目的：比较七种主要干预措施的有效性[Bulevirtide（BLV），干扰素（IFN），核苷类似物(NAs),BLV+IFN，BLV+NA,IFN+NAs，和安慰剂]治疗慢性D型肝炎。
方法：我们遵循PRISMA-NMA指南，搜索数据库(Cochrane图书馆，PubMed,EMBASE,和WebOfScience）用于符合条件的随机对照试验（RCT），并应用STATA17.0软件进行Meta分析。
结果：我们纳入了14项随机对照试验（814例患者），比较了7种不同的干预措施。网络荟萃分析结果显示:①持续病毒学应答(随访24周后):4个干预组(BLV+IFN,单独使用IFN，IFN+NAs，和单独的NA)是有效的(相对风险(RR)=13.30，95%置信区间(Cl)[1.68,105.32]，RR=12.13，95%Cl[1.46,101.04]，RR=5.05,95%Cl[1.68,15.19],RR=5.03，95%Cl[1.66,15.20])，四组之间无统计学差异。概率排名前三的是：BLV+NA，BLV+IFN，和单独的BLV(累积排序曲线下的表面(SUCRA)=86.8%，80.3%,和48.4％；②持续的生化反应（随访24周后）：BLVIFN和IFN优于BLV（RR=14.71，95％Cl[1.14，189.07]，RR=16.67,95%Cl[1.39,199.52])。前三名是BLV，BLV+NA,和BLV+IFN(SUCRA=86.9%，81.2%,和64.3%）。③组织学反应:NAs优于BLV(RR=2.08,95%Cl[1.10,3.93]),而其他治疗方案之间的差异无统计学意义，概率排名前三名是BLV，BLV+NA,和BLV+IFN(SUCRA=75.6%，75.6%,和61.8%）。
结论：IFN，IFN+BLV，IFN+NAs可有效清除HDVRNA并使丙氨酸转氨酶水平正常化；然而，IFN和IFN+NA在治疗后随访24周具有高的病毒复发率。在慢性丁型肝炎的IFN治疗中加入NA没有额外的益处;然而，IFN+BLV的组合显着提高短期HDVRNA清除，表现出很强的协同作用。研究中包括的七个方案对肝脏组织学改善没有显着贡献。因此,IFN+BLV联合疗法作为改善长期预后甚至治愈慢性D型肝炎的治疗选择最有潜力。
背景：这项系统评估和荟萃分析已在PROSPERO注册，注册号：CRD42022314544。).
OBJECTIVE: To compare the effectiveness of seven major interventions [
Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV + IFN, BLV + NAs, IFN + NAs, and Placebo] to treat chronic hepatitis D.
METHODS: We followed PRISMA-NMA guidelines, searched databases (Cochrane Library, PubMed, EMBASE, and Web Of Science) for eligible randomized controlled trials (RCTs), and applied STATA17.0 software to execute the meta-analysis.
RESULTS: We included 14 randomized controlled trials (814 patients) comparing seven different interventions. The results of the network meta-analysis showed that: ① Sustained virological response (after 24 weeks of follow-up): Four intervention groups (BLV + IFN, IFN alone, IFN + NAs, and NAs alone) were effective (relative risk (RR) = 13.30, 95% confidence interval (Cl) [1.68,105.32], RR = 12.13, 95% Cl [1.46,101.04], RR = 5.05, 95% Cl [1.68,15.19], RR = 5.03, 95% Cl [1.66,15.20]), with no statistically significant differences between the four groups. The top three in probability rankings were: BLV + NAs, BLV + IFN, and BLV alone (surface under the cumulative ranking curve (SUCRA) = 86.8%, 80.3%, and 48.4%; ② Sustained biochemical response (after 24 weeks of follow-up): BLV + IFN and IFN were superior to BLV (RR = 14.71, 95% Cl [1.14,189.07], RR = 16.67, 95% Cl [1.39,199.52]). The top three were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 86.9%,81.2%, and 64.3%). ③ Histological response: NAs were superior to BLV (RR = 2.08, 95% Cl [1.10,3.93]), whereas the difference between other treatment regimens was not statistically significant, and the top three in the probability ranking were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 75.6%, 75.6%, and 61.8%).
CONCLUSIONS: IFN, IFN + BLV, and IFN + NAs were effective in clearing HDV RNA and normalizing alanine aminotransferase levels; however, IFN and IFN + NAs had a high rate of viral relapse at 24 weeks post-treatment follow-up. There was no additional benefit of adding NAs to IFN therapy for chronic hepatitis D; however, the combination of IFN + BLV significantly improved short-term HDV RNA clearance, which showed strong synergistic effects. The seven regimens included in the study did not contribute significantly to liver histological improvement. Therefore, the IFN + BLV combination has the most potential as a treatment option to improve the long-term prognosis or even cure chronic hepatitis D.
BACKGROUND: This systematic evaluation and meta-analysis was registered with PROSPERO under the registration number: CRD42022314544.).
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