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July 26, 1993

Hepatitis C-Related Hepatocellular Carcinoma: Prevalence and Significance

Author Affiliations

From the Departments of Medicine, Beth Israel Hospital, Boston, Mass (Dr Resnick), and Metrowest Medical Center, Framingham (Mass) Union Campus (Dr Koff).

Arch Intern Med. 1993;153(14):1672-1677. doi:10.1001/archinte.1993.00410140054007

Background:  In reports from worldwide sources, antibodies to hepatitis C virus (HCV) have been observed in patients with primary hepatocellular carcinoma (HCC). The current survey is designed to analyze the prevalence and significance of the relationship of HCV infection to HCC.

Methods:  A MEDLINE search terminating on October 1, 1991, produced 15 reports from eight nations in which the frequency of antibodies to HCV by an enzyme-linked immunosorbent assay test in HCC and control groups was obtained. Patient gender, occurrence of cirrhosis, role of alcoholism and transfusion history, and seropositivity for HCV and hepatitis B viral (HBV) markers were recorded.

Results:  Among 1930 patients with HCC, antibodies to HCV were found in 47% (95% confidence interval [CI], 37% to 57%), while HBV markers occurred in 59% (95% CI, 27% to 91%) of subjects studied; hepatitis B surface antigen (HBsAg) positivity was noted in 37% (95% CI, 18% to 56%). The odds ratio (OR) for HBV markers relative to HCV antibodies was 1.73 (95% CI, 1.52 to 1.96) and for HCV antibodies relative to HBsAg, 1.40 (95% CI, 1.23 to 1.59). Among HBsAg-positive subjects, 25% had seropositivity for HCV, but for HBsAg-negative patients, 59% were HCV antibody positive (P<.001). Male gender and cirrhosis were prominent factors (92%±7% and 88±6%, respectively). The OR for HCC in patients with antibody to HCV compared with controls was 25 (95% CI, 18 to 33). The OR comparing HCC with chronic liver disease with respect to HCV antibodies was 0.81 (95% CI, 0.65 to 1.01). We applied χ2 tests to each report to detect, if present, a pattern of dominance favoring HCV, HBV markers, or HBsAg; none was observed.

Conclusions:  The prevalence of HCV seropositivity in HCC is substantial and virtually comparable with HBV. Hepatocellular carcinoma is usually associated with chronic liver disease, which may be required for tumor transformation. Both HCV and HBV may function independently in the pathogenesis of HCC.(Arch Intern Med. 1993;153:1672-1677)