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Khera T, Du Y, Todt D, et al. Long-lasting Imprint in the Soluble Inflammatory Milieu despite Early Treatment of Acute Symptomatic Hepatitis C. J Infect Dis. 2021;doi: 10.1093/infdis/jiab048.
Khera, T., Du, Y., Todt, D., Deterding, K., Strunz, B., Hardtke, S., Aregay, A., Port, K., Hardtke-Wolenski, M., Steinmann, E., Björkström, N. K., Manns, M. P., Hengst, J., Cornberg, M., Wedemeyer, H. (2021). Long-lasting Imprint in the Soluble Inflammatory Milieu despite Early Treatment of Acute Symptomatic Hepatitis C. The Journal of infectious diseases, . https://doi.org/10.1093/infdis/jiab048
Khera, Tanvi, et al. "Long-lasting Imprint in the Soluble Inflammatory Milieu despite Early Treatment of Acute Symptomatic Hepatitis C." The Journal of infectious diseases vol. (2021). doi: https://doi.org/10.1093/infdis/jiab048
Khera T, Du Y, Todt D, Deterding K, Strunz B, Hardtke S, Aregay A, Port K, Hardtke-Wolenski M, Steinmann E, Björkström NK, Manns MP, Hengst J, Cornberg M, Wedemeyer H. Long-lasting Imprint in the Soluble Inflammatory Milieu despite Early Treatment of Acute Symptomatic Hepatitis C. J Infect Dis. 2021 Jan 31; doi: 10.1093/infdis/jiab048. Epub 2021 Jan 31. PMID: 33517457.
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J Infect Dis. 2021 Jan 31; doi: 10.1093/infdis/jiab048. Epub 2021 Jan 31.

Long-lasting Imprint in the Soluble Inflammatory Milieu despite Early Treatment of Acute Symptomatic Hepatitis C.

The Journal of infectious diseases

Tanvi Khera, Yanqin Du, Daniel Todt, Katja Deterding, Benedikt Strunz, Svenja Hardtke, Amare Aregay, Kerstin Port, Matthias Hardtke-Wolenski, Eike Steinmann, Niklas K Björkström, Michael P Manns, Julia Hengst, Markus Cornberg, Heiner Wedemeyer,

Affiliations

  1. Department of Gastroenterology and Hepatology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
  2. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany, HepNet Study-House, German Liver Foundation, Hannover, Germany.
  3. Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
  4. European Virus Bioinformatics Center (EVBC), Jena, Germany.
  5. Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  6. German Center for Infection Research (DZIF), partner site Braunschweig, Germany.
  7. Center for individualized infection medicine (CIIM), Hannover, Germany.

PMID: 33517457 DOI: 10.1093/infdis/jiab048

Abstract

BACKGROUND: Treatment with direct acting antivirals (DAAs) in patients with chronic hepatitis C infection leads to partial restoration of soluble inflammatory mediators (SIMs). In contrast, we hypothesized that early DAA treatment of acute hepatitis C with DAAs may normalize most SIMs.

METHODS: In this study, we made use of a unique cohort of acute symptomatic hepatitis C who cleared HCV with a 6-week course of ledipasvir/sofosbuvir. Plasma samples were used for proximity extension assay (PEA) measuring 92 proteins.

RESULTS: Profound SIM alterations were observed in acute HCV patients, with marked upregulation of IL-6 and CXCL10 while certain mediators were down-regulated (e.g. MCP-4, IL-7). During treatment and follow-up, the majority of SIMs decreased but not all normalized (e.g. CDCP1, IL-18). Of note, SIMs that were down-regulated before DAA treatment remained suppressed while others that were initially unchanged, declined to lower values during treatment and follow-up (e.g.CD244).

CONCLUSIONS: Acute hepatitis C was associated with marked changes in the soluble inflammatory milieu as compared to both chronic hepatitis patients and healthy controls. Whereas early DAA treatment partly normalized this altered signature, long-lasting imprints of HCV remained. Thus, acute HCV-induced changes in the immune system may persist even after a short duration of viremia.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Keywords: acute infection; direct acting antivirals; hepatitis C virus; proximity extension assay; soluble inflammatory milieu

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