We read with great interest the article by Freedman et al.1 The authors have evaulated the effect of coffee consumption on liver disease progression in chronic hepatitis C and found an inverse correlation between coffee intake and liver disease progression. We would like to stress some points before making a judgement about the results of the study.
First, as the authors mentioned in the article, coffee contains a variety of chemical compounds. The standardization of these compounds' concentration in a cup of coffee is almost impossible. Moreover, some authors reported that caffeine concentrations may fluctuate from one coffee house to another and may change even in the same company on the same day.2 For that reason, to measure the coffee consumption via the number of consumed cups of coffee may not correctly reflect the differences between the groups.
Second, authors reported that correction for lifetime or current alcohol intake or smoking did not influence risk estimates for the association of coffee and liver disease progression. We agree with the authors, but there are some crucial points that deserve further comment. Smoking accelerates caffeine metabolism.3 We could come to the conclusion that smokers have a tendency to consume more coffee than nonsmokers because of the shorter half-life of caffeine. Even though the authors adjusted the lifetime risk, this fact may require a second review when the patients are classified. As a result, smokers who have a propensity to consume more coffee than nonsmokers may intensify their risks with this vicious circle. In our opinion, smokers and nonsmokers must be evaluated in different categories.
Nevertheless, if we could make a conclusion in spite of the aforementioned limitations, we would like to add a little contribution to the suggested mechanisms regarding why coffee consumption may slow the liver disease progression in patients in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial. Caffeine, which is the most-studied active substance in coffee, is mainly metabolized with cytochrome P450 (CYP) 1A2. CYP 1A2 has a very important role in the metabolism of caffeine and many clinically important drugs. Some drugs which are eliminated this by pathway may be affected by coffee consumption.4 Although we did not encounter any specific data about the interaction between caffeine and the drugs which are used in the treatment of chronic hepatitis C, a possible interaction may make the patients more resistant to hepatitis C virus. As an habitual behavior, these patients had consumed coffee for the duration of the treatment phase. Coffee consumption may increase the drug levels, competitively inhibiting the activity of CYP 1A2. For that reason, coffee consumers may be exposed to higher doses of antiviral treatment. We were wondering about whether this point makes a difference between groups by creating a better treated group.
In conclusion, we found the study to be a very valuable contribution to the literature. Still, when we consider the limitations of the study and potential drug interactions between coffee and other drugs, we are far from advising coffee consumption as safe for our patients, even though we would like it.