File:Steatohepatitis high mag.jpg
Micrograph of steatohepatitis. Liver biopsy. Trichrome stain
Classification and external resources
ICD-10 K70.1, K76.0
ICD-9 571.0, 571.8
DiseasesDB 29786
eMedicine article/170539
NCI Steatohepatitis
Patient UK Steatohepatitis
MeSH C06.552.241

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.[1] 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.[2] 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. [3] [4]


No pharmacological treatment has received approval as of 2015.[5] 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.[6][7]

Pioglitazone, an insulin sensitizer, was found in a placebo-controlled trial to lead to metabolic and histologic improvement.[8]

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.[9]

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.[10][11]

Galmed Pharmaceuticals is developing an investigational drug, aramchol, for NASH.[12]

Reversal of Non-alcoholic fatty liver disease (NAFLD) has been demonstrated in rats using 2,4-dinitrophenol (DNP), DNP-methyl ether (DNPME).[13] 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."[14]


NASH was first described in 1980 in a series of patients of the Mayo Clinic.[15] 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.[16]

See also


  1. Vuppalanchi R, Chalasani N (January 2009). "Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management". Hepatology 49 (1): 306–17. PMC 2766096. PMID 19065650. doi:10.1002/hep.22603. 
  2. Yeh, Matthew; Brunt, Elizabeth (2007). "Pathology of Nonalcoholic Fatty Liver Disease". American Journal of Clinical Pathology: 837–841. 
  3. 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. 
  4. 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. 
  5. 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. 
  6. Adams LA, Angulo P (2006). "Treatment of non-alcoholic fatty liver disease". Postgrad Med J 82 (967): 315–22. PMC 2563793. PMID 16679470. doi:10.1136/pgmj.2005.042200. 
  7. Veena J, Muragundla A, Sidgiddi S, Subramaniam S (2014). "Non-alcoholic fatty liver disease: need for a balanced nutritional source". Br. J. Nutr. 112 (11): 1858–72. PMID 25274101. doi:10.1017/S0007114514002591. 
  8. Belfort R, Harrison SA, Brown K et al. (2006). "A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis". N. Engl. J. Med. 355 (22): 2297–307. PMID 17135584. doi:10.1056/NEJMoa060326. 
  9. Sanyal AJ, Chalasani N, Kowdley KV et al. (May 2010). "Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis". N. Engl. J. Med. 362 (18): 1675–85. PMC 2928471. PMID 20427778. doi:10.1056/NEJMoa0907929. 
  10. 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. 
  11. 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. 
  12. "Galmed's Aramchol Gets Fast-Track Designation in the U.S.". Retrieved 8 January 2015. 
  13. 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. 
  14. Hui JM, Kench JG, Chitturi S et al. (2003). "Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C". Hepatology 38 (2): 420–7. PMID 12883486. doi:10.1053/jhep.2003.50320. 
  15. Ludwig J, Viggiano TR, McGill DB, Oh BJ (1980). "Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease". Mayo Clin Proc 55 (7): 434–438. PMID 7382552. 
  16. Cassiman D, Jaeken J (2008). "NASH may be trash". Gut 57 (2): 141–4. PMID 18192446. doi:10.1136/gut.2007.123240. 

External links

  • Hepatitis C Long-Term Outcomes of Cirrhosis in Nonalcoholic Steatohepatitis Compared With Hepatitis C
pt:Esteato-hepatite não alcoólica