The second trial evaluated the therapy with a very potent antiviral drug: clevudine (previously called L-FMAU) combined with a WHsAg-based immunization [74, 109, 110] . A large cohort of thirty 1-2-year-old chronically WHVinfected woodchucks was enrolled in the study. Half of the animals were orally treated with clevudine (10 mg/kg/day) for 32 weeks; the other 15 woodchucks received placebo. After withdrawal of clevudine treatment, 8 animals from each group were vaccinated with the four doses of formalin inactivated alum-adsorbed WHsAg and 7 were injected with the saline as a control. Combination of the drug and vaccine therapy resulted in marked reductions WHV DNA (6-8 logs) and WHsAg in serum during the 60-week monitoring period, in contrast to the vaccine only and placebo groups, where both markers remained at high levels. Combination therapy did not enhanced anti-WHs responses beyond those measured for vaccine alone. However, treatment with clevudine and vaccine together led to more sustained and robust lymphoproliferative responses to WHsAg and additionally to WHcAg, WHeAg, and WHxAg. Moreover, combination therapy delayed the onset of the liver disease and prevented HCC development in up to 38% of treated chronic WHV carriers in the long-term follow-up study [111] .