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-IFNalpha-2a monotherapy were evaluated. The associations between elevated serum ALT levels (> or =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-IFNalpha-2a.