Human leukocyte antigen class I alleles can predict response to pegylated interferon/ribavirin therapy in chronic hepatitis C Egyptian patients.
BACKGROUND
Racial differences and broad spectrum response to anti-hepatitis C (anti-HCV) therapy suggest a possible role for host genetic diversity in treatment outcomes. We aim to determine the association and predictive value of certain human leukocyte antigen (HLA) class I alleles with either susceptibility to viral clearance or persistence following pegylated interferon (Peg-IFN) plus ribavirin therapy in chronic hepatitis C (HCV) genotype 4 patients in Egypt.


METHODS
This study included 200 unrelated chronic HCV patients who received Peg-IFN plus ribavirin therapy [112 patients with sustained virological response (SVR) and 88 non-responders (NR)]. Serological testing of HLA class I antigens (HLA-A and HLA-B alleles) were performed by standard complement-dependent microlymphocytotoxicity assay.


RESULTS
The frequency of HLA-A01 was significantly higher in SVR than in NR cases [OR: 0.51; 95% CI: 0.27-0.981; P = 0.042], while the frequency of alleles B38 (P = 0.011), B40 (P < 0.001) and B41 (P < 0.001) was significantly higher in NR cases (OR/95% CI: 7.05/(1.39-18.01), 10.31/3.14-36.1 . On logistic regression analysis, presence of the HLA-A01 allele was associated with SVR  (OR: 0.50; 95% CI: 0.28-0.89; P = 0.02) and HLA-B38 can predict non response to therapy (OR: 7.92; 95% CI: 1.67-37.54; P = 0.009) with an overall accuracy of 60%.Severe fibrosis (OR: 3.035; 95% CI: 1.521-6.091; P = 0.002), high viremia (OR: 2.69; 95% CI: 1.11-6.53; P = 0.005) and steatosis (OR: 2.1; 95% CI: 1.002-3.90; P = 0.041) predicted no response with an overall accuracy of 81.8%.


CONCLUSIONS
HLA-A01 and HLA-B38 alleles are associated with and may have a role in the outcome of response to Peg-IFN plus ribavirin therapy in Egyptian patients diagnosed with chronic HCV infection. The use of immunologic markers to predict the outcome of treatment may help pharmacogenetic personalization of treatment for HCV infection.
Tropical Medicine Unit, Mansoura University Hospital, Mansoura Faculty of Medicine, Egypt. raghda.farag@yahoo.com
Raghda E
RE
Farag
Mona M
MM
Arafa
Shahira
S
El-Etreby
Niveen S
NS
Saudy
Basem S
BS
Eldeek
Hatem A
HA
El-Alfy
Inas F
IF
Goda
Rabab M
RM
Ali
D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004534:Egypt; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons