Nonalcoholic Steatohepatitis (NASH)

Last Updated: April 10, 2023

Nonalcoholic steatohepatitis (NASH) is a condition where fat buildup in the liver leads to liver inflammation and damage. Progression of NASH can cause liver hardening (fibrosis) and scarring (cirrhosis).

Nonalcoholic Steatohepatitis (NASH) falls under theLiver Healthcategory.

What is NASH?

NASH is a severe and aggressive type of nonalcoholic fatty liver disease (NAFLD) characterized by inflammation (hepatitis) and damage to the liver caused by excessive fat accumulation. NASH is associated with an increased risk of cