Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis

Objective: The prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NAFLD/NASH) is increasing. NAFLD/NASH may progress to cirrhosis and hepatocellular carcinoma. However, most patients with NAFLD/NASH will die from a vascular cause. There are no approved pharmacological...

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Main Authors: Maryam Mahjoubin-Tehran, Antonio De Vincentis, Dimitri P. Mikhailidis, Stephen L. Atkin, Christos S. Mantzoros, Tannaz Jamialahmadi, Amirhossein Sahebkar
Format: Article
Language:English
Published: Elsevier 2021-08-01
Series:Molecular Metabolism
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S221287782030123X
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author Maryam Mahjoubin-Tehran
Antonio De Vincentis
Dimitri P. Mikhailidis
Stephen L. Atkin
Christos S. Mantzoros
Tannaz Jamialahmadi
Amirhossein Sahebkar
author_facet Maryam Mahjoubin-Tehran
Antonio De Vincentis
Dimitri P. Mikhailidis
Stephen L. Atkin
Christos S. Mantzoros
Tannaz Jamialahmadi
Amirhossein Sahebkar
author_sort Maryam Mahjoubin-Tehran
collection DOAJ
description Objective: The prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NAFLD/NASH) is increasing. NAFLD/NASH may progress to cirrhosis and hepatocellular carcinoma. However, most patients with NAFLD/NASH will die from a vascular cause. There are no approved pharmacological treatments for NASH/NAFLD. Many clinical trials have been, or are being, undertaken; however, the challenge is the assessment of the clinical endpoint. The main objective of this narrative review was to evaluate the efficacy of drugs used in clinical trials for the treatment of NAFLD/NASH that included a liver biopsy as the gold standard. Methods: A literature search was conducted using 3 databases (PubMed, Scopus, and Google Scholar) to identify the clinical trials that included liver biopsy assessment before and after treatment. Results: Interventional clinical trials (n = 33) involving 18 different agents, alone and in combination, were identified. Pioglitazone is the only agent that has shown consistent benefit and efficacy in clinical trials. Pentoxifylline, rosiglitazone, and ursodeoxycholic acid had both positive and negative results from clinical trials. There is also evidence for vitamin E and metformin. Other drugs, including bicyclol, cysteamine bitartrate, l-carnitine, liraglutide, obeticholic acid, oligofructose, selonsertib, silymarin, and statins, each had a single clinical study. Conclusions: In summary, the available molecules demonstrated a significant improvement in NASH and/or liver fibrosis in a minority of patients; thus, other drugs should be identified, possibly those acting on alternative pathophysiological pathways, and tested for their safety and efficacy.
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spelling doaj.art-21e91722ef7b4997b1f5f2c231790b902022-12-21T19:57:52ZengElsevierMolecular Metabolism2212-87782021-08-0150101049Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosisMaryam Mahjoubin-Tehran0Antonio De Vincentis1Dimitri P. Mikhailidis2Stephen L. Atkin3Christos S. Mantzoros4Tannaz Jamialahmadi5Amirhossein Sahebkar6Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranClinical Medicine and Hepatology Unit, Campus Bio-Medico University of Rome, via Alvaro del Portillo, 200, 00128 Rome, ItalyDepartment of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, United KingdomWeill Cornell Medicine Qatar, Doha, QatarDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USABiotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranHalal Research Center of IRI, FDA, Tehran, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Corresponding author. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, P.O. Box: 91779-48564, Iran. Fax: +98 5118002287.Objective: The prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NAFLD/NASH) is increasing. NAFLD/NASH may progress to cirrhosis and hepatocellular carcinoma. However, most patients with NAFLD/NASH will die from a vascular cause. There are no approved pharmacological treatments for NASH/NAFLD. Many clinical trials have been, or are being, undertaken; however, the challenge is the assessment of the clinical endpoint. The main objective of this narrative review was to evaluate the efficacy of drugs used in clinical trials for the treatment of NAFLD/NASH that included a liver biopsy as the gold standard. Methods: A literature search was conducted using 3 databases (PubMed, Scopus, and Google Scholar) to identify the clinical trials that included liver biopsy assessment before and after treatment. Results: Interventional clinical trials (n = 33) involving 18 different agents, alone and in combination, were identified. Pioglitazone is the only agent that has shown consistent benefit and efficacy in clinical trials. Pentoxifylline, rosiglitazone, and ursodeoxycholic acid had both positive and negative results from clinical trials. There is also evidence for vitamin E and metformin. Other drugs, including bicyclol, cysteamine bitartrate, l-carnitine, liraglutide, obeticholic acid, oligofructose, selonsertib, silymarin, and statins, each had a single clinical study. Conclusions: In summary, the available molecules demonstrated a significant improvement in NASH and/or liver fibrosis in a minority of patients; thus, other drugs should be identified, possibly those acting on alternative pathophysiological pathways, and tested for their safety and efficacy.http://www.sciencedirect.com/science/article/pii/S221287782030123XNon-alcoholic fatty liver diseaseLiver biopsyNon-alcoholic steatohepatitis
spellingShingle Maryam Mahjoubin-Tehran
Antonio De Vincentis
Dimitri P. Mikhailidis
Stephen L. Atkin
Christos S. Mantzoros
Tannaz Jamialahmadi
Amirhossein Sahebkar
Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis
Molecular Metabolism
Non-alcoholic fatty liver disease
Liver biopsy
Non-alcoholic steatohepatitis
title Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis
title_full Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis
title_fullStr Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis
title_full_unstemmed Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis
title_short Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis
title_sort non alcoholic fatty liver disease and steatohepatitis state of the art on effective therapeutics based on the gold standard method for diagnosis
topic Non-alcoholic fatty liver disease
Liver biopsy
Non-alcoholic steatohepatitis
url http://www.sciencedirect.com/science/article/pii/S221287782030123X
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