Association of HLA alleles with response (especially biochemical response) to interferon therapy in Japanese patients with chronic hepatitis C.
The response of chronic hepatitis C to interferon (IFN) treatment is classified as complete response (CR), biochemical response (BR), or no response (NR). Several studies have found no difference in prevention of hepatocellular carcinoma by IFN therapy between patients with CR and those with BR. We investigated whether specific human leukocyte antigen (HLA) alleles were associated with response to IFN, especially BR, in 138 patients with chronic hepatitis C. Comparing patients with and without CR, male, a low viral titer, genotype 2a or 2b, HLA-B55, and HLA-DRB1-0803 were more common in the group with CR. Multivariate analysis showed that age (adjusted odds ratio [OR], 0.95 by every year [95% confidence interval [CI] 0.90 - 0.99], p = 0.028), genotype 2a or 2b (5.21 [95% CI 1.63 - 16.6], p = 0.005), and low viral titer (8.58 (2.66 - 27.7), p < 0.001) were associated with CR. Comparing patients with BR and NR, the pretreatment alanine aminotransferase (ALT) level was lower in the BR group (p < 0.001). Both HLA-B7 and HLA-DRB1-0101 were more common in this group (p = 0.002). As the alleles HLA-B7 and HLA-DRB1-0101 were in linkage disequilibrium, the HLA-B7-DRB1-0101 haplotype may be associated with BR. Multivariate analysis indicated that a low ALT level (0.98 by every 1 IU/L [95% CI 0.98 - 0.99], p = 0.001) and HLA-B7-DRB1-0101 haplotype (32.3 [95% CI 1.50 - 693.1], p = 0.026) contributed significantly to BR. This study suggested that host HLA expression, but not viral factors, can influence BR.
Nishiguchi
Shuhei
S
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan. snishiguch@med.osaka-cu.ac.jp
Kaneshiro
Satoshi
S
Tanaka
Motoharu
M
Enomoto
Masaru
M
Akihiro
Tamori
T
Habu
Daiki
D
Takeda
Tadashi
T
Fujino
Keizo
K
Tanaka
Takashi
T
Yano
Yoshihisa
Y
Shiomi
Susumu
S
D000483:Alleles; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005355:Fibrosis / Q000150:complications / Q000188:drug therapy; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006650:Histocompatibility Testing; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D015415:Biomarkers; D006680:HLA Antigens; D015234:HLA-A Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D016899:Interferon-beta; D007372:Interferons