IL28B polymorphism as a predictor of antiviral response in chronic hepatitis C

AIM： To evaluate the effect of single nucleotide poly- morphisms of interleukin （IL）-28B, rs12979860 on progression and treatment response in chronic hepatitis C. METHODS： Patients （n = 64; 37 men, 27 women; mean age, 44 ＋ 12 years） with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was per- formed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, ami- notransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured. RESULTS： A sustained virological response （SVR） was significantly associated with IL28B polymorphism （CC vs -l-r allele： odds ratio （OR）, 25; CC vs CT allele： OR, 5.4）, inflammation activity （G 〈 1 vs G 〉 1： OR, 3.9）, fibrosis （F 〈 1 vs F 〉 1： OR, 5.9）, platelet count （〉 200 × 109/L vs 〈 200 ×109/L： OR, 4.7; OR in patients with genotype CT： 12.8）, fatty liver （absence vs presence of steatosis： OR, 4.8）, insulin resistance index （〈 2.5 vs 〉 2.5： OR, 3.9）, and baseline HCV viral load （〈 106 IU/mL vs 〉 106 IU/mL： OR, 3.0）. There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance （P = 0.064） of increased fibrosis in patients with the I-I allele, and no differences in the insulin resistance index between groups of patients with CC, CT and -IF alleles （P = 0.12）. Spearman＇s rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively （P 〈 0.001）. Significant dif- ferences were found in the insulin resistance index （P = 0.01） between patients with and without steatosis. Patients with the C-I- allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon （P = 0.07）. CONCLUSION： IL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy. Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.

Real world experience with Pegylated Interferon and ribavirin in Hepatitis C Genotype 1 population with favourable IL28B polymorphism

Background and aim:Conventional hepatitis C treatment using pegylated interferon(PEG-IFN)and ribavirin is associated with significant side effects.IL28B polymorphism can predict response to treatment,with CC genotype having a better response.ITPA gene deficiency protects against clinically significant anaemia induced by treatment.The purpose of this study was to determine IL28B polymorphismand ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response(SVR).Methods:All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study.Blood samples for IL28B and ITPA genotyping were obtained.Medical records were reviewed for verification of treatment response,development of anaemia and if treatment reduction was required during the treatment.Results:A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin,of whom 42 agreed to participate in the study.Mean age was 45.6±12.9 years at time of treatment,and 83.3%of patients weremales.Thirty-three(78.6%)had IL28B CC genotype,of whom 25(75.8%)obtained SVR compared with only 3 of 9(33.3%)non C/C genotype patients who achieved SVR(P=0.041).Eleven(26.1%)patients had ITPA AC genotype,and 30(71.4%)had CC genotype.There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia(45.5%vs 63.3%,P=0.302).Even among patients who developed anaemia,70.8%stillmanaged to achieve SVR.Treatment reduction also had no impact on SVR.Conclusion:Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.

Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C

AIM To determine whether hepatitis C virus(HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients. METHODS One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein(Big Dye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28 B gene rs12979860(Custom TaqM an 5' allelic discrimination assay; Applied Biosystems).RESULTS Of the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response(SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70(R70Q/H) or/and position 91(L91M). The favorable IL28 B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age(P < 0.001), urban residence(P = 0.004), IL28 B CC genotype(P < 0.001), absence of core mutations(P = 0.005), achievement of rapid virologic response(P < 0.001) and early virological response(P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age(P < 0.001), absence of core substitutions(P = 0.04) and IL28 B CC genotype(P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%. CONCLUSION HCV core mutations can help distinguish between patients who can still benefit from the affordable IFNbased therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.