Liver Fibrogenesis in Non-Alcoholic Steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common chronic liver diseases in developed western countries. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD, and can progress to more severe forms of liver disease, including fibrosis, cirrhosis, and even hepatocellular carcinoma. The activation of hepatic stellate cells plays a critical role in NASH-related fibrogenesis. Multiple factors, such as insulin resistance, oxidative stress, pro-inflammatory cytokines and adipokines, and innate immune responses, are known to contribute to the development of NASH-related fibrogenesis. Furthermore, these factors may share synergistic interactions, which could contribute to the process of liver fibrosis. Given the complex etiology of NASH, combined treatment regimes that target these different factors provide potential treatment strategies for NASH-related liver fibrosis.

• Publication year

  2012

• Venue

  Front. Physio.

• Publication date

  2012-07-11

• Fields of study

  Medicine

• Identifiers
  DOI 10.3389/fphys.2012.00248PMID 22934006PMCID 3429026
• 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.

• Potential Role of Leptin, Adiponectin and Three Novel Adipokines—Visfatin, Chemerin and Vaspin—in Chronic Hepatitis

  2011cited by this paper
• Modulation of Liver Fibrosis by Adipokines

  2011cited by this paper
• Nifedipine prevents hepatic fibrosis in a non-alcoholic steatohepatitis model induced by an L-methionine-and choline-deficient diet.

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

  2011influential reference
• Liver visfatin expression in morbidly obese patients with nonalcoholic fatty liver disease undergoing bariatric surgery.

  2011cited by this paper
• Reactive oxygen species and NADPH oxidase 4 induced by transforming growth factor β1 are the therapeutic targets of polyenylphosphatidylcholine in the suppression of human hepatic stellate cell activation

  2011cited by this paper
• Circulating vaspin levels and epicardial adipose tissue thickness are associated with impaired coronary flow reserve in patients with nonalcoholic fatty liver disease.

  2011cited by this paper
• Full-spectrum antioxidant therapy featuring astaxanthin coupled with lipoprivic strategies and salsalate for management of non-alcoholic fatty liver disease.

  2011cited by this paper
• Liver X receptor signaling is a determinant of stellate cell activation and susceptibility to fibrotic liver disease.

  2011cited by this paper
• Reactive Oxygen Species Released from Hypoxic Hepatocytes Regulates MMP-2 Expression in Hepatic Stellate Cells

  2011cited by this paper
• Intrahepatic natural killer T cell populations are increased in human hepatic steatosis.

  2011cited by this paper
• The liver X receptor in hepatic stellate cells: a novel antifibrogenic target?

  2011cited by this paper
• Critical role of tumor necrosis factor receptor 1, but not 2, in hepatic stellate cell proliferation, extracellular matrix remodeling, and liver fibrogenesis

  2011cited by this paper
• CD1d-restricted natural killer T cells contribute to hepatic inflammation and fibrogenesis in mice.

  2011cited by this paper
• SHP-dependent and -independent induction of peroxisome proliferator-activated receptor-γ by the bile acid sensor farnesoid X receptor counter-regulates the pro-inflammatory phenotype of liver myofibroblasts

  2011cited by this paper
• Combination treatment of angiotensin II type I receptor blocker and new oral iron chelator attenuates progression of nonalcoholic steatohepatitis in rats.

  2011cited by this paper
• Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study.

  2011cited by this paper
• Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease

  2011cited by this paper
• Nuclear receptors in liver disease

  2011cited by this paper
• The role of oxidative stress in non-alcoholic steatohepatitis.

  2011cited by this paper
• Pathophysiology of Non-Alcoholic Steatohepatitis and Basis for Treatment

  2011cited by this paper
• Fibrogenesis in nonalcoholic steatohepatitis

  2011cited by this paper
• Leptin Promotes the Myofibroblastic Phenotype in Hepatic Stellate Cells by Activating the Hedgehog Pathway

  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
• Animal Models of Non-Alcoholic Steatohepatitis: Of Mice and Man

  2010cited by this paper
• Role and cellular source of nicotinamide adenine dinucleotide phosphate oxidase in hepatic fibrosis

  2010cited by this paper
• Study of adiponectin in chronic liver disease and cholestasis

  2010cited by this paper
• Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease

  2010cited by this paper
• The role of adiponectin in the pathogenesis and treatment of non‐alcoholic fatty liver disease

  2010cited by this paper
• Molecular Mechanisms of Hepatic Fibrosis in Non-Alcoholic Steatohepatitis

  2010cited by this paper
• Nonalcoholic fatty liver disease.

  2010cited by this paper
• Kupffer cell and interleukin‐12–dependent loss of natural killer T cells in hepatosteatosis

  2010cited by this paper
• Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery.

  2010cited by this paper
• Inhibition of Endothelin-1-Mediated Contraction of Hepatic Stellate Cells by FXR Ligand

  2010cited by this paper
• Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice.

