HLA class I B44 is associated with sustained response to interferon + ribavirin therapy in patients with chronic hepatitis C

Am J Gastroenterol. 2003 Jul;98(7):1621-6. doi: 10.1111/j.1572-0241.2003.07537.x.


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.

MeSH terms

  • Adult
  • Aging
  • Alleles
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Genotype
  • HLA-B Antigens / analysis*
  • HLA-B44 Antigen
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology
  • Histocompatibility Antigens Class II / analysis
  • Humans
  • Interferons / therapeutic use*
  • Middle Aged
  • Multivariate Analysis
  • Ribavirin / therapeutic use*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics


  • Antiviral Agents
  • HLA-B Antigens
  • HLA-B44 Antigen
  • Histocompatibility Antigens Class II
  • Tumor Necrosis Factor-alpha
  • Ribavirin
  • Interferons