FOR THE BRESCIA HCC STUDY risk (RR) estimates for these factors. The relationships be-We performed a case-control study to assess the association tween HBV and HCV infections, and between these infections of hepatocellular carcinoma (HCC) with hepatitis B virus and alcohol drinking, may be of relevance and may contrib-(HBV) and hepatitis C virus (HCV) infection and alcohol ute to the discrepancies observed. Mutual negative confounddrinking. We recruited as cases 172 subjects with an initial ing interactions between HBV and HCV infections have been diagnosis of HCC, who were admitted to the two major hospifound in most studies, [3][4][5][6] whereas positive interactions have tals in the province of Brescia, northern Italy, and 332 subbeen observed in a few. 3,4 Positive interaction between HBV jects, sex-, age-, and hospital-matched, who were admitted to infection and alcohol intake as a cause of liver injury has the Departments of Ophthalmology, Dermatology, Urology, been suggested in some studies but has not been confirmed Cardiology, and Internal Medicine, as controls. Of the HCC by others. 7,8 Few studies have yet documented the joint effect cases, 23.8% were positive for HBsAg and 37.8% for HCV of HCV infection and alcohol drinking: some data suggest RNA; among the controls, 5.4% were positive for HBsAg and synergism between the two, but further research is needed 4.8% for HCV RNA. History of heavy alcohol intake (ΓΊ80 g to clarify the relationship. 9 of ethanol per day for at least 5 years) was found among
In this study, we address the role of HBV, HCV infection 58.1% of the cases and among 36.4% of the controls. The and its genotypes, and alcohol drinking, and their interacrelative risks (RRs) for HBsAg, HCV RNA positivity, and tions in HCC causation, through a case-control study perheavy alcohol intake were, respectively: 11.4 (95% confidence formed in Brescia, North Italy. This locality showed a high interval: 5.7-22.8), 23.2 (95% confidence interval: 11.8-45.7), incidence of liver cancer as compared with the nine Italian and 4.6 (95% confidence interval: 2.7-7.8). Positive interacareas covered by a Cancer Registry, especially in men: the tions (synergisms) between both HBsAg positivity and HCV incidence rate, age-standardized on the Italian population, RNA positivity and heavy alcohol intake were found, sugwas 32.2 per 100,000 in Brescia versus 15 per 100,000 in gesting more than additive effects of viral infections and alcothe provinces of Turin and Varese, North Italy. 10 hol drinking on the risk of HCC. Infection with HCV genotype 1b showed a higher risk than type 2 (RR Γ
2.9; 95% confi-PATIENTS AND METHODS dence interval: 0.9-10), suggesting a major role for the former type in causing HCC. On the basis of population attributable Design and Subjects risks (AR), heavy alcohol intake seems to be the single most
The study base was the population resident in the province of relevant cause of HCC in this area (AR: 45%), followed by Brescia, North Italy. The province includes the city of Brescia (about HCV (AR: 36%), and HBV (AR: 22%) infection. (HEPATOLOGY 325,000 inhabitants), which is composed of the town and 23 sur- 1997;26:579-584.) rounding villages, and the rest of the province (about 725,000 inhabitants). We recruited the HCC cases admitted to the two main hospitals in the province of Brescia, since a previous study 10 and Hepatitis B virus (HBV) and hepatitis C virus (HCV) infecdata provided by the Lombardy Region showed that almost all the tions and alcohol drinking have been recognized as the major incident HCC cases occurring in the city, and about a half of those risk factors for hepatocellular carcinoma (HCC) in developed reported in the rest of the province, were usually admitted to these countries. 1,2 However, large variations exist in the relative two hospitals.
A total of 172 subjects, hospitalized with an initial diagnosis of HCC between January 1995 and July 1996, were enrolled as cases. Among them, 149 were confirmed by histology or cytology (86.6%), Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HCC, hepatocellular the remaining having been diagnosed with sonography or compucarcinoma; RR, relative risk; ELISA, enzyme-linked immunosorbent assay; RIBA, recombinant immunoblot assay; RT-PCR, reverse-transcription polymerase chain reac-terized tomography. We enrolled as controls 332 subjects admitted tion; PCR, polymerase chain reaction; CI, confidence interval; S, synergy index; AR, to the Departments of Ophthalmology, Dermatology, Urology, Carattributable risk.