Association Of Genetic Polymorphisms At Il28 B Amongst Different Disease Groups And Interferon Responsiveness In Chronic Hcv Patients From Eastern ...

1225 words - 5 pages

Chronic Hepatitis C Virus (HCV) infection is a major cause for developing cirrhosis and hepatocellular carcinoma, with an estimated global prevalence of 3% occurring in about 180 million carriers and approximately 4 million people are being newly infected annually (1). According to WHO, HCV is found worldwide with certain countries having chronic infection rates as high as 5% or above. In India 12.5 million people are infected with HCV (2). This virus is spread primarily by blood to blood contact associated with intravenous drug use, poorly sterilized medical equipment and transfusions (3). The gold standard therapy for chronic hepatitis C (CHC) consists of Pegylated Interferon (Peg-IFN) and ribavirin, but reports show that the drugs are not well tolerated (4). Recent observations on the genetic determinants of CHC established that a single nucleotide polymorphism in the interleukin (IL)-28B gene influences the treatment outcome of the HCV. The genomic region associated with HCV treatment response lies on chromosome 19 and contains multiple SNP’s in linkage disequilibrium around the IL28B gene (5). Some of these variations may result in the altered IL28B gene, which is strongly associated with more than 2 fold difference in the rate of sustained virological response (SVR) in IFN based treatment (4). IL28B rs 12979860 (rs 60) genotype (CC, CT, TT) was the first polymorphism of the IL28B gene to be identified and was associated with two fold improvement amongst European, Hispanic and African –American population. The second polymorphism identified at rs 8099917(rs 17) genotype (TT, TG, GG) was found to be strongly associated in individuals of Australian and northern European ancestry (6).
Different studies have shown that race, genotype, HCV RNA viral load, age, gender, Basal Metabolic Index (BMI), fibrosis are important predictors for information regarding the IFN –ribavirin treatment response (7). The impact of IL28B associations in Interferon responsiveness amongst Indian population remains understudied. In the current era of direct acting antiviral (DAA), the new treatment paradigm includes one direct- acting antiviral (DAA), a protease inhibitor (PI), in combination with Peg IFN and ribavirin. The addition of DAA to Peg-IFN/RBV nearly doubles the chances of response to treatment but at the cost of increased toxicity. These drugs have shown significant increase in SVR rates but the problem remains in the developing countries like India, where the DAA is still not introduced and if commenced initial costs might be high for the people to afford the expensive treatment. Thus in these clinical settings; IL28B genotyping in predicting IFN responsiveness would be beneficial for individualizing treatment approaches such that patients who carry good alleles might be eligible for shorter and cheaper regimens and inversely with non mutant alleles would require longer therapy.
In the existing study, the host gene polymorphisms at rs 12979860 and rs...

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