Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection

Entecavir (ETV) is a guanosine nucleoside analogue with potent antiviral ef ficacy in woodchucks chronically infected with woodchuck hepatitis virus. T o explore the consequences of prolonged virus suppression, woodchucks recei ved ETV orally for 8 weeks and then weekly for 12 months. Of the 6 animals withdrawn from therapy and monitored for an additional 28 months, 3 had a s ustained antiviral response and had no evidence of hepatocellular carcinoma (HCC). Of the 6 animals that continued on a weekly ETV regimen for an addi tional 22 months, 4 exhibited serum viral DNA levels near the lower limit o f detection for >2 years and had no evidence of HCC. Viral antigens and cov alently closed circular DNA levels in liver samples were significantly redu ced in all animals. ETV was well tolerated, and there was no evidence of re sistant variants. On the basis of historical data, long-term ETV treatment appeared to significantly prolong the life of treated animals and delay the emergence of HCC.