曼皇家医院医学部消化内科和肝病科，阿曼马斯喀特。
5
    菲律宾马尼拉UP菲律宾总医院医学科胃肠病和肝病科。
6
    新加坡临床研究所，新加坡，新加坡。
7
    新加坡国立杜克大学医学院。
8
    新加坡国立大学卫生系统医学系胃肠病和肝病学系。
9
    新加坡国立大学Yong Loo Lin医学院，新加坡。

抽象

当前的慢性乙型肝炎（CHB）疗法包括核苷酸类似物（NA）和干扰素（IFN），但尚未针对单药治疗或联合治疗HBsAg丢失（功能治愈）对其相对功效进行系统检查。因此，我们系统地回顾了接受IFN，NA或联合治疗的CHB患者的HBsAg丢失的证据。使用Cochrane偏倚风险工具v2.0和GRADE方法。根据NA遗传障碍，肝硬化，联合治疗类型，HBeAg，治疗天真的，干扰素剂量/持续时间和结果持续时间对分析进行分层。对选定的阶层进行了敏感性分析，并在研究结束（EOS），治疗结束（EOT）或随访结束（EOF）时测量了HBsAg的损失。使用随机效应模型将效应报告为具有95％置信区间（CI）的风险差异（RD）。纳入了45项研究，所有研究的偏倚风险均较低。对于在EOS时HBsAg损失，将联合治疗与IFN进行比较时，RD = 1％，95％CI-1％，2％；相对于NA，RD = 5％，95％CI 3％，7％; IFN相对于NA，RD ＝ 3％，95％CI 2％，5％。亚组分析显示标准干扰素剂量与非标准剂量相比有显着影响。 IFN持续时间≥48周而<48周，且疗效丧失> 2年随访。在HBsAg血清转化中也发现了类似的发现，但只有3项研究报道了HBsAg血清转化。总之，与标准剂量的IFN和≥48周的治疗相关，IFN单药/联合用药的HBsAg损失较NA轻度但显着增加，尽管这种作用随时间逐渐消失。

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关键字：

慢性乙型肝炎； HBsAg丢失；联合疗法功能性治疗干扰素核苷类似物

PMID：
    32170983
DOI：
    10.1111 / jvh.13283