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Role of serum level and genetic variation of IL-28B in interferon responsiveness and advanced liver disease in chronic hepatitis C patients

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Abstract

Interleukin-28B (IL-28B) is suspected to be associated with response to treatment and one of the basic immunological backgrounds in liver transplant candidate (LTC). We aimed to assess whether genotypes of IL-28B can play a role in therapeutic response or advanced stages of liver disease. A total of 364 subjects were genotyped for IL-28B rs12979860 and rs8099917 SNPs using PCR-RFLP assay. Moreover, IL-28 serum level, HCV loads, and genotype were performed. A significant increase was observed in the frequencies of unfavorable rs12979860 genotypes/CT + TT in the chronic hepatitis C (CHC) and LTC groups. In the case of rs8099917, CHC group had a significantly higher frequency of unfavorable genotypes/GT + GG compared to the healthy group. IL-28B serum level was also significantly higher in healthy group compared with the CHC and LTC groups. There were no differences in the distribution of the IL-28B genotypes and haplotypes between responder and non-responder patients. Our results suggest, for the first time, that unfavorable rs12979860 genotypes can be considered one of the important immunological backgrounds in the Iranian LTC population that was confirmed with the lower IL-28 serum level compared to healthy group. Besides, there was a possible association of favorable IL-28B genotypes with lower odds of susceptibility to CHC infection but no support for a positive association between analyzed SNPs and an outcome of therapy. Moreover, non-CT haplotypes may be regarded as a genetic risk factor that can increase the chance of infection with HCV and progression toward end-stage HCV-related liver disease.

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Acknowledgements

The authors would like to thank personnel of Digestive Disease Research Institute (DDRI) of Shariati Hospital, affiliated with Tehran University of Medical Sciences for excellent work in collecting blood samples. We also express special thanks to Saeed Ghanbari, Ph.D. Student of Department of Biostatistics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran, for his statistical assistance and Ali Nasimi (Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran), and Jean Krugman, retired professor of General Studies, DeVry University, Decatur, Georgia, USA, for help in revising the English of the manuscript. This study was financially supported by Iran’s National Elites Foundation, Allame Tabatabai National Award.

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    1. Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

      Abdolvahab Alborzi, Tayebeh Hashempour, Javad Moayedi, Zahra Musavi & Gholamreza Pouladfar

    2. Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

      Shahin Merat

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    A. Alborzi, T. Hashempour, and J. Moayedi contributed equally to this work.

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    Alborzi, A., Hashempour, T., Moayedi, J. et al. Role of serum level and genetic variation of IL-28B in interferon responsiveness and advanced liver disease in chronic hepatitis C patients. Med Microbiol Immunol 206, 165–174 (2017). https://doi.org/10.1007/s00430-017-0497-y

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