Sodium taurocholate cotransporting polypeptide (NTCP) polymorphisms may influence HDV RNA load and early response to bulevirtide.

Bulevirtide HDV RNA Hepatitis Delta genetic polymorphisms sodium taurocholate cotransporting polypeptide

Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
18 Jun 2024
Historique:
received: 17 09 2023
revised: 03 06 2024
accepted: 10 06 2024
medline: 21 6 2024
pubmed: 21 6 2024
entrez: 20 6 2024
Statut: aheadofprint

Résumé

Sodium taurocholate cotransporting peptide (NTCP) genetic polymorphisms have been described, but their role in untreated and treated patients with Chronic Hepatitis Delta (CHD) remains unknown. Virological response (VR) to NTCP inhibitor Bulevirtide (BLV) was achieved at week 48 by >70% of CHD patients, but nearly 15% experienced virological nonresponse (VNR) or partial response (PR). This study aimed to evaluate whether NTCP genetic polymorphisms affect baseline HDV RNA load and response to BLV in CHD patients. Untreated and BLV treated patients were enrolled in a retrospective cross-sectional and longitudinal study. Clinical and virological characteristics were collected at baseline and up to 96 weeks in the BLV-treated patients. NTCP genetic polymorphisms were identified by Sanger sequencing. Of the 6 NTCP polymorphisms studied in 209 CHD untreated patients, carriers of rs17556915 TT/CC (N=142) compared to CT (N=67) genotype presented higher median HDV RNA levels (5.39 vs. 4.75 log The NTCP rs17556915 C>T genetic polymorphisms may influence baseline HDV RNA load both in untreated and BLV treated patients with CHD and may contribute to identify patients with different early virological responses to BLV.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
Sodium taurocholate cotransporting peptide (NTCP) genetic polymorphisms have been described, but their role in untreated and treated patients with Chronic Hepatitis Delta (CHD) remains unknown. Virological response (VR) to NTCP inhibitor Bulevirtide (BLV) was achieved at week 48 by >70% of CHD patients, but nearly 15% experienced virological nonresponse (VNR) or partial response (PR). This study aimed to evaluate whether NTCP genetic polymorphisms affect baseline HDV RNA load and response to BLV in CHD patients.
METHODS METHODS
Untreated and BLV treated patients were enrolled in a retrospective cross-sectional and longitudinal study. Clinical and virological characteristics were collected at baseline and up to 96 weeks in the BLV-treated patients. NTCP genetic polymorphisms were identified by Sanger sequencing.
RESULTS RESULTS
Of the 6 NTCP polymorphisms studied in 209 CHD untreated patients, carriers of rs17556915 TT/CC (N=142) compared to CT (N=67) genotype presented higher median HDV RNA levels (5.39 vs. 4.75 log
CONCLUSIONS CONCLUSIONS
The NTCP rs17556915 C>T genetic polymorphisms may influence baseline HDV RNA load both in untreated and BLV treated patients with CHD and may contribute to identify patients with different early virological responses to BLV.

Identifiants

pubmed: 38901675
pii: S0168-8278(24)02319-5
doi: 10.1016/j.jhep.2024.06.013
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare no conflicts of interest.

Auteurs

Pierluigi Toniutto (P)

Hepatology and Liver Transplantation Unit, University of Udine, Italy. Electronic address: pierluigi.toniutto@uniud.it.

Edmondo Falleti (E)

Hepatology and Liver Transplantation Unit, University of Udine, Italy.

Sara Cmet (S)

Clinical Pathology, Azienda Ospedaliero Universitaria Friuli Centrale, Udine, Italy.

Annarosa Cussigh (A)

Clinical Pathology, Azienda Ospedaliero Universitaria Friuli Centrale, Udine, Italy.

Elisabetta Degasperi (E)

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Maria Paola Anolli (MP)

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Dana Sambarino (D)

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Floriana Facchetti (F)

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Marta Borghi (M)

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Riccardo Perbellini (R)

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Sara Monico (S)

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Pietro Lampertico (P)

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; D-SOLVE consortium, an EU Horizon Europe funded project (No 101057917).

Classifications MeSH