IL-28B polymorphisms are predictors of response to therapy in adults infected with hepatitis C. We do not know whether they are markers of response to therapy in children and adolescents. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the IL-28B gene could influence the probability of response to therapy compared with other known baseline prognostic factors and correlate with clinical findings in pediatric patients infected with hepatitis C virus (HCV) genotypes 1 or 4. We determined three SNPs of IL-28B (rs12979860, rs12980275, and rs8099917) in 82 patients with chronic HCV infection treated with pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Treatment response and clinical data were analyzed. Overall, sustained virological response (SVR) was achieved by 45 % of patients infected with difficult-to-treat HCV genotypes 1 and 4. Except for IL-28B polymorphisms, there was no association of SVR with any other clinical data. IL-28B rs12979860 CC [odds ratio (OR), 6.81; p = 0.001] and rs8099917 TT (OR, 3.14; p = 0.013) genotypes were associated with higher SVR rates. IL-28B rs12980275 was not significantly associated with SVR (p = 0.058). Only the distribution between CC and CT–TT genotypes of rs12979860 significantly differentiated patients achieving early virological response (EVR) (OR, 10.0; p = 0.011). Children with the rs12979860 CC genotype had significantly higher baseline viral load compared with CT–TT patients (p = 0.010). In children and adolescents chronically infected with HCV genotypes 1 and 4, IL-28B rs12979860 and rs8099917 polymorphisms were the only predictors of response to peg-IFN/RBV.
Universal screening of pregnant women for HBV infection, early identification of HBV DNA level in HBV-infected mothers, maternal treatment with class B according to FDA antivirals and passive/active anti-HBV immunoprophylaxis to newborns of HBV-positive mothers are crucial strategies for reducing vertical HBV transmission rates. Consideration of caesarean section in order to reduce the risk of vertical HBV transmission should be recommend in HBV infected pregnant women with high viral load despite antiviral therapy or when the therapy in the third trimester of pregnancy is not available.
AIMTo investigate the impact of IL28B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODSWe enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response (PR) and a complete response (CR) upon measurement at the 24-wk post-treatment follow-up.RESULTSThe PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response (partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown (P < 0.05). The allele association analysis revealed that only the IL-28B rs12979860 (C vs T) and IL28B rs12980275 (A vs G) markers significantly affected the achievement of PR (P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28B rs12980275 was significantly associated with PR (AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28B rs12979860 was present only in the no-CR group (P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the no-CR group (P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype (P = 0.0002 and P = 0.001, respectively), but no association with IL28B haplotype was observed.CONCLUSIONIL28B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.
Combined therapy with pegylated IFN-α2b and ribavirin in patients with chronic hepatitis C, infected with hepatitis C virus genotypes 1 and 4, was more effective in treatment-naïve patients (63.9%) as compared with re-therapy cases (27.9%). SVR was maintained for at least the next 6 months in all of the patients. The applied treatment has limited efficacy and evokes numerous adverse effects; thus, search for new methods of treatment is mandatory.
BackgroundTreatment of hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin (RBV) is associated with adverse events, which may affect the patient's adherence to the treatment regimen and the treatment efficacy.ObjectivesThe aim of this study was to assess the sustained viral response (SVR) and interdependence between the haematological characteristics (leukocyte count, platelet count, and haemoglobin levels) in patients with chronic hepatitis C (CHC) infection during treatment with IFN and RBV.Patients and MethodsWe conducted a retrospective cohort study of 170 children with CHC infection who completed treatment with IFN-α and RBV. The children were divided into 2 groups: the first group (group I, n = 119) underwent a 48-week course of treatment with recombinant IFN α-2b (Intron A) at a dosage of 3 MU 3 times a week subcutaneously and RBV at a dosage of 15 mg/kg per day orally, and the second group (group II, n = 51) was administered pegylated IFN (peg-IFN)-α-2b (PegIntron) at a dosage of 1.5 μg/kg per week subcutaneously and RBV at a dosage of 15 mg/kg per day orally for 48 weeks. The dose of IFN was not adjusted but that of ribavirin was in 2 children from group II. Hematological growth factors and erythropoietin were not used. SVR was defined as undetectable serum HCV RNA 24 weeks after the end of treatment (study week 72). Serum HCV RNA was determined by performing polymerase chain reaction, and the HCV genotypes and hematological parameters were evaluated. Serum HCV RNA levels were analysed by descriptive statistics. Means and standard deviations were calculated for values collected at the baseline, on the 12th and 48th weeks during treatment, and after 24 weeks of untreated follow-up (study week 72).ResultsEighty-six (50%) of the 170 patients who underwent treatment achieved SVR: 62 (51%) out of 119 children from group I and 24 (47%) out of 51 from group II. The mean serum hemoglobin levels and leukocyte and platelet counts at week 12 were significantly lower than the baseline values in both responders and non-responders from both the groups (P < 0.05). In the responders in group I, the mean levels of serum hemoglobin after 24 weeks of treatment and at the end of therapy were significantly lower than the mean levels at baseline. In the group treated with peg-IFN-α-2b and RBV (group II), the mean serum hemoglobin levels at week 12 was lower in the responders than in the non-responders (P < 0.05). The decrease in the hemoglobin levels was associated with viral response. In both the responders and non-responders from both the groups, leukocyte counts decreased during treatment, and after 12 weeks, they were more significantly lower than the baseline value. The decrease was more marked in children treated with peg-IFN-α-2b + RBV (P < 0.05). After 12 weeks of treatment, the platelet count was low in children from group II who had achieved SVR.ConclusionsA mild decrease in hemoglobin levels and leukocyte and platelet counts during treatment with IFN and RBV in children with CHC infection may be f...
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