Coffee's beneficial effect on liver disease confirmed in NASH cohort, but only partially confirmation of in vitro pre-described differentially expressed genes in this patient cohort

Abstract

BACKGROUND; Coffee consumption has been associated with reduced liver fibrosis. Cultured cells and animal models have been used to identify differently-regulated genes that might explain this effect. No studies evaluating the effect of coffee consumption on liver gene expression in patients with liver disease have been reported. PATIENTS AND METHODS: Patients with biopsy-proven NAFLD who completed questionnaires about coffee consumption were classified into 3 groups: none (n = 108), minimal-to moderate (<7 servings/week; n = 100) and daily (> or = 7 servings/week; n = 88). Univariate and multivariate 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 48 of these subjects and subjected to microarray analysis using Affymetrix genechip HGU133-plus 2.0 to determine changes in liver gene expression associated with coffee consumption. 37% of these 48 patients had advanced fibrosis (F3-4) and 63% had early fibrosis (F0-1). Of the 23 patients who drank more than 7 cups/week, 18 (78%) had F0-1 fibrosis and 5 (22%) had F3-4 fibrosis (p=0.06). RESULTS: Coffee consumption was inversely associated with fibrosis severity in univariate analysis (p<0.012). 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, was not associated with fibrosis stage. Using linear regression analysis our microarray analysis confirmed a significant relationship between daily coffee consumption and lower expression of transforming growth factor -beta1(TGFβ1) and higher expression of stearoyl-CoA desaturase 1 (SCD), Peroxisome proliferator-activated receptor alfa (PPARα) and gluthation-S-transferase (GST). CONCLUSION: Coffee consumption of at least a cup a day appears protective against fibrosis progression in NAFLD. The underlying mechanism might involve induction of protective mechanism leading to reduced fibrogenesis.