Summary To assess whether there is an additive effect between chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC), 400 consecutive cirrhotic patients were followed prospectively with periodic abdominal ultrasound examination and measurement of serum a-fetoprotein (AFP) level every 4 months. During a follow-up of 1185 person-years, 80 (20%) patients developed HCC, with an annual incidence of 6.8%. The annual incidence was 2.0% in patients negative for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV), 6.6% in patients with HBsAg alone, 7.0% in patients with anti-HCV alone and 13.3% in patients co-infected with HBV and HCV. There was a positive linear trend in the annual incidence of HCC among patients without either marker, patients with single viral infection and patients with dual viral infection (Pfortrend < 0.0001). Cox (Simonetti et al, 1991;Jeng and Tsai, 1991; Tsai et al, 1994a Tsai et al, -d, 1996aColombo, 1995;Moradpour and Wand, 1996). The sequential development of cirrhosis and HCC in patients with post-transfusion hepatitis (Kiyosawa et al, 1990; Tong et al, 1995) and the high prevalence of antibodies to hepatitis C virus (anti-HCV) in patients with HCC are clues leading to the identification of HCV carriers as another important patient population at risk for HCC (Jeng and Tsai, 1991; Simonetti et al, 1991; Tsai et al, 1994a Tsai et al, -d, 1996a. Persistent infection and chronic liver disease are hallmarks of HCV infection (Tsai et al, 1993(Tsai et al, , 1994e-g, 1995a(Tsai et al, ,b, 1996b(Tsai et al, , 1997Sherlock and Dooley, 1997). Although HCC may occasionally develop in a normal liver, most cases are associated with long-lasting chronic liver disease (Sherlock and Dooley, 1997). Between 2.2% and 55% of autopsied cirrhotic patients have HCC, and about 80% of HCC patients have coexisting cirrhosis (Jeng and Tsai, 1991; Simonetti et al, 1991; Tsai et al, 1994a Tsai et al, -d, 1996aSherlock and Dooley, 1997 Simonetti et al, 1992; Tsai et al, 1993 Tsai et al, , 1994a Tsai et al, -g, 1996aBenvegnu et al, 1994;Alberti et al, 1995). It is not certain whether this co-infection increases the likelihood of the development of HCC. Our previous case-control studies have shown that there is an interacting role between HBV and HCV infection in the development of chronic hepatitis (Tsai et al, 1996b), cirrhosis (Tsai et al, 1993(Tsai et al, , 1994a, and HCC (Tsai et al, 1994a(Tsai et al, -d, 1996a. A synergistic interaction between HBV and HCV in the development of HCC has also been speculated by other investigators (Kaklamani et al, 1991;Simonetti et al, 1992). However, most previous studies have aimed to explore the association between HCV/HBV and HCC and have been limited to case-series studies (Jeng and Tsai, 1991;Kaklamani et al, 1991) or cross-sectional case-control studies (Simonetti et al, 1992; Tsai et al, 1994a Tsai et al, -d, 1996a. Because blood samples for the detection of viral markers ...

To assess whether hepatitis C virus infection was a risk factor for the development of non-alcoholic liver cirrhosis, antibody to hepatitis C virus (anti-HCV; detected by a second generation HCV enzyme immunoassay), hepatitis B surface antigen (HBsAg; detected by radioimmunoassay) were tested in 150 cirrhotics and 150 sex-matched and age-matched healthy controls. The prevalence of anti-HCV and HBsAg in cirrhotics was higher than in controls (22.0%, 73.3% vs. 2%, 18.7%; P = 0.001). The prevalence of anti-HCV in HBsAg-negative cirrhotics (45.0%) was higher than that in HBsAg-positive patients (13.6%; P = 0.001). Both the anti-HCV and carriage of HBsAg were associated significantly with liver cirrhosis, showing odds ratio of 12.0 for HBsAg carriers and 13.8 for patients with anti-HCV. Compared with those without HBsAg and anti-HCV, there was a significantly positive linear trend for developing cirrhosis with the presence of HBsAg alone (odds ratio = 19.9), anti-HCV alone (odds ratio = 49.0), and those positive for HBsAg and anti-HCV (odds ratio = 81.8) (P = 0.00001). The population-attributable risk for developing liver cirrhosis was estimated as 10.8% for anti-HCV alone, 55.2% for HBsAg alone, and 9.4% for both anti-HCV and HBsAg in southern Taiwan. In conclusion, this study shows that hepatitis B and C virus infection act independently and synergistically in the development of non-alcoholic liver cirrhosis among Chinese in Taiwan.

TNF308.2 allele carriage and chronic hepatitis B virus/hepatitis C virus infection are independent risk factors for HCC. Carriage of the TNF308.2 allele correlates with disease severity and hepatic fibrosis, which may contribute to a higher risk for HCC.