Mechanisms of NAFLD development and therapeutic strategies

There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but c...

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Published in	Nature medicine Vol. 24; no. 7; pp. 908 - 922
Main Authors	Friedman, Scott L., Neuschwander-Tetri, Brent A., Rinella, Mary, Sanyal, Arun J.
Format	Journal Article
Language	English
Published	New York Nature Publishing Group US 01.07.2018 Nature Publishing Group
Subjects	631/154/309/2144 692/308/2779/109 Abnormalities Animal models Biomedical and Life Sciences Biomedicine Cancer Research Care and treatment Cellular signal transduction Cirrhosis Clinical trials Comorbidity Diabetes mellitus Diagnosis Drug development Drug efficacy Fatty liver Gene expression Genetic aspects Infectious Diseases Liver Liver cancer Liver cirrhosis Liver diseases Medical schools Metabolic Diseases Metabolic disorders Metabolic syndrome Molecular Medicine Neurosciences Review Article Therapeutic applications Type 2 diabetes
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Abstract	There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression. Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials.
AbstractList	There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression. There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression. Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials. There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression. Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials.
Audience	Academic
Author	Rinella, Mary Friedman, Scott L. Neuschwander-Tetri, Brent A. Sanyal, Arun J.
AuthorAffiliation	3 Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 2 Division of Gastroenterology and Hepatology, St. Louis University School of Medicine, St. Louis, MO, USA 1 Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA 4 Division of Gastroenterology, Virginia Commonwealth University, Richmond, VA, USA
AuthorAffiliation_xml	– name: 1 Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA – name: 4 Division of Gastroenterology, Virginia Commonwealth University, Richmond, VA, USA – name: 3 Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA – name: 2 Division of Gastroenterology and Hepatology, St. Louis University School of Medicine, St. Louis, MO, USA
Author_xml	– sequence: 1 givenname: Scott L. orcidid: 0000-0003-1178-6195 surname: Friedman fullname: Friedman, Scott L. email: scott.friedman@mssm.edu organization: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai – sequence: 2 givenname: Brent A. surname: Neuschwander-Tetri fullname: Neuschwander-Tetri, Brent A. organization: Division of Gastroenterology and Hepatology, St. Louis University School of Medicine – sequence: 3 givenname: Mary surname: Rinella fullname: Rinella, Mary organization: Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University – sequence: 4 givenname: Arun J. surname: Sanyal fullname: Sanyal, Arun J. organization: Division of Gastroenterology, Virginia Commonwealth University
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29967350$$D View this record in MEDLINE/PubMed
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Snippet	There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome....
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SubjectTerms	631/154/309/2144 692/308/2779/109 Abnormalities Animal models Biomedical and Life Sciences Biomedicine Cancer Research Care and treatment Cellular signal transduction Cirrhosis Clinical trials Comorbidity Diabetes mellitus Diagnosis Drug development Drug efficacy Fatty liver Gene expression Genetic aspects Infectious Diseases Liver Liver cancer Liver cirrhosis Liver diseases Medical schools Metabolic Diseases Metabolic disorders Metabolic syndrome Molecular Medicine Neurosciences Review Article Therapeutic applications Type 2 diabetes
Title	Mechanisms of NAFLD development and therapeutic strategies
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