Cargando…

Advances in hepatitis B therapeutics

Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality,...

Descripción completa

Detalles Bibliográficos
Autores principales: Soriano, Vicente, Barreiro, Pablo, Cachay, Edward, Kottilil, Shyamasundaran, Fernandez-Montero, José V., de Mendoza, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570774/
https://www.ncbi.nlm.nih.gov/pubmed/33117536
http://dx.doi.org/10.1177/2049936120965027
_version_ 1783597024903430144
author Soriano, Vicente
Barreiro, Pablo
Cachay, Edward
Kottilil, Shyamasundaran
Fernandez-Montero, José V.
de Mendoza, Carmen
author_facet Soriano, Vicente
Barreiro, Pablo
Cachay, Edward
Kottilil, Shyamasundaran
Fernandez-Montero, José V.
de Mendoza, Carmen
author_sort Soriano, Vicente
collection PubMed
description Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality, accounting for nearly 1 million annual deaths. Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss. Thus, treatment has to be given lifelong to prevent viral rebound. A broad spectrum of antivirals that block the HBV life cycle at different steps are in clinical development, including entry inhibitors, cccDNA disrupters/silencers, translation inhibitors, capsid assembly modulators, polymerase inhibitors and secretion inhibitors. Some of them exhibit higher potency than current oral nucleos(t)ides. Drugs in more advanced stages of clinical development are bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV and REP-2139. To date, only treatment with ARO-HBV and with REP-2139 have resulted in HBsAg loss in a significant proportion of patients. Combination therapies using distinct antivirals and/or immune modulators are expected to maximize treatment benefits. The current goal is to achieve a ‘functional cure’, with sustained serum HBsAg after drug discontinuation. Ultimately, the goal of HBV therapy will be virus eradication, an achievement that would require the elimination of the cccDNA reservoir within infected hepatocytes.
format Online
Article
Text
id pubmed-7570774
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-75707742020-10-27 Advances in hepatitis B therapeutics Soriano, Vicente Barreiro, Pablo Cachay, Edward Kottilil, Shyamasundaran Fernandez-Montero, José V. de Mendoza, Carmen Ther Adv Infect Dis Review Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality, accounting for nearly 1 million annual deaths. Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss. Thus, treatment has to be given lifelong to prevent viral rebound. A broad spectrum of antivirals that block the HBV life cycle at different steps are in clinical development, including entry inhibitors, cccDNA disrupters/silencers, translation inhibitors, capsid assembly modulators, polymerase inhibitors and secretion inhibitors. Some of them exhibit higher potency than current oral nucleos(t)ides. Drugs in more advanced stages of clinical development are bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV and REP-2139. To date, only treatment with ARO-HBV and with REP-2139 have resulted in HBsAg loss in a significant proportion of patients. Combination therapies using distinct antivirals and/or immune modulators are expected to maximize treatment benefits. The current goal is to achieve a ‘functional cure’, with sustained serum HBsAg after drug discontinuation. Ultimately, the goal of HBV therapy will be virus eradication, an achievement that would require the elimination of the cccDNA reservoir within infected hepatocytes. SAGE Publications 2020-10-15 /pmc/articles/PMC7570774/ /pubmed/33117536 http://dx.doi.org/10.1177/2049936120965027 Text en © The Author(s), 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Soriano, Vicente
Barreiro, Pablo
Cachay, Edward
Kottilil, Shyamasundaran
Fernandez-Montero, José V.
de Mendoza, Carmen
Advances in hepatitis B therapeutics
title Advances in hepatitis B therapeutics
title_full Advances in hepatitis B therapeutics
title_fullStr Advances in hepatitis B therapeutics
title_full_unstemmed Advances in hepatitis B therapeutics
title_short Advances in hepatitis B therapeutics
title_sort advances in hepatitis b therapeutics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570774/
https://www.ncbi.nlm.nih.gov/pubmed/33117536
http://dx.doi.org/10.1177/2049936120965027
work_keys_str_mv AT sorianovicente advancesinhepatitisbtherapeutics
AT barreiropablo advancesinhepatitisbtherapeutics
AT cachayedward advancesinhepatitisbtherapeutics
AT kottililshyamasundaran advancesinhepatitisbtherapeutics
AT fernandezmonterojosev advancesinhepatitisbtherapeutics
AT demendozacarmen advancesinhepatitisbtherapeutics