Expression of interferon receptor genes in the liver as a predictor of interferon response in patients with chronic hepatitis C.
Interferon (IFN) receptor mRNA expression patterns in the liver have been shown to correlate with the effectiveness of IFN therapy in patients with hepatitis C virus (HCV) infection. However, it is not clear to what extent this factor contributes to the short (primary)- and long (sustained)-term results of IFN treatment with respect to biochemical and virological remission. Eighty-two patients who subsequently received lymphoblastoid IFN-alpha therapy underwent liver biopsies before IFN therapy. Possible factors that might correlate with IFN response were chosen and analyzed. The primary biochemical and virological responses at the end to treatment (24 weeks) were 63% and 43% vs. 46% and 32% for sustained biochemical and virological remission at the end of follow-up (48 weeks), respectively. In univariate analysis, the absence of HCV genotype 1b, a low titer of HCV RNA, and the expression of IFN receptor mRNA were significantly correlated with sustained biochemical and virological responses to IFN therapy. Multiple logistic regression analysis showed that IFN receptor mRNA expression and the absence of genotype 1b were significant predictors of the sustained biochemical and virological effectiveness of IFN therapy. IFN receptor mRNA expression predicted a sustained virological response to IFN therapy with a positive predictive value of 100% with genotype non-1b and had a negative predictive value of 97% with genotype 1b. It is concluded that expression of IFN receptor genes in the liver is a useful index for predicting the short- and long-term efficacy of IFN therapy in patients with chronic HCV infection.
Third Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
K
K
Morita
K
K
Tanaka
S
S
Saito
T
T
Kitamura
T
T
Kiba
T
T
Fujii
K
K
Numata
H
H
Sekihara
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000595:Amino Acid Sequence; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects; D017471:Receptors, Interferon / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D000410:Alanine Transaminase; D007372:Interferons; D012333:RNA, Messenger; D012367:RNA, Viral; D017471:Receptors, Interferon; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase