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Progression to these endpoints depends on the severity of iron overload and cofactors, such as alcohol. We evaluated alcohol and iron-related risk factors in relation to cirrhosis at diagnosis and future development of HCC in a retrospective analysis of 197 HH subjects. The proportion of subjects either with cirrhosis or who developed HCC during follow-up were 29\/197 (14.7%) or 10\/197 (5.1%), respectively. The median (IQR) follow-up time after diagnosis was 15.2 (4.6 to 22.1) years. The median mobilizable iron stores and daily alcohol consumption (IQR) were 6.0 (3.8\u201311.0) g and 20 (0\u201340) g, respectively. An optimal logistic regression model for the odds of cirrhosis was developed by adding candidate liver insult variables (mobilizable iron, alcohol consumption, and age as a surrogate for duration of exposure) in a forward stepwise strategy using area under the receiver operating characteristic curve (AUROC) analysis and the corrected Akaike information criterion. This model demonstrated an AUROC (95% CI) of 0.966 (0.935\u20130.996), with sensitivity 76 (58\u201388)% and specificity 97 (93\u201399) % for prediction of cirrhosis and had a negative predictive value of 99.4 (95% CI 96.7\u201399.97) % for development of HCC. Thus, future risk of HCC can be assessed from mobilizable iron stores and alcohol consumption of HH subjects.<\/jats:p>","DOI":"10.1038\/s41598-025-99672-8","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T04:03:06Z","timestamp":1746676986000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk profiling for cirrhosis and hepatocellular carcinoma in HFE hemochromatosis using mobilizable iron stores and alcohol consumption"],"prefix":"10.1038","volume":"15","author":[{"given":"Natasha D. 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