Viral pathogenesis of hepatocellular carcinoma in the United States

T. Jake Liang, Lennox J. Jeffers, K. Rajender Reddy, Maria De Medina, I. Talley Parker, Hugo Cheinquer, Victor Idrovo, Alfredo Rabassa, Eugene R. Schiff

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


Chronic hepatitis B virus infection is closely associated with the development of hepatocellular carcinoma, which is a major cause of cancer death worldwide. Recent studies have implicated hepatitis C virus infection as a major pathogenic agent of HBsAg-negative hepatocellular carcinoma. The significance of hepatitis C virus and hepatitis B virus infections in the occurrence of HBsAg-negative hepatocellular carcinoma has not been well established in the United States. We studied 91 HBsAg-negative American patients with hepatocellular carcinoma for evidence of hepatitis C virus or hepatitis B virus infection. These patients had no other predisposing factors to hepatocellular carcinoma. A sensitive polymerase chain reaction was employed to detect hepatitis C virus RNA and hepatitis B virus DNA in serum and liver. Three sets of hepatitis C virus and hepatitis B virus primers were used to optimize the detection of viral genomes. Hepatitis C virus antibodies were measured with second-generation immunoassays. Twenty-six (29%) of these patients carried low levels of hepatitis B virus DNA in either serum, liver/tumor tissue or both. On the basis of the results from serological and polymerase chain reaction analyses of serum and liver, we found that 53 of 91 patients (58%) exhibited evidence of hepatitis C virus infection. When data were combined, 14 patients (15%) had evidence of hepatitis B virus/hepatitis C virus coinfection, whereas 12 (13%) were infected with hepatitis B virus alone and 39 (43%) had hepatitis C virus only. Twenty-six (29%) had no markers of hepatitis B virus or hepatitis C virus infection. All patients with identifiable viral markers had coexisting chronic liver disease. Our study suggests that hepatitis C virus and occult hepatitis B virus infections account for most (71%) hepatocellular carcinoma cases of unknown pathogenesis in the United States. However, in some patients with hepatocellular carcinoma no defined pathogenesis is associated with development of disease.

Original languageEnglish (US)
Pages (from-to)1326-1333
Number of pages8
Issue number6
StatePublished - Dec 1993
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology


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