Risk profiling for cirrhosis and hepatocellular carcinoma in HFE hemochromatosis using mobilizable iron stores and alcohol consumption

• Published in: Scientific reports Vol. 15; no. 1; pp. 16011 - 8
• Main Authors: Mitchell, Natasha D. P., Pierre, Timothy G. St, Ramm, Louise E., Ramm, Grant A., Olynyk, John K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.05.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4020/4021; 692/4020/4021/1607/1604; 692/4020/4021/1607/1610; Adult; Aged; Alcohol; Alcohol Drinking - adverse effects; Alcohol use; Alcohols; Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - etiology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cirrhosis; Diagnosis; Female; Hemochromatosis; Hemochromatosis - complications; Hemochromatosis - genetics; Hemochromatosis - metabolism; Hemochromatosis Protein - genetics; Hemochromatosis Protein - metabolism; Hepatic iron concentration (HIC); Hepatic iron index (HII); Hepatocellular carcinoma; Hepatocellular carcinoma (HCC); HFE hemochromatosis (HH); Humanities and Social Sciences; Humans; Iron; Iron - metabolism; Liver cancer; Liver cirrhosis; Liver Cirrhosis - epidemiology; Liver Cirrhosis - etiology; Liver Cirrhosis - metabolism; Liver Neoplasms - epidemiology; Liver Neoplasms - etiology; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Middle Aged; Mobilizable iron (MobFe); multidisciplinary; Retrospective Studies; Risk Factors; ROC Curve; Science; Science (multidisciplinary); HFE hemochromatosis (HH); Mobilizable iron (MobFe); Hepatic iron index (HII); Hepatocellular carcinoma (HCC); Hepatic iron concentration (HIC)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-99672-8

HFE hemochromatosis (HH) may cause cirrhosis and hepatocellular carcinoma (HCC). 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 (3.8–11.0) g and 20 (0–40) 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 (0.935–0.996), with sensitivity 76 (58–88)% and specificity 97 (93–99) % for prediction of cirrhosis and had a negative predictive value of 99.4 (95% CI 96.7–99.97) % for development of HCC. Thus, future risk of HCC can be assessed from mobilizable iron stores and alcohol consumption of HH subjects.