Re: Association of meat and fat intake with liver disease and hepatocellular carcinoma in the NIH-AARP cohort.

JNCI Vol. 103, Issue 5 | March 2, 2011 revealed an inverse association of hepatocellular carcinoma (HCC) with white meat intake and a positive one with red meat and saturated fat intakes. The authors acknowledged a lack of information on infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) as a potential study limitation; nonetheless, they considered confounding from viral status unlikely because white and red meat consumption were not associated with HBV and HCV infection in the United States (1). However, a modifying effect of hepatitis virus infections on the association between diet and HCC cannot be ruled out. To shed further light on this topic, we used data from an Italian case–control study (2,3) to assess the association between HCC risk and intake of meat and fat according to HBV and HCV status. In this study, dietary habits during the 2 years preceding the enrollment had been explored through a validated foodfrequency questionnaire (3). Intakes of total energy and fats were computed using an Italian food composition database (4). Informed consent was obtained from all study subjects. Screening for hepatitis B surface antigen was conducted by microparticle enzyme immunoassay (MEIA) and for HCV antibodies (anti-HCV) by thirdgeneration MEIA (2). Energy-adjusted odds ratios were calculated by means of logistic regression models according to the nutrient density method (5), adjusting for potential confounders. Despite many similarities with the NIH-AARP study, we found somewhat different results. Risk estimates for consumption of white and red meats were similar to those reported in the NIHAARP cohort (Table 1). No heterogeneity of these associations emerged between subjects with and without HBV and/or HCV infection, although the small sample size precluded reaching statistical significance. By contrast with Freedman et al. (1), however, we found no direct association of HCC risk with saturated or monounsaturated fat intake and an inverse association with polyunsaturated fat intake. Differences in dietary sources of fat could partially explain the discrepancies between the two studies. The contribution of saturated and monounsaturated fats to total energy in the NIH-AARP cohort and in our study was similar (Table 1), whereas the consumption of white and red meats was much higher in the American cohort than in the Italian case–control study. Furthermore, in the United States, beef is an important source of saturated and monounsaturated fats (6), whereas in Italy, the most important sources are dairy products and vegetable oils (7). Salad dressings, margarine, and oils accounted for approximately 45% of polyunsaturated fat in the US diet (6), whereas white meats and vegetable oils were the predominant sources of this type of fat in Italy (7). The small number of control subjects affected with HBV and/or HCV infections and of HCC patients without infections did not allow final conclusions about whether hepatitis infection affects the relationship between diet and HCC risk. Our results confirm the finding from the NIH-AARP cohort on the effect of white and red meats on HCC risk in a population where the fraction of HCC attributable to HBV and/or HCV infection is larger than in the United States (2), providing a partial reassurance about the validity of the present dietary findings.