Serum thioredoxin levels as an indicator of oxidative stress in patients with hepatitis C virus infection.
OBJECTIVE
It has recently been suggested that oxidative stress may be associated with hepatitis C virus (HCV) infection. Thioredoxin (TRX) is a stress-inducible thiol-containing protein. The aim of this study was to evaluate the clinical significance of serum TRX levels in patients with HCV-related chronic liver diseases.


METHODS
Serum TRX levels were determined with a sandwich enzyme-linked immunosorbent assay kit in 174 serum HCV-RNA positive patients, including 6 asymptomatic carriers, 124 chronic hepatitis, 20 liver cirrhosis, and 24 hepatocellular carcinoma, and in 15 healthy volunteers.


RESULTS
The serum TRX levels (medians and [ranges], ng/ml) were significantly elevated in the HCV-infected patients; 30.9 [20.7-37.7] in asymptomatic carriers, 34.5 [8.6-135.6]* in chronic hepatitis, 42.5 [21.4-97.2]* in liver cirrhosis, and 43.9 [11.7-180.3]** in hepatocellular carcinoma (*p<0.05, **p<0.001, vs. 24.9 [1.3-50.7] in healthy controls). Serum TRX levels were significantly correlated with the serum levels of ferritin and fibrogenesis markers, and with the histological stage of hepatic fibrosis. The serum TRX levels before interferon treatment of patients whose serum HCV-RNA was still positive on day 14 following interferon treatment (42.6 [20.1-90.0]) were significantly higher than those of patients whose serum HCV-RNA was negative on day 14 following interferon treatment (25.8 [7.4-59.8], p<0.05).


CONCLUSIONS
The serum TRX levels of patients with HCV infection increased with their serum ferritin levels and the progression of liver fibrosis. Patients with higher serum TRX levels exhibited resistance to interferon therapy. Oxidative stress may therefore be responsible for the pathological mechanism of HCV-related liver diseases and be one of the impediments to eradication of HCV during interferon treatment.
Sumida
Y
Y
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan. redox@sun.kpu-m.ac.jp
Nakashima
T
T
Yoh
T
T
Nakajima
Y
Y
Ishikawa
H
H
Mitsuyoshi
H
H
Sakamoto
Y
Y
Okanoue
T
T
Kashima
K
K
Nakamura
H
H
Yodoi
J
J
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000097:blood; D002353:Carrier State / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005293:Ferritins / Q000097:blood; D016174:Hepacivirus / Q000145:classification; D006526:Hepatitis C / Q000097:blood* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012367:RNA, Viral / Q000097:blood; D012016:Reference Values; D012703:Serotyping; D013879:Thioredoxins / Q000097:blood*
D015415:Biomarkers; D012367:RNA, Viral; D013879:Thioredoxins; D005293:Ferritins; D000410:Alanine Transaminase