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HBV infection and HCC: the ‘dangerous liaisons’
  1. Antonio Bertoletti1,
  2. Patrick T F Kennedy2,
  3. David Durantel3
  1. 1 Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore
  2. 2 Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, London, UK
  3. 3 Cancer Research Center of Lyon (CRCL), INSERM U1052, UMR-5286 CNRS, University of Lyon, Lyon, France
  1. Correspondence to Professor Antonio Bertoletti, Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore; antonio{at}

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Long-term relationships are somehow unpredictable. Periods of harmony are often followed by times of conflict with outcomes which are difficult to predict. This precept can apply to the relationship between HBV and human species. HBV acquired at birth or in early childhood establishes lifelong persistent infection in the majority of subjects, which is evolving, and characterised by fluctuations of virological and clinical parameters. The overall impact of these fluctuations in the development of liver fibrosis and hepatocellularcarcinoma has often puzzled clinicians and researchers studying this complex and somewhat fascinating interaction between HBV and our species. An interesting new piece of information, related to this interaction, has now been added, thanks to the work of the group of GA Kim and YS Lim, published in Gut.1

Let’s try to first summarise the main points of this puzzle. The early phase of the HBV-host relationship is characterised by normal serum alanine aminotransferase (ALT) and high-titre viraemia. This phase has been historically considered as ‘immune tolerant’ (IT) and ‘disease-free’. Based on this clinical categorisation, excluding both immunological and interindividual virus spreading considerations, patients in this disease phase have been excluded from treatment recommendations. This early phase in natural history is then followed by a period of ALT perturbation and fluctuations of viraemia (ie, defined as immune active or HBeAg+/anti-HBe +hepatitis by new European Association for the Study of the Liver nomenclature),2 in which immunological and pathological events within the liver are considered more active and where treatment is recommended.2

This simplified interpretation has, however, been disputed in recent years initially by work pointing out that the initial phase of HBV disease is not immunologically inert3 and that serum ALT values are a poor surrogate measurement of the strength of anti-HBV immunity.4

More recently, the belief that events …

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  • Contributors All the authors have contributed to the writing of the article.

  • Funding (Singapore Translational Research (STaR) Investigator Award (NMRC/STaR/013/2012).

  • Competing interests AB declares the following relationship with commercial entities developing therapeutics for HBV treatment. He collaborates and receives research support from Gilead Sciences to test the effect of HBV antigens on immune cell function. He acted as a consultant and served on the advisory boards of Gilead Sciences, MedImmune, Jansseen-Cilag, IONIS, Abivax, HUMABS BioMed. AB is also a cofounder of LION TCR pte. ltd. a biotech company developing T cell receptors for treatment of virus-related cancers and chronic viral diseases.

  • Provenance and peer review Commissioned; internally peer reviewed.

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