William F. Balistreri, MD
I heard a report that coffee may protect against liver fibrosis in patients with fatty liver disease -- is it true?
Response from William F. Balistreri, MD
Professor of Medicine, University of Cincinnati College of Medicine; Staff Physician, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Coffee and Fatty Liver Disease
That report likely refers to a recent study in which investigators attempted to correlate coffee (caffeine) consumption with the severity of nonalcoholic fatty liver disease (NAFLD). As Malloy and colleagues point out, an association between coffee consumption and a reduced risk for liver disease progression was established years ago.[2-5] Coffee intake has been shown to correlate with lower liver enzyme levels and a reduced risk for hospitalizations and mortality in patients with cirrhosis. A recent example: Coffee consumption was linked to lower rates of clinical and pathologic progression of liver fibrosis in patients with chronic hepatitis C infection.
Investigators at Brooke Army Medical Center in Fort Sam Houston, Texas, therefore, questioned whether coffee ingestion by patients with NAFLD would similarly slow the progression of liver disease from steatosis to nonalcoholic steatosis (NASH). In their study, more than 300 patients underwent liver ultrasound; those in whom the ultrasound was negative for fatty liver served as controls. Patients with steatosis suggested by ultrasound underwent liver biopsies to categorize the patients into 3 groups:
- Bland steatosis without evidence of NASH;
- NASH with stage 0-1 fibrosis; and
- NASH with stage 2-4 fibrosis.
A validated questionnaire was used to determine whether a relationship existed between caffeine consumption (assessing the average mgs of total caffeine/coffee per day) and the degree of steatosis/NASH. A negative relationship was found between caffeine/coffee consumption and the degree of hepatic fibrosis. A significant difference in caffeine/coffee consumption was found between patients who had bland steatosis compared with those who had NASH stage 0-1, as well as between patients who had NASH stage 0-1 compared with those who had NASH stage 2-4. Therefore, this study demonstrates a histopathologic correlation between progression of fatty liver disease and estimated coffee intake. In their cohort of patients with NASH, increased intake of coffee seemed to confer a significantly reduced risk for advanced fibrosis. What is not clear from their data is the amount of coffee or caffeine that must be ingested to lower the risk for fibrosis. Also, because the study was not prospective, the impact of the observed effects on clinical outcomes over time is unknown. Further prospective studies are required.
What Is the Mechanism?
Assuming that the beneficial effects are real, what is the mechanism? Does coffee intake have a direct effect -- attributable to caffeine or to "magical powers of the bean"? Or is the effect indirect -- related to the preferential intake of coffee as a substitute for high-calorie, high-fructose-containing beverages? The investigators point out that the effects may be "more than strictly related to caffeine’s antioxidant behaviors." They cite a study in which rats receiving a high-fat diet given decaffeinated coffee had lower levels of hepatic fat and collagen, reduced liver oxidative stress (an effect of glutathione metabolism), and less liver inflammation -- emphasizing the likely importance of coffee itself, not caffeine, in preventing the progression of NASH. Potential beneficial components include aromatic extracts isolated from coffee beans and/or an elevation of glutathione levels or other antifibrogenic agents by coffee intake.[7-9]
The Bottom Line
What advice can we offer to patients with fatty liver disease? Despite the preliminary results about the beneficial effects of vitamin E and omega-3 fatty acids, lifestyle changes (ie, weight loss through diet and exercise) are the only strategies proven to be effective.[10,11] Moderate consumption of coffee may be a useful, benign adjunct -- but hold the cream and sugar!
- Molloy JW, Calcagno CJ, Williams CD, Jones FJ, Torres DW, Harrison SA. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology. 2012;55:429-436.
- Casiglia E, Spolaore P, Ginocchio G, Ambrosio G. Unexpected effects of coffee consumption on liver enzymes. Eur J Epidemiol. 1993;9:293-297.
- Corrao G, Zambon A, Bagnardi V, D’Amicis A, Klastky A. Coffee, caffeine, and the risk of liver cirrhosis. Ann Epidemiol. 2001;11:458-465.
- Ruhl E, Everhart J. Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2005;128:24-32.
- Modi A, Feldman J, Park Y, et al.. Increased coffee consumption is associated with reduced hepatic fibrosis. Hepatology. 2010;51:201-209.
- Freedman N, Everhart J, Lindsay K, et al. Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology. 2009;50:1360-1369.
- Lee K, Mitchell A, Shibamoto T. Antioxidative activities of aroma extracts isolated from natural plants. BioFactors. 2000;13:173-178.
- Huber W, Scharf G, Rossmanith W, et al. The coffee components kahweol and cafestol inducegamma-glutamylcysteine synthetase, the rate limiting enzyme of chemoprotective glutathione synthesis, in several organs of the rat. Arch Toxicol. 2002;75:685-694.
- Scharf G, Prustomersky, Huber W. Elevation of glutathione levels by coffee components and its potential mechanisms. Adv Exp Med Biol. 2001;500:535-539.
- Sanyal A, Chalasani N, Kowdley K, et al. Pioglitizone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675-1685.
- Centis E, Marzocchi R, Di Domizio S, Ciaravella MF, Marchesini G. The effect of lifestyle changes in non-alcoholic fatty liver disease. Dig Dis. 2010;28:267-273.