Several studies suggest an inverse relation between coffee drinking and risk of hepatocellular carcinoma (HCC). We conducted a meta-analysis of published studies on HCC that included quantitative information on coffee consumption. Ten studies were retrieved (2,260 HCC cases), including 6 case-control studies from southern Europe and Japan (1551 cases) and 4 cohort studies from Japan (709 cases). The summary relative risk (RR) for coffee drinkers versus non-drinkers was 0.54 (95% confidence interval [CI] 0.38-0.76) for casecontrol studies and 0.64 (95% CI 0.56-0.74) for cohort studies. The overall RR was 0.59 (95% CI 0.49-0.72), with significant heterogeneity between studies. The overall summary RR for low or moderate coffee drinkers was 0.70 (95% CI 0.57-0.85), and that for high drinkers was 0.45 (95% CI 0.38-0.53). The summary RR for an increase of 1 cup of coffee per day was 0.77 (95% CI 0.72-0.83) from case-control studies, 0.75 (95% CI 0.65-0.85) from cohort studies, and 0.77 (95% CI 0.72-0.82) overall. The consistency of an inverse relation between coffee drinking and HCC across study design and geographic areas weighs against a major role of bias or confounding. Coffee drinking has also been related to reduced risk of other liver diseases, thus suggesting a continuum of the favorable effect of coffee on liver function. However, subjects with liver conditions may selectively reduce their coffee consumption. Conclusion: The present analysis provides evidence that the inverse relation between coffee and HCC is real, though inference on causality remains open to discussion.
(HEPATOLOGY 2007;46:430-435.) S everal data have been reported on a potentially favorable effect of coffee on liver function and liver diseases, including liver enzymes, cirrhosis, and hepatocellular carcinoma (HCC). Coffee consumption has been inversely related to ␥-glutamyltransferase and aminotransferase activity in studies from Europe, Japan, and the United States. Such inverse relations are stronger in high-risk subjects, particularly in heavy drinkers. Coffee drinking has also been inversely related to the risk of cirrhosis-a major correlate of HCC -in studies from North America and Europe. At least 11 studies conducted in southern Europe and Japan have considered the relation between coffee drinking and the risk of HCC. A Greek case-control study of 333 cases reported an age-adjusted and sex-adjusted odds ratio (OR) of 0.7 for drinkers of Ն20 cups of coffee per week compared with those who never drink coffee. An Italian case-control study of 151 cases of HCC reported a multivariate OR of 0.78 for drinkers of Ն3 cups of coffee per day compared with occasional drinkers. An update analysis of the Italian study, 20 including 501 HCC cases, reported an OR of 0.5 for drinkers of Ն3 cups per day compared with never drinkers, with a significant trend in risk with dose. The combined analysis of the Greek and Italian case-control studies 20 gave an OR of 0.7 for drinkers of Ն3 cups per day compared with never drinkers, with a significant trend in risk. The inverse relation was also evident among subjects with a history of infection with HBV and/or HCV. In another Italian case-control study of 250 cases, OR was 0.8 for drinkers of 1-2 cups per day, 0.4 for drinkers of 3-4 cups per day, Abbreviations: HCC, hepatocellular carcinoma; OR, odds ratio; RR, relative risk.