Cirrhosis in Hemochromatosis: Independent Risk Factors in 368 HFE p.C282Y Homozygotes

Abstract

Introduction and aim: We sought to identify independent risk factors for cirrhosis in HFE p.C282Y homozygotes in a cross-sectional study.

Material and methods: We evaluated 368 p.C282Y homozygotes who underwent liver biopsy and compared characteristics of those with and without cirrhosis. We performed multivariable logistic regression on cirrhosis with: age; sex; race/ethnicity; diabetes; blood pints/units donated voluntarily; erythrocyte pints/units received; iron supplement use; alcohol intake, g/d; body mass index, kg/m2; swollen/tender 2nd/3rd metacarpophalangeal joints; elevated alanine aminotransferase; elevated aspartate aminotransferase; steatosis/fatty liver; iron removed by phlebotomy, g; and GNPAT p.D519G positivity.

Results: Mean age of 368 participants (73.6% men) was 47 ± 13 (standard deviation) y. Cirrhosis was diagnosed in 86 participants (23.4%). Participants with cirrhosis had significantly greater mean age, proportion of men, diabetes prevalence, mean daily alcohol intake, prevalence of swollen/ tender 2nd/3rd metacarpophalangeal joints, mean serum ferritin, elevated alanine aminotransferase, elevated aspartate aminotransferase, and mean iron removed; and significantly fewer mean blood pints/units donated. GNPAT p.D519G positivity was detected in 82 of 188 participants (43.6%). In a multivariable model for cirrhosis, there were four significant positive associations: age (10-y intervals) (odds ratio 2.2 [95% confidence interval 1.5, 3.3]); diabetes (3.3; [1.1, 9.7]); alcohol intake (14 g alcohol drinks/d) (1.5 [1.2, 1.8]); and iron removed, g (1.3 [1.2, 1.4]). There was no statistical evidence of two-way interactions between these variables.

Conclusion: In conclusion, cirrhosis in HFE p.C282Y homozygotes is significantly associated with age, diabetes, daily alcohol intake, and iron removed by phlebotomy, taking into account the effect of other variables.

Keywords: Alcohol intake; Diabetes; Iron overload; rs11558492; rs1800562.

Figure 1.

Odds ratios (black dots) and 95% confidence intervals for prediction of cirrhosis. The odds ratios for the continuous predictor variables including age increments since diagnosis (10 y intervals), incremental alcohol intake (g/14 (drink/d)), and additional iron removed to achieve iron depletion (g) represent the increased risks of biopsy-proven cirrhosis for the indicated increase in each individual predictor variable, adjusted for the presence of the remaining predictors. The diagnosis of diabetes also increases cirrhosis risk, adjusted for the presence of the remaining predictors.