HLA class I B44 is associated with sustained response to interferon + ribavirin therapy in patients with chronic hepatitis C.
OBJECTIVE
The aim of this study was to assess the influence of host genetic factors on response to combination therapy for chronic hepatitis C infection.


METHODS
Patients with biopsy-proved chronic hepatitis C infection were treated with interferon alone (n = 143) or combined therapy of interferon + ribavarin (n = 105; 46 treatment naïve, 59 relapsers). Human leukocyte antigen (HLA) class I was determined by microlymphocytotoxicity and class II by polymerase chain reaction-single specific oligonucleotide. The two biallelic tumor necrosis factor-alpha promoter polymorphisms were studied by a polymerase chain reaction-amplification refractory mutation system. Other variables measured were viral genotype, hepatitis C virus RNA load, liver function tests, and ferritin concentration.


RESULTS
Univariate analysis indicated that patients bearing HLA B44+, DRB1*03, infected by genotype non-1, with higher concentrations of transaminases and shorter duration of infection showed a higher sustained response (SR) rate than those on combination therapy. HLA class II and TNF-alpha promoter polymorphisms were not related to SR. In multivariate analysis, non-1 genotype (OR 2.42, 95% CI 1.12-5.55, p = 0.026) and HLA B44+ (OR 4.84, 95% CI 1.3-17.8, p = 0.017) were the independent variables associated with SR. However, HLA B44+ was not associated with SR in patients treated with interferon alone.


CONCLUSIONS
HLA class I B44 is related to a higher rate of SR in combination therapy but not in interferon monotherapy, whereas HLA class II, tumor necrosis factor-alpha -238A or -308A seem not to influence response to the antiviral therapy. These findings may be of value in therapy selection for hepatitis C-infected patients.
Romero-Gómez
Manuel
M
Hepatology Unit, Hospital Universitario de Valme, Seville, Spain.
González-Escribano
María Francisca
MF
Torres
Belén
B
Barroso
Natalia
N
Montes-Cano
Marco Antonio
MA
Sánchez-Muñoz
Diego
D
Núñez-Roldan
Antonio
A
Aguilar-Reina
José
J
D000328:Adult; D000375:Aging; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005838:Genotype; D015235:HLA-B Antigens / Q000032:analysis*; D059948:HLA-B44 Antigen; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000998:Antiviral Agents; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; D012254:Ribavirin; D007372:Interferons