Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia

Authors

  • Nikola S. Kokanov Vinča Institute of Nuclear Sciences – National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0002-2380-2028
  • Snežana P. Jovanović-Ćupić Vinča Institute of Nuclear Sciences – National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0002-3389-7278
  • Marina M. Šiljić Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia https://orcid.org/0000-0002-5250-1953
  • Valentina S. Ćirković Group for Medical Entomology, Centre of Excellence for Food and Vector Borne Zoonoses, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia https://orcid.org/0000-0003-0453-5945
  • Nina M. Petrović Vinča Institute of Nuclear Sciences – National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0003-2503-1228
  • Bojana R. Kožik Vinča Institute of Nuclear Sciences – National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0002-2983-4151
  • Milena M. Krajnović Vinča Institute of Nuclear Sciences – National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0001-5638-2042

DOI:

https://doi.org/10.2298/ABS230316020K

Keywords:

hepatitis C virus, variability of HCV core region, IL28B, RASSF1A and p16 methylation, therapy response

Abstract

Paper description:

  • Variations in the hepatitis C virus core sequence are related to the progression of liver fibrosis and response to therapy.
  • We previously showed that host genetic and epigenetic factors affect the response to pegylated interferon/ribavirin therapy. Herein we examine whether amino acid substitutions in the HCV core region have similar effects on therapy outcome and disease progression.
  • Patients with amino acid substitution at position 75 and CT/TT IL28B genotype were non-responders. Patients with amino acid substitution at position 91 and CC IL28B genotype had a sustained virologic response.
  • Variability in the HCV core protein may help in predicting treatment response.

Abstract: Variations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were non-responders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients.

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2023-10-26

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Kokanov NS, Jovanović-Ćupić SP, Šiljić MM, Ćirković VS, Petrović NM, Kožik BR, Krajnović MM. Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia. Arch Biol Sci [Internet]. 2023Oct.26 [cited 2024Apr.29];75(3):251-62. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/8542

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