Comparative effectiveness and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in patients with HBV-associated decompensated cirrhosis: insights from a retrospective analysis.

backgroundHBV infection is a global health issue. Given the severity of decompensated cirrhosis, selecting the most appropriate first-line antiviral medication is crucial for optimizing treatment outcomes and providing the best possible disease control. This retrospective real-world study aimed to evaluate the comparative effectiveness and safety profiles of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in patients with hepatitis B virus (HBV)-related decompensated cirrhosis. We hypothesised that TAF is non-inferior to TDF for virologic response and superior for renal safety, with corresponding statistical tests to assess non-inferiority and superiority.

methodsPatients receiving TAF or TDF were categorized into respective groups based on their treatment regimen. The study spanned 48 weeks, during which the impact on HBV replication, liver enzyme levels, and renal function was assessed. Propensity score matching (PSM) was utilized to minimize disparities between TAF and TDF cohorts.

resultsAfter 48-week treatment, the percentage of patients with detectable HBV DNA significantly decreased from 27.9 to 13.1% (p = 0.044). HBeAg positivity remained stable, increasing slightly from 27.9 to 31.15% (p = 0.887). Mean ALT levels decreased slightly from 26 U/L to 25 U/L, with 85.25% of patients achieving normal ALT levels by week 48. TAF was well-tolerated with no significant impact on renal function, as indicated by stable serum creatinine and eGFR levels (eGFR decline ≥ 25% occurred in 5.2%). After PSM (propensity score matching), both groups showed virologic suppression, but TAF demonstrated superior renal safety: serum creatinine remained stable in TAF (P = 0.921) versus a trend toward increase in TDF (P = 0.831); eGFR significantly declined in TDF (103.58 → 99.05 mL/min/1.73 m²) but remained stable in TAF (101.88 → 101.86 mL/min/1.73 m²); clinically relevant eGFR decline (≥ 25%) was lower with TAF (5.2% vs. 10.5% in TDF). TAF also showed a higher rate of ALT normalization (71.1% → 81.6%, P < 0.05) compared to stable rates in TDF (84%). For liver fibrosis markers, APRI scores decreased non-significantly in TAF (P = 0.365) but increased in TDF (P = 0.763), while FIB-4 scores slightly decreased in TAF (P = 0.527) versus a non-significant increase in TDF. Child-Pugh scores remained minimally changed in both groups.

conclusionTAF appears to offer similar virologic response rates to TDF, with potentially superior renal safety. This study provides valuable insights into the management of HBV-related decompensated cirrhosis, advocating for TAF's consideration in treatment protocols.

trial registrationAll procedures were performed in accordance with the guidelines of the institutional ethics committee and adhered to the tenets of the Declaration of Helsinki. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University, China, which also waived the need for informed consent (approval number: KY2024-101). The registration date is April 24, 2024.