Transient Interferon-Driven Natural Killer Cell Activation in Acute Hepatitis C - Report - MDSpire

Transient Interferon-Driven Natural Killer Cell Activation in Acute Hepatitis C

  • By

  • Benedikt Strunz

  • Qiuyao Zhan

  • Tanvi Khera

  • Julia Hengst

  • Marija Jankovic

  • Katja Deterding

  • Annika Niehrs

  • Markus Cornberg

  • Cheng-Jian Xu

  • Heiner Wedemeyer

  • Niklas K Björkström

  • the HepNet Acute HCV IV Study Group

  • Christoph D Spinner

  • Eckart Schott

  • Tania M Welzel

  • Guido Gerken

  • Hartwig Klinker

  • Ulrich Spengler

  • Johannes Wiegand

  • Julian Schulze zur Wiesch

  • Anita Pathil

  • Andreas Umgelter

  • Caroline Zöllner

  • Stefan Zeuzem

  • Armin Papkalla

  • Kristina Weber

  • Svenja Hardtke

  • Heiko von der Leyen

  • Armin Koch

  • Dorothee von Witzendorff

  • Michael P Manns

  • Kerstin Port

  • Bernhard Schlevogt

  • Marc Ringelhan

  • Ulrich Mayr

  • Judith Schrewe

  • Katharina Sosnowsky

  • Christoph Jochum

  • Gudrun Hilgard

  • Petra Schulze

  • Susanne Wiebecke

  • Ji-Eun Lee

  • Peter Hoffmann

  • December 29, 2025

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Temporary Activation of NK Cells by Interferon in Acute Hepatitis C Infection

Overview

This study identifies a transiently activated subset of natural killer (NK) cells with a strong type I interferon (IFN) signature during acute hepatitis C virus (HCV) infection. These activated NK cells diminish after direct-acting antiviral (DAA) treatment and viral clearance, although a long-term phenotypic imprint remains compared to healthy controls.

Background

Hepatitis C virus infection often progresses to chronic disease, leading to significant liver morbidity and mortality if untreated. Acute symptomatic HCV infection is rare but can now be effectively treated with DAAs. Natural killer cells, enriched in the liver, play a critical role in antiviral immunity, and their function is known to be impaired in chronic HCV. The impact of natural type I IFN responses on NK cells during acute HCV infection and subsequent viral clearance has not been fully elucidated.

Data Highlights

GroupNK Cell ActivationISG ExpressionCD56bright NK Frequency
Acute HCV (pre-treatment)High (activated NK subset present)Elevated (IFIT2, IFIT3, ISG15)Increased
Acute HCV (post-DAA cure)Normalized (activated NK subset vanished)ReducedNormalized
Chronic HCVMinor alterationsMinor ISG changesLower than acute HCV
Healthy ControlsBaselineBaselineBaseline

Key Findings

  • A distinct NK cell cluster with high expression of interferon-stimulated genes (ISGs) such as IFIT2, IFIT3, and ISG15 was identified during acute HCV infection.
  • This activated NK cell subset showed elevated functional markers including CCL3, CCL4, and TNF.
  • The frequency of CD56bright NK cells and overall NK cell activation were increased in acute HCV compared to chronic infection and healthy controls.
  • Following DAA-mediated viral clearance, the activated NK cell population largely disappeared, indicating reversibility of activation.
  • Despite normalization, a long-term phenotypic imprint of prior acute infection on NK cells was observed when compared to healthy controls.

Clinical Implications

These findings highlight the dynamic role of NK cells and type I IFN responses in the immune control of acute HCV infection. Monitoring NK cell activation and ISG signatures could provide insights into antiviral immune status during acute infection and treatment. The reversibility of NK cell activation post-DAA therapy supports the effectiveness of viral clearance in restoring immune homeostasis.

Conclusion

Acute hepatitis C infection induces a transient, interferon-driven activation of a specific NK cell subset that normalizes after successful DAA treatment, underscoring the importance of innate immunity in viral clearance and recovery.

References

  1. HepNet Acute HCV IV Trial (NCT02309918) -- Ledipasvir/Sofosbuvir treatment in acute HCV
  2. Study Authors, 2024 -- Temporary Activation of Natural Killer Cells Induced by Interferon in Acute Hepatitis C Infection

Original Source(s)

Transient Interferon-Driven Natural Killer Cell Activation in Acute Hepatitis C

  • by Benedikt Strunz, Qiuyao Zhan, Tanvi Khera, Julia Hengst, Marija Jankovic, Katja Deterding, Annika Niehrs, Markus Cornberg, Cheng-Jian Xu, Heiner Wedemeyer, Niklas K Björkström, the HepNet Acute HCV IV Study Group, Christoph D Spinner, Eckart Schott, Tania M Welzel, Guido Gerken, Hartwig Klinker, Ulrich Spengler, Johannes Wiegand, Julian Schulze zur Wiesch, Anita Pathil, Andreas Umgelter, Caroline Zöllner, Stefan Zeuzem, Armin Papkalla, Kristina Weber, Svenja Hardtke, Heiko von der Leyen, Armin Koch, Dorothee von Witzendorff, Michael P Manns, Kerstin Port, Bernhard Schlevogt, Marc Ringelhan, Ulrich Mayr, Judith Schrewe, Katharina Sosnowsky, Christoph Jochum, Gudrun Hilgard, Petra Schulze, Susanne Wiebecke, Ji-Eun Lee, Peter Hoffmann

  • December 29, 2025

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