Published online Jun 7, 2017. doi: 10.3748/wjg.v23.i21.3815
Peer-review started: February 12, 2017
First decision: March 3, 2017
Revised: March 17, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: June 7, 2017
To evaluate the association of IFNL3 (IL28B) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C (CHC).
The study enrolled 196 CHC Polish patients (82 women and 114 men in age 20-64) infected with hepatitis C virus (HCV) genotype 1. They were treatment naïve and qualified to pegylated interferon alpha (PEG-IFN-α) and ribavirin (RBV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase (ALT), asparagine aminotransferase (AST) and total bilirubin (TBIL). The analysis of response to therapy included: sustained virological response (SVR), defined as undetectable serum HCV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HCV genotyping and HCV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms (SNPs) (rs12979860, rs8099917 and rs12980275) of known significance in predicting of HCV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons.
Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for CC, CA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of CHC (grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TBIL). It was demonstrated that the rs4803217C allele is associated with SVR (C vs A: P < 0.0001; dose of C allele: P = 0.0002) and non-relapse (C vs A: P = 0.001; dose of C allele: P = 0.002). Moreover, it was found that patients with CC genotype have significantly higher response rates as compared with CA/AA patients (P < 0.0001), whereas patients carrying A allele are significantly predisposed to relapse after treatment (P = 0.0007). Moreover, the association of rs4803217 with SVR was comparable to that of rs12979860 and stronger as observed for rs12980275 and rs8099917. Association of rs4803217 with relapse, was the strongest as compared with the other SNPs. The analysis of combined rs4803217 and rs8099917 genotypes demonstrated that additional genotyping of rs8099917 had no significant impact on the prediction of SVR. Multivariate analysis revealed that among analyzed SNPs only rs4803217 is an independent predictor of SVR (P = 0.016) and relapse (P = 0.024).
The rs4803217 SNP is a strong, independent and superior predictor of SVR and relapse in HCV genotype 1 infected CHC patients treated with PEG-IFN-α and RBV.
Core tip: The rs4803217 single nucleotide polymorphism of IFNL3 (IL28B) gene, which encodes, interferon lambda 3 (interleukin 28B), has been proposed as a causal variant that may influence hepatitis C virus (HCV) clearance. In the present study it was found that rs4803217 is a strong and independent predictor of sustained virological response and relapse in HCV genotype 1 infected chronic hepatitis C patients treated with pegylated interferon alpha and ribavirin. Moreover, it was indicated that rs4803217 seems to be much better predictor of therapy outcome than well-establish IFNL3 SNPs (rs12979860, rs8099917 and rs12980275).