Comment

The uncertainties in the natural history of hepatitis C virus (HCV) infection and the inadequacies of current antiviral therapies continue to challenge those with clinical and financial responsibility for the care of patients with this apparently indolent disease. Nevertheless, it is clear that most patients infected with HCV develop chronic infection and that a proportion of these, in time, will develop cirrhosis and that a proportion of these, in time, will develop hepatocellular carcinoma (HCC). The proportions and time intervals remain unclear and variables such as age at exposure, mode of infection, race, sex, alcohol consumption, and genotype of virus are frequently cited as cofactors that modify disease progression.

The traditional goals for antiviral therapy comprise sustained clearance of viral nucleic acid from the serum and liver with amelioration of biochemical and histopathological necroinflammatory markers. The conventional rationale for antiviral therapy has been to achieve these goals before the development of advanced fibrotic liver disease. Although we have acquired enormous global experience in the treatment of precirrhotic liver disease in only a decade, relatively few studies of long term benefit to patients with advanced liver disease have been reported. This is because: (i) the traditional therapeutic goals are harder to achieve; (ii) the conventional rationale is irreversibly inapplicable; (iii) few centres have enough untreated patients with advanced liver disease to evaluate in a randomised prospective manner; (iv) the required length of follow up is approaching the duration that effective antiviral therapy has been available to humans; and (v) …