Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

Abstract

Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r 2 5 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P 5 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) 5 4.27, 95% confidence interval (CI) 5 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR 5 0.28, 95% CI 5 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR 5 3.10, 95% CI 5 1.34-7.21, P 5 0.008), and the pretreatment level of aspartate aminotransferase (OR 5 0.996, 95% CI 5 0.99-1.00, P 5 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI 5 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. (HEPATOLOGY 2011;53:7-13)

Treatment of Hepatitis C Virus Infection in the HIV- Infected Patients by Pegylated Interferon and Ribavirin in Tehran, Iran

“…Researchers have detected a polymorphism (rs129798060) close to IL28B gene that encodes interferon lambda-3, which has a strong statistical relationship with response to IFN therapy (11,12). In our study, all patients attaining RVR reached SVR and this shows that those getting to RVR can reach SVR in a significantly higher manner.…”

Variants of the inosine triphosphate pyrophosphatase gene and relapse risk following treatment for HCV genotype 2/3

“…3,4 Because the RVR was reported as the most important predictor of SVR in HCV G2-infected patients, even when interleukin-28B variants were taken into consideration, 5,6 and ITPA variants were reported not to increase SVR in G2/3-infected patients with higher dose of RBV, 7 it is interesting to know whether the RVR is associated with ITPA variations and SVR in the present study of the NORDynamIC trial. 4 Particularly, because RVR is currently the most important factor for individualized therapy for G2/3-infected patients, the effect of the ITPA variants on determining the duration of Peg-IFN/RBV therapy for patients with or without RVR deserves to be explored.…”

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

“…Host single-nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B, IFN-lambda 3) gene are associated with spontaneous and peginterferon/ribavirin treatment-induced viral clearance in HCV GT-1/GT-4 patients [184,185] but have a limited role in HCV-2/3 patients [186]. Combined with baseline viral loads, viral kinetics, and previous treatment responses [177], the IL28B genotype could provide important information for decision-making in clinical practice, including: (1) identification of HCV GT-1 treatment-naïve patients who are eligible for 24-week peginterferon/ribavirin (IL28B favorable genotype with baseline viral loads \400,000 IU/mL) [160], (2) early identification of HCV GT-1 nonresponders (IL28B unfavorable genotype with HCV RNA [1000 IU/mL at treatment week 4) [165], and (3) exclusion of retreatment with peginterferon/ribavirin for treatment-experienced HCV GT-1 patients who carry the IL28B unfavorable genotype [187].…”