Intrahepatic mRNA levels of type I interferon receptor and interferon-stimulated genes in genotype 1b chronic hepatitis C. Association between IFNAR1 mRNA level and sustained response to interferon therapy.
OBJECTIVE
The aim of this study was to determine the association between pretreatment intrahepatic mRNA levels of interferon receptor and interferon-stimulated genes and response to interferon therapy for genotype 1b chronic hepatitis C.


METHODS
Forty-four patients with genotype 1b chronic hepatitis C who underwent liver biopsy and then received interferon therapy participated in this study. Pretreatment intrahepatic mRNA levels of interferon receptor genes (IFNAR1, IFNAR2b, and IFNAR2c) and interferon-stimulated genes (OAS1 and PKR) were quantified by competitive polymerase chain reaction.


RESULTS
In the genes examined, only IFNAR1 mRNA level was significantly higher in patients with sustained virological and biochemical response to interferon therapy versus those with nonsustained response (p < 0.01). Moreover, mRNA expression ratios of IFNAR1 to IFNAR2 were also significantly higher in patients with sustained virological and biochemical response to IFN therapy (p < 0.01 and p < 0.05, respectively). On the other hand, mRNA levels of IFNAR2b, IFNAR2c, and PKR were significantly higher in patients with histologically active or advanced liver rather than patients with mild or less advanced liver.


CONCLUSIONS
High intrahepatic mRNA levels of IFNAR1 and mRNA ratio of IFNAR1 to IFNAR2 before treatment may be associated with a favorable response to interferon therapy.
Taniguchi
Hideaki
H
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Iwasaki
Yoshiaki
Y
Takahashi
Akira
A
Shimomura
Hiroyuki
H
Moriya
Akio
A
Yu
Piao Cheng
PC
Umeoka
Fumi
F
Fujioka
Shin-ichi
S
Koide
Norio
N
Shiratori
Yasushi
Y
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000097:blood; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
D000998:Antiviral Agents; C507964:IFNAR1 protein, human; D016898:Interferon-alpha; D012333:RNA, Messenger; D012367:RNA, Viral; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D019892:eIF-2 Kinase; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase