Coffee Consumption, Hepatitis C and Liver Cancer Risk

Abstract & Commentary

By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.

Synopsis: In a nested cohort analysis of a large Japanese sample, coffee drinking was associated with a decreased risk of death from hepatocellular carcinoma in all subjects, and specifically, those infected with hepatitis C virus.

Source: Wakai K, et al. Liver cancer risk, coffee, and hepatitis C virus infection: a nested case-control study in Japan. Br J Cancer. 2007;97:426-428.

Recently, an inverse association of coffee consumption and risk for hepatocellular carcinoma has been identified, based upon case-control1-3 and cohort studies.4-6 In Japan, where hepatocellular cancer is more common, hepatitis C virus (HCV) infection is a known risk factor.7 To determine whether coffee consumption might mediate a protective effect on a high risk for HCC population (ie, HCV positive individuals), Wakai and colleagues conducted a nested case-control study capitalizing on the Japan Cohort Study for Evaluation of Cancer Risk. This cohort includes 110,792 individuals, aged 40-79 at baseline, from 45 areas throughout Japan who answered a questionnaire on lifestyle and medical factors during the years 1988-1990. Among the questions were those relating to habitual coffee consumption, with possible responses including "scarcely any," "1-2 cups per month," "1-2 cups per week," "3-4 cups per week," and "almost every day." Those who answered "almost every day" were asked to report the number of cups consumed per day. Of the entire sample, 39,242 agreed to donate blood as a component of the health assessment phase of this study.

Of the cohort, there were 96 subjects who died with HCC, and 60% of these were HCV positive. For controls, age, sex, HCV status, and geographic region-matched individuals were selected. There were 7 controls for each HCV+ and 84 controls for each HCV-HCC patient. Former alcohol consumption, a history of diabetes mellitus and a history of liver disease were more common among the HCC cases than controls.

Drinking one or more cups of coffee per day was inversely associated with HCC mortality among all subjects (multivariate odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0-96). When examined in the context of HCV status, it was apparent that the association was more robust for those who were HCV positive. The OR for HCC among HCV positive individuals consuming one or more cups of coffee per day was 0.31; 95% CI, 0.11-0.85. Although daily coffee consumption in the HCV negative group had a similar trend there was overlap with unity and thus, the association did not reach statistical significance.


The results of this prospective cohort study support the earlier observations of a protective effect of coffee with regard to hepatocellular carcinoma in the general population3 and particularly among individuals considered at high risk for HCC including heavy drinkers and those with HCV infection.2-8 However, the protective effect has not been universally observed for those at high risk. For example, Montella and colleagues3 in Italy performed a hospital-based case-control analysis including 185 patients with HCC and 412 matched controls and although they also found an association of coffee and reduced HCC risk, it was most noticeable in those without HCC risk factors.

Why would coffee have such an effect? First, it is notable that the favorable effect of coffee drinking on HCC parallels the inverse association with liver cirrhosis9,10 and chronic liver disease.11 An Italian study12 investigated the role of caffeine in cirrhosis onset and found a protective effect of caffeine intake from coffee, but not from other beverages. This would argue that the protective effect is not from caffeine directly. Coffee itself is rich in antioxidants and other components which may have molecular consequences. For example cafestol and kahweol are two coffee-specific diterpenes with anticarcinogenic activity,13 and it is likely that others exist. These coffee components may act by modulation of enzymes involved in carcinogen detoxification, as has been suggested in various experimental models.14

Thus, it appears that coffee consumption has some protective effect against the development of HCC. Additional studies are warranted to establish a mechanism and hopefully derive an effective prevention strategy for those at high risk.


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