Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease

A structurally optimized FXR agonist, MET409, reduced liver fat content over 12 weeks in patients with non-alcoholic steatohepatitis

(2021) Stephen A. Harrison et al.   JOURNAL OF HEPATOLOGY

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

(2021) Haleh Chehrehgosha et al.   Diabetes Therapy

Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

(2021) Amedeo Lonardo et al.   ADVANCES IN THERAPY

Saroglitazar, a PPAR‐α/γ Agonist, for Treatment of Nonalcoholic Fatty Liver Disease: A Randomized Controlled Double‐Blind Phase 2 Trial

(2021) Samer Gawrieh et al.   HEPATOLOGY

The GLP‐1 Receptor Agonist Semaglutide for the Treatment of Nonalcoholic Steatohepatitis

(2021) Laura E. Dichtel   HEPATOLOGY

Flame Retardants-Mediated Interferon Signaling in the Pathogenesis of Nonalcoholic Fatty Liver Disease

(2021) Chander K. Negi et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Mitochondrial dynamics and nonalcoholic fatty liver disease (NAFLD): new perspectives for a fairy-tale ending?

(2021) Miriam Longo et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial

(2021) Stephen A. Harrison et al.   NATURE MEDICINE

Fructose and hepatic insulin resistance

(2020) Samir Softic et al.   CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES

Tropifexor, a highly potent FXR agonist, produces robust and dose-dependent reductions in hepatic fat and serum alanine aminotransferase in patients with fibrotic NASH after 12 weeks of therapy: FLIGHT-FXR Part C interim results

(2020) K.J. Lucas et al.   DIGESTIVE AND LIVER DISEASE

MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease

(2020) Mohammed Eslam et al.   GASTROENTEROLOGY

Cenicriviroc Treatment for Adults with Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study

(2020) Vlad Ratziu et al.   HEPATOLOGY

Cilofexor, a Nonsteroidal FXR Agonist, in Non‐Cirrhotic Patients with Nonalcoholic Steatohepatitis: A Phase 2 Randomized Controlled Trial

(2020) Keyur Patel et al.   HEPATOLOGY

Selonsertib for Patients with Bridging Fibrosis or Compensated Cirrhosis Due to NASH: Results from Randomized Ph III STELLAR Trials

(2020) Stephen A. Harrison et al.   JOURNAL OF HEPATOLOGY

Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis

(2020) Stergios A. Polyzos et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

Targeting FGF21 for the Treatment of Nonalcoholic Steatohepatitis

(2020) Mohammad Zarei et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Liver‐Targeting Acetyl‐CoA Carboxylase Inhibitor (PF‐05221304): A Three‐Part Randomized Phase 1 Study

(2020) Arthur Bergman et al.   Clinical Pharmacology in Drug Development

FXR Agonists as Therapy for Liver Disease

(2020) Jay H. Hoofnagle   HEPATOLOGY

The herbal extract ALS-L1023 from Melissa officinalis alleviates visceral obesity and insulin resistance in obese female C57BL/6J mice

(2020) Dongju Lee et al.   JOURNAL OF ETHNOPHARMACOLOGY

A novel non‐bile acid FXR agonist EDP‐305 potently suppresses liver injury and fibrosis without worsening of ductular reaction

(2020) Ping An et al.   LIVER INTERNATIONAL

Comparison of the effects of three kinds of glucose‐lowering drugs on non‐alcoholic fatty liver disease in patients with type 2 diabetes: A randomized, open‐label, three‐arm, active control study

(2020) Tomoe Kinoshita et al.   Journal of Diabetes Investigation

1830-P: Therapeutic Effect of a Novel Long-Acting GLP-1/GIP/Glucagon Triple Agonist (HM15211) in CDHFD-Induced NASH and Fibrosis Mice

(2020) JAEHYUK CHOI et al.   DIABETES

Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease

(2020) Muhammad Nadzim Bin Ramli et al.   GASTROENTEROLOGY

Perturbation of the circadian clock and pathogenesis of NAFLD

(2020) Atish Mukherji et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

NAFLD as a continuum: from obesity to metabolic syndrome and diabetes

(2020) Amélio F. Godoy-Matos et al.   Diabetology & Metabolic Syndrome

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

(2020) Anne Fougerat et al.   Cells

Effect of Empagliflozin on Liver Steatosis and Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease Without Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

