Drs. Patil and Mallath suggest that the variability of caffeine metabolism may partly or largely explain the inverse relation between coffee and hepatocellular carcinoma observed in several studies and quantified in our meta-analysis.1
Apart from genetic variability, we also noted in our discussion that a broad spectrum of digestive tract and liver disorders may lead to changes in caffeine metabolism and hence to a reduction in coffee consumption. Thus, such a variability in metabolism may be both genetic and disease-induced. This is the major difficulty in the interpretation of these findings, as already discussed in our paper.