  2010cited by this paper
• Serum chemerin and vaspin in non-alcoholic fatty liver disease

  2010cited by this paper
• Increased Soluble Leptin Receptor Levels in Morbidly Obese Patients With Insulin Resistance and Nonalcoholic Fatty Liver Disease

  2010cited by this paper
• Autoreactive natural killer T cells: promoting immune protection and immune tolerance through varied interactions with myeloid antigen‐presenting cells

  2010cited by this paper
• Nonalcoholic fatty liver disease.

  2010influential reference
• Pioglitazone in the treatment of NASH: the role of adiponectin

  2010influential reference
• Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis

  2010cited by this paper
• Regulation of oxidative stress and inflammation by hepatic adiponectin receptor 2 in an animal model of nonalcoholic steatohepatitis.

  2010cited by this paper
• c-Jun N-terminal kinase-1 from hematopoietic cells mediates progression from hepatic steatosis to steatohepatitis and fibrosis in mice.

  2009cited by this paper
• Immature myeloid cells induced by a high‐fat diet contribute to liver inflammation

  2009cited by this paper
• Adipokines in liver diseases

  2009influential reference
• Serum adipokine levels predictive of liver injury in non‐alcoholic fatty liver disease

  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
• Role of liver-infiltrating CD3+CD56+ natural killer T cells in the pathogenesis of nonalcoholic fatty liver disease

  2009cited by this paper
• [Prevalence of nonalcoholic fatty liver disease and metabolic syndrome in obese children].

  2009cited by this paper
• Adiponectin knockout mice on high fat diet develop fibrosing steatohepatitis

  2009cited by this paper
• The obesity epidemic: pharmacological challenges.

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

  2008cited by this paper
• Oxidative and nitrosative stress and fibrogenic response.

  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
• Risk of severe liver disease in nonalcoholic fatty liver disease: Role of insulin resistance

  2008cited by this paper
• Mechanisms of disease progression in nonalcoholic fatty liver disease.

  2008cited by this paper
• Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: A role for insulin resistance and diabetes

  2008cited by this paper
• Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells.

  2007cited by this paper
• Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll‐like receptor 9

  2007cited by this paper
• Combination of N‐acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non‐alcoholic steatohepatitis

  2007cited by this paper
• Hypoadiponectinemia accelerates hepatic tumor formation in a nonalcoholic steatohepatitis mouse model.

  2007cited by this paper
• Transgenic mice expressing nuclear sterol regulatory element-binding protein 1c in adipose tissue exhibit liver histology similar to nonalcoholic steatohepatitis.

  2007cited by this paper
• TLR4 enhances TGF-beta signaling and hepatic fibrosis.

  2007cited by this paper
• Intrahepatic insulin resistance in a murine model of steatohepatitis: effect of PPARγ agonist pioglitazone

  2007cited by this paper
• Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis.

  2007cited by this paper
• Relationship between oxidative stress levels and activation state on a hepatic stellate cell line

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

  2006cited by this paper
• LIVER FAILURE AND LIVER DISEASE Nonalcoholic Fatty Liver Disease: From Steatosis to Cirrhosis

  2006cited by this paper
• Hepatic stellate cells and alcoholic liver disease.

  2006cited by this paper
• Paradoxical effects of short‐ and long‐term interleukin‐6 exposure on liver injury and repair

  2006cited by this paper
• Mechanisms of liver fibrosis.

  2006influential reference
• Amelioration of non‐alcoholic steatohepatitis and glucose intolerance in ob/ob mice by oral immune regulation towards liver‐extracted proteins is associated with elevated intrahepatic NKT lymphocytes and serum IL‐10 levels

  2006cited by this paper
• NADPH oxidase in the liver: defensive, offensive, or fibrogenic?

  2006cited by this paper
• c-Jun N-terminal kinase 抑制による大動脈瘤薬物治療

  2006cited by this paper
• Células estrelladas hepáticas y hepatopatía alcohólica

  2006cited by this paper
• Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease

  2005cited by this paper
• Review article: the pathogenesis of fibrosis in non‐alcoholic steatohepatitis

  2005cited by this paper
• Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellate cells.

  2005cited by this paper
• Steatohepatitis induced by intragastric overfeeding in mice

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

  2005cited by this paper
• Liver Fibrogenesis: A New Role for the Renin–Angiotensin System

  2005cited by this paper
• IL-6-deficient mice are susceptible to ethanol-induced hepatic steatosis: IL-6 protects against ethanol-induced oxidative stress and mitochondrial permeability transition in the liver.

  2004cited by this paper
• A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis.

  2004cited by this paper
• Nonalcoholic steatohepatitis

  2004cited by this paper
• Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo.

  2004cited by this paper
• Upregulation of osteopontin expression is involved in the development of nonalcoholic steatohepatitis in a dietary murine model.

  2004cited by this paper
• The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis.

  2004cited by this paper
• Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver

  2004cited by this paper
• Nonalcoholic Steatohepatitis

  2004cited by this paper
• Systemic Levels of Lipid Peroxidation and Its Metabolic and Dietary Correlates in Patients with Nonalcoholic Steatohepatitis

  2004cited by this paper
• A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis

  2004cited by this paper
• The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance.