(2020) Hoda Taheri et al.   ADVANCES IN THERAPY

Nidufexor, a non-bile acid FXR agonist, decreases ALT and hepatic fat fraction in patients with NASH after 12 weeks dosing

(2020) Richard Aspinall et al.   JOURNAL OF HEPATOLOGY

Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose

(2020) Kentaro Futatsugi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Precision medicine in nonalcoholic fatty liver disease: New therapeutic insights from genetics and systems biology

(2020) Silvia Sookoian et al.   Clinical and Molecular Hepatology

Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention

(2020) Daniel Q. Huang et al.   Nature Reviews Gastroenterology & Hepatology

Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH

(2020) Rohit Loomba et al.   HEPATOLOGY

A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis

(2020) Philip N. Newsome et al.   NEW ENGLAND JOURNAL OF MEDICINE

Separate and Combined Gluco-Metabolic Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 in Healthy Individuals

(2019) Lærke S. Gasbjerg et al.   DIABETES

The Circadian Clock and Liver Function in Health and Disease

(2019) Atish Mukherji et al.   JOURNAL OF HEPATOLOGY

Impact of dapagliflozin, an SGLT2 inhibitor, on serum levels of soluble dipeptidyl peptidase-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease

(2019) Yoshimasa Aso et al.   INTERNATIONAL JOURNAL OF CLINICAL PRACTICE

NGM 282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients with Nonalcoholic Steatohepatitis

(2019) Stephen A. Harrison et al.   HEPATOLOGY

The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients

(2019) Aino Latva-Rasku et al.   DIABETES CARE

Gut microbiome–targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression

(2019) Suzanne R Sharpton et al.   AMERICAN JOURNAL OF CLINICAL NUTRITION

Biological mechanisms and related natural modulators of liver X receptor in nonalcoholic fatty liver disease

(2019) Mingzhu Ni et al.   BIOMEDICINE & PHARMACOTHERAPY

Prevalence and long-term outcomes of non-alcoholic fatty liver disease among elderly individuals from the United States

(2019) Pegah Golabi et al.   BMC GASTROENTEROLOGY

PS-110-Ketohexokinase inhibitor PF-06835919 administered for 6 weeks reduces whole liver fat as measured by magnetic resonance imaging-proton density fat fraction in subjects with non-alcoholic fatty liver disease

(2019) Roberto Calle et al.   JOURNAL OF HEPATOLOGY

Pnpla3 silencing with antisense oligonucleotides ameliorates nonalcoholic steatohepatitis and fibrosis in Pnpla3 I148M knock-in mice

(2019) Daniel Lindén et al.   Molecular Metabolism

140-LB: NGM313, a Novel Activator of b-Klotho/FGFR1c, Improves Insulin Resistance and Reduces Hepatic Fat in Obese, Nondiabetic Subjects

(2019) ALEX DEPAOLI et al.   DIABETES

A Cholecystokinin Receptor Antagonist Halts Nonalcoholic Steatohepatitis and Prevents Hepatocellular Carcinoma

(2019) Robin D. Tucker et al.   DIGESTIVE DISEASES AND SCIENCES

A liver-specific thyromimetic, VK2809, decreases hepatosteatosis in glycogen storage disease type Ia (GSD Ia)

(2019) Jin Zhou et al.   THYROID

Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial

(2019) Sabine Kahl et al.   DIABETES CARE

A Pan-Cyclophilin Inhibitor, CRV431, Decreases Fibrosis and Tumor Development in Chronic Liver Disease Models

(2019) Joseph Kuo et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists

(2019) Rohit A. Sinha et al.   THYROID

First‐in‐class fatty acid synthase inhibitor TVB‐2640 reduces hepatic de novo lipogenesis in males with metabolic abnormalities

(2019) Majid M. Syed‐Abdul et al.   HEPATOLOGY

Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled phase IIb study

(2019) Stephen A. Harrison et al.   JOURNAL OF HEPATOLOGY

Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

(2019) Stephen A Harrison et al.   LANCET

Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension

(2019) Naga Chalasani et al.   GASTROENTEROLOGY

Randomized placebo-controlled trial of emricasan for non-alcoholic steatohepatitis-related cirrhosis with severe portal hypertension

(2019) Guadalupe Garcia-Tsao et al.   JOURNAL OF HEPATOLOGY

A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis

(2019) Stephen A. Harrison et al.   JOURNAL OF HEPATOLOGY

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

(2019) Zobair M Younossi et al.   LANCET

Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial

(2019) Takara L Stanley et al.   Lancet HIV

Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis

(2018) Eric J. Lawitz et al.   Clinical Gastroenterology and Hepatology

Effect of a Novel Long-Acting GLP-1/GIP/Glucagon Triple Agonist (HM15211) in a NASH and Fibrosis Animal Model

(2018) IN YOUNG CHOI et al.   DIABETES

Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study

(2018) Jan W. Eriksson et al.   DIABETOLOGIA

Simtuzumab Is Ineffective for Patients with Bridging Fibrosis or Compensated Cirrhosis Caused by Nonalcoholic Steatohepatitis

(2018) Stephen A. Harrison et al.   GASTROENTEROLOGY

A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis

(2018) Scott L. Friedman et al.   HEPATOLOGY

NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

(2018) Stephen A Harrison et al.   LANCET

MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study

(2018) Philip Ambery et al.   LANCET

A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease

(2018) Noura S. Abul-Husn et al.   NEW ENGLAND JOURNAL OF MEDICINE

Apoptosis and non-alcoholic fatty liver diseases

(2018) Tatsuo Kanda et al.   WORLD JOURNAL OF GASTROENTEROLOGY

Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease

(2018) Mohammad Zarei et al.   Molecular Metabolism

Evaluation of the effects of dapagliflozin, an SGLT2 inhibitor, on hepatic steatosis and fibrosis by transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease

(2018) Masanori Shimizu et al.   DIABETES OBESITY & METABOLISM

Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes

(2018) Kenneth Cusi et al.   DIABETES OBESITY & METABOLISM

GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic Fatty Liver Disease

(2018) Rohit Loomba et al.   GASTROENTEROLOGY

HSD17B13 is a Hepatic Retinol Dehydrogenase Associated with Histological Features of Non-Alcoholic Fatty Liver Disease

(2018) Yanling Ma et al.   HEPATOLOGY

Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease

(2018) Carlos J. Pirola et al.   JOURNAL OF LIPID RESEARCH

Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial

(2018) Arun Sanyal et al.   LANCET

Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease

(2018) Mitsuko Inoue et al.   Journal of Diabetes Investigation

JKB-122 is effective, alone or in combination with prednisolone in Con A-induced hepatitis

(2017) Mei-Chi Hsu et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Fatty liver and FGF21 physiology

(2017) Eleftheria Maratos-Flier   EXPERIMENTAL CELL RESEARCH

The lemon balm extract ALS-L1023 inhibits obesity and nonalcoholic fatty liver disease in female ovariectomized mice

(2017) Jeongjun Kim et al.   FOOD AND CHEMICAL TOXICOLOGY

The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial

(2017) Rohit Loomba et al.   HEPATOLOGY

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases

(2017) Naga Chalasani et al.   HEPATOLOGY

The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral Adipose-Tissue Function

(2017) Jeongjun Kim et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 2: Management and special groups

(2017) Shiv Chitturi et al.   JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY

Adverse outcome pathways: Application to enhance mechanistic understanding of neurotoxicity

(2017) Anna Bal-Price et al.   PHARMACOLOGY & THERAPEUTICS

Metabolism disrupting chemicals and metabolic disorders

(2017) Jerrold J. Heindel et al.   REPRODUCTIVE TOXICOLOGY

Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus

(2016) Kenneth Cusi et al.   ANNALS OF INTERNAL MEDICINE

Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial

(2016) Shun Ishibashi et al.   ATHEROSCLEROSIS

Hepatocyte β-Klotho regulates lipid homeostasis but not body weight in mice

(2016) Kanako Kobayashi et al.   FASEB JOURNAL

Elafibranor, an Agonist of the Peroxisome Proliferator−Activated Receptor−α and −δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening

(2016) Vlad Ratziu et al.   GASTROENTEROLOGY

Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes

(2016) Zobair M. Younossi et al.   HEPATOLOGY

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

(2016)   JOURNAL OF HEPATOLOGY

Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study

(2016) Matthew James Armstrong et al.   LANCET

Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis

(2016) Eric Lefebvre et al.   PLoS One

Adverse Outcome Pathways and Drug-Induced Liver Injury Testing

(2015) Mathieu Vinken   CHEMICAL RESEARCH IN TOXICOLOGY

PPARα gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis

(2015) Sven Francque et al.   JOURNAL OF HEPATOLOGY

NAFLD: A multisystem disease

(2015) Christopher D. Byrne et al.   JOURNAL OF HEPATOLOGY

Glucocorticoids and non-alcoholic fatty liver disease

(2015) Conor P. Woods et al.   JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial

(2015) Brent A Neuschwander-Tetri et al.   LANCET

The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy

(2015) Jia Liu et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis

(2015) Byung Young Park et al.   PLoS One

The Fatty Acid–Bile Acid Conjugate Aramchol Reduces Liver Fat Content in Patients With Nonalcoholic Fatty Liver Disease

(2014) Rifaat Safadi et al.   Clinical Gastroenterology and Hepatology

Expression of Liver X Receptor Correlates with Intrahepatic Inflammation and Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

(2014) Sang Bong Ahn et al.   DIGESTIVE DISEASES AND SCIENCES

Cyclophilin inhibition as potential therapy for liver diseases

(2014) Nikolai V. Naoumov   JOURNAL OF HEPATOLOGY

The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis

(2014) Fernando J. Barreyro et al.   LIVER INTERNATIONAL

Nonalcoholic fatty liver disease and aging: Epidemiology to management

(2014) Marco Bertolotti   WORLD JOURNAL OF GASTROENTEROLOGY

Extrahepatic complications of nonalcoholic fatty liver disease

(2013) Matthew J. Armstrong et al.   HEPATOLOGY

The global NAFLD epidemic

(2013) Rohit Loomba et al.   Nature Reviews Gastroenterology & Hepatology

SGLT inhibitors in management of diabetes

(2013) Abd A Tahrani et al.   Lancet Diabetes & Endocrinology

Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology

(2013) Huating Li et al.   Frontiers of Medicine

Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver [Review]

(2012) Yutaka Takahashi   ENDOCRINE JOURNAL

Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy

(2012) H. Nishizawa et al.   EUROPEAN JOURNAL OF ENDOCRINOLOGY

Vitamin E and the Risk of Prostate Cancer

(2011) Eric A. Klein et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Liver X receptors bridge hepatic lipid metabolism and inflammation

(2011) Yuan LIU et al.   Journal of Digestive Diseases

Biology of Human Sodium Glucose Transporters

(2011) Ernest M. Wright et al.   PHYSIOLOGICAL REVIEWS

Enhanced expression of pro-inflammatory mediators and liver X-receptor-regulated lipogenic genes in non-alcoholic fatty liver disease and hepatitis C

(2010) Elena Lima-Cabello et al.   CLINICAL SCIENCE

Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis

(2010) Herbert Tilg et al.   HEPATOLOGY

Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

(2010) Arun J. Sanyal et al.   NEW ENGLAND JOURNAL OF MEDICINE

GIP and GLP-1, the two incretin hormones: Similarities and differences

(2010) Yutaka Seino et al.   Journal of Diabetes Investigation

Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: Results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial

(2009) Vlad Ratziu et al.   HEPATOLOGY

Randomized, Placebo-Controlled Trial of Pioglitazone in Nondiabetic Subjects With Nonalcoholic Steatohepatitis

(2008) Guruprasad P. Aithal et al.   GASTROENTEROLOGY

Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice

(2008) Catherine Postic et al.   JOURNAL OF CLINICAL INVESTIGATION

Molecular Mechanisms of Lipotoxicity in Nonalcoholic Fatty Liver Disease

(2008) Harmeet Malhi et al.   SEMINARS IN LIVER DISEASE