BESIFOVIR DIPIVOXIL MALEATE VS. TENOFOVIR ALAFENAMIDE FOR TREATMENT-NAIVE CHRONIC HEPATITIS B: A REAL-WORLD COHORT STUDY

초록

Background: Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as primary drugs for chronic hepatitis B (CHB). These drugs showed equivalent efficacy and fewer side effects compared to entecavir and tenofovir disoproxil fumarate in previous clinical trials. However, outcomes of these drugs from real-world data have not yet been fully elucidated. We conducted a non-inferiority analysis using real-world data to compare the clinical outcomes of two nucleotide analogues in treatment-naïve CHB patients. Methods: We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The outcomes included achievement of virological and biochemical responses, hepatitis B e antigen (HBeAg) seroclearance, change of hepatitis B s antigen (HBsAg) titer, virologic breakthrough, the episodes of kidney injury and hypophosphatemia, the development of hepatocellular carcinoma (HCC), and death. In addition, to reduce selection bias and the effect of potential confounders, we performed propensity score (PS) matching based on age, sex, cirrhosis status, HBeAg status, hepatitis B virus (HBV) DNA level, platelet count, total bilirubin level, albumin level, and prothrombin time. Results: A total of 537 patients who consisted of 202 and 335 patients administered BSV and TAF, respectively, were followed-up to 42 months. The baseline characteristics were not significantly different between the two treatment groups. In terms of the outcomes, there was no significant differences between the two groups (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.81–1.25) in the rates of virological response. Two drugs also showed similar efficacies in achieving biochemical response, hepatitis B e antigen seroclearance. During follow-up, there was no virologic breakthrough and acute kidney injury. Episodes of hypophosphatemia were experienced only 6 patients with TAF, but difference was not significant. There were no significant difference in HCC development (HR 0.74, 95% CI 0.20–2.72) and mortality (HR 0.45, 95% CI 0.03–7.35). In the multivariable analysis, older age (adjusted HR [aHR] 1.10, 95% CI 1.03–1.18), alcohol abuse (aHR 7.95, 95% CI 1.69–37.5), and the presence of cirrhosis (aHR 12.1, 95% CI 1.44–101.8) were independently associated with an increased risk of HCC. These results were consistent even in the 1:1 propensity score-matched cohorts with 200 pairs and various subgroup analyses according to status of HBeAg, cirrhosis, HBV DNA levels. In addition, the matched cohort showed the VR rate of 97.0% and 91.5% in the BSV and TAF groups at 2 years; the absolute value of 95% CI of difference (0.00–0.11) satisfied the priori limit of a non-inferiority of 0.15. Conclusion: BSV is non-inferior to TAF for VR and their clinical outcomes are comparable.