Increased caffeine consumption is associated with reduced hepatic fibrosis

Abstract

Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. This study was undertaken to use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Patients undergoing liver biopsy completed a detailed caffeine questionnaire on three occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. One hundred seventy-seven patients (99 male, 104 white, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75(th) percentile for the cohort (308 mg = approximately 2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.80; P = 0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index, and alcohol intake in all patients (OR, 0.25; 95% CI, 0.09-0.67; P = 0.006), as well as the subset with HCV infection (OR, 0.19; 95% CI, 0.05-0.66; P = 0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis.

Figure 1

Comparison of estimated daily caffeine intake between first and final completed questionnaire (2^nd or 3^rd) for each individual, demonstrating consistency of responses. Box indicates 308 mg of caffeine consumption per day, the 75^th percentile for the cohort. Responses above or below 308 mg/day were consistent between questionnaires in 96% of patients.

Figure 2

Forest plot showing odds ratios with 95% confidence intervals for the association with advanced fibrosis. Results of univariate and multivariable logistic regression are shown for the association of each of the following with advanced hepatic fibrosis (Ishak ≥ 3): caffeine consumption above the 75^th percentile for the cohort (308 mg/day), coffee consumption >2 cups per day, caffeine and coffee consumption for HCV patients only (n=121) and caffeine consumption for patients reporting no change in caffeine intake in the past 5 years (n=119). Multivariable odds ratios are adjusted for age, sex, liver disease diagnosis, BMI, race and alcohol intake. Increased caffeine and coffee consumption are associated with a reduced risk of advanced fibrosis.