Interleukin-28b: a key piece of the hepatitis C virus recovery puzzle.
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ABSTRACT:
SUBMITTER: Thio CL
PROVIDER: S-EPMC3805379 | biostudies-literature | 2010 Apr
REPOSITORIES: biostudies-literature
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Interleukin-28b: a key piece of the hepatitis C virus recovery puzzle.
Thio Chloe L CL Thomas David L DL
Gastroenterology 20100223 4
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Project description:In 2009, several independent studies revealed a strong association between genetic variation in the interleukin-28B (IL28B) locus and the outcome of treatment for chronic infection with hepatitis C virus (HCV). Hundreds of studies followed, and a recent meta-analysis reports more precise odds ratios than previously published for associations between commonly reported IL28B polymorphisms and spontaneous HCV clearance or treatment outcome. These results should facilitate the interpretation of IL28B genotyping as part of personalized treatment approaches.
| S-EPMC3738156 | biostudies-literature
Project description:Interleukin (IL) 28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-? (PEG-IFN) plus ribavirin and with spontaneous hepatitis C virus clearance. However, a consensus on the relationship between IL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion, and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-IFN has not been reached. Several reports failed to show a positive association, while some studies demonstrated a positive association in certain subject settings. More prospective studies including large cohorts are needed to determine the possible association between IL28B genetic polymorphism and the outcome of interferon or PEG-IFN treatment for chronic hepatitis B.
| S-EPMC4161790 | biostudies-literature
Project description:AimTo analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.MethodsA total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.ResultsSNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07).ConclusionThe higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.
| S-EPMC3831221 | biostudies-literature
Project description:BACKGROUND/AIMS:This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene with respect to clinical outcomes and the antiviral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea. METHODS:Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection. RESULTS:The CC genotype frequency was significantly higher in the spontaneous recovery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predictor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic responses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients. CONCLUSIONS:The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea.
| S-EPMC3916691 | biostudies-literature
Project description:ObjectiveTo preliminarily explore the association of rs12979860 and rs8099917 SNPs with chronic HCV infection in Chinese Han children.MethodsChronic HCV infection patients (n=277; 1-17 years old, 4.5 years old in average) and healthy subjects (n=150, children; 2-17 years old, 5.2 years old in average) were recruited and tested by PCR combining direct sequencing. The differences between the rs12979860 and rs8099917 genotypes in patients and healthy subjects were compared.ResultsThe genetic variations at rs12979860 and rs8099917 in chronic hepatitis C (CHC) children and healthy subjects did not differ significantly. The frequency of spontaneous clearance in CHC children was higher (47%), which is related to the genetic variations. The histological changes of patients were more significant compared to their clinical and biochemical indices, but they did not correlate with the genetic mutations at rs12979860 and rs8099917 significantly.ConclusionThe rs12979860 and rs8099917 SNPs are independent factors predicting the spontaneous clearance of Chinese CHC children patients. The correlation between diseases outcomes are in need of further study.
| S-EPMC4048498 | biostudies-literature
Project description:UnlabelledThe identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected.ConclusionWe identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.
| S-EPMC3128709 | biostudies-literature
Project description:The surveillance and correct subtyping of hepatitis C virus strains require available and up-to-date publicly available reference genomes. Here, we present the complete open reading frame sequence of a hepatitis C virus genotype 6 strain of an unknown subtype that was discovered during routine subtyping of patients in the clinic.
| S-EPMC6797537 | biostudies-literature
Project description:UNLABELLED:Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ?26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). CONCLUSION:During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes.
| S-EPMC2947598 | biostudies-literature
Project description:BackgroundRecent genome wide association studies (GWAS) have shown important roles of single nucleotide polymorphisms (SNP) near region of interleukin B 28 (IL28B) gene in spontaneous and drug-induced clearance of hepatitis C virus (HCV) in genotype 1 HCV infection.ObjectivesThis meta-analysis was designed to determine the world-wide distribution patterns of IL28B genotypes and alleles, and to find possible linkages between IL28B and HCV genotypes.Patients and methodsManual and electronic databases were searched. Critical appraisal was performed. According to the results of heterogeneity tests, we used fix/random model for the analysis. The data concerning patients' ethnicity and HCV genotypes were analyzed by using statistical analysis software.ResultsA total of 255 articles were found. After article review and quality assessment, 50 studies, including 18662 patients and 1313 healthy subjects, were analyzed. Presence of HCV genotype 3 versus genotype 1 was significantly associated with a higher frequency of CC genotype and C allele, with an odds ratio (OR) of 1.68 (95% CI: 1.44-1.99) and 1.49 (95% CI: 1.33-1.67), respectively. Prevalence of the rs12979860 CC genotype among genotype 1 HCV infected patients of Asian ethnicity was 69.48% (95% CI: 65.20-73.77), which was significantly higher than its prevalence [33.27% (95% CI: 28.88-37.67)] in the Caucasian genotype 1 HCV infected patients. Prevalence of rs12979860 TT genotype in the African-American genotype 1 HCV infected patients was the highest [36.20% (95% CI: 32.91-39.49)], and significantly different compared to all other ethnicities.ConclusionsThere were significant linkages between HCV genotypes and IL28B genotypes/alleles. Patients with a favorable IL28B and genotypes 1 and 4 HCV infection stand a better chance to clear HCV in the acute phase.
| S-EPMC3984474 | biostudies-literature
Project description:Single nucleotide polymorphisms near the interleukin 28B (IL-28B) gene have been identified as strong predictors of both spontaneous or Peg-interferon (Peg-IFN) and ribavirin (RBV) induced clearance of hepatitis C virus (HCV). Several studies have shown that, in patients with genotype 1 (GT-1), rs12979860 C/C and rs8099917 T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment. Although new treatment regimens based on combination of DAA with or without IFN are in the approval phase, until combination regimens with a backbone of Peg-IFN will be used, we can expect that IL28B holds its importance. The clinical relevance of IL28B genotyping in treatment of patients infected with HCV genotype 2 (GT-2) and 3 (GT-3) remains controversial. Therefore, after a careful examination of the available literature, we analyzed the impact of IL28B in GT-2 and -3. Simple size of the studies and GT-2 and GT-3 proportion were discussed. An algorithm for the practical use of IL28B in these patients was suggested at the aim of optimizing treatment.
| S-EPMC3870545 | biostudies-literature