García-López, M;
Lens, S;
Pallett, LJ;
Testoni, B;
Rodríguez-Tajes, S;
Mariño, Z;
Bartres, C;
... Pérez-Del-Pulgar, S; + view all
(2020)
Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients.
Journal of Hepatology
10.1016/j.jhep.2020.11.043.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jhep.2020.11.043 |
| Publisher version: | https://doi.org/10.1016/j.jhep.2020.11.043 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Hepatitis B virus (HBV); Chronic hepatitis B (CHB); Nucleos(t)ide analog (NA); Antiviral therapy discontinuation; HBsAg; HBcrAg; Covalently closed circular DNA (cccDNA); HBV-RNA; Immune response; HBV-specific T cells. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10118581 |
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