Meta-analysis: implications of interleukin-28B polymorphisms in spontaneous and treatment-related clearance for patients with hepatitis C

Abstract

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.

Profile of HIV subtypes in HIV/HBV- and HIV/HCV-coinfected patients in Southern Brazil

“…Recent studies have demonstrated the effect of some favorable genotypes (the CC and TT genotypes, and the C and T alleles of polymorphisms rs8099917 and rs12979860, respectively) on the response to the standard treatment for chronic hepatitis C, as well as their relationship with spontaneous HCV clearance in mono-and coinfected individuals 29,35 .…”

“…Currently, the vaccination program has been extended to individuals up to 49 years of age, in addition to all HIV-infected patients 29 . However, as HIV+ individuals respond poorly to the HBV vaccine, regular monitoring of the immunological status in these patients is recommended 30 .…”

British HIV Association guidelines for the management of hepatitis viruses in adults infected with HIV 2013

“…IL28B genotype has been associated with response to pegylated interferon and ribavirin in monoinfected and coinfected populations with a similar effect on outcome in both in a recent meta-analysis [82]. The Sprint 2 study demonstrated response rates to PEG-IFN and RBV with boceprevir were 80%, 71% and 59% with CC, CT and TT genotype respectively [83].…”

Polymorphism of IL28B gene and response to pegylated interferon α2a in chronic hepatitis B

“…Genetic variants of IL28B explain differences in IFN efficacy between races due to different distributions of individual gene alleles [7][8][9][10][11]. Studies on HCV provided an inspiration for investigations of the influence of IL28B polymorphisms on infections with the other hepatotropic viruses, since IFN λ shows broad and non-specific antiviral activity [18].…”

“…Recently, a single nucleotide polymorphism (SNP) near the IL28B gene was shown to be highly predictive of a sustained viral response (SVR) to PegIFN and ribavirin in chronic C hepatitis. Homozygous genotypes classified as CC at locus rs12979860 were associated with more than twice as high SVR rate in comparison with TT alleles, whereas CT heterozygotes exerted an intermediate treatment response [7][8][9][10]. A favorable CC constellation was also shown to increase spontaneous HCV clearance and predicts better outcomes of HCV reinfection after liver transplantation [11].…”