Dataset Information

Spontaneous Viral Load Decline and Subsequent Clearance of Chronic Hepatitis C Virus in Postpartum Women Correlates With Favorable Interleukin-28B Gene Allele.

ABSTRACT: Background:Postpartum hepatitis C viral (HCV) load decline followed by spontaneous clearance has been previously described. Herein we identify predictors for viral decline in a cohort of HCV-infected postpartum women. Methods:Pregnant women at Cairo University were screened for anti-HCV antibodies and HCV RNA, and viremic women were tested for quantitative HCV RNA at 3, 6, 9, and 12 months postpartum. Spontaneous clearance was defined as undetectable viremia twice at least 6-months apart. Associations between viral load and demographic, obstetrical, HCV risk factors, and interleukin-28B gene (IL28B) polymorphism (rs12979860) were assessed. Results:Of 2514 women, 97 (3.9%) had anti-HCV antibodies, 54 (2.1%) were viremic and of those, 52 (2.1%) agreed to IL28B testing. From pregnancy until 12 months postpartum, IL28B-CC allele women had a significant viral decline (P = .009). After adjusting, the IL28B-CC allele had a near significant difference compared to the CT allele (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.75,1.00; P = .05), but not the TT allele (OR, 0.91; 95% CI, 0.61,1.38; P = .64). All 14/52 (26.9%) women who subsequently cleared were among the 15 with undetectable viremia at 12 months, making that time point a strong predictor of subsequent clearance (sensitivity = 100%, specificity = 97.4%, positive predictive value = 93.3%, negative predictive value = 100%). Conclusions:IL28B-CC genotype and 12-month postpartum undetectable viremia were the best predictors for viral decline and subsequent clearance. These 2 predictors should influence clinical decision making.

SUBMITTER: Hashem M

PROVIDER: S-EPMC6248538 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Spontaneous Viral Load Decline and Subsequent Clearance of Chronic Hepatitis C Virus in Postpartum Women Correlates With Favorable Interleukin-28B Gene Allele.

Hashem Mohamed M Jhaveri Ravi R Saleh Doa'a A DA Sharaf Sahar A SA El-Mougy Fatma F Abdelsalam Lobna L Shardell Michelle D MD El-Ghazaly Hesham H El-Kamary Samer S SS

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20170901 6

<h4>Background</h4>Postpartum hepatitis C viral (HCV) load decline followed by spontaneous clearance has been previously described. Herein we identify predictors for viral decline in a cohort of HCV-infected postpartum women.<h4>Methods</h4>Pregnant women at Cairo University were screened for anti-HCV antibodies and HCV RNA, and viremic women were tested for quantitative HCV RNA at 3, 6, 9, and 12 months postpartum. Spontaneous clearance was defined as undetectable viremia twice at least 6-month ...[more]

PMID: 28903504

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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:BackgroundSince 2009, several studies have identified single-nucleotide polymorphisms (SNPs) near the gene encoding for interleukin (IL)-28 (IL28B) that are strongly associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Because this large amount of data includes some inconsistencies, we consider assessment of the global estimate for each SNP to be essential.MethodsRelevant studies assessing IL28B polymorphisms associated with sustained virologic response (SVR) and spontaneous clearance (SC) were identified from a literature search of PubMed up to 9 July, 2012. Studies were eligible studies if they included patients infected with HCV or HCV/HIV, or assessed any SNP located within or near the IL28B gene, SVR data available under standard treatment, and/or SC data in patients with acute HCV infection. Pooled odds ratios were estimated by fixed or random effects models when appropriate. Variables such as HCV genotype, ethnicity, and type of co-infection were studied.ResultsOf 282 screened studies, 67 were selected for SVR and 10 for SC. In total, 20,163 patients were studied for SVR and 3,554 for SC. For SVR, we found that all SNPs showed strong associations in patients with HCV genotypes 1 and 4, whereas the pooled ORs were almost three times lower for genotypes 2 and 3 (rs12979860 and rs8099917). Regarding ethnicity, the SNP most associated with SVR was rs12979860 in white patients, whereas in East Asians it seemed to be rs8099917. The most studied SNP (rs12979860) showed similar results for patients co-infected with HCV/HIV, as for those infected with HCV only. Finally, rs12979860 and rs8099917 both appeared to be associated with SC.ConclusionsIL28B polymorphisms influence both the outcome of interferon treatment and the natural clearance of HCV. However we did not identify a universal predictor SNP, as the best genetic markers differed depending on patient ethnicity, genotype, and type of infection. Nevertheless, our results may be useful for more precise treatment decision-making.

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

Spontaneous Viral Load Decline and Subsequent Clearance of Chronic Hepatitis C Virus in Postpartum Women Correlates With Favorable Interleukin-28B Gene Allele.

Publications

Spontaneous Viral Load Decline and Subsequent Clearance of Chronic Hepatitis C Virus in Postpartum Women Correlates With Favorable Interleukin-28B Gene Allele.

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