Efficacy comparison of high-genetic barrier nucleos(t)ide analogues in treatment-naive chronic hepatitis B patients: a network meta-analysis

• Published in: The Korean journal of internal medicine Vol. 39; no. 4; pp. 577 - 603
• Main Authors: Jaejun Lee, Ahlim Lee, Pil Soo Sung, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Hyun Yang
• Format: Journal Article
• Language: Korean
• Published: 대한내과학회 31.07.2024
• Subjects: Biochemical response; Chronic hepatitis B; High-genetic barrier nucleos(t)ide analogue; Virologic response
• ISSN: 1226-3303; 2005-6648

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. Methods: 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-naive 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. 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). Conclusions: 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.