MUTUAL CONFOUNDING AND INTERACTIVE EFFECTS BETWEEN HEPATITIS-C AND HEPATITIS-B VIRAL-INFECTIONS IN HEPATOCELLULAR CARCINOGENESIS - A POPULATION-BASED CASE-CONTROL STUDY IN TAIWAN

A population-based case-control study was conducted in Taiwan to deter mine the hepatitis C virus (HCV)-associated risk of hepatocellular car cinoma (HCC) in a hyperendemic area for hepatitis B virus (HBV) infect ion, A total of 58 recently diagnosed HCC patients and 225 matched com munity controls, who participated in a community-based liver cancer sc reening program, were recruited between March 1991 and March 1994, Con trol subjects were matched to HCC patients by age (+/- 5 years), sex, residence, and date of serum sample collection (+/- 3 months), Serum s amples from all study subjects were tested for hepatitis B surface ant igen (HBsAg) and antibodies to HCV (anti-HCVs) by enzyme immunoassays, as well as HCV RNA by reverse transcription-PCR assays, Accordingly, patients with HCC were more likely than were controls to be positive f or HBsAg [82,8% versus 12.9%, with an odds ratio (OR) of 22.9], anti-H CVs (13.8% versus 4.4%, with an OR of 3.9), and HCV RNA (13.8% versus 5.8%, with an OR of 2.7), After adjustment for anti-HCVs and HCV RNA p ositivities, the matched ORs associated with HBsAg increased to 27.6 a nd 28.1, respectively, whereas the corresponding adjusted ORs for anti -HCVs and HCV RNA after controlling for HBsAg status were increased to 8.8 and 6.2, respectively, In the meantime, interactive effects betwe en HCV and HBV on risk were also observed, Compared with those who wer e negative for both anti-HCVs and HBsAg, the matched ORs associated wi th the sole positivity of anti-HCVs and HBsAg were 4.0 (95% confidence interval = 0.7-24.0) and 24.6 (95% Confidence interval = 9.5-64.1), r espectively, whereas 6 HCC cases but none of control subjects were pos itive for both anti-HCVs and HBsAg, These results indicate that there are mutual confounding and interactive effects between HCV and HBV wit h respect to their links to HCC in this endemic area of chronic HBV in fections.