title: HLA class I B44 is associated with sustained response to interferon + ribavirin therapy in patients with chronic hepatitis C.
abstract: 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.
authors.affiliation: Hepatology Unit, Hospital Universitario de Valme, Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.forename: María Francisca
authors.initials: MF
authors.lastname: González-Escribano
authors.forename: Belén
authors.initials: B
authors.lastname: Torres
authors.forename: Natalia
authors.initials: N
authors.lastname: Barroso
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Montes-Cano
authors.forename: Diego
authors.initials: D
authors.lastname: Sánchez-Muñoz
authors.forename: Antonio
authors.initials: A
authors.lastname: Núñez-Roldan
authors.forename: José
authors.initials: J
authors.lastname: Aguilar-Reina
mesh_terms: 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
chemical_list: 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