  2004cited by this paper
• Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver

  2004cited by this paper
• Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin.

  2003cited by this paper
• Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis.

  2003cited by this paper
• NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome

  2002cited by this paper
• High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: A potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis

  2001cited by this paper
• Serum leptin levels in patients with nonalcoholic steatohepatitis

  2000cited by this paper
• Steatohepatitis: a tale of two "hits"?

  1998cited by this paper
• Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice

  1996cited by this paper

• Adipokine profiles reflect metabolic dysfunction but not fibrosis in patients with primary biliary cholangitis

  2026cites this paper
• Association between frailty and hepatic fibrosis in NAFLD among middle-aged and older adults: results from NHANES 2017–2020

  2024cites this paper
• Liver fibrosis pathologies and potentials of RNA based therapeutics modalities

  2024cites this paper
• CETP-derived Peptide Seq-1, the Key Component of HB-ATV-8 Vaccine Prevents Stress Responses, and Promotes Downregulation of Pro-Fibrotic Genes in Hepatocytes and Stellate Cells.

  2024cites this paper
• Cyanotoxins Increase Cytotoxicity and Promote Nonalcoholic Fatty Liver Disease Progression by Enhancing Cell Steatosis

  2023cites this paper
• Extracellular volume fraction obtained by dual-energy CT depicting the etiological differences of liver fibrosis

  2023cites this paper
• Per‐ and polyfluoroalkyl substances activate UPR pathway, induce steatosis and fibrosis in liver cells

  2022influential citation
• Promising hepatoprotective effects of lycopene in different liver diseases.

  2022cites this paper
• Liver Fibrosis in Non-alcoholic Fatty Liver Disease: From Liver Biopsy to Non-invasive Biomarkers in Diagnosis and Treatment

  2021cites this paper
• Advances in the research of nanodrug delivery system for targeted treatment of liver fibrosis.

  2021cites this paper
• FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases

  2020cites this paper
• The PPAR α/γ Agonist Saroglitazar Improves Insulin Resistance and Steatohepatitis in a Diet Induced Animal Model of Nonalcoholic Fatty Liver Disease

  2020cites this paper
• Molecular mechanisms of hepatic fibrosis in chronic liver diseases

  2020cites this paper
• Histological evaluation of nintedanib in non-alcoholic steatohepatitis mice.

  2019cites this paper
• Isorhamnetin Alleviates Steatosis and Fibrosis in Mice with Nonalcoholic Steatohepatitis

  2019cites this paper
• Combined effects of ambient particulate matter exposure and a high-fat diet on oxidative stress and steatohepatitis in mice

  2019cites this paper
• Association of metabolic syndrome with the risk of developing liver disease in chronic hepatitis B patients

  2019cites this paper
• Non‐alcoholic fatty liver disease, liver fibrosis score and cognitive function in middle‐aged adults: The Framingham Study

  2019cites this paper
• Combination effects of airborne particulate matter exposure and high-fat diet on hepatic fibrosis through regulating the ROS-endoplasmic reticulum stress-TGFβ/SMADs axis in mice.

  2018cites this paper
• Genomic studies in non-alcoholic fatty liver disease

  2017cites this paper
• Nanoparticles for the treatment of liver fibrosis

  2017cites this paper
• Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role for the androgen receptor pathway?

  2017cites this paper
• Activation of Insulin-PI3K/Akt-p70S6K Pathway in Hepatic Stellate Cells Contributes to Fibrosis in Nonalcoholic Steatohepatitis

  2017cites this paper
• High carbohydrate diet induces nonalcoholic steato-hepatitis (NASH) in a desert gerbil.

  2017cites this paper
• Mechanisms of hepatic stellate cell activation

  2017cites this paper
• The potential of silymarin for the treatment of hepatic disorders

  2016cites this paper
• Review article: emerging anti‐fibrotic therapies in the treatment of non‐alcoholic steatohepatitis

  2016cites this paper
• Insulin Resistance but Not Visceral Adiposity Index Is Associated with Liver Fibrosis in Nondiabetic Subjects with Nonalcoholic Fatty Liver Disease

  2015cites this paper
• The Therapeutic Promise of Mesenchymal Stem Cells for Liver Restoration.

  2015cites this paper
• Fibrogenesis and Carcinogenesis in Nonalcoholic Steatohepatitis (NASH): Involvement of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinase (TIMPs)

  2014influential citation
• Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model.

  2014cites this paper
• Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update.

  2014cites this paper
• Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease--14 months follow up.

  2014cites this paper
• Primary hepatocellular carcinoma and metabolic syndrome: An update.

  2013cites this paper
• Elongation factor 1A-1 and hepatocyte response to fatty acid excess

  2013cites this paper
• Potential drug mechanism(s) targeting the contractile status of hepatic stellate cells

  2012cites this paper