title: Role of IL-28B and inosine triphosphatase polymorphisms in efficacy and safety of Peg-Interferon and ribavirin in chronic hepatitis C compensated cirrhosis with and without oesophageal varices.
abstract: Genetic factors can influence the outcome of antiviral therapy in chronic hepatitis C (HCV). We evaluated the role of interleukin-28B single nucleotide polymorphisms (SNPs) and inosine triphosphatase (ITPA) gene variants in HCV cirrhosis treated with Peg-Interferon and ribavirin. A prospective cohort of 233 patients with compensated cirrhosis received 1-1.5 μg/kg/week of Peg-Interferon alpha-2b plus 1000-1200 mg/day of RBV for 48 weeks. A sustained virologic response (SVR) was achieved in 27% of patients. On multivariate logistic analysis, the absence of oesophageal varices (OR 3.64 CI 95% 1.27-10.44 P = 0.016), infection with genotype 2 or 3 (OR 4.06, CI 95% 1.08-15.26, P = 0.038), C/C alleles of rs12979860 SNP (OR 7.04, CI 95% 2.40-20.72, P < 0.001) and rapid virologic response (RVR) (OR 78.29, CI 95% 16.07-381.29, P < 0.001) were independently associated with SVR. Patients who experienced post-treatment relapse received lower total doses of Peg-Interferon (52.0 ± 15.8 μg/kg vs 65.7 ± 13.3 μg/kg, P < 0.001) and lower total dose of RBV (3829 ± 1210 mg vs 4709 ± 954 mg, P < 0.001) than patients who achieved an SVR. ITPA variants predictive of high ITPase activity were associated with reduction of haemoglobin ≥3 g/dL in the first 4 weeks (P < 0.001), and with reduction of haemoglobin <10 g/dL (P = 0.03) on treatment. In conclusion, combination therapy with Peg-Interferon and RBV in patients with HCV cirrhosis must be guided by virus genotype, severity of portal hypertension, favourable IL-28B polymorphisms and ITPA variants, and RVR on treatment.
authors.affiliation: Sezione di Gastroenterologia & Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy. vito.dimarco@unipa.it
authors.forename: V
authors.initials: V
authors.lastname: Di Marco
authors.forename: V
authors.initials: V
authors.lastname: Calvaruso
authors.forename: S
authors.initials: S
authors.lastname: Grimaudo
authors.forename: D
authors.initials: D
authors.lastname: Ferraro
authors.forename: R M
authors.initials: RM
authors.lastname: Pipitone
authors.forename: R
authors.initials: R
authors.lastname: Di Stefano
authors.forename: A
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000368:Aged; D000743:Anemia, Hemolytic / Q000139:chemically induced; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004932:Esophageal and Gastric Varices / Q000821:virology*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011755:Pyrophosphatases / Q000235:genetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D000095022:Interferon Lambda; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; 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