Therapeutic decisions in chronic HCV infection have been made difficult by the subclinical nature of most acute and chronic infections. This is because, in many cases, infections are not even detected unless anti-HCV or HCV RNA tests are performed (Section 1.6 and Ch. 19). This does not lessen the danger of chronic HCV, which often does not become symptomatic until the development of cirrhosis some 20 years following infection. Given the high morbidity and mortality associated with cirrhosis, combined with the insidious nature and variable progression of CLD, it is not surprising that so many chronically infected patients are not treated until liver disease is fairly advanced and considerable permanent damage is done. For example, patients that become symptomatic and then present with cirrhosis may already be in end-stage liver disease. Such patients are also at very high risk for the development of HCC (Chs. 4 and 6). Given these considerations, HCV is often not diagnosed for a long period after virus exposure, since patients are ‘well’ and do not seek medical help. This represents one of the major challenges in treating HCV infection.

IFN-α is one of a family of naturally occurring glycoproteins that have both direct antiviral and immunomodulatory activities. Initially, IFN-α was obtained from leukocyte cultures in very limited quantities, but the availability of recombinant IFN-α in the 1980s finally permitted large-scale, controlled trials of its utility.