The hepato-protective effect(s) of three cups of a coffee a day: Relevance for patients with chronic hepatitis C

Related; Caffeine and Liver Disease in People with Hepatitis C

The hepato-protective effect(s) of three cups of a coffee a day: relevance for patients with chronic hepatitis C

Volume 54, Issue 6, Pages 1085-1086 (June 2011)

Coffee intake has been reported to exert a number of beneficial effects on health including among others, reducing the risk of type 2 diabetes, reducing inflammatory activity and C reactive protein in various diseases and diminishing oxidative stress. The first observations regarding potential beneficial effects of coffee consumption on alanine aminotransferase and γ-glutamtyl transferase activities in patients with chronic liver disease (CLD) were already reported in the 1990s [1], [2]. Since then, evidence for this association gained significant support in several studies performed in Japan, Europe and the US. Recently Freedman and co-workers have conducted a large prospective study in 766 participants of the HALT-C study who had chronic hepatitis C (CHC) with bridging fibrosis and cirrhosis and who failed to achieve a sustained virologic response to pegylated interferon and ribavirin [3]. In this study coffee consumption at base line was shown to be associated with a number of factors including less severe steatosis and lower alanine aminotransferase levels. Furthermore, regular coffee consumption during the observation period (median follow-up 3.8years) was associated with lower rates of disease progression.

In this study, association of coffee intake with progression of liver disease was independent of alcohol intake and cigarette smoking. One year later, Modi and co-workers reported that caffeine consumption, mainly from regular coffee, at an equivalent of 2–3 cups a day, was associated with less severe fibrosis on liver biopsies, as observed in a cohort of 177 patients, of whom 68% had CHC [4]. Finally, two recent meta-analyses confirmed the protective effect of coffee intake on the development of hepatocellular carcinoma in patients with cirrhosis [5], [6].

In the present issue of the Journal, Costentin and co-workers assessed the impact of caffeine consumption on necroinflammatory disease activity and grade of fibrosis in a relatively homogenous cohort of 238 treatment naïve patients with histologically proven CHC, predominantly with genotype 1. Caffeine intake was established as the sum of mean consumption of coffee, tea and caffeine containing beverages and categorized into four levels according to the calculated daily dose. Multivariate analysis revealed that daily caffeine consumption of 408mg was associated with a lesser risk of necro-inflammatory activity as determined by the Metavir score. However, in contrast to previous observations, the investigators did not find a relationship between the degree of caffeine intake and fibrosis stage.

The results in the present study confirm a number of previous observations that caffeine intake has an indirect or direct effect on suppression of necroinflammtory activity as assessed by ALT measurements or by a liver biopsy in CLD in general and in CHC in particular. However, it stands in contrast to a number of previous studies including the recent report of Modi et al. who found a beneficial effect of caffeine on progression of fibrosis in CHC and most probably in CLD of other etiologies. How can these conflicting observations be reconciled? Costentin and co-workers try to provide a hypothesis to explain this difference which suggests that suppression of necroinflammatory liver injury by caffeine directly or indirectly slows down the progression of fibrosis.

Although this may be the case, such a hypothesis does not provide a clue to decipher the mechanism involved in the hepato-protective effect(s) of coffee and caffeine in CLD. In their study, Modi et al. could not establish a link between coffee consumption and hepatic inflammation and suggest that caffeine may have an independent anti-fibrogenic effect in the liver, possibly through inhibition of the transforming growth factor β pathway [4]. The impact of such a putative anti-fibrotic effect was not observed in the present study by Costentin et al. Last but not least, in addition to caffeine, coffee contains hundreds of other compounds which may act in concert with caffeine in suppressing the necro-inflammatory activity in patients with CHC and CLD. The lack of a control group of CHC patients consuming decaffeinated coffee in the present study does not enable assessment of the specific hepato-protective effect of caffeine on such activity.

In conclusion, many previous reports as well as the report discussed herewith, suggest that coffee consumption has a beneficial effect on disease progression in CHC and possibly also in CLD of other etiologies as reviewed in the articles by Freedman and Modi et al. [3], [4]. Thus, irrespective of the controversy regarding the mechanism involved and regardless of other potential confounding factors such as alcohol consumption and/or cigarette smoking, the already available evidence suggests that 2–3 cups of coffee a day are beneficial in patients with chronic liver disease in general and in CHC patients with advanced fibrosis in particular.