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1.
Gut ; 73(10): 1737-1748, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39033025

ABSTRACT

OBJECTIVE: Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on. DESIGN: 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs. Serum hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels as well as peripheral blood NK cell phenotype and function and HBV-specific T cell responses upon in vitro stimulation with overlapping HBV peptides were measured longitudinally before, during and after pegIFN-α therapy. RESULTS: Two cohorts of pegIFN-α treated patients were identified according to HBsAg decline greater or less than 0.5 log at week 24 post-treatment. PegIFN-α add-on did not significantly improve HBV-specific T cell responses during therapy but elicited a significant multispecific and polyfunctional T cell improvement at week 24 post-pegIFN-α treatment compared with baseline. This improvement was maximal in patients who had a higher drop in serum HBsAg levels and a lower basal HBcrAg values. CONCLUSIONS: PegIFN-α treatment can induce greater functional T cell improvement and HBsAg decline in patients with lower baseline HBcrAg levels. Thus, HBcrAg may represent an easily and reliably applicable parameter to select patients who are more likely to achieve better response to pegIFN-α add-on to virally suppressed patients.


Subject(s)
Antiviral Agents , Hepatitis B e Antigens , Hepatitis B, Chronic , Interferon-alpha , Killer Cells, Natural , Polyethylene Glycols , Recombinant Proteins , Humans , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/blood , Interferon-alpha/therapeutic use , Antiviral Agents/therapeutic use , Recombinant Proteins/therapeutic use , Female , Adult , Male , Polyethylene Glycols/therapeutic use , Killer Cells, Natural/immunology , Killer Cells, Natural/drug effects , Middle Aged , Hepatitis B e Antigens/blood , Hepatitis B Core Antigens/immunology , Hepatitis B Core Antigens/blood , Drug Therapy, Combination , Hepatitis B Surface Antigens/blood , Hepatitis B virus/immunology , T-Lymphocytes/immunology , T-Lymphocytes/drug effects , Treatment Outcome , Nucleosides/therapeutic use
2.
Acta Biomed ; 93(S1): e2022115, 2022 06 08.
Article in English | MEDLINE | ID: mdl-35674476

ABSTRACT

Redo surgical aortic valve replacement has been the gold standard for the treatment of degenerated bioprostheses; however it carries an inherent risk associated with a reoperative open heart surgery. Valve-in-Valve transcatheter aortic valve implantation (ViV-TAVI) has emerged as an alternative approach. Few articles in literature review transcatheter aortic valve replacement's failure rates, complications (i.e., valve dislocation, paravalvular leaks) and their surgical management. The rate of reoperations after a percutaneous approach is expected to increase, with the currently rising number of transcatheter procedures worldwide even in patients with a longer life expectancy. Valve dislocation is a rare but serious complication that can severely impact on the outcome of patients. Paravalvular leaks and structural valve degeneration are the most common causes of surgical re-intervention. We present the case of a complex patient with previous surgical aortic valve and ascending aorta replacement who underwent a transfemoral valve-in-valve TAVI for bioprosthesis degeneration, complicated by valve dislocation requiring surgical reoperation.


Subject(s)
Bioprosthesis , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Aortic Valve/surgery , Bioprosthesis/adverse effects , Humans , Prosthesis Design , Prosthesis Failure , Reoperation/methods , Risk Factors , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Treatment Outcome
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