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Risk profiling for cirrhosis and hepatocellular carcinoma in HFE hemochromatosis using mobilizable iron stores and
Natasha D P Mitchell1, Timothy G St Pierre2, Louise E Ramm3,4
1Department of Gastroenterology, Fiona Stanley Hospital, Murdoch, WA, Australia.
Insights
HFE hemochromatosis (HH) patients with high iron stores and alcohol consumption face increased cirrhosis risk. Early assessment of these factors can predict future liver cancer (HCC) development in HH.
Area of Science:
- Hepatology
- Genetics
- Oncology
Background:
- HFE hemochromatosis (HH) is a genetic disorder causing excessive iron absorption.
- Iron overload in HH can lead to liver cirrhosis and hepatocellular carcinoma (HCC).
- Alcohol consumption is a known cofactor exacerbating liver damage in HH.
Purpose of the Study:
- To evaluate alcohol and iron-related risk factors for cirrhosis at diagnosis and HCC development in HH patients.
- To develop a predictive model for cirrhosis and assess future HCC risk based on identified factors.
Main Methods:
- Retrospective analysis of 197 HH subjects.
- Logistic regression modeling incorporating mobilizable iron stores, alcohol consumption, and age.
- Area Under the Receiver Operating Characteristic Curve (AUROC) analysis for model validation.
Main Results:
- The study identified a significant association between iron overload, alcohol consumption, and cirrhosis risk.
- The developed logistic regression model demonstrated high accuracy (AUROC 0.966) in predicting cirrhosis.
- The model showed a high negative predictive value (99.4%) for future HCC development.
Conclusions:
- Mobilizable iron stores and alcohol consumption are key predictors of cirrhosis in HH.
- These factors can be used to assess the future risk of HCC in HH patients.
- Early identification and management of these risk factors are crucial for preventing severe liver outcomes.
Abstract:
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.
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