VIRAL PATHOGENESIS OF HEPATOCELLULAR-CARCINOMA IN THE UNITED-STATES

Chronic hepatitis B virus infection is closely associated with the dev elopment of hepatocellular carcinoma, which is a major cause of cancer death worldwide. Recent studies have implicated hepatitis C virus inf ection as a major pathogenic agent of HBsAg-negative hepatocellular ca rcinoma. The significance of hepatitis C virus and hepatitis B virus i nfections in the occurrence of HBsAg-negative hepatocellular carcinoma has not been well established in the United States. We studied 91 HBs Ag-negative American patients with hepatocellular carcinoma for eviden ce of hepatitis C virus or hepatitis B virus infection. These patients had no other predisposing factors to hepatocellular carcinoma. A sens itive polymerase chain reaction was employed to detect hepatitis C vir us RNA and hepatitis B virus DNA in serum and liver. Three sets of hep atitis C virus and hepatitis B virus primers were used to optimize the detection of viral genomes. Hepatitis C virus antibodies were measure d with second-generation immunoassays. Twenty-six (29%) of these patie nts carried low levels of hepatitis B virus DNA in either serum, liver /tumor tissue or both. On the basis of the results from serological an d polymerase chain reaction analyses of serum and liver, we found that 53 of 91 patients (58%) exhibited evidence of hepatitis C virus infec tion. When data were combined, 14 patients (15%) had evidence of hepat itis B virus/hepatitis C virus coinfection, whereas 12 (13%) were infe cted with hepatitis B virus alone and 39 (43%) had hepatitis C virus o nly. Twenty-six (29%) had no markers of hepatitis B virus or hepatitis C virus infection. All patients with identifiable viral markers had c oexisting chronic liver disease. Our study suggests that hepatitis C v irus and occult hepatitis B virus infections account for most (71%) he patocellular carcinoma cases of unknown pathogenesis in the United Sta tes. However, in some patients with hepatocellular carcinoma no define d pathogenesis is associated with development of disease.