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A decrease in hepatitis C virus RNA to undetectable levels in chronic hepatitis C patients after PegIFNα + RVB or sofosbuvir + NS5A inhibitor treatment is associated with decreased insulin resistance and persistent oxidative stress

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Abstract

Oxidative stress (OS) and insulin resistance (IR) induced by hepatitis C virus (HCV) infection, are involved in the development of chronic hepatitis C (CHC) complications and progression to hepatocellular carcinoma. The aim of this study was to investigate the effect of pegylated interferon alpha (IFNα) + ribavirin (PegIFNα+RVB) or sofosbuvir + NS5A inhibitor (SOF+InNS5A) on IR and the components of OS. HCV was genotyped in 20 CHC patients grouped by treatment with either PegIFNα+RVB (n = 10) or SOF+InNS5A (n = 10). The treatment’s effect on OS-induced damage to lipids (HNE-HDL), proteins (advanced glycation end products [AGEs]), and DNA (8-OHdG) as well as the concentrations of proinflammatory cytokines (IL-2, TNFα, IFNγ), ALT, AST, GSH and platelets was determined. Superoxide dismutase (SOD) and catalase activity as well as IR, determined by the HOMA1-IR index, was evaluated. The HCV genotypes (GT) found were GT1b (45%), GT1a (30%), GT2b (20%), and GT2a (5%). Viral RNA became undetectable by week 12 with SOF+InNS5A in 100% of the cases and with PegIFNα+RVB in 70% of the cases. After viral RNA became undetectable, regardless of treatment and GT, a significant increase in the platelet concentration and SOD activity was observed, whereas ALT, insulin, and IR decreased (p < 0.05). However, only for the SOF+InNS5A treated group was there an increase in oxidative damage to lipids (p < 0.017) and proteins (p < 0.05). None of the other parameters demonstrated any differences. These data confirm that OS persisted after treatment with either SOF+InNS5A or PegIFNα+RVB. IR could be considered a response biomarker to treatment with direct-acting antivirals.

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Acknowledgements

The authors wish to acknowledge all the patients who kindly gave their consent to participate in this study. The authors would also like to thank the staff of the Infectious Diseases Department and of the Medical Research Unit, and to Dr. Leonardo M. Porchia for his input with respect to the manuscript content and grammar.

Funding

This work was funded by the Consejo Nacional de Ciencia y Tecnología (CONACYT)-[SALUD-2015-1-261113] and the Fondo en Investigación en Salud (FIS) of the Instituto Mexicano del Seguro Social [FIS/IMSS/PROT/G15/1411] and [FIS/IMSS/PROT/G11/952].

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Authors and Affiliations

  1. Laboratorio Central de Epidemiología, División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, IMSS, Calzada vallejo s/n Col. La Raza, Del. Azcapotzalco, CP 02990, México City, México

    Allison Cázares-Cortazar, Luis A. Uribe-Noguez & Alicia Ocaña-Mondragón

  2. Departamento de Enfermedades Infecciosas, Hospital de Infectología, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, IMSS, México City, México

    José Antonio Mata-Marín, Jesús Gaytán-Martínez, María de la Luz Martínez-Rodríguez & Alberto Chapararro-Sánchez

  3. Laboratorio de Medicina Nuclear, Unidad Médica de Alta Especialidad, Hospital de Especialidades, CMN “La Raza”, Instituto Mexicano del Seguro Social, IMSS, México City, México

    Pedro Esteban Villavicencio-Ferrel

  4. Center for HIV and Hepatogastroenterology, Düsseldorf, Germany

    Stefan Mauss

Authors
  1. Allison Cázares-Cortazar
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  2. Luis A. Uribe-Noguez
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Contributions

Alicia Ocaña-Mondragón, Luis A. Uribe-Noguez, José Antonio Mata-Marin, Jesús Gaytán-Martínez, and Stefan Mauss designed and conducted the study, interpreted the results, participated in the writing of the report, and agreed to its content. Allison Cázares-Cortáazar, María de la Luz Martínez-Rodríguez, Alberto Chapararro-Saánchez, and Stefan Mauss collaborated on the revision of the paper. Allison Cázares-Cortáazar, Luis A. Uribe-Noguez, and Pedro Esteban Villavicencio-Ferrel collaborated on the assays.

Corresponding author

Correspondence to Alicia Ocaña-Mondragón.

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The authors declare that they have no conflict of interest.

Ethical approval

The research protocol was approved by the local ethics committee (register no. R 2017-1302-101).

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In accordance with the Declaration of Helsinki, written, informed consent was collected from each patient.

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The datasets generated and/or analyzed in the current study are available from the corresponding author on reasonable request.

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Handling Editor: Michael A. Purdy.

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Cázares-Cortazar, A., Uribe-Noguez, L.A., Mata-Marín, J.A. et al. A decrease in hepatitis C virus RNA to undetectable levels in chronic hepatitis C patients after PegIFNα + RVB or sofosbuvir + NS5A inhibitor treatment is associated with decreased insulin resistance and persistent oxidative stress. Arch Virol 165, 2759–2766 (2020). https://doi.org/10.1007/s00705-020-04797-y

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