After lung and stomach cancer, liver cancer is the third largest cause of cancer deaths in the world.

A new study on the relationship between coffee drinking and the risk of hepatocellular carcinoma (HCC) confirmed that there is an inverse association between coffee consumption and HCC, although the reasons for this relationship are still unresolved.

At least eleven studies conducted in southern Europe and Japan have examined the relationship between coffee drinking and the risk of primary liver cancer. The current study, led by Francesca Bravi of the Istituto di Ricerche Farmacologiche Mario Negri in Milan, Italy, was a meta-analysis of published studies on HCC that included how much coffee patients had consumed. Researchers combined all published data to obtain an overall quantitative estimate of the association between coffee consumption and HCC.

The results showed a 41 percent reduction of HCC risk among coffee drinkers compared to those who never drank coffee. "Moreover, the apparent favorable effect of coffee drinking was found both in studies from southern Europe, where coffee is widely consumed, and from Japan, where coffee consumption is less frequent, and in subjects with chronic liver diseases," the researchers state.

They point out that animal and laboratory studies have indicated that certain compounds found in coffee may act as blocking agents by reacting with enzymes involved in carcinogenic detoxification. Other components, including caffeine, have been shown to have favorable effects on liver enzymes. Coffee has also been related to a reduced risk of liver diseases and cirrhosis, which can lead to liver cancer.

"Despite the consistency of these results, it is difficult to derive a causal inference on the basis of the observational studies alone," the authors note. It may be that patients with digestive tract diseases, including liver disorders, naturally reduce their coffee consumption, even though avoidance of coffee is not routinely recommended. Also, they note that the assessment of coffee intake was based on patients self-reporting, although recall of coffee drinking has been shown to be accurate. The fact that the inverse relationship between coffee drinking and HCC was shown in both southern Europe and Japan suggests a lack of bias in these studies. Allowance for other confounding factors, such as hepatitis B and C, cirrhosis, social class indicators, alcohol use and smoking, also suggests that such factors did not influence the results.

"In conclusion, the results from this meta-analysis provide quantitative evidence of an inverse relation between coffee drinking and liver cancer," the authors state. "The interpretation of this association remains, however, unclear and the consequent inference on causality and worldwide public health implications is still open for discussion."