The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown.

Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling, may improve the effectiveness of TACE when given as an adjuvant to TACE. In this multinational, randomized, double-blind, placebo-controlled, phase III study, 870 patients with TACE-eligible HCC were planned to be randomly assigned (1:1) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily. The primary endpoint was overall survival (OS). Secondary endpoints included time to disease progression (TTDP; a composite endpoint based on development of extrahepatic spread or vascular invasion, deterioration of liver function or performance status, or death), time to extrahepatic spread or vascular invasion (TTES/VI), rate of TACE, and safety. Time to radiographic progression (TTP) and objective response rate were exploratory endpoints. The trial was terminated after randomization of 502 patients (brivanib, 249; placebo, 253) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives. At termination, median follow-up was approximately 16 months. Intention-to-treat analysis showed no improvement in OS with brivanib versus placebo (median, 26.4 [95% confidence interval {CI}: 19.1 to not reached] vs. 26.1 months [19.0-30.9]; hazard ratio [HR]: 0.90 [95% CI: 0.66-1.23]; log-rank P = 0.5280). Brivanib improved TTES/VI (HR, 0.64 [95% CI: 0.45-0.90]), TTP (0.61 [0.48-0.77]), and rate of TACE (0.72 [0.61-0.86]), but not TTDP (0.94 [0.72-1.22]) versus placebo. Most frequent grade 3-4 adverse events included hyponatremia (brivanib, 18% vs. placebo, 5%) and hypertension (13% vs. 3%). Conclusions : In this study, brivanib as adjuvant therapy to TACE did not improve OS. (Hepatology 2014;60:1697–1707)

: 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 = 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 log₁₀ copies/mL [95% confidence interval −2.30, −1.18]; 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 −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 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;)