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Objectives: The purpose of this study was to describe the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the etiology of hepatocellular carcinoma (HCC)., Methods: During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of HCC from Athens, Greece, as well as from patients in two control groups, also from Athens. Controls were 272 metastatic liver cancer (MLC) patients and 360 patients hospitalized for injuries or eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays., Results: The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 48.8 (30.5-78.3) for the presence of HBsAg and 23.2 (11.4-47.3) for the presence of anti-HCV. The odds ratio for concurrent infection with HBV and HCV was 46.2 (9.9-216.6) compared to infection with neither virus., Conclusions: Although HBV and HCV are both important causes of HCC in this study population the data do not suggest, neither do they conclusively refute, a super-additive interaction between the two infections in the development of this malignancy. In this population, 58% of HCC cases can be attributed to HBV, 12% to HCV, and 3% to dual infection with these viruses.

During a 16-month period in 1991-1992, blood samples and questionnaire data were obtained from 65 incident cases of hepatocellular carcinoma (HCC) as well as from 2 control groups of hospitalized patients matched on gender and age, which included 65 metastatic liver cancer (MLC) patients and 65 patients hospitalized for eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg and antibody to hepatitis C virus (anti-HCV) by enzyme immunoassay. The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 18.8 (8.2-43.2) for the presence of HBsAg and 7.7 (1.7-35.1) for anti-HCV. In the present hospital-based case-control study anti-HCV testing was conducted on recently collected sera, using a second-generation enzyme immunoassay with confirmation by immunoblot assay. Comparisons with previous work in a similar population demonstrated that, when second-generation anti-HCV assays are applied to sera stored for 7-15 years, confirmatory assays or a higher diagnostic cut-off point may be necessary to ensure that the testing is specific.

It is frequently assumed that the risk of hepatocellular carcinoma related to hepatitis B virus is higher when chronic hepatitis B virus infection is acquired early in life. This hypothesis has never been directly evaluated. However, firstborn and secondborn children are exposed to common infections after their school enrollment, whereas laterborn children are exposed much earlier, through their older siblings. The authors analyzed sibship size and birth order data from a large case-control study of patients admitted to Athens, Greece, hospitals between April 1976 and October 1984. The analyses included 185 patients with hepatocellular carcinoma, 35 patients with metastatic liver cancer, and 432 other hospital controls. There was a tendency for cases of hepatocellular carcinoma to concentrate at higher birth orders. When the analysis was restricted to cases and controls who were positive for hepatitis B surface antigen, this tendency was even more notable. These results are compatible with the hypothesis that establishment of chronic hepatitis B virus infection at an early age increases the risk of hepatocellular carcinoma substantially more than does chronic infection with this virus established at a later age.

Serum taken from patients in a case-control study in Athens, Greece, was used to examine the interactive roles of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the origin of hepatocellular carcinoma (HCC). An enzyme immunoassay for anti-HCV was used to test serum taken from 185 cases with HCC, 35 cases with metastatic liver cancer (MLC), and 432 hospital controls. Weakly positive anti-HCV results were more strongly related to MLC than to HCC, implying that these anti-HCV results are false positive. By contrast, strongly positive anti-HCV results were significantly related to HCC (relative risk [RR], 6.3), whereas no significant association was evident for MLC (RR, 0.6). The association of anti-HCV with HCC was substantially higher among subjects whose radioimmunoassay was positive for hepatitis B surface antigen (RR, 20.0) than among those whose radioimmunoassay was negative for this marker (RR, 4.8). These findings indicate that HCV infection has an interactive role in the origin of HCC.

The prevalence of HBsAg, anti-HBs, and anti-HBc in the sera of 217 patients with the two polar types of leprosy and 382 hospital controls was studied in order to investigate the degree of exposure of Greek leprosy patients to HBV and the ability of these patients to clear HBV from the blood. Two distinct serological patterns were analyzed: effective exposure, characterized by the presence of one or more of the three serological markers, and active infection, characterized by the presence of HBsAg. From the statistical analysis it was found that TT as well as LL cases had a higher prevalence of effective exposure in comparison to controls (p less than 10(-5) and p less than 10(-6)). No significant difference was found between the two polar leprosy types (p greater than 0.30) or between bacteriologically positive and negative LL cases (p greater than 0.30). As far as the prevalence of active infection is concerned among the effectively exposed subjects of all groups, no significant difference existed between TT cases and controls, LL cases and controls, the two polar leprosy cases combined and controls, the two polar leprosy groups, and LL cases positive and negative for Mycobacterium leprae (p for all comparisons greater than 0.30). It is concluded that leprosy cases are at a high risk of HBV infection, but the prevalence of active infection among those effectively exposed does not differ between leprosy cases and hospital controls.

The incorporation of 14C-thymidine by peripheral blood lymphocytes stimulated by phytohemagglutinin (PHA) and the proportion and absolute number of E-rosettes were determined in 28 prostitutes and the results were correlated with hepatitis B virus (HBV) serology. Women were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) as well as for antibody to the hepatitis B core antigen (anti-HBc). It was found that women who were carriers of HBsAg had significantly lower incorporation of 14C-thymidine (median value 14451 counts per minute-cpm) compared to women positive for anti-HBc but negative for the other two markers (median value 28590 cpm) as well as to women negative for all the tested markers (median value 30600 cpm). No significant difference was found among the three groups studied with respect to either the absolute number or the percentage of E-rosettes. The results indicate that the presence of anti-HBc alone, is not related to the responsiveness of lymphocytes to PHA.

Tobacco smoking and alcohol drinking histories were obtained from 194 patients with hepatocellular carcinoma (HCC) and 456 hospital controls, and the results were analysed in conjunction with the results of serological determinations of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) in all subjects, as well as the presence or absence of cirrhosis in HCC patients. The relative risk (RR) of HCC (and 95% confidence interval) among HBsAg-positive subjects was 13.7 (8.0-23.5), whereas the excess risk among antibody-positive subjects was small and statistically non-significant. In the presence of cirrhosis the RR for HBsAg-positive subjects was considerably higher (30.7 vs. 7.1 among HBsAg-positive subjects without cirrhosis) indicating that HBV may affect the development of HCC through at least two different and potentially multiplicative mechanisms (DNA integration and liver regeneration). Moderate ethanol consumption does not affect the risk of HCC, but there is a statistically significant and dose-dependent association between tobacco smoking and HBsAg-negative HCC. In most of the developed countries of Europe and North America, where the prevalence of HBsAg carrier state is very low and tobacco smoking very common, more cases of HCC may be due to tobacco smoking than to HBV, even though the RR for HCC is much higher among HBsAg carriers than among tobacco smokers.