Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research.
BACKGROUND
The outcome of infection with hepatitis C virus (HCV) varies substantially among individuals. Host genetic factors are likely to give rise to some of this variability. Polymorphisms in the MHC class II loci may influence the outcome of HCV infection; however, reports of MHC class II allele associations have been inconsistent. We aimed to confirm these associations in a cohort of European patients with different clinical outcomes.


METHODS
The distribution of MHC class II alleles was compared between patients with self-limiting infection (n=85) and matched patients with persistent infection (n=170); between patients with mild (n=321) and severe (n=321) histological injury; and between patients who responded to interferon (n=96) and those who did not (n=192). The results of these comparisons were confirmed with a second-stage study of self-limiting infection (n=52) versus persistent infection (n=152).


RESULTS
Self-limiting HCV infection was associated with HLA-DRB1*1101 (odds ratio 2.14 [95% CI 1.11-4.12]; p=0.013) and HLA-DQB1*0301 (2.22 [1.24-3.96], p=0.004). Persistent HCV infection was associated with HLA-DRB1*0701 (2.04 [1.03-4.17], p=0.027), and HLA-DRB4*0101 (2.38 [1.29-4.35], p=0.002). These results were confirmed in the second-stage study. No significant associations (p<0.05 after Bonferroni correction) were found between MHC class II alleles and severe histological injury or response to interferon therapy.


CONCLUSIONS
Specific MHC class II alleles influence susceptibility or resistance to persistent HCV infection.
Thursz
M
M
Division of Medicine A, Imperial College, School of Medicine at St Mary's Hospital, London, UK. m.thursz@ic.ac.uk
Yallop
R
R
Goldin
R
R
Trepo
C
C
Thomas
H C
HC
D015331:Cohort Studies; D005060:Europe; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics / Q000302:isolation & purification; D006684:HLA-DR Antigens / Q000235:genetics / Q000302:isolation & purification; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007372:Interferons