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Enolase: a metabolic checkpoint behind diverse exhaustion stages of CD8+ T cells in chronic HBV and HCV
  1. Nina Le Bert1,
  2. Paola Fisicaro2
  1. 1 Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
  2. 2 Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
  1. Correspondence to Dr Nina Le Bert, Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore; nina{at}; Dr Paola Fisicaro, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; pfisicaro{at}

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Resolving chronic hepatic infections caused by hepatitis B and C viruses (HBV and HCV) could be realised through two primary approaches: direct targeting of the virus or enhancement of the immune response, encompassing antiviral and immune-based therapies, respectively. Although direct-acting antiviral (DAA) medications exhibit remarkable efficacy in curing chronic HCV infection, the current approach to treating chronic HBV infection relies on long-term administration of nucleos(t)ide analogues, which inhibits viral replication but falls short of resolving the infection.1

The importance of functional virus-specific T cells in clearing HBV and HCV infections is suggested by the contrasting levels of virus-specific T cell immunity observed between individuals who successfully recover from acute hepatic viral infections and those who experience prolonged chronic infections. Chronic HBV and HCV infections manifest with diminished quantities of virus-specific T cells, which exhibit signs of exhaustion and functional impairment. The enhancement of virus-specific T cell functionality in patients with HCV who successfully cleared the virus through DAA therapy,2 as well as in patients with HBV achieving functional cure,3 supports the concept that immune interventions aimed at revitalising virus-specific T cell immunity hold the potential to ameliorate patient outcomes.

To date, clinical trials aimed at overcoming T cell exhaustion have centred on anti-programmed cell death protein-1 (PD1) therapy. Initially, the concept of targeting PD1 expression …

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  • Contributors NLB and PF wrote the commentary.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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