Clinical burden of liver disease from hemochromatosis at an academic medical center

Hereditary hemochromatosis (HH) can cause cirrhosis and hepatocellular carcinoma (HCC), but the frequency of these complications is controversial. To address this question, we reviewed the experience with HH at an academic medical center that is the sole liver transplantation center in a state with a population that is >90% Caucasian. The records of all subjects with International Classification of Diseases, Ninth Revision, code 275, "disorders of iron metabolism" seen at the University of Iowa Hospitals and Clinics between January 1, 2004 and December 31, 2014 were reviewed, and HFE C282Y homozygotes and C282Y/H63D compound heterozygotes were identified. Clinical, pathologic, and laboratory data from these subjects were examined in detail. We identified 118 C282Y homozygotes and 44 compound heterozygotes; 22 of the former and 3 of the latter had advanced hepatic fibrosis (bridging or cirrhosis). Male patients predominated in both groups. Most of the C282Y homozygotes and all compound heterozygotes had causes of chronic liver disease in addition to iron overload. Together, these accounted for 0.42% of cases of cirrhosis seen at the University of Iowa Hospitals and Clinics during this period. Two male patients with cirrhosis attributable solely to iron overload presented with cardiac dysfunction and atrial fibrillation; this classical presentation was rare, representing approximately one per 3,000 cases of cirrhosis. Eight homozygotes were diagnosed with HCC, representing 1.8% of patients with HCC. Conclusion: Despite the expected high prevalence of HH mutations in our state and the referral bias inherent in our study, serious hepatic manifestations of HH were uncommon. These data support claims that the penetrance of frank clinical hemochromatosis is low. (Hepatology Communications 2017;1:453-459).