Patients with chronic hepatitis C may be more sensitive to iron hepatotoxicity than patients with HEF-Hemochromatosis

Aim In chronic hepatitis C, iron might play an important role as a hepatotoxic co-factor. Therefore, venesection, a standard treatment for hemochromatosis, has been proposed as an alternative for patients who respond poorly to anti-viral therapy. To improve our understanding of iron-induced hepatotoxicity, we compared the responses to venesection between patients with chronic hepatitis C and those with HFEhemochromatosis. Methods Fourteen Japanese patients with chronic hepatitis C and eight Italian patients with HFEhemochromatosis underwent repeated venesection with a serum ferritin endpoint of 20 and 50 ng/mL, respectively. Serum iron indices and liver function tests were measured in pre- and post treatment blood samples from each patient. Body iron stores were calculated using the removed blood volume. Results In both patients with hepatitis and hemochromatosis, serum ferritin, aminotransferase and hepcidin 25 were reduced after venesection. The serum aminotransferase activity, but not the serum ferritin level, was predictive of effective iron removal treatment. Hepcidin regulation was set at an inappropriately low level in hemochromatosis patients (11.1 ± 9.2 ng/mL), but not so in hepatitis patients (30.7 ± 14.5 ng/mL). Inversely, the estimated body iron stores of hemochromatosis patients were 5,960 ± 2,750 mg, while those of hepatitis patients were 730 ± 560 mg. Judging from the liver enzyme reduction ratio, patients with hepatitis seemed to be more sensitive to iron hepatotoxicity than hemochromatosis patients. Conclusion Even though the threshold of iron hepatotoxicity and benefit of its removal differ between patients with chronic hepatitis C and those with HFE-hemochromatosis, venesection is a valid choice of treatment to reduce liver disease activity in both diseases.