|Classification and external resources|
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.  
Recent studies suggest diet, exercise, and antiglycemic drugs may alter the course of the disease. A randomized controlled trial found, "pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis".
As of 2007, no treatment has yet emerged as the "gold standard". General recommendations include improving metabolic risk factors and reducing alcohol intake. However, vitamin E can improve some symptoms of NASH and was superior to insulin sensitizer in one large study. In the Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (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. The primary outcome was an improvement in certain histological features as measured by biopsy, but it did not improve fibrosis. Pioglitazone, an insulin sensitizer, improved some features of NASH, but not the primary outcome, and resulted in a significant weight gain (mean 4.7 kilograms) which persisted after pioglitazone was discontinued.
On Jan 9, 2014 the FLINT trial of obeticholic acid for the treatment of nonalcoholic steatohepatitis was stopped early for efficacy, which means that an interim analysis showed that the efficacy target had been reached.
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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