we conclude that IL28B polymorphism is highly associated with SVR to therapy in the Egyptian population infected with HCV genotype 4 and patients who carry CC genotype have a higher chance of SVR.
Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT).
IFN levels were higher among patients with HIV coinfection (p=0.044) and patients with better renal function (p=0.041), without association with the IL28B genotype or the hepatitis C stage.
Because the interleukin-28B genetic variant, associated with a high sustained virologic response (SVR), is common in Asians, this treatment is still acceptable in Asian patients with HCV infections.
We characterized the IL28B genotype (for rs12980275 and rs8099917) in 308 patients (mean age, 56 y; 25% African American; 38% with advanced-stage fibrosis) with genotype 1 HCV infection seen at the Michael E. DeBakey Veterans Administration Medical Center in Houston, Texas, from May 1, 2009, through April 1, 2012.
Conversely, patients with lymphoproliferative disorders had not any significantly different IL28Brs1297860 allelic distribution than those with chronic HCV, but, like all chronic HCV-related diseases, they showed a lower CC frequency than patients who spontaneously cleared HCV.
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).
This study suggest that IL28B genotyping may be a valid pretreatment predictor of which patients are likely to respond to treatment in this group of difficult-to-treat HCV/HBV dually-infected patients.
To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.
Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy.
To compare the predictability for treatment outcome among those polymorphisms, we estimated haplotype structure of IFNL4/IL-28B consisting of the three SNPs in 4630 Japanese chronic hepatitis C patients and 1122 healthy controls and then compared their impact on response to pegylated-IFN (PEG-IFN) plus ribavirin (RBV) combined therapy in 903 HCV-1b-infected patients.
We show that genetic variants within the IFN lambda 4 (<i>IFNL4</i>) locus are the major factors associated with the studied traits, accordingly with observations in other HCV genotypes and with comparable effect sizes.
Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks.
In the nonresponders, the IL28B TT genotype population was very small, and inosine triphosphatase (ITPA) and undetectable plasma HCV RNA at week 4 were associated (OR; 2.506 and 3.333, respectively).
Single-nucleotide polymorphisms (SNPs) in the IL28B and PNPLA3 gene regions have been associated with hepatic steatosis in genotype 1 (G1) chronic HCV infection but their clinical impacts remain to be determined.
A nationwide, multi-center prospective study in Japan determined IL28B (rs8099917) genotype, (TA)n of rs72258881, and amino acid substitutions of hepatitis C virus and used these for multivariate analysis together with other parameters at pretreatment.