title: The role of tumour necrosis factor in hepatitis B infection: Jekyll and Hyde.
abstract: Chronic hepatitis B (CHB) is a major health problem worldwide and is associated with significant long-term morbidity and mortality. The hepatitis B virus (HBV) is a hepatotropic virus that is capable of integrating in the host nucleus permanently resulting in lifelong infection. To date, there is no definitive cure for HBV, as our current treatments cannot eradicate the viral reservoir that has integrated in the liver. Elucidating the immunopathogenesis is key to finding a therapeutic target for HBV as the virus is not in itself cytopathic but the immune response to the virus causes the majority of the cellular injury. In most cases, the virus reaches a state of equilibrium with low viral replication constrained by host immunity. Multiple cytokines have been implicated in the pathogenesis of CHB. Tumor necrosis factor (TNF) has emerged as a key player; on one hand it can facilitate immune-mediated virological control but on the other hand it can cause collateral hepatocyte damage, cirrhosis and possibly promote hepatocellular carcinoma. In this review, we discuss the current understanding of the immunopathogenesis of HBV, focusing on TNF and whether it can be harnessed in therapeutic strategies to cure HBV infection.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Gastroenterology, St Vincent's Hospital, Fitzroy,Victoria, Australia; Division of Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Parkville, Victoria, Australia; Department of Medicine, Eastern Hill Academic Centre, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Zina
authors.initials: Z
authors.lastname: Valaydon
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Marc
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Fitzroy,Victoria, Australia; Division of Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Parkville, Victoria, Australia; Department of Medicine, Eastern Hill Academic Centre, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Thompson
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Fitzroy,Victoria, Australia; Division of Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Parkville, Victoria, Australia; Department of Medicine, Eastern Hill Academic Centre, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Desmond
authors.affiliation: Department of Medicine, Eastern Hill Academic Centre, The University of Melbourne, Parkville, Victoria, Australia; Department of Microbiology and Immunology, Peter Doherty Institute, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Revill
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Ebert