Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: A randomized, open-label study

Abstract

A randomized, open-label comparative study of entecavir versus adefovir therapy was performed in subjects with chronic hepatitis B who had hepatic decompensation (Child-Turcotte-Pugh score !7). Adult subjects were randomized and treated (n 5 191) with entecavir 1.0 mg or adefovir 10 mg daily for up to 96 weeks from the date of last subject randomization. Subjects were positive or negative for hepatitis B e antigen and experienced or naive for treatment with nucleos(t)ide analogues. The primary efficacy endpoint was the mean reduction in serum hepatitis B virus (HBV) DNA, as determined by polymerase chain reaction, 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% confidence interval 22.30, 21.18]; P < 0.0001). The entecavir group showed a greater change from baseline in HBV DNA at all time points through week 48 and a higher proportion of subjects who 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 Child-Turcotte-Pugh status. Model for End-Stage Liver Disease score change at week 48 was 22.6 for entecavir and 21.7 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 a population of patients with chronic hepatitis B who had 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 treated with lamivudine. (HEPATOLOGY 2011;54:91-100) H epatic decompensation is a serious clinical complication associated with high mortality. The reported 5-year survival rate for patients with chronic hepatitis B (CHB) with decompensated cirrhosis is considerably lower than rates reported in patients with compensated cirrhosis (14%-35% versus 80%-86%, respectively). 1Studies have shown that interferon-a is contraindicated in this patient population.2,3 The majority of data on nucleos(t)ide analogue therapy in decompensated

Hepatitis B virus treatment: Which patients require immediate treatment

“…In a multinational study, 191 patients with decompensated cirrhosis (mean CTP score 8.8, Model for End-Stage Liver Disease [MELD] score 17.1) were treated with entecavir or adefovir for up to 96 weeks. 8 Although entecavir was more effective in viral suppression, both drugs caused improvement or stabilization in both scores.…”

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease

“…21 Another study compared ETV (1.0 mg) to ADV (10 mg/day) in decompensated CHB patients (34% with lamivudine resistance). 22 Preliminary results demonstrated ETV was superior to ADV with respect to reduction in HBV DNA, although overall 1-year patient survival rates were nearly identical (84% ETV, 83% ADV).…”

Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients With liver cirrhosis

“…16 In a randomized trial of 191 patients with decompensated cirrhosis, entecavir-treated patients tended to have lower incidence of HCC than those treated with adefovir at 48 weeks. 17 However, due to the short duration of follow-up, the difference between the two groups was uncertain, and some patients might have already harbored undiagnosed HCC before antiviral therapy. Moreover, the findings cannot be extrapolated to patients with milder disease.…”