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

Background & Aims: 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. Methods: 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. Results: 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. Conclusions: Elevated serum TS is associated with an increased incidence of cirrhosis or liver cancer particularly in the presence of elevated alcohol consumption.