Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients.
Autor: | García-López M; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Lens S; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Pallett LJ; Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, UK., Testoni B; INSERM U1052-Cancer Research Center of Lyon (CRCL), University of Lyon, UMR_S1052, CRCL, Lyon, France., Rodríguez-Tajes S; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Mariño Z; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Bartres C; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., García-Pras E; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Leonel T; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Perpiñán E; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Lozano JJ; Bioinformatics Platform, CIBERehd, Barcelona, Spain., Rodríguez-Frías F; Liver Pathology Unit, Department of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, CIBERehd, Barcelona, Spain., Koutsoudakis G; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Zoulim F; INSERM U1052-Cancer Research Center of Lyon (CRCL), University of Lyon, UMR_S1052, CRCL, Lyon, France., Maini MK; Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, UK., Forns X; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. Electronic address: xforns@clinic.cat., Pérez-Del-Pulgar S; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. Electronic address: sofiapp@clinic.cat. |
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Jazyk: | angličtina |
Zdroj: | Journal of hepatology [J Hepatol] 2021 May; Vol. 74 (5), pp. 1064-1074. Date of Electronic Publication: 2020 Dec 02. |
DOI: | 10.1016/j.jhep.2020.11.043 |
Abstrakt: | Background & Aims: Factors associated with a successful outcome upon nucleos(t)ide analogue (NA) treatment withdrawal in HBeAg-negative chronic hepatitis B (CHB) patients have yet to be clarified. The objective of this study was to analyse the HBV-specific T cell response, in parallel with peripheral and intrahepatic viral parameters, in patients undergoing NA discontinuation. Methods: Twenty-seven patients without cirrhosis with HBeAg-negative CHB with complete viral suppression (>3 years) were studied prospectively. Intrahepatic HBV-DNA (iHBV-DNA), intrahepatic HBV-RNA (iHBV-RNA), and covalently closed circular DNA (cccDNA) were quantified at baseline. Additionally, serum markers (HBV-DNA, HBsAg, HBV core-related antigen [HBcrAg] and HBV-RNA) and HBV-specific T cell responses were analysed at baseline and longitudinally throughout follow-up. Results: After a median follow-up of 34 months, 22/27 patients (82%) remained off-therapy, of whom 8 patients (30% of the total cohort) lost HBsAg. Baseline HBsAg significantly correlated with iHBV-DNA and iHBV-RNA, and these parameters were lower in patients who lost HBsAg. All patients had similar levels of detectable cccDNA regardless of their clinical outcome. Patients achieving functional cure had baseline HBsAg levels ≤1,000 IU/ml. Similarly, an increased frequency of functional HBV-specific CD8+ T cells at baseline was associated with sustained viral control off treatment. These HBV-specific T cell responses persisted, but did not increase, after treatment withdrawal. A similar, but not statistically significant trend, was observed for HBV-specific CD4+ T cell responses. Conclusions: Decreased cccDNA transcription and low HBsAg levels are associated with HBsAg loss upon NA discontinuation in patients with HBeAg-negative CHB. The presence of functional HBV-specific T cells at baseline are associated with a successful outcome after treatment withdrawal. Lay Summary: Nucleos(t)ide analogue therapy can be discontinued in a high proportion of chronic hepatitis B patients without cirrhosis. The strength of HBV-specific immune T cell responses may contribute to successful viral control after antiviral treatment interruption. Our comprehensive study provides in-depth data on virological and immunological factors than can help guide individualised therapy in patients with chronic hepatitis B. Competing Interests: Conflicts of interest SL has received lecture and advisory fees from Gilead, Abbvie, and MSD. XF has acted as advisor for Gilead and Abbvie. SRT has received lecture fees from Gilead and Abbvie. ZM has received fees for lectures and consulting from Gilead and Abbvie, and a research grant from Gilead. The Maini lab has received research funding from Gilead, Hoffmann La Roche and Immunocore. MKM has sat on advisory boards/provided consultancy for Gilead, Hoffmann La Roche, Immunocore, VIR, Galapagos NV, GSK, Abbvie, and Freeline. LJP has received fees from Gilead for consultancy work. FZ received research grants and consultancy honoraria from Hoffmann-La-Roche, Gilead Sciences, Janssen, Assembly Biosciences, Arbutus, Contravir, Sanofi, and Transgene. All other authors have declared no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details. (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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