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Engineered IFN-α and anti-PDL1 containing compounds to target the liver and restore antiviral protection for HBV cure
  1. Paola Fisicaro
  1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
  1. Correspondence to Dr Paola Fisicaro, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, 43126, Italy; pfisicaro{at}

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Chronic HBV infection, with hepatic inflammation and viral genome persistence in the hepatocytes either in the form of cccDNA or partially integrated into the host nucleus, is one of the major causes of liver cirrhosis and hepatocellular carcinoma.1 Available therapies for chronic hepatitis B (CHB) include long-term administration of nucleos(t)ide analogues or a finite treatment with polyethylene-glycol (PEG)–interferon alpha (IFN-α) that rarely allow reaching a functional cure, defined as loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA in the serum.1 Thus, a major effort is currently devoted to studies aimed at finding new effective therapies.

Different factors contribute to viral persistence. HBV can elude the host immune response, being poorly detected by the innate system and inducing variable degrees of dysfunction of the adaptive immune response up to T-cell and B-cell exhaustion in chronic infection. Moreover, the liver represents a peculiar tolerogenic environment that plays a central role in the induction of immune unresponsiveness due to its unique anatomy and composition of resident cell population, as well as to the presence of different regulatory mechanisms, including high expression of coinhibitory receptors by immune cells.2

Therefore, strategies aimed at activating innate immunity components or at reconstituting an efficient antiviral T-cell and B-cell response represent a rational approach to allow virus control and to complement the effect of available antiviral therapies. For this reason, immunotherapy represents a rationale option among many different therapeutic approaches currently under investigation.

The rationale for the use of IFN-α is based not only on its direct antiviral effect but also on its immunomodulatory properties. IFN-α signalling leads to the induction of more than 300 interferon-stimulated genes (ISG), most of which encode pattern-recognition receptors that detect viral molecules, while some of them encode proteins that act as antiviral …

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  • Contributors PF wrote the this 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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