Role of serum soluble Fas/soluble Fas ligand and TNF-alpha on response to interferon-alpha therapy in chronic hepatitis C.
OBJECTIVE
To determine the relationship between host factors and host response to interferon (IFN) therapy, serum soluble Fas (sFas), soluble Fas ligand (sFas ligand), and tumor necrosis factor-alpha (TNF-alpha) were analyzed in 41 patients with chronic hepatitis C (CH-C) treated with IFN-alpha.


METHODS
Serum levels of sFas, sFas ligand, and TNF-alpha were measured at 0, 4, and 24 weeks of IFN therapy.


RESULTS
Eighteen patients were complete responders (CR) and 23 patients were non-responders (NR). Serum levels of sFas and TNF-alpha in patients with CHC were significantly higher than those in healthy controls (p<0.01 and p<0.01, respectively). Serum sFas ligand levels were significantly lower in CH-C patients than in healthy controls (p<0.01). Before IFN therapy, serum levels of sFas in NR were significantly higher than those in CR (p<0.05). At 4 weeks of IFN therapy, serum levels of sFas of CR were significantly elevated compared with levels before IFN therapy (p<0.05). Serum levels of sFas correlated with the histological activity of the liver (p<0.05) and alanine aminotransferase (p<0.05). None of the three parameters, serum sFas, sFas ligand, or TNF-alpha levels, correlated with each other, with HCV-RNA genotype or with serum HCV-RNA load. Multiple logistic regression analysis showed that serum sFas levels before IFN therapy were a contributive factor to predict efficacy of IFN therapy.


CONCLUSIONS
Serum sFas/sFas ligand and TNF-alpha play a possible role in pathogenesis of CH-C and also in IFN therapy. Serum sFas levels before IFN therapy may be one of the host-related factors used for evaluating the response of CH-C patients to IFN therapy.
Toyoda
M
M
The First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Kakizaki
S
S
Horiguchi
N
N
Sato
K
K
Takayama
H
H
Takagi
H
H
Nagamine
T
T
Mori
M
M
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D053222:Fas Ligand Protein; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019562:Viral Load; D019014:fas Receptor / Q000097:blood*
D000998:Antiviral Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor