Dataset Information

Association of Overt Diabetes Mellitus with the Non-CC but not the CC Genotype of Interleukin-28B in Hepatitis C Virus Infected Patients.

ABSTRACT: BACKGROUND:Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response. Whether IL-28b genotypes also influence other nontreatment related clinical parameters is unclear. METHODS:Patients with HCV-related chronic liver diseases who attended our department during 2012-2014 were retrospectively analyzed. The single nucleotide polymorphisms (SNPs) of rs12979860 (IL-28B) were correlated with various clinical parameters. We also compared these parameters in patients with and without overt diabetes to identify possible associations. RESULTS:A total of 115 patients were included (median age 48, range 15-76 years; 70% males). Overall, 43/115 (37%) patients had chronic hepatitis, while the remaining 72/115 (63%) had cirrhosis. The most common IL-28B genotype was CC, which was found in 53% of patients (61/115), while the remaining 47% were nonCC [CT 42% (48/115) and TT 5% (6/115)]. Clinical and laboratory parameters like Hb, white blood cell (WBC), platelets, bilirubin, transaminases, and albumin were similar in the CC and nonCC genotypes. Overt diabetes mellitus was present in 22% (25/115) of patients. Patients with nonCC genotype had significantly higher prevalence of overt diabetes mellitus than patients with CC genotype (31% [17/54] versus 13% [8/61]; p < 0.05). When parameters were compared in patients with and without overt diabetes mellitus, only IL-28B and age were significantly associated with overt diabetes mellitus (p < 0.05). CONCLUSION:In HCV patients, overt diabetes mellitus was more commonly associated with the nonCC genotype of IL-28B than the CC genotype. Carriers of the T-allele of SNP rs12979860 were more likely to have insulin resistance than CC homozygotes, and this finding may explain the higher prevalence of diabetes in non-CC genotypes. Thus, an IL-28B test may be useful in patients of HCV in order to determine their likelihood of developing diabetes mellitus.

SUBMITTER: Kumar A

PROVIDER: S-EPMC4807140 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Association of Overt Diabetes Mellitus with the Non-CC but not the CC Genotype of Interleukin-28B in Hepatitis C Virus Infected Patients.

Kumar Ashish A Kumar Ashish A Gupta Varun V Sharma Praveen P Bansal Naresh N Singla Vikas V Arora Anil A

Journal of clinical and translational hepatology 20160315 1

<h4>Background</h4>Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response. Whether IL-28b genotypes also influence other nontreatment related clinical parameters is unclear.<h4>Methods</h4>Patients with HCV-related chronic liver diseases who attended our department during 2012-2014 were retrospectively analyzed. The single nucleotide polymorphisms (SNPs) of rs12979860 (IL-28B) were correlated with various clinical parameters. We also compar ...[more]

PMID: 27047769

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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.

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.

Project description:Background/Aims The addition of protease inhibitors to standard of care (SOC) dramatically increases treatment response in Hepatitis C Virus (HCV) genotype 1 patients. Moreover, Interleukin 28B (IL28B) genotyping helps predict responsiveness for these patients. However, the economic implications of incorporating IL28B genotyping in HCV genotype 2 or 3 infected patients are unknown. This study used a treatment algorithm that included IL28B genotype-guided therapy to examine the short and long-term cost-effectiveness of utilizing these single-nucleotide polymorphisms in treatment-naïve HCV genotype 2 or 3 infected patients. Methods A treatment algorithm was constructed to reflect a therapy regimen for treatment-naïve patients with HCV genotype 2 or 3 infection using pegylated-interferon, ribavirin, and telaprevir. To examine the role of the IL28B gene in affecting costs and health outcomes, a decision tree was derived from the treatment algorithm in order to populate a predictive cost model for therapy using our treatment algorithm. Results Expected short-term costs of therapy following our algorithm were $21,648.92 and $47,972.84 for the CC and TT genotypes at rs12979860, respectively, and $47,972.84 and $21,648.92 for patients with the CT genotype at rs12979860 and the TG/GG and TT genotypes at rs8099917, respectively. Predicted costs among patients undergoing SOC therapy were $20,758.92. Sustained virologic response (SVR) rates for genotypes 2/3 were predicted to occur in 82.2% (8,220 of 10,000) of patients overall—88.83% (8,883 of 10,000) and 65.91% (6,591 of 10,000) for the CC and TT genotypes at rs12979860 and 81.01% (8,101 of 10,000) overall for patients with the CT genotype at rs12979860 [72.08% (7,208 of 10,000) and 86.78% (8,678 of 10,000) for the TG/GG and TT genotypes at rs8099917]. Markov modeling predicted a 27.29 quality-adjusted life-expectancy (QALE) after following our treatment algorithm while adding $7,766.51 in long-term costs. The model predicted only a 26.65 QALE after SOC therapy (while adding $9,599.05 in long-term costs). Conclusions Although short-term treatment costs of an IL28B genotype-guided approach exceed those of SOC for treatment-naïve HCV genotype 2/3 infected patients, Markov modeling suggests that lower long-term costs and improved health outcomes may be achieved by the proposed algorithm and provides a dominant cost-effective strategy for treating this population of HCV infected patients.

Dataset Information

Association of Overt Diabetes Mellitus with the Non-CC but not the CC Genotype of Interleukin-28B in Hepatitis C Virus Infected Patients.

Publications

Association of Overt Diabetes Mellitus with the Non-CC but not the CC Genotype of Interleukin-28B in Hepatitis C Virus Infected Patients.

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