Occult Hepatitis B in patients with hepatocellular carcinoma and controls with and without hepatitis C virus infection

Background: Hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol intake have been recognized as the the main causes of hepatocellular carcinoma (HCC) in developed countries. We investigated the prevalence of occult HBV infection in HBsAg-negative HCC cases and controls with and without HCV infection (NBNC). Methods: Between 1995-2002 we prospectively recruited 417 patients with a first diagnosis of HCC as cases and 534 subjects unaffected by liver diseases as controls. Among cases, 204 HCV RNA-positive and 213 NBNC patients, and among controls, 37 HCV RNA-positive and 497 NBNC subjects were tested for the presence of occult HBV. DNA was extracted by proteinase K and phenol/chloroform. HBV DNA was detected by in-house PCR with nested primers (detection limit 500 copies/ml) from highly conserved S-gene region encompassing a-determinant. Results: The relations between occult HBV infection and each of the other risk factors for HCC are shown in table. An increased risk statistically significant for HCC (OR = 5.4) was estimated among HCV RNA-negative subjects and among subjects who drank < 60 g/day of alcohol (OR = 6.8). An interaction was found between occult HBV infection and both HCV infection and heavy alcohol intake. Conclusions: These findings provide a new perspective on the role of occult HBV infection in the HCC aetiology.