guest ::
| Home > Articles > Published articles > Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients |
| Home > Articles > Published articles > Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients |
(Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Hospital Universitari Vall d'Hebron) (Institut d'Investigacions Biomèdiques August Pi i Sunyer)| Date: | 2021 |
| Abstract: | 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. 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. 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. 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. 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. |
| Grants: | Instituto de Salud Carlos III PI16/00111 Instituto de Salud Carlos III PI15/00151 Instituto de Salud Carlos III PI18/00079 Instituto de Salud Carlos III PI18/01436 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Hepatitis B virus ; Chronic hepatitis B ; Nucleos(t)ide analogue ; Antiviral therapy discontinuation ; HBsAg ; HBcrAg ; Covalently closed circular DNA ; HBV-RNA ; Immune response ; HBV-Specific T cells |
| Published in: | Journal of Hepatology, Vol. 74 (may 2021) , p. 1064-1074, ISSN 1600-0641 |
