The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Korean J Intern Med. 2024 Jul;39(4):577-589. doi: 10.3904/kjim.2023.311. Epub 2024 Jun 13.
BACKGROUND/AIMS: Four high-genetic barrier nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB), namely entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and besifovir dipivoxil maleate (BSV), have been established. The aim of this study is to investigate the efficacy of four high-genetic barrier NAs using a network meta-analysis of randomized trials and propensity score-matched cohorts.
Systematic search was performed using PubMed, Cochrane library, and EMBASE and included randomized controlled trials and cohort studies that used propensity score matching. Studies on treatment-naïve CHB patients treated with ETV, TDF, TAF, or BSV were included. Outcomes included alanine aminotransferase normalization and hepatitis B e antigen seroclearance at week 48 and undetectable hepatitis B virus DNA at weeks 48 and 96. Network meta-analysis was performed to synthesize the results.
In total, 15,000 patients from 16 studies were included. In terms of 48- and 96-week virologic response (VR), TDF outperformed ETV with statistical significance (48 weeks: odds ratio [OR], 1.38; p < 0.001; 96 weeks: OR, 1.57; p = 0.004). ETV was ranked first for 48-week biochemical response (BR) and outperformed TDF (OR, 0.76; p = 0.028). In the sensitivity analyses, 48-week VR from randomized-controlled trials were compiled, and the same trend toward the superiority of TDF over ETV was found (OR, 1.51; p = 0.030).
Four high-genetic barrier NAs were compared, and TDF was more likely to achieve a VR after 48 weeks, while ETV provided a superior BR after 48 weeks.
背景/目的：四种高遗传屏障核苷（酸）类似物（NAs），即恩替卡韦（ETV）、富马酸替诺福韦二吡呋酯（TDF）、替诺福韦艾拉酚胺（TAF）和马来酸贝福替诺福韦二吡呋酯（BSV），已被确立用于慢性乙型肝炎（CHB）的治疗。本研究旨在通过对随机试验和倾向评分匹配队列的网络荟萃分析，评估这四种高遗传屏障 NAs 的疗效。
通过PubMed、Cochrane 图书馆和 EMBASE 进行系统检索，纳入使用倾向评分匹配的随机对照试验和队列研究。研究对象为初治 CHB 患者，接受 ETV、TDF、TAF 或 BSV 治疗。主要结局为治疗 48 周时的丙氨酸氨基转移酶（ALT）复常和乙型肝炎 e 抗原（HBeAg）血清学清除，以及治疗 48 周和 96 周时的乙型肝炎病毒（HBV）DNA 不可检测。采用网络荟萃分析综合结果。
共纳入来自 16 项研究的 15000 例患者。在 48 周和 96 周的病毒学应答（VR）方面，TDF 优于 ETV，差异具有统计学意义（48 周：比值比[OR]，1.38；p<0.001；96 周：OR，1.57；p=0.004）。在 48 周的生化学应答（BR）方面，ETV 优于 TDF，排名第一（OR，0.76；p=0.028）。在敏感性分析中，综合了随机对照试验的 48 周 VR 结果，发现 TDF 仍优于 ETV（OR，1.51；p=0.030）。
本研究比较了四种高遗传屏障 NAs，结果显示 TDF 在 48 周时更有可能实现 VR，而 ETV 在 48 周时则具有更好的 BR。
