Assessing immunological and virological responses in the liver: Implications for the cure of chronic hepatitis B virus infection

Tobias Boettler; Upkar S Gill; Lena Allweiss; Teresa Pollicino; John E Tavis; Fabien Zoulim

doi:10.1016/j.jhepr.2022.100480

Assessing immunological and virological responses in the liver: Implications for the cure of chronic hepatitis B virus infection

JHEP Rep. 2022 Apr 2;4(6):100480. doi: 10.1016/j.jhepr.2022.100480. eCollection 2022 Jun.

Authors

Tobias Boettler¹, Upkar S Gill², Lena Allweiss^{3

4}, Teresa Pollicino⁵, John E Tavis⁶, Fabien Zoulim⁷

Affiliations

¹ Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Blizard Institute, Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
³ I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴ German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems sites, Germany.
⁵ Department of Human Pathology, University Hospital "G. Martino" of Messina, Messina, Italy.
⁶ Department of Molecular Microbiology and Immunology and Institute for Drug and Biotherapeutic Innovation, Saint Louis University, Saint Louis MO USA.
⁷ INSERM Unit 1052 - Cancer Research Center of Lyon, Department of Hepatology Hospices Civils de Lyon, Lyon University, France.

Abstract

Cure from chronic HBV infection is rare with current therapies. Basic research has helped to fundamentally improve our knowledge of the viral life cycle and virus-host interactions, and provided the basis for several novel drug classes that are currently being developed or are being tested in clinical trials. While these novel compounds targeting the viral life cycle or antiviral immune responses hold great promise, we are still lacking a comprehensive understanding of the immunological and virological processes that occur at the site of infection, the liver. At the International Liver Congress 2021 (ILC 2021), a research think tank on chronic HBV infection focused on mechanisms within the liver that facilitate persistent infection and looked at the research questions that need to be addressed to fill knowledge gaps and identify novel therapeutic strategies. Herein, we summarise the discussion by the think tank and identify the key basic research questions that must be addressed in order to develop more effective strategies for the functional cure of HBV infection.

Keywords: B cells; CHB, chronic hepatitis B; FNA, fine needle aspiration; HBcrAg, HBV core-related antigen; HBsAg; T cells; biomarker; cccDNA; cccDNA, covalently closed circular DNA; fine needle aspirates; liver biopsy; pgRNA, pregenomic RNA; viral hepatitis; viral integration.

Publication types

Review