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Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation, and hepatocyte injury with or without fibrosis. It has emerged as the second leading indication for liver transplantation with a rising death rate in the non-transplantable population. While there are many drugs in e...

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Autores principales: Suri, Jaspreet, Borja, Sebastian, Lim, Joseph K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516677/
https://www.ncbi.nlm.nih.gov/pubmed/36188726
http://dx.doi.org/10.3748/wjg.v28.i35.5129
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author Suri, Jaspreet
Borja, Sebastian
Lim, Joseph K
author_facet Suri, Jaspreet
Borja, Sebastian
Lim, Joseph K
author_sort Suri, Jaspreet
collection PubMed
description Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation, and hepatocyte injury with or without fibrosis. It has emerged as the second leading indication for liver transplantation with a rising death rate in the non-transplantable population. While there are many drugs in evaluation, currently no approved therapies are on the market for this condition. Given this importance, the Food and Drug Administration has provided formal guidance regarding drug development for stopping or reversing NASH or NASH associated fibrosis. The complex pathogenesis of NASH and its bidirectional relationship with metabolic syndrome has highlighted multiple drugs of interest that address metabolic, inflammatory, and fibrotic factors. A few promising liver specific targets include farnesoid X receptor agonists and peroxisome proliferator-activated receptor agonists. Previously studied drug classes such as glucagon-like peptide-1 analogs or sodium/glucose transport protein 2 inhibitors have also demonstrated ability to improve hepatic steatosis. Here we discuss current rationale, scientific work, and preliminary data in combining multiple drugs for the purposes of a multimodal attack on the pathogenesis of NASH. We highlight multiple Phase 2 and Phase 3 studies that demonstrate the potential to achieve a response rate higher than previously assessed monotherapies for this condition. Ultimately, one of these combination strategies may rise above in its safety and efficacy to become a part of a standardized approach to NASH.
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spelling pubmed-95166772022-09-29 Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis Suri, Jaspreet Borja, Sebastian Lim, Joseph K World J Gastroenterol Minireviews Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation, and hepatocyte injury with or without fibrosis. It has emerged as the second leading indication for liver transplantation with a rising death rate in the non-transplantable population. While there are many drugs in evaluation, currently no approved therapies are on the market for this condition. Given this importance, the Food and Drug Administration has provided formal guidance regarding drug development for stopping or reversing NASH or NASH associated fibrosis. The complex pathogenesis of NASH and its bidirectional relationship with metabolic syndrome has highlighted multiple drugs of interest that address metabolic, inflammatory, and fibrotic factors. A few promising liver specific targets include farnesoid X receptor agonists and peroxisome proliferator-activated receptor agonists. Previously studied drug classes such as glucagon-like peptide-1 analogs or sodium/glucose transport protein 2 inhibitors have also demonstrated ability to improve hepatic steatosis. Here we discuss current rationale, scientific work, and preliminary data in combining multiple drugs for the purposes of a multimodal attack on the pathogenesis of NASH. We highlight multiple Phase 2 and Phase 3 studies that demonstrate the potential to achieve a response rate higher than previously assessed monotherapies for this condition. Ultimately, one of these combination strategies may rise above in its safety and efficacy to become a part of a standardized approach to NASH. Baishideng Publishing Group Inc 2022-09-21 2022-09-21 /pmc/articles/PMC9516677/ /pubmed/36188726 http://dx.doi.org/10.3748/wjg.v28.i35.5129 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Minireviews
Suri, Jaspreet
Borja, Sebastian
Lim, Joseph K
Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis
title Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis
title_full Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis
title_fullStr Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis
title_full_unstemmed Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis
title_short Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis
title_sort combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516677/
https://www.ncbi.nlm.nih.gov/pubmed/36188726
http://dx.doi.org/10.3748/wjg.v28.i35.5129
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