Molecular characterization of hepatitis C virus in end-stage renal disease patients under hemodialysis

Rafael Alves da Silva1,2, Jardelina de Souza Todão1, Fernando Luiz Kamitani2

  • 1Laboratório de Hepatologia Molecular Aplicada (LHeMA), Departamento de Gastroenterologia, Unidade de Hepatologia, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil.

Insights

Hepatitis C virus (HCV) genetic diversity in hemodialysis patients shows higher mutation rates in genotype 1a, potentially impacting direct-acting antiviral (DAA) drug resistance. This finding highlights the importance of molecular characterization in chronic HCV infection management.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology
  • Nephrology

Background:

  • Direct-acting antiviral (DAA) agents are revolutionizing chronic hepatitis C virus (HCV) treatment.
  • HCV drug resistance can arise from pre-existing viral variants, influenced by host immunity and viral genetics.
  • End-stage renal disease patients on hemodialysis (ESRD-HD) represent a unique population for studying viral evolution.

Purpose of the Study:

  • To perform molecular characterization of HCV in ESRD-HD patients.
  • To analyze genetic diversity and identify mutations within the NS5B region.
  • To investigate the relationship between viral genetics, host factors, and potential DAA resistance.

Main Methods:

  • Nested PCR and Sanger sequencing were used to analyze the NS5B region of HCV from 86 treatment-naïve ESRD-HD patients.
  • Bioinformatics tools, including phylogenetic reconstruction and informational entropy, were employed for comparative analysis with public genomic data.
  • Analysis considered geographical location, HCV genotype, and renal function status.

Main Results:

  • HCV genotypes 1a, 1b, 2a, 2b, and 3a were identified in ESRD-HD patients.
  • Phylogenetic analysis revealed two distinct clades for HCV subtype 1a.
  • Entropy analysis identified two amino acid positions in the NS5B region associated with T-cell epitopes. Genotype 1a exhibited greater genetic diversity and higher amino acid changes in ESRD-HD patients compared to controls.

Conclusions:

  • Significant genetic diversity exists within the NS5B HCV partial protein in hemodialysis patients, particularly for genotype 1a.
  • Identified mutations in T-cell epitopes may correlate with host immunological characteristics and geographical patterns.
  • This elevated genetic diversity in ESRD-HD patients could influence the development of resistance mechanisms against new DAAs.

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