Analysis Validates Reduced Risk of Liver Cancer by Coffee Drinking

MILAN, Italy, Aug. 2 -- The oft-reported inverse relationship between coffee and liver cancer is real, but the reasons for it remain unclear, researchers here said.

A meta-analysis of 10 studies with quantitative estimates of coffee drinking found a 41% reduction of liver cancer risk among coffee drinkers compared with rates for non-drinkers, Francesca Bravi, Sc.D., of the Instituto di Ricerche Farmacologiche Mario Negri, and colleagues reported in the August issue of Hepatology.

Several studies have reported a potentially favorable effect of coffee on liver enzymes, cirrhosis, and hepatocellular carcinoma, while others have shown decreasing risk with the number of cups a day consumed, the researchers wrote.

To get an overall quantitative estimate of the association, the researchers undertook a meta-analysis of studies including 2,260 patients with hepatocellular carcinoma in six case-control studies in southern Europe, where coffee is a favorite drink, and Japan (1,551 cases), where coffee drinking is less frequent. There were also four cohort studies in Japan (709 cases).

Interestingly, the definition of high coffee consumption included drinking three or more cups a day in Europe but only one or more in Japan, yet reduced risks were similar in both regions

The overall relative risk for coffee drinkers versus non-drinkers was 0.59 (95% confidence interval 0.49-0.72), the meta-analysis found.

The RR in case-control studies for coffee drinkers versus non-drinkers was 0.54 (CI 0.38-0.76), and for cohort studies 0.64 (CI 0.56-0.74).

Analyzed by actual consumption, the increase of one cup of coffee a day amounted to a decreased overall risk of 23% (RR 0.77, CI 0.72-0.82), the researchers reported.

Analyzed by case-control and cohort studies, the RR from case- control studies for an increase of one cup of coffee per day was 0.77 (CI 0.72-0.83) and for cohort studies, the RR was 0.75 (CI 0.65-0.85).

The overall relative risk for low or moderate coffee drinkers was 0.70 (CI 0.57-0.85). For high-quantity drinkers (three or more cups a day in Europe), the RR was 0.45 (CI 0.38-0.53).

The consistency of an inverse relation between coffee drinking and the risk of liver carcinoma across the two study designs and various geographic areas weighs against a major role of bias or confounding, the researchers said.

However, they added, the inverse relationship observed may in fact be spurious and may be due to the fact that patients with a broad spectrum of digestive-tract diseases, liver disorders, and cirrhosis may reduce their coffee consumption, even though it is not routinely recommended.

The researchers noted that animal models and cell-culture systems have indicated that some coffee compounds including diterpenes, cafestol, and kahweol, may act as blocking agents by modulating enzymes involved in carcinogenic detoxification.

Other components of coffee, including caffeine and antioxidant substances in coffee beans, have been shown to have favorable effects on liver enzymes.

The beneficial effect of coffee on liver cancer may also result from its inverse relationship with cirrhosis, although a clinical history of cirrhosis did not totally account for this, the researchers added. Nevertheless, they said, there seems to be a continuum for the favorable effect of coffee on liver enzymes, cirrhosis, and hepatocellular carcinoma.

Discussing the study's limitations, the researchers wrote that it is difficult to derive a causal inference on the basis of observational studies alone. The patients with digestive disorders may have reduced their coffee consumption, and, in addition, the assessment of coffee drinking was based on patients' self-reports.

However, allowance for other confounding factors, such as hepatitis B and C, cirrhosis, social class, alcohol use, and smoking, suggests that such factors did not influence the results, the researchers said.