Retrospective Study
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World J Gastroenterol. Sep 28, 2014; 20(36): 13146-13152
Published online Sep 28, 2014. doi: 10.3748/wjg.v20.i36.13146
IL28B polymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients
Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Giovanni Antonio Touscoz, Mario Rizzetto, Rinaldo Pellicano, Antonina Smedile
Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy
Alessia Ciancio, Giovanni Antonio Touscoz, Mario Rizzetto, Rinaldo Pellicano, Antonina Smedile, Department of Gastroenterology and Hepatology, Molinette Hospital, 10126 Turin, Italy
Author contributions: Rosso C and Abate ML wrote the paper and contributed equally to this work; Abate ML and Smedile A designed the research; Ciancio A, Strona S, Olivero A and Touscoz GA collected the data; Rosso C and Caviglia GP performed statistical analysis; Rizzetto M, Smedile A and Pellicano R revised the paper critically for important and intellectual content.
Supported by Department of Medical Science, University of Turin
Correspondence to: Rinaldo Pellicano, MD, Department of Gastroenterology and Hepatology, Molinette Hospital, Via Cavour 31, 10126 Turin, Italy. rinaldo_pellican@hotmail.com
Telephone: +39-633-6333913 Fax: +39-633-6333976
Received: January 8, 2014
Revised: February 18, 2014
Accepted: May 12, 2014
Published online: September 28, 2014
Processing time: 266 Days and 3.1 Hours
Abstract

AIM: To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response.

METHODS: A cohort of 118 Caucasian treatment-naïve HCV-G1 infected patients, treated with pegylated-IFN alpha 2a or 2b associated with ribavirin (53 responders, 65 non-responders) during the period 2010-2012, were genotyped for IL28B SNPs rs12979860 C>T and rs8099917 T>G. Genotyping was performed by real-time allelic discrimination assay. Serum HCV RNA levels were assayed at 2, 4, 12, 24 and 48 wk during therapy. Correlation between IL28B genotypes and serum HCV RNA kinetics was investigated. Multivariable logistic regression analysis was performed to identify predictors of null-response.

RESULTS: Twenty-six out of 118 patients (22%) had no HCV RNA decline ≥ 1 log IU/mL at therapy week 4 (null-responders). IL28B genotype was rs8099917 (G*)/rs1297860(**) in 21/26 (80%) of null-responder patients. Using multivariate analysis, it was shown that the presence of the rs8099917 G allele was the best predictor of null-response (OR = 7.9, 95%CI: 1.99-31.18). The presence of at least one favorable genotype showed a positive predictive value of above 90% for HCV RNA reduction ≥ log at week 4. Analysis of the HCV RNA kinetics during 12 wk of therapy in patients with IL28B rs12979860 CT heterozygosis (n = 73), according to their rs8099917 status, showed that the viremia reduction was significantly different in patients carrying the rs8099917 G allele compared to those with favorable homozygosis.

CONCLUSION: Our findings emphasize the association of the IL28B rs8099917 G allele with HCV. Genotyping for both IL28B SNPs is useful in clinical practice for thorough patient risk stratification based on IFN responsiveness.

Keywords: Hepatitis C virus-G1; Interleukin-28B rs12979860; Interleukin-28B rs8099917; Interferon sensitivity; Triple therapy

Core tip: This work provides more insights into the advantage of interleukin-28B rs12979860 and rs8099917 genotyping for therapy management in hepatitis C virus-G1 infected patients. The relevance of this approach is cost-effective at the time of decisions regarding triple therapy. We observed that in rs12979860 heterozygous patients, carriage of the rs8099917 G allele correlated with lack of viremia decrease early during treatment, when it is critical to assess for interferon sensitivity.