Serum Levels of Soluble Tumor Necrosis Factor Receptors and Effects of Interferon Therapy in Patients With Chronic Hepatitis C Virus Infection

Itoh, Yoshito; Okanoue, Takeshi; Ohnishi, Naoki; Sakamoto, Masafumi; Nishioji, Kenichi; Nakagawa, Yoshio; Minami, Masahito; Murakami, Yoshiki; Kashima, Kei
May 1999
American Journal of Gastroenterology;May1999, Vol. 94 Issue 5, p1332
Academic Journal
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 (9.24 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, γ-glutamyl transpeptidase, and γ-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 α-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.


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