title: [PROGNOSTIC VALUE OF THE COMBINATION OF BLOOD GROUP SPECIFICITY AND INTERLEUKIN 28B GENE POLYMORPHISM FOR ESTIMATION OF EFFICIENCY OF THERAPY WITH THE USE OF PEGYLATED INTERFERON α-2 AND RIBAVARIN IN PATIENTS WITH CHRONIC GENOTYPE 1 HEPATITIS C].
abstract: OBJECTIVE
  To estimate the prognostic value of the combination of blood group specificity and interleukin 28B gene polymorphism for the achievement of sustained virologic response (SVR) to antiviral therapy (AVT) with the use of pegylated interferon α-2 and ribavarin in patients with chronic genotype 1 hepatitis C (CHC-1). The secondary aim was to evaluate the influence of these genetic factors on the progress of hepatic fibrosis in case of failure of the above treatment.
  
  
  METHODS
  A total of 146 patients with CHC-1 were examined. We studied the RNA genotype of hepatitis C virus, blood group specificity, IL-28B gene polymorphism, and severity of hepatic fibrosis (puncture biopsies). Dynamics of hepatic fibrosis was followed up in 40 patients who failed to develop the virologic response. 20 control patients did not receive AVT. The multifactor significance criterion was used to identify the initial factor that produced the highest effect on SVR.
  
  
  RESULTS
  SVR was observed in 56.8% of the patients. Its efficiency was most significantly influenced by. the combination of blood group specificity and interleukin 28B gene polymorphism (p = 0.000024). Combination of blood group (0)1 with C/C or T/T IL-28B genotypes, A(II) with C/T or T/T and B(III) with T/G was associated with SVR in 100, 88.2, and 94.4% cases respectively. It was absent in patients with blood group A(II) in combination with double-nucleotide substitution in rs8099917 of the IL-28B gene (TG and GG genotypes); these patients suffered progressive fibrosis. SVR occurred in 83.8% of the patients with blood group B(III).
  
  
  CONCLUSIONS
  The knowledge of blood group in patients with CHC-1 and IL-28B gene polymorphism treated with the use of pegylated interferon α-2 and ribavarin allows to predict SVR with a probability of 100% in case of blood group 0(1) and C/C or T/T genotypes, 88.2% in case of blood group A(II) and single-nucleotide C>Tsubstitution in rs8099917 locus of the IL-28B gene, 94.4% in case of blood group B(II) and single-nucleotide T>G substitution in the rs809991.7 locus, 83.8% in case of blood group B(III). Treatment of patients with these genetic traits with antiviral drugs of direct action has no appreciable advances over treatment with AVT in combination with pegylated interferon α-2 and ribavarin (SVR above or around 85%). Patients with blood group A(II) and single- or double-nucleotide substitution in rs8099917 (TG or GG genotypes) have minimal chances to produce SVR to the above treatment. Simultaneous progression of hepatic fibrosis suggest that such therapy is undesirable in these cases. They should be regarded as main candidates for interferon-free therapy. Combination of blood group specificity and interleukin 28B gene polymorphism is a simple and reliable predictor of SVR and dynamics of fibrosis in patients with CHC-I receiving AVT with pegylated interferon α-2 and ribavirin; also, it may be an instrument of selection of patients for interferon-free therapy.
authors: P P
authors: PP
authors: Ogurtsov
authors: E I
authors: EI
authors: Kukhareva
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D001789:Blood Group Antigens / Q000032:analysis*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D015203:Reproducibility of Results; D012254:Ribavirin / Q000627:therapeutic use*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D001789:Blood Group Antigens; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a