Is Serum Hepcidin Causative in Hemochromatosis? Novel Analysis from a Liver Transplant with Hemochromatosis

Abstract

Hepcidin is a circulating hepatic hormone that regulates iron balance. It has been speculated that hepcidin insufficiency or dysregulation may be the primary defect in genetic hemochromatosis. A 62-year-old woman underwent elective liver transplantation for chronic hepatitis C cirrhosis. Genetic testing for hemochromatosis was subsequently performed on the donor and recipient. Liver iron concentration was measured in the donated liver at the time of transplantation, and at day 2 and day 652 post-transplant. Serum hepcidin was measured at day 935 in the recipient and in three other liver transplant recipients. The donor was discovered to have significant iron overload without fibrosis, with a liver iron concentration of 326 micromol/g (normal is 0 micromol/g to 35 micromol/g). Genetic testing confirmed that the 89-year-old female donor was a typical C282Y homozygote for hemochromatosis. The recipient did not carry either the C282Y or the H63D mutation of the HFE gene for hemochromatosis. Liver biopsy was performed on the recipient on day 2 and day 652 post-transplant; the liver iron concentrations were 333 micromol/g and 253 micromol/g, respectively. Serum hepcidin in the recipient was elevated at 111 ng/mL compared with that of the three other ambulatory liver transplant recipients (66 ng/mL, 76 ng/mL and 81 ng/mL). The liver transplant recipient described in the present report demonstrated a slight decrease in liver iron concentration over a 1.8-year follow-up period without specific therapy. Hepcidin insufficiency as a primary cause of genetic hemochromatosis seems unlikely based on the clinical profile of the present patient and the hepcidin measurements.