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Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients
Mireia García-López 1 , Sabela Lens 1 , Laura J Pallett 2 , Barbara Testoni 3 , Sergio Rodríguez-Tajes 1 , Zoe Mariño 1 , Concepción Bartres 1 , Ester García-Pras 1 , Thais Leonel 1 , Elena Perpiñán 1 , Juan José Lozano 4 , Francisco Rodríguez-Frías 5 , George Koutsoudakis 1 , Fabien Zoulim 3 , Mala K Maini 2 , Xavier Forns 6 , Sofía Pérez-Del-Pulgar 7
Affiliations
Affiliations
1
Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
2
Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, UK.
3
Cancer Research Center of Lyon (CRCL), University of Lyon, UMR_S1052, UCBL, INSERM, U1052, Lyon, France.
4
Bioinformatics Platform, CIBERehd, Barcelona, Spain.
5
Liver Pathology Unit, Department of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, CIBERehd, Barcelona, Spain.
6
Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. Electronic address: [email protected].
7
Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. Electronic address: [email protected].
PMID: 33278456 DOI: 10.1016/j.jhep.2020.11.043
Abstract
Background aims: Factors associated with a successful outcome upon nucleos(t)ide analog (NA) treatment withdrawal in chronic hepatitis B (CHB) HBeAg-negative patients have yet to be clarified. The objective of this study was to analyze the HBV-specific T cell response, in parallel with peripheral and intrahepatic viral parameters, in patients undergoing NA discontinuation.
Methods: Twenty-seven non-cirrhotic patients 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 analyzed 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 ≤1000 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.
Keywords: Antiviral therapy discontinuation; Chronic hepatitis B (CHB); Covalently closed circular DNA (cccDNA); HBV-RNA; HBV-specific T cells; HBcrAg; HBsAg; Hepatitis B virus (HBV); Immune response; Nucleos(t)ide analog (NA).
Copyright © 2020. Published by Elsevier B.V. |
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