Serum levels of soluble tumor necrosis factor receptors and effects of interferon therapy in patients with chronic hepatitis C virus infection.
OBJECTIVE
The aim of this study was to understand the significance of the tumor necrosis factor receptor (TNFR)-mediated signaling pathway in the pathophysiology of chronic hepatitis C.


METHODS
The serum levels of soluble TNFRs (sTNFRs; sTNFR p55 and sTNFR p75) were measured in 84 patients with chronic hepatitis C virus (HCV) infection (24 sustained responders and 25 nonresponders to interferon [IFN] therapy and 35 patients with persistent normal blood chemistries) and 20 healthy controls, then compared with clinical parameters.


RESULTS
The serum levels of sTNFRs increased in proportion to the severity of liver disease. The levels of sTNFRs revealed significant correlations with the serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and gamma-globulin, but not with the serum levels of HCV-core protein. In the sustained responder group, the levels of sTNFR p75 showed a significant decrease (p < 0.0002) 1 yr after IFN therapy, although the levels of sTNFR p55 did not. The levels of sTNFR p75 were correlated with the serum levels of macrophage-colony stimulating factor both before and after IFN therapy. In the nonresponder group, the levels of both sTNFRs were unaltered after IFN therapy.


CONCLUSIONS
The TNF alpha-TNFRs system, especially the TNFR p75-mediated pathway, is involved in the hepatic inflammation-fibrosis process in chronic hepatitis C. The serum levels of sTNFR p75, but not sTNFR p55, were correlated with the serum levels of macrophage colony stimulating factor in this process.
Itoh
Y
Y
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Okanoue
T
T
Ohnishi
N
N
Sakamoto
M
M
Nishioji
K
K
Nakagawa
Y
Y
Minami
M
M
Murakami
Y
Y
Kashima
K
K
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000097:blood / Q000628:therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood* / Q000502:physiology; D014758:Viral Core Proteins / Q000097:blood
D000998:Antiviral Agents; D016898:Interferon-alpha; D018124:Receptors, Tumor Necrosis Factor; D014758:Viral Core Proteins; D016173:Macrophage Colony-Stimulating Factor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase