Elevated serum ALT levels during pegylated interferon monotherapy may be caused by hepatic iron overload.
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.


CONCLUSIONS
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.
Nagashima
Miki
M
Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Ohno-Higashi, Osaka-Sayama, Japan.
Kudo
Masatoshi
M
Chung
Hobyung
H
Ishikawa
Emi
E
Inoue
Tatsuo
T
Nakatani
Tatsuya
T
Dote
Kensaku
K
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001706:Biopsy; D005260:Female; D005293:Ferritins / Q000097:blood; D005355:Fibrosis / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use*; D007501:Iron; D019190:Iron Overload / Q000139:chemically induced*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use*; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D005293:Ferritins; D007501:Iron; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a