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The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment

Sodium taurocholate cotransporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus infection of host hepatocytes. Previously, many studies confirmed that the NTCP p.Ser267Phe variant was a protective factor against HBV-related disease progression. We therefore designed this...

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Autores principales: Wu, Lina, Xu, Wenxiong, Li, Xuejun, Liu, Ying, Wang, Lu, Zhu, Shu, Yang, Fangji, Xie, Chan, Peng, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943921/
https://www.ncbi.nlm.nih.gov/pubmed/33716744
http://dx.doi.org/10.3389/fphar.2021.616858
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author Wu, Lina
Xu, Wenxiong
Li, Xuejun
Liu, Ying
Wang, Lu
Zhu, Shu
Yang, Fangji
Xie, Chan
Peng, Liang
author_facet Wu, Lina
Xu, Wenxiong
Li, Xuejun
Liu, Ying
Wang, Lu
Zhu, Shu
Yang, Fangji
Xie, Chan
Peng, Liang
author_sort Wu, Lina
collection PubMed
description Sodium taurocholate cotransporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus infection of host hepatocytes. Previously, many studies confirmed that the NTCP p.Ser267Phe variant was a protective factor against HBV-related disease progression. We therefore designed this study to investigate whether the NTCP p.Ser267Phe variant exerts an additive anti-HBV effect in chronic hepatitis B (CHB) patients on mainstream NAs treatment. After propensity score matching (PSM), a total of 136 CHB patients were included, among whom 68 were heterozygous carriers and 68 were wild-type controls. Proportions of primary nonresponse, partial virological response, virological breakthrough and hepatitis B reactivation and the HBV DNA clearance rate at each time point were compared using the chi-square test. Kaplan-Meier analysis and matched t-tests were also performed to estimate the speed of viral clearance and serum HBV DNA reduction, respectively. The proportion of primary nonresponse was significantly lower in heterozygous carriers than in wild-type controls (p < 0.001), especially in patients using entecavir (p = 0.013). Specifically, heterozygous carriers achieved HBV DNA clearance faster than wild-type controls (log-rank p = 0.0198). HBV DNA levels were reduced more in heterozygous carriers after 12 weeks (p < 0.001) and 24 weeks (p = 0.006) of treatment, especially among patients using ETV. Here, our study demonstrated that heterozygous mutations in rs2296651 enhanced the antiviral response of first-line NAs and helped to explore the possibility of combining NAs and NTCP blockers for a better anti-HBV effect.
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spelling pubmed-79439212021-03-11 The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment Wu, Lina Xu, Wenxiong Li, Xuejun Liu, Ying Wang, Lu Zhu, Shu Yang, Fangji Xie, Chan Peng, Liang Front Pharmacol Pharmacology Sodium taurocholate cotransporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus infection of host hepatocytes. Previously, many studies confirmed that the NTCP p.Ser267Phe variant was a protective factor against HBV-related disease progression. We therefore designed this study to investigate whether the NTCP p.Ser267Phe variant exerts an additive anti-HBV effect in chronic hepatitis B (CHB) patients on mainstream NAs treatment. After propensity score matching (PSM), a total of 136 CHB patients were included, among whom 68 were heterozygous carriers and 68 were wild-type controls. Proportions of primary nonresponse, partial virological response, virological breakthrough and hepatitis B reactivation and the HBV DNA clearance rate at each time point were compared using the chi-square test. Kaplan-Meier analysis and matched t-tests were also performed to estimate the speed of viral clearance and serum HBV DNA reduction, respectively. The proportion of primary nonresponse was significantly lower in heterozygous carriers than in wild-type controls (p < 0.001), especially in patients using entecavir (p = 0.013). Specifically, heterozygous carriers achieved HBV DNA clearance faster than wild-type controls (log-rank p = 0.0198). HBV DNA levels were reduced more in heterozygous carriers after 12 weeks (p < 0.001) and 24 weeks (p = 0.006) of treatment, especially among patients using ETV. Here, our study demonstrated that heterozygous mutations in rs2296651 enhanced the antiviral response of first-line NAs and helped to explore the possibility of combining NAs and NTCP blockers for a better anti-HBV effect. Frontiers Media S.A. 2021-02-24 /pmc/articles/PMC7943921/ /pubmed/33716744 http://dx.doi.org/10.3389/fphar.2021.616858 Text en Copyright © 2021 Wu, Xu, Li, Liu, Wang, Zhu, Yang, Xie and Peng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wu, Lina
Xu, Wenxiong
Li, Xuejun
Liu, Ying
Wang, Lu
Zhu, Shu
Yang, Fangji
Xie, Chan
Peng, Liang
The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment
title The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment
title_full The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment
title_fullStr The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment
title_full_unstemmed The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment
title_short The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment
title_sort ntcp p.ser267phe variant is associated with a faster anti-hbv effect on first-line nucleos(t)ide analog treatment
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943921/
https://www.ncbi.nlm.nih.gov/pubmed/33716744
http://dx.doi.org/10.3389/fphar.2021.616858
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