The studies summarized in this chapter demonstrate that the WHV/wood-chuck model of experimental chronic hepatitis infection can be applied to the analysis of aspects of the natural history of HDV infection, the development of HDV vaccine strategies, and therapeutic studies of chronic HDV superinfection. The relatively rapid progression to hepatocellular carcinoma in WHV-infected woodchucks does pose challenges for the use of this model for evaluating drug efficacy against chronic HDV disease. Further, HDV infection appears to increase the risk of hepatocellular carcinoma in patients with compensated cirrhosis type B (Fattovich et al. 2000) and the influence of chronic HDV on progression of end-stage liver disease in the woodchuck model has not been established. Indeed, many of the woodchucks in the clevudine study progressed to hepatocellular carcinoma, which precluded post-treatment follow-up studies. Perhaps these limitations can be overcome by the use of younger WHV-carrier animals or use of less virulent WHV strains. Clearly, further studies of the natural history of HDV disease in this model are needed before many important therapeutic issues can be addressed.

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