title: HBV cure: why, how, when?
abstract: Current HBV treatments control replication and liver disease progression in the vast majority of treated patients. However, HBV patients often require lifelong therapies due to the persistence of transcriptionally active viral cccDNA mini-chromosome in the nucleus, which is not directly targeted by current antiviral therapies. A true complete cure of HBV would require clearance of intranuclear cccDNA from all infected hepatocytes. An intermediate but still relevant step forward that would allow treatment cessation would be reaching a functional cure, equivalent to resolved acute infection, with a durable HBsAg loss±anti-HBs seroconversion, undetectable serum DNA and persistence of cccDNA in a transcriptionally inactive status. Recent advances in technologies and pharmaceutical sciences, including the cloning of the mayor HBV receptor (i.e. the NTCP transporter) and the development in vitro HBV infection models, have heralded a new horizon of innovative antiviral and immune-therapeutic approaches.
authors.affiliation: Cancer Research Center of Lyon (CRCL), Lyon 69008, France; INSERM, U1052, Lyon 69003, France; Hospices Civils de Lyon (HCL), 69002 Lyon, France; Department of Internal Medicine - DMISM, Sapienza University, 00161 Rome, Italy; CLNS@SAPIENZA, Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy. Electronic address: massimo.levrero@inserm.fr.
authors.forename: Massimo
authors.initials: M
authors.lastname: Levrero
authors.affiliation: Cancer Research Center of Lyon (CRCL), Lyon 69008, France; INSERM, U1052, Lyon 69003, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Testoni
authors.affiliation: Cancer Research Center of Lyon (CRCL), Lyon 69008, France; INSERM, U1052, Lyon 69003, France; Hospices Civils de Lyon (HCL), 69002 Lyon, France; University of Lyon, UMR_S1052, UCBL, 69008 Lyon, France; Institut Universitaire de France (IUF), 75005 Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000378:metabolism; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens