Open Access Articles- Top Results for Steatohepatitis
Journal of Clinical Case ReportsAssociation of Obstructive Sleep Apnea Syndrome (OSAS) and Nonalcoholic Steatohepatitis (NASH)
Journal of Clinical Case ReportsCase of Nonalcoholic Steatohepatitis Occurring in Combination with Sleep Apnea Syndrome, Who Showed Improvement of Liver Function by Continuous Posi
Journal of Carcinogenesis & MutagenesisExocycilic DNA Adducts in a Murine Model of Non-alcoholic Steatohepatitis
Journal of Diabetes & MetabolismA Pilot Randomised Study of the Metabolic and Histological Effects of Exercise in Non-alcoholic Steatohepatitis
Journal of Clinical & Cellular ImmunologyNon-Alcoholic Fatty Steatohepatitis an Inflammatory Disorder Beyond the Liver
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Steatohepatitis (also known as fatty liver disease) is a type of liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver (steato-, meaning "fat", hepatitis, meaning "inflammation of the liver"). More deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes.
Classically seen in alcoholics as part of alcoholic liver disease, steatohepatitis is also frequently found in people with diabetes and obesity and is related to metabolic syndrome. When not associated with excessive alcohol intake, it is referred to as nonalcoholic steatohepatitis, or NASH, and is the progressive form of the relatively benign non-alcoholic fatty liver disease. Steatohepatitis of either etiology may progress to cirrhosis, and NASH is now believed to be a frequent cause of unexplained cirrhosis (at least in Western societies). NASH is also associated with lysosomal acid lipase deficiency.
Steatohepatitis is characterized microscopically by hepatic fat accumulation (steatosis), mixed lobular inflammation, ballooning degeneration of hepatocytes (sometimes with identifiable Mallory bodies), glycogenated hepatocyte nuclei, and pericellular fibrosis. The "chicken wire" pattern of the pericellular fibrosis, which affects portal areas only secondarily in later stages, is very characteristic and is identified on trichrome stains. NASH is commonly associated with metabolic syndrome: obesity, dyslipidemia and insulin resistance. This leads to accumulation of hepatic fat. Further progression of the disease is probably caused by chronic inflammation and reactive oxygen species formation. Metabolically induced liver inflammation recruits additional inflammatory components (neutrophils, AP-1 pathway) and causes NASH.  
No pharmacological treatment has received approval as of 2015. Some studies suggest diet, exercise, and antiglycemic drugs may alter the course of the disease. General recommendations include improving metabolic risk factors and reducing alcohol intake.
Vitamin E can improve some symptoms of NASH and was compared to pioglitazone in one large study (the PIVENS trial), for patients with NASH but without diabetes mellitus. The use of very high dosages of vitamin E (800 IU/day) for four years was associated with a significantly higher rate of improvement than placebo (43% vs. 19%) in the primary outcome, an improvement in certain histological features. Pioglitazone improved some features of NASH, but not the primary outcome, and resulted in a significant weight gain (mean 4.7 kg) which persisted after pioglitazone was discontinued.
Intercept Pharmaceuticals has conducted clinical trials of obeticholic acid, a semi-synthetic bile acid and potent farnesoid X receptor (FXR) agonist, for the treatment of nonalcoholic steatohepatitis. The FLINT trial of obeticholic acid was stopped early for efficacy, meaning that an interim analysis showed that the efficacy target had been reached. 45% of patients met the criteria of histological improvement compared with 21% of placebo-treated controls.
Reversal of Non-alcoholic fatty liver disease (NAFLD) has been demonstrated in rats using 2,4-dinitrophenol (DNP), DNP-methyl ether (DNPME). DNPME appears to have far fewer of the side effects compared to DNP due to it being metabolized to DNP in the liver and thus having a lower systemic concentration.
A retrospective cohort study concluded, "liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis."
NASH was first described in 1980 in a series of patients of the Mayo Clinic. Its relevance and high prevalence were recognized mainly in the 1990s. Some think NASH is a diagnosis of exclusion, and many cases may in fact be due to other causes.
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- Yeh, Matthew; Brunt, Elizabeth (2007). "Pathology of Nonalcoholic Fatty Liver Disease". American Journal of Clinical Pathology: 837–841.
- Sakaguchi S (Dec 2011). "Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress.". Drug Metab Pharmacokinet. 26 (1): 30–46. PMID 21150132. doi:10.2133/dmpk.dmpk-10-rv-087.
- Liang W (May 2014). "Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1β-induced chronic inflammation.". Lab Invest. 94 (5): 491–502. PMID 24566933. doi:10.1038/labinvest.2014.11.
- Ratziu V (2015). "Starting the battle to control non-alcoholic steatohepatitis". Lancet 385 (9972): 922–4. PMID 25468161. doi:10.1016/S0140-6736(14)62010-9.
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- Intercept Pharmaceuticals, Inc. (January 9, 2014). "Intercept Announces NASH Primary Endpoint Met: FLINT Trial Stopped Early for Efficacy Based on Highly Statistically Significant Improvement in Liver Histology". Acquire Media. Retrieved January 9, 2014.
- Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF et al. (2015). "Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial". Lancet 385 (9972): 956–65. PMID 25468160. doi:10.1016/S0140-6736(14)61933-4.
- "Galmed's Aramchol Gets Fast-Track Designation in the U.S.". Zacks.com. Retrieved 8 January 2015.
- Perry, Rachel; Taehan, Kim; Shulman, Gerald (November 5, 2013). "Reversal of Hypertriglyceridemia, Fatty Liver Disease and Insulin Resistance by a Liver-Targeted Mitochondrial Uncoupler". Cell Metabolism 18 (5): 740–748. PMC 410468. doi:10.1016/j.cmet.2013.10.004. Retrieved November 5, 2013.
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- Cassiman D, Jaeken J (2008). "NASH may be trash". Gut 57 (2): 141–4. PMID 18192446. doi:10.1136/gut.2007.123240.
- Hepatitis C Long-Term Outcomes of Cirrhosis in Nonalcoholic Steatohepatitis Compared With Hepatitis C