Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil in chronic hepatitis b: a systematic review and meta-analysis of randomized controlled trials

Abstract

BACKGROUND: In treating Chronic Hepatitis B (CHB), tenofovir disoproxil fumarate (TDF) carries risks like renal toxicity and reduced bone mineral density (BMD). TAF, the next-generation prodrug of TFV, is more stable in plasma than TDF, requires a significantly lower dose (25 mg vs. 300 mg), and results in approximately 90% lower plasma TFV levels, contributing to a more favorable renal and bone safety profile. This study aimed to evaluate the efficacy and safety of tenofovir alafenamide fumarate (TAF) compared to TDF in CHB. METHODS: We conducted a search on PubMed, Google Scholar, and the Cochrane Library. Only four RCTs that studied the comparison of efficacy and safety of TAF and TDF in treating CHB were included. The Primary outcome of interest was the proportion of patients with Hepatitis B virus (HBV) DNA below 15-29 IU/ml as all the RCT's included in this study report the same HBV DNA levels. We used a random-effects model to calculate the Risk Ratio (RR) and Mean Difference (MD) with 95% CI. RESULTS: This meta-analysis includes four eligible RCTs including 1,960 total patients. The comparison between TAF and TDF groups regarding HBV DNA level revealed no significant difference (RR = 1.00, 95% CI = 0.96 to 1.05; P = 0.82). Pooled data showed beneficial effects of TAF compared with TDF for ALT Normalization (RR = 1.38; 95% CI = 1.16 TO 1.64; p = 0.0002), Hip BMD (MD = 1.44, 95% CI = 0.98 to 1.91; P ‹ 0.00001), Spine BMD (MD = 1.93, 95% CI = 1.42 to 2.44; P ‹ 0.00001), serum creatinine concentration (MD= -0.02, 95% CI=-0.03 to -0.01; P ‹ 0.00001) and eGFR (MD = 3.55, 95% CI = 2.97 to 4.14; P ‹ 0.00001). However, the TAF group showed a significantly greater proportion of patients (46/1080 vs. 5/662) with LDL levels > 190 or 300 mg/dl than the TDF group (RR = 4.95, 95% CI = 1.21 to 20.29; P = 0.03). CONCLUSION: The TAF demonstrated improved BMD and renal function compared to TDF. There was no significant difference between TAF and TDF in achieving viral suppression. CLINICAL TRIAL NUMBER: This was a systematic review and meta-analysis not a clinical trial. STUDY REGISTRATION: This systematic review and meta-analysis is registered at PROSPERO (CRD42023456006).