title: Roles of ITPA and IL28B genotypes in chronic Hepatitis C patients treated with peginterferon plus ribavirin in Tunisian population.
abstract: BACKGROUND
  Despite considerable progress in the treatment of chronic hepatitis C, many countries do not have access to these new treatments.
  
  
  OBJECTIVE
  Predictive markers of response to treatment are therefore necessary before initiating with historical combination therapy (PEG-IFN+ribavirin) for these populations.
  
  
  METHODS
  We therefore evaluated the influence of IL28B polymorphisms on treatment response and Inosine Triphosphate (ITPA) polymorphisms on the incidence of anaemia in a population of 120 Tunisian patients infected with HCV genotype 1b and treated.
  
  
  RESULTS
  The frequencies of favourable IL28B genotypes were 47% (CC for rs12979860) and 63% (TT for rs8099117). Patients in whom favourable IL28B alleles were identified had a higher chance of successful therapy: 82% for CC (rs12979860) and 75% for TT (rs8099117). Viral load decline during the first twelve weeks of treatment was more pronounced in patients with a favourable genotype (p<0.0001). For patients with an unfavourable genotype, the second phase of viral decline was more pronounced in patients with SVR. A viral load decline cut-off of 2.68logIU/mL at week 12 was best suited to discriminate responders from non-responders with an odds ratio of 40 (95% CI:11.53-170.3). Analysis of ITPA polymorphisms revealed that 16% of Tunisian patients presented ITPase deficiency. None of these patients experienced a decline of ribavirin doses during treatment versus 67% for patients without ITPase deficiency (p<0.001).
  
  
  CONCLUSIONS
  These data obtained in a Tunisian population should optimize before and during treatment the chances of success for treatments currently available in Tunisia for chronic HCV infection.
authors.affiliation: University of Tunis El Manar, Faculty of Sciences of Tunis, LR 206 Micro-Organisms and Bio-molecules Actives, 2092, Tunisia.
authors.forename: Ikram
authors.initials: I
authors.lastname: Sghaier
authors.affiliation: Charles Nicolle Hospital, Hepato-Gastro-Enterology department, Tunis, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Mouelhi
authors.affiliation: Military Hospital of Tunis, Laboratory of Immunology, Tunis, Tunisia.
authors.forename: Ezzedine
authors.initials: E
authors.lastname: Gazouani
authors.affiliation: Department of Virology, Amiens University Medical Centre, Amiens, France; Virology Research Unit, EA 4294, Jules Verne University of Picardie, Amiens, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Morel
authors.affiliation: University of Tunis El Manar, Faculty of Sciences of Tunis, LR 206 Micro-Organisms and Bio-molecules Actives, 2092, Tunisia.
authors.forename: Yacoubi Loueslati
authors.initials: YL
authors.lastname: Besma
authors.affiliation: Department of Virology, Amiens University Medical Centre, Amiens, France; Virology Research Unit, EA 4294, Jules Verne University of Picardie, Amiens, France. Electronic address: etienne.brochot@u-picardie.fr.
authors.forename: Etienne
authors.initials: E
authors.lastname: Brochot
mesh_terms: D000740:Anemia / Q000453:epidemiology; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014416:Tunisia / Q000453:epidemiology; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007378:Interleukins; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: Hepatitis C; IL28B polymorphism; ITPA polymorphism; Peginteferon; Ribavirin; Therapy success