Prior to the discovery of HCV, a series of studies in patients with acute NANB PTH (which was mostly caused by HCV) (Hopf et al., 1990; Di Bisceglie et al., 1991; Tremolada et al., 1992; Koretz et al., 1993a,b; Mattsson, Sonnerborg & Weiland, 1993) showed that only 4–13% of 406 patients became symptomatic over an 8–14 year follow-up. Histologically defined cirrhosis was identified in 8–24% of patients, and HCC was observed in 0.7–1.3%. While these studies did not provide a longer follow-up, they did help to establish a link between NANB PTH, cirrhosis, and HCC. Independent observations in HCV-infected patients with chronic hepatitis who were followed for 4–11 years (Roberts, Searle & Cooksley, 1993; Takahashi et al., 1993; Yano et al., 1993) revealed cirrhosis in 8–46% and HCC in 11–19%. In these studies, however, the time and duration of infection were not known. Additional longitudinal studies among patients chronically infected with HCV, where the time of transmission through transfusion was known, estimated that chronic hepatitis developed within 10 years of transfusion, cirrhosis by 21 years, and HCC by 29 years (Kiyosawa et al., 1990). Some patients developed HCC only after 40–50 years of infection. These results were independently confirmed (Tong et al., 1995) and highlight both the protracted asymptomatic phase of infection, lasting for 10–20 years, and the seriousness of the sequelae. By comparison, clinical observations have shown that cirrhosis could appear several years after infection.