Abstract

A randomized, open-label comparative study of entecavir versus adefovir therapy was performed in chronic hepatitis B (CHB) subjects with hepatic decompensation (Child-Turcotte-Pugh [CTP] score ≥7). Adult subjects were randomized and treated (n=191) with entecavir 1.0 mg or adefovir 10 mg daily for up to 96 weeks from the date of last subject randomization. Subjects were hepatitis B e antigen-positive or -negative, and nucleos(t)ide analog naïve or lamivudine experienced. The primary efficacy endpoint was the mean reduction in serum hepatitis B virus (HBV) DNA by PCR at Week 24, adjusted for baseline HBV DNA and lamivudine resistance status, by linear regression analysis. Entecavir demonstrated superiority to adefovir for this endpoint (treatment difference 1.74 log(10) copies/mL [95% CI -2.30, -1.18]; p<0.0001). The entecavir group showed a greater change from baseline in HBV DNA at all timepoints through Week 48 and higher proportion of subjects that achieved HBV DNA <300 copies/mL at Weeks 24 (entecavir 49%; adefovir 16%; p<0.0001) and 48 (entecavir 57%; adefovir 20%; p<0.0001). Approximately two-thirds of subjects in both groups showed improvement/stabilization in CTP status. Model for End-Stage Liver Disease score change at Week 48 was -2.6 for entecavir and -1.7 for adefovir. Adverse event rates were comparable between groups. Cumulative hepatocellular carcinoma rates were 12% for entecavir and 20% for adefovir. Cumulative death rates were 23% for entecavir and 33% for adefovir. Week 24 mortality rates were 12% for both groups. Conclusion: Entecavir demonstrated superior virologic efficacy to adefovir in CHB population with hepatic decompensation. Biochemical and clinical benefits were also demonstrated. Entecavir was well tolerated and early mortality rates were consistent with rates observed in similar populations with lamivudine.