Viewpoint: Is Coffee Drinking Associated With Lower Cirrhosis Risk?
Viewpoint: Is Coffee Drinking Associated With Lower Cirrhosis Risk?
Klatsky AL, Morton C, Udaltsova N, Friedman GD
Arch Intern Med. 2006;166:1190-1195
A minority of individuals at risk for chronic liver disease ultimately develop liver cirrhosis, yet knowledge in regard to the risk modulators is sparse. Several reports have suggested that coffee drinking is associated with lower cirrhosis risk. The mechanism by which this hepatic protection might occur is unknown, but speculation includes effects of caffeine via adenosine receptor antagonists or perhaps antioxidant actions. Additionally, it is possible that cafestol (a fat-soluble noncaffeine component of boiled coffee) may induce glutathione synthesis, which is a cellular protective factor well known for the role it plays in detoxifying acetaminophen.
This cohort study involved 125,580 multiethnic members of a comprehensive prepaid healthcare plan without known liver disease who provided baseline data during voluntary health examinations from 1978 to 1985. Subsequently, through 2001, 330 of these patients were diagnosed with liver cirrhosis; 199 were diagnosed with alcoholic cirrhosis and 131 with nonalcoholic cirrhosis. A retrospective review of the medical records confirmed the diagnosis of cirrhosis and ascertained probable etiology. Sixty-five percent of patients with alcoholic cirrhosis and 54% of patients with nonalcoholic cirrhosis were men, and in both groups, about half were aged 50 years or younger. The risk for cirrhosis, both alcoholic and nonalcoholic, increased with age, male sex, and obesity, but education was protective, that is, cirrhosis risk declined as years of education increased. Coffee drinking was positively correlated with smoking and alcohol drinking.
Drinking 1-3 cups of coffee per day was associated with a 40% decrease in the risk for alcoholic cirrhosis vs drinking less than 1 cup (P < .001). This protective effect was dose-dependent: less than 1 cup per day, 0.7 (95% confidence interval [CI], 0.4-1.1); 1-3 cups, 0.6 (95% CI, 0.4-0.8; P < .001); and 4 or more cups per day, 0.2 (95% CI, 0.1-0.4; P < .001). This means that patients who drank 4 or more cups of coffee had an 80% decrease in the relative risk for alcoholic cirrhosis. Among subgroups of patients with nonalcoholic cirrhosis, coffee had a similar, weak, albeit not statistically significant inverse relation to risk for either viral hepatitis-associated cirrhosis or to miscellaneous, other cirrhosis. Tea drinking, on the other hand, was unrelated to the risk for either alcoholic or nonalcoholic cirrhosis.
In a cross-sectional analysis, coffee drinking was also related to a lower prevalence of high aspartate aminotransferase and alanine aminotransferase levels. The odds ratio of 4 or more cups per day (vs none) for a high aspartate aminotransferase level was 0.5 (95% CI, 0.4-0.6; P < .001) and for a high alanine aminotransferase level, 0.6 (95% CI, 0.6-0.7; P < .001), with stronger inverse relations in those patients who drank large quantities of alcohol.
A number of limitations need to be considered in the interpretation of these study findings, including the fact that smoking, drinking, and coffee consumption are often related habits, which makes it difficult to rule out residual confounding by alcohol amount or drinking pattern. The study authors proposed that smoking may prolong the persistence of caffeine in the body. Thus, any residual confounding effect that is related to coffee drinking would tend to produce an inverse smoking-cirrhosis relation, not the positive one evident in this study. This study was also limited by its reliance on baseline ascertainment of habits and incomplete follow-up of the cohort. Finally, the observational nature of these data and the absence of an established mechanism limit a causal interpretation.
Clearly these data suggested that further research focusing on hepatic coffee-ethanol interactions is warranted. Although this association with coffee consumption is extremely interesting, it would be the wrong message for patients to think that increasing coffee consumption rather than reduction of alcohol intake is the best strategy to avoid significant alcohol-related liver disease.
