Coffee consumption increases hepatic expression of cytochrome P450S and significantly reduces liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD)

Abstract

Background: Coffee consumption has been associated with milder liver disease in the setting of alcoholic liver disease, hepatitis B, and hepatitis C. Whether coffee consumption is also protective against liver injury and/or fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. Patients and Methods: Patients with biopsy proven NAFLD (n = 296) for whom life-style questionnaire with coffee consumption history was obtained at time of liver biopsy were evaluated. Coffee consumption was classified as none, minimal-to moderate (<7 servings/week) and daily (≥7 servings/week). In this group, univariant and multivariant analysis were used to assess the relationship between coffee consumption, various histologic parameters (e.g., steatosis, NAS activity score, ballooning, fibrosis), and potentially-relevant demographic variables (e.g., age, gender, BMI). RNA was also isolated from the liver biopsies of 72 of these subjects and subjected to microarray analysis using “Affymetrix genechip HGU133-plus 2.0” to determine if changes in liver gene expression might be attributable to coffee consumption. Results: In univariate analysis, fibrosis stage was inversely related to the amount of coffee consumed (see figure), with higher coffee consumers (≥7 cups weekly) having significantly lower fibrosis stage than those who drank less coffee (p = 0.011). Similar trends were noted for coffee consumption and ballooning (p = 0.089), steatosis (p = 0.094) and NASH activity score (p = 0.059). In multivariate analysis, advanced fibrosis was positively correlated with age (p < 0.04) and negatively correlated with coffee consumption (p < 0.01). Coffee consumption was also associated with lower HbA1c values (r-0.17; p = 0.01), however, the association of coffee consumption and lower fibrosis was independent of HbA1c (p = 0.047). Consumption of other caffeine containing beverages, such as tea and soda, were not associated with fibrosis stage. Unbiased expression array data in patients with NASH who drank one or more cups of coffee/day compared to NASH patients with lower coffee consumption revealed 4 genes of interest differentially expressed, all of which were up-regulated with habitual coffee consumption: UGT2, CYP26A1, CYP3A7, CYP7B1. Conclusion: Habitual coffee consumption appears protective against fibrosis progression in NAFLD. The underlying mechanism might involve induction of certain cytochrome P450 enzymes that are involved in lipid intermediary metabolism.