Relationship Between Transferrin-Iron Saturation, Alcohol Consumption, and the Incidence of Cirrhosis and Liver Cancer

Abstract

Excessive alcohol consumption and iron overload might act in synergy to promote hepatic fibrogenesis and carcinogenesis. We examined the relation between baseline serum transferrin-iron saturation (TS) and the incidence of hospitalizations or deaths related to cirrhosis and liver cancer as well as the influence of alcohol consumption on this relationship. Participants included 8767 persons aged 25-74 years without evidence of cirrhosis at entry into the study or during the first 5 years of follow-up who were subsequently followed for a mean of 13.3 years as part of the first National Health and Nutrition Examination Survey. During 116,656 person-years of follow-up, 115 participants were hospitalized for or died of cirrhosis and 4 more of liver cancer. Compared with persons with low TS (<40%) and low alcohol consumption (</=1 drink/day) who had an incidence of cirrhosis/liver cancer of 70/100,000 person-years, the incidence was increased in persons with elevated TS (>/=40%) and low alcohol consumption (154/100,000; adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8) and in persons with low TS and elevated (>1 drink/day) alcohol consumption (198/100,000; adjusted hazard ratio, 2.9; 95% confidence interval, 1.7-5.0). The incidence of cirrhosis/liver cancer was particularly high among persons with both elevated TS and elevated alcohol consumption (480/100,000; adjusted hazard ratio, 6.8; 95% confidence interval, 3.6-12.9), exceeding the rate predicted by the addition of the separate attributable risks associated with drinking and elevated serum TS. Elevated serum TS is associated with an increased incidence of cirrhosis or liver cancer particularly in the presence of elevated alcohol consumption.