Abstract URL:http://www.medscape.com/medline/abstract/16772246
Coffee, Cirrhosis, and Transaminase Enzymes
Klatsky AL, Morton C, Udaltsova N, Friedman GD
Arch Intern Med. 2006;166:1190-1195
Summary
A minority of individuals at risk for chronic liver disease ultimately develop liver cirrhosis, yet knowledge in regard to the risk modulators is sparse. Several reports have suggested that coffee drinking is associated with lower cirrhosis risk. The mechanism by which this hepatic protection might occur is unknown, but speculation includes effects of caffeine via adenosine receptor antagonists or perhaps antioxidant actions. Additionally, it is possible that cafestol (a fat-soluble noncaffeine component of boiled coffee) may induce glutathione synthesis, which is a cellular protective factor well known for the role it plays in detoxifying acetaminophen.
This cohort study involved 125,580 multiethnic members of a comprehensive prepaid healthcare plan without known liver disease who provided baseline data during voluntary health examinations from 1978 to 1985. Subsequently, through 2001, 330 of these patients were diagnosed with liver cirrhosis; 199 were diagnosed with alcoholic cirrhosis and 131 with nonalcoholic cirrhosis. A retrospective review of the medical records confirmed the diagnosis of cirrhosis and ascertained probable etiology. Sixty-five percent of patients with alcoholic cirrhosis and 54% of patients with nonalcoholic cirrhosis were men, and in both groups, about half were aged 50 years or younger. The risk for cirrhosis, both alcoholic and nonalcoholic, increased with age, male sex, and obesity, but education was protective, that is, cirrhosis risk declined as years of education increased. Coffee drinking was positively correlated with smoking and alcohol drinking.
Drinking 1-3 cups of coffee per day was associated with a 40% decrease in the risk for alcoholic cirrhosis vs drinking less than 1 cup (P < .001). This protective effect was dose-dependent: less than 1 cup per day, 0.7 (95% confidence interval [CI], 0.4-1.1); 1-3 cups, 0.6 (95% CI, 0.4-0.8; P < .001); and 4 or more cups per day, 0.2 (95% CI, 0.1-0.4; P < .001). This means that patients who drank 4 or more cups of coffee had an 80% decrease in the relative risk for alcoholic cirrhosis. Among subgroups of patients with nonalcoholic cirrhosis, coffee had a similar, weak, albeit not statistically significant inverse relation to risk for either viral hepatitis-associated cirrhosis or to miscellaneous, other cirrhosis. Tea drinking, on the other hand, was unrelated to the risk for either alcoholic or nonalcoholic cirrhosis.
In a cross-sectional analysis, coffee drinking was also related to a lower prevalence of high aspartate aminotransferase and alanine aminotransferase levels. The odds ratio of 4 or more cups per day (vs none) for a high aspartate aminotransferase level was 0.5 (95% CI, 0.4-0.6; P < .001) and for a high alanine aminotransferase level, 0.6 (95% CI, 0.6-0.7; P < .001), with stronger inverse relations in those patients who drank large quantities of alcohol.
Viewpoint
A number of limitations need to be considered in the interpretation of these study findings, including the fact that smoking, drinking, and coffee consumption are often related habits, which makes it difficult to rule out residual confounding by alcohol amount or drinking pattern. The study authors proposed that smoking may prolong the persistence of caffeine in the body. Thus, any residual confounding effect that is related to coffee drinking would tend to produce an inverse smoking-cirrhosis relation, not the positive one evident in this study. This study was also limited by its reliance on baseline ascertainment of habits and incomplete follow-up of the cohort. Finally, the observational nature of these data and the absence of an established mechanism limit a causal interpretation.
Clearly these data suggested that further research focusing on hepatic coffee-ethanol interactions is warranted. Although this association with coffee consumption is extremely interesting, it would be the wrong message for patients to think that increasing coffee consumption rather than reduction of alcohol intake is the best strategy to avoid significant alcohol-related liver disease.
Abstract URL:http://www.medscape.com/medline/abstract/16772246