Hepatitis C virus (HCV) is a major public health problem around the world, with a prevalence ranging from 0.5 to 2% in most developed countries. After acute infection, spontaneous remission is a rare event. Although long term consequences of HCV infection are controversial, there is a consensus emerging that HCV infection is a progressive disease resulting in liver failure in some but probably in a minority of infected individuals. Patients who lack biochemical evidence of liver injury may be an important subset with a “more benign” natural history.1

In the rare situation where spontaneous cure occurs after acute infection, aminotransferase activities normalise and HCV RNA becomes undetectable in serum. By contrast, the serological profile shows minor modifications with time. With chronicity, serum HCV RNA remains detectable in the vast majority of individuals. Undetectable HCV RNA in serum in patients with abnormal liver enzymes may be related to low viraemia, be under the limit of detection of virological assays, or be due to a fluctuating course. In anti-HCV positive individuals with normal enzymes, however, the lack of serum HCV RNA has been interpreted as complete cure of the infection. However, the study by Haydonet al in this issue (see page 570) challenges this interpretation. These investigators have documented HCV RNA in liver in the majority of patients with exposure to HCV (confirmed by RIBA 3) whether or not virus was detectable in serum, suggesting that residual HCV infection occurs not only among those individuals with abnormal liver enzymes but also among those considered to have “resolved infection”.

Although a high correlation exists between third generation assays and HCV RNA in serum,2 a small subgroup of patients remains, focused on in this study, which …