Type I interferon receptor and response to interferon therapy in chronic hepatitis C patients: a prospective study.
The type I interferon (IFN) receptor consists of at least two subunits, IFNAR1 and IFNAR2. We previously found a correlation between IFNAR1 and IFNAR2 expression in liver, and a correlation in IFNAR2 expression, but not in IFNAR1, between liver and peripheral blood mononuclear cells (PBMCs). The aim of this study was to prospectively assess whether IFNAR2 expression levels in PBMCs as well as in liver act as markers for predicting response to IFN therapy in chronic hepatitis C patients. Fifty-two Japanese patients with chronic hepatitis C, were enrolled. IFNAR2 mRNA was quantified using competitive polymerase chain reaction, in liver and PBMC specimens, and of the 52 patients assigned to receive a 6-month course of interferon-alpha therapy, 36 patients who received more than 300 million units of interferon were analysed. IFNAR2 mRNA expression levels were significantly higher in liver than in PBMCs in all 36 patients (P = 0.016). Seventeen sustained virologic responders showed lower pretreatment hepatitis C virus (HCV)-RNA levels (P = 0.017) in serum and higher pretreatment levels of IFNAR2 mRNA in liver (P = 0.007), but not in PBMCs, compared with nonsustained virologic responders. In multivariate analysis, these factors were independently associated with a sustained virologic response (i.e. HCV-RNA level: odds ratio 0.23, 95% CI 0.038-0.864; and IFNAR2 in liver: odds ratio 1.116, 95% CI 1.015-1.227). Hence, IFNAR2 expression levels in liver, but not in PBMCs, is predictive of response to IFN treatment in chronic hepatitis C patients.
Department of Gastroenterology and Hepatology, School of Medicine, Yamaguchi University, Yamaguchi, Japan.
D
D
Fujiwara
K
K
Hino
Y
Y
Yamaguchi
Y
Y
Kubo
S
S
Yamashita
K
K
Uchida
T
T
Konishi
H
H
Nakamura
M
M
Korenaga
M
M
Okuda
K
K
Okita
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins
D000998:Antiviral Agents; C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008565:Membrane Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta