Non-alcoholic steatohepatitis: the therapeutic challenge of a global epidemic

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Nonalcoholic steatohepatitis (NASH) reflects severe liver disease within the NAFLD spectrum and can progress to end-stage liver disease. Within this manuscript we review the available evidence for the treatment of NASH as well as the newer therapeutic agents that are currently being investigated.

• Publication year

  2012

• Venue

  Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology

• Publication date

  2012-06-22

• Fields of study

  Medicine

• Identifiers
  PMID 24713803PMCID 3959359
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review.

  2012cited by this paper
• Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

  2012cited by this paper
• Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

  2012cited by this paper
• Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial.

  2011cited by this paper
• A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis.

  2011cited by this paper
• Pentoxifylline improves nonalcoholic steatohepatitis: A randomized placebo‐controlled trial

  2011cited by this paper
• Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction.

  2011cited by this paper
• Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: A 12‐month randomized, prospective, open‐ label trial

  2011influential reference
• Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury.

  2011cited by this paper
• Vitamin E and adiponectin: proposed mechanism for vitamin E-induced improvement in insulin sensitivity.

  2011cited by this paper
• Pharmacotherapy: Statins are safe in NAFLD

  2011cited by this paper
• NASH: A global health problem

  2011cited by this paper
• High-Dose Treatment With Telmisartan Induces Monocytic Peroxisome Proliferator-Activated Receptor-&ggr; Target Genes in Patients With the Metabolic Syndrome

  2011cited by this paper
• Plasma levels of vitamin E and carotenoids are decreased in patients with nonalcoholic steatohepatitis (NASH)

  2011cited by this paper
• L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

  2011cited by this paper
• Human Fatty Liver Disease: Old Questions and New Insights

  2011cited by this paper
• Assessing the Association of Pioglitazone Use and Bladder Cancer Through Drug Adverse Event Reporting

  2011cited by this paper
• Fibrosing NASH: on being a blind man in a dark room looking for a black cat (that isn't there).

  2011cited by this paper
• Genetic determinants of hepatic steatosis in man

  2011cited by this paper
• Pathologic criteria for nonalcoholic steatohepatitis: Interprotocol agreement and ability to predict liver‐related mortality

  2011cited by this paper
• Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial.

  2011cited by this paper
• The Role of Metformin in the Management of NAFLD

  2011cited by this paper
• Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials

  2010cited by this paper
• Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis

  2010cited by this paper
• Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis.

  2010cited by this paper
• A meta‐analysis of randomized trials for the treatment of nonalcoholic fatty liver disease

  2010cited by this paper
• Weight loss: cornerstone in the treatment of non-alcoholic fatty liver disease.

  2010cited by this paper
• l-Carnitine Supplementation to Diet: A New Tool in Treatment of Nonalcoholic Steatohepatitis—A Randomized and Controlled Clinical Trial

  2010cited by this paper
• Use of endoscopy for management of acute upper gastrointestinal bleeding in the UK: results of a nationwide audit

  2010cited by this paper
• Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

  2010cited by this paper
• Novel treatment modalities for nonalcoholic steatohepatitis.

  2010cited by this paper
• A pilot trial of high-dose ursodeoxycholic acid in nonalcoholic steatohepatitis

  2010cited by this paper
• Gut microbiota as a regulator of energy homeostasis and ectopic fat deposition: mechanisms and implications for metabolic disorders

  2010cited by this paper
• High‐dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double‐blind, randomized, placebo‐controlled trial

  2010cited by this paper
• Meta‐analysis: insulin sensitizers for the treatment of non‐alcoholic steatohepatitis

  2010cited by this paper
• Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH

  2010cited by this paper
• Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.

  2010cited by this paper
• Pioglitazone in the treatment of NASH: the role of adiponectin

  2010cited by this paper
• Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis

  2010cited by this paper
• Effects of incretin hormones on beta-cell mass and function, body weight, and hepatic and myocardial function.

  2010cited by this paper
• In vivo effects of pentoxifylline on enzyme and non‐enzyme antioxidant levels in rat liver after carrageenan‐induced paw inflammation

  2010cited by this paper
• Bariatric surgery for non-alcoholic steatohepatitis in obese patients.

  2010cited by this paper
• Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

  2009influential reference
• Open‐labeled pilot study of cysteine‐rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients

  2009cited by this paper
• VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet‐induced nonalcoholic steatohepatitis model in mice

  2009cited by this paper
• Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

  2009cited by this paper
• Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein.

  2009cited by this paper
• Systematic Review and Meta-analysis Supplements for Primary and Secondary Prevention: Mortality in Randomized Trials of Antioxidant

  2009cited by this paper
• Clinical trial: pilot study of metformin for the treatment of non‐alcoholic steatohepatitis

  2009cited by this paper
• High‐dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis

  2009cited by this paper
• A Pilot Study Using Simvastatin in the Treatment of Nonalcoholic Steatohepatitis: A Randomized Placebo-controlled Trial

  2009cited by this paper
• Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis

  2009cited by this paper
• Effects of ursodeoxycholic acid in combination with vitamin E on adipokines and apoptosis in patients with nonalcoholic steatohepatitis

  2009cited by this paper
• Betaine for nonalcoholic fatty liver disease: Results of a randomized placebo‐controlled trial

  2009cited by this paper
• Non‐alcoholic fatty liver disease from pathogenesis to management: an update

  2009cited by this paper
• Randomized, Placebo-Controlled Trial of Pioglitazone in Nondiabetic Subjects With Nonalcoholic Steatohepatitis

  2009cited by this paper
• Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management

  2009cited by this paper
• Adiponectin Expression Is Induced by Vitamin E via a Peroxisome Proliferator-Activated Receptor (cid:1) -Dependent Mechanism

  2009cited by this paper
• Safety and Tolerability of Pioglitazone in High-Risk Patients with Type 2 Diabetes

  2009cited by this paper
• Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats.

  2009cited by this paper
• Adiponectin expression is induced by vitamin E via a peroxisome proliferator-activated receptor gamma-dependent mechanism.

  2009cited by this paper
• Long‐term efficacy of rosiglitazone in nonalcoholic steatohepatitis: Results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial

  2009cited by this paper
• Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial.

  2008cited by this paper
• Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells.

  2008cited by this paper
• Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial.

  2008cited by this paper
• Highly Purified Eicosapentaenoic Acid Treatment Improves Nonalcoholic Steatohepatitis

  2008cited by this paper
• Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia.

  2008cited by this paper
• A core gut microbiome in obese and lean twins

  2008cited by this paper
• Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis.

  2008cited by this paper
• Effect of 6‐Month Calorie Restriction and Exercise on Serum and Liver Lipids and Markers of Liver Function

  2008cited by this paper
• Liver Histology Changes in Nonalcoholic Steatohepatitis after One Year of Treatment with Probucol

  2008cited by this paper
• The effect of thiazolidinediones on adiponectin serum level: a meta‐analysis

  2008cited by this paper
• Angiotensin receptor blockers in the treatment of NASH/NAFLD: Could they be a first-class option?

  2008influential reference
• Molecular Mechanisms of Lipotoxicity in Nonalcoholic Fatty Liver Disease

  2008cited by this paper
• Hepatic triglyceride synthesis and nonalcoholic fatty liver disease

  2008cited by this paper
• Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years.

  2008influential reference
• Combined pantethine and probucol therapy for Japanese patients with non‐alcoholic steatohepatitis

  2007cited by this paper
• Comparative effects of telmisartan and valsartan on insulin resistance in hypertensive patients with metabolic syndrome.

  2007cited by this paper
• Weight loss induced by orlistat reverses fatty infiltration and improves hepatic fibrosis in obese patients with non-alcoholic steatohepatitis

  2007cited by this paper
• High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis

  2007cited by this paper
• Bile acids for non-alcoholic fatty liver disease and/or steatohepatitis.

  2007cited by this paper
• Efficacy and safety of high‐dose pravastatin in hypercholesterolemic patients with well‐compensated chronic liver disease: Results of a prospective, randomized, double‐blind, placebo‐controlled, multicenter trial

  2007cited by this paper
• Effects of vitamin E treatment on peroxisome proliferator‐activated receptor‐α expression and insulin resistance in patients with non‐alcoholic steatohepatitis: results of a pilot study

  2007cited by this paper
• Probiotics for non-alcoholic fatty liver disease and/or steatohepatitis.

  2007cited by this paper
• GI Epidemiology: nonalcoholic fatty liver disease

  2007cited by this paper
• Effects of vitamin E treatment on peroxisome proliferator-activated receptor-alpha expression and insulin resistance in patients with non-alcoholic steatohepatitis: results of a pilot study.

  2007cited by this paper
• Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis.

  2006influential reference
• Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non‐alcoholic steatohepatitis

  2006cited by this paper
• Thiazolidinedione use and bone loss in older diabetic adults.

  2006cited by this paper
• Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis.

  2006cited by this paper
• Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: relationship to histological improvement.

  2006cited by this paper
• A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis.

  2006cited by this paper
• An obesity-associated gut microbiome with increased capacity for energy harvest

  2006cited by this paper
• Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis

  2006cited by this paper
• Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2

  2005cited by this paper
• Design and validation of a histological scoring system for nonalcoholic fatty liver disease

  2005cited by this paper
• Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study

  2005cited by this paper
• One-Year Intense Nutritional Counseling Results in Histological Improvement in Patients with Nonalcoholic Steatohepatitis: A Pilot Study

  2005cited by this paper
• The natural history of nonalcoholic fatty liver disease: a population-based cohort study.

  2005cited by this paper
• Metformin in the treatment of patients with non‐alcoholic steatohepatitis

  2004cited by this paper

• Co-treatment of trigonelline and everolimus synergistically prevented chronic steatohepatitis induced by fast food diet and thioacetamide in a novel murine nonalcoholic steatohepatitis model

  2025cites this paper
• The Green Path to Liver Health: Herbal Solutions for Non-alcoholic Steatohepatitis.

  2025cites this paper
• Glabridin ameliorates intracellular events caused by palmitic acid and alcohol in mouse hepatocytes and fast food diet and alcohol -induced steatohepatitis and fibrosis in C57BL/6J mice model.

  2023cites this paper
• Eugenol alleviated nonalcoholic fatty liver disease in rat via a gut-brain-liver axis involving glucagon-like Peptide-1.

  2022cites this paper
• Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis

  2022cites this paper
• The effect of different weight loss strategies to treat non-alcoholic fatty liver disease focusing on fibroblast growth factor 21

  2022cites this paper
• Effects of Artichoke Supplementation on Liver Enzymes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

  2022cites this paper
• Influence of vitamins (C, B3, D, and E) in liver health

  2021cites this paper
• The Evaluation of Effective Drugs for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis

  2020cites this paper
• NASH Syndrome: The Coming Epidemic.

  2018cites this paper
• Pharmacological interventions for non-alcoholic fatty liver disease: a systematic review and network meta-analysis

  2018cites this paper
• NASH Syndrome: The Coming Epidemic.

  2018cites this paper
• Analysis of proautophagic activities of Citrus flavonoids in liver cells reveals the superiority of a natural polyphenol mixture over pure flavones.

  2018cites this paper
• Impact of intracellular glyceraldehyde-derived advanced glycation end-products on human hepatocyte cell death

  2017cites this paper
• The Transcriptomic Signature Of Disease Development And Progression Of Nonalcoholic Fatty Liver Disease

  2017cites this paper
• Liver-specific deletion of RORα aggravates diet-induced nonalcoholic steatohepatitis by inducing mitochondrial dysfunction

  2017cites this paper
• Comparación de los factores de riesgo cardiovascular, adipocitoquinas, antropometría e ingesta dietética de pacientes obesos con ALT/GPT alterada frente a pacientes obesos con ALT/GPT normal

  2017cites this paper
• The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis

  2016cites this paper
• Treatment of Nonalcoholic Fatty Liver Disease: Where do we Stand? An Overview

  2016cites this paper
• Protective effect of salvianolic acid B on NASH rat liver through restoring intestinal mucosal barrier function.

  2015cites this paper
• Can NASH lipidome provide insight into the pathogenesis of obesity-related non-alcoholic fatty liver disease?

  2015cites this paper
• Effects of coenzyme Q10 supplementation on the anthropometric variables, lipid profiles and liver enzymes in patients with non-alcoholic fatty liver disease

  2015cites this paper
• Herbal Medicines for the Treatment of Nonalcoholic Steatohepatitis: Current Scenario and Future Prospects

  2014cites this paper
• [Non-alcoholic fatty liver: position document of the Catalan Society of Gastroenterology].

  2014cites this paper
• Increasing Whole Grain Intake as Part of Prevention and Treatment of Nonalcoholic Fatty Liver Disease

  2013cites this paper
• Chalmers Publication Library Increasing Whole Grain Intake as Part of Prevention and Treatment of Nonalcoholic Fatty Liver Disease

  2013cites this paper