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IL-28B genetic variation, gender, age, jaundice, hepatitis C virus genotype, and hepatitis B virus and HIV co-infection in spontaneous clearance of hepatitis C virus.

ABSTRACT: BACKGROUND/AIMS:Spontaneous viral clearance observed in some patients is one of the variants of the hepatitis C virus (HCV) infection natural history. We aimed to look at the complexity of factors affecting the spontaneous clearance of HCV (SC HCV). MATERIALS AND METHODS:A total of 357 anti-HCV positive patients (309 with chronic hepatitis C and 48 patients with SC HCV) were included into the study. We studied the effects of the interleukin-28B (IL-28B) gene polymorphism, gender, age, the routes of virus transmission, past hepatitis C with jaundice, HCV genotype, and hepatitis B virus (HBV) and HIV co-infection on the outcome of HCV infection. RESULTS:Based on the study results, the SC HCV was found in 48 individuals (13.4%). The most significant positive factors affecting the SC HCV included IL-28B single nucleotide polymorphism (SNP) rs12979860 (CC) and SNP rs8099917 (TT) (OR 4.03, p<0.001) and (OR 3.14, p<0.002), female gender (OR 2.72, p<0.001), young age (OR 2.30, p<0.008), and past history of jaundice (OR 5.12, p<0.001). The markers of a past HBV infection were found significantly more often in SC. CONCLUSION:Positive predictors of the SC HCV include favorable IL-28B genotype, female gender, young age, a history of jaundice, markers of a past HBV infection, the absence of HIV infection, but not the viral genotype.

SUBMITTER: Fedorchenko SV

PROVIDER: S-EPMC6505656 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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IL-28B genetic variation, gender, age, jaundice, hepatitis C virus genotype, and hepatitis B virus and HIV co-infection in spontaneous clearance of hepatitis C virus.

Fedorchenko Sergii V SV Klimenko Anna A Martynovich Tetyana T Liashok Olga O Yanchenko Vitaliy V

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 20190501 5

<h4>Background/aims</h4>Spontaneous viral clearance observed in some patients is one of the variants of the hepatitis C virus (HCV) infection natural history. We aimed to look at the complexity of factors affecting the spontaneous clearance of HCV (SC HCV).<h4>Materials and methods</h4>A total of 357 anti-HCV positive patients (309 with chronic hepatitis C and 48 patients with SC HCV) were included into the study. We studied the effects of the interleukin-28B (IL-28B) gene polymorphism, gender, ...[more]

PMID: 31060998

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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.

Project description:BACKGROUND:Cytokines play an important role in the regulation of the immune response. In hepatitis C virus (HCV) infection, cytokine levels may influence the outcome of acute HCV infection. Polymorphisms in cytokine genes have been associated to different expression levels in response to infection. This study was carried out to investigate the association of several cytokine gene polymorphisms with disease outcome in HCV-infected patients. FINDINGS:Patients with chronic or spontaneously resolved HCV infection were included in a cross-sectional study. A comparative analysis was performed between the groups regarding frequency distribution of the following cytokines' gene polymorphisms: IL-10 (-1082 A/G; -819?T/C; -592 A/C), IL-4 (+33C/T), IFN-? (+874?T/A), TNF-? (-238?G/A and -308?G/A) and IL-28B (rs12979860 C/T and rs8099917 T/G). RESULTS:Eighteen patients with spontaneous viral clearance and 161 with chronic HCV infection were included. In the comparative analysis, the GG genotype of the IL-10 polymorphism -1082A/G was more frequent in patients with spontaneous viral clearance when compared to patients with chronic HCV (41.2% vs 6.2%; p = 0.001). This association was also found for the CC genotype of the IL-4 polymorphism +33C/T (72.2% vs 36.7%; p = 0.017) and the CC and TT genotypes of the IL-28B polymorphisms rs 12979860 and rs 8099917 (88.9% vs 30.3%; p?<?0.001 and 88.9% vs 49.6%; p = 0.002). The IL10 (A-1082?G) and IL-28B (Crs12979860T) gene polymorphisms showed odds ratios of 12.848 and 11.077, respectively, and thus may have a greater influence on HCV spontaneous viral clearance. The IFN-? (+874?T/A), TNF-? (-238?G/A and -308?G/A) polymorphisms did not show significant association with spontaneous viral clearance or chronicity. CONCLUSION:The G allele for IL-10 (-1082 A/G), the C allele for IL-4 (+3 C/T) and the C and T alleles for IL-28B (rs12979860 and rs8099917, respectively) are associated with spontaneous viral clearance in hepatitis C infection.

Dataset Information

IL-28B genetic variation, gender, age, jaundice, hepatitis C virus genotype, and hepatitis B virus and HIV co-infection in spontaneous clearance of hepatitis C virus.

Publications

IL-28B genetic variation, gender, age, jaundice, hepatitis C virus genotype, and hepatitis B virus and HIV co-infection in spontaneous clearance of hepatitis C virus.

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