Elevated Serum ALT Levels during Pegylated Interferon Monotherapy May Be Caused by Hepatic Iron Overload

Abstract

Objective: Persistently elevated serum alanine aminotransferase (ALT) levels have been observed in chronic hepatitis C (CHC) patients during pegylated interferon (PEG-IFN) therapy. We investigated whether elevated serum ALT levels during PEG-IFN therapy are associated with iron overload. Methods: Sixty-three CHC patients treated with PEG-IFNα-2a monotherapy were evaluated. The associations between elevated serum ALT levels (≧70 IU/l) were investigated before and 24 weeks after therapy. We classified patients as follows: patients with no elevated serum ALT levels (group NE: n = 35), patients with elevated serum ALT levels (group E: n = 28), and patients with no elevated serum ALT level and negative HCV RNA (group NE–: n = 24), and patients with elevated serum ALT level and negative HCV RNA (group E–: n = 19). We also compared total iron score (TIS) and fibrosis stage in liver specimens obtained before and during therapy from 3 patients with elevated serum ALT levels. Results: Serum ferritin levels were significantly increased after 24 weeks compared to baseline levels in group E (218 ± 273 vs. 438 ± 308 ng/ml; p < 0.0001) and group E– (146 ± 152 vs. 410 ± 291 ng/ml; p < 0.0001). Serum ALT and ferritin levels were significantly correlated after 24 weeks. The liver specimens revealed that TIS and fibrosis progressed during therapy. Conclusion: Our findings suggest that the elevation in serum ALT levels during therapy is caused by iron overload which may be induced by PEG-IFNα-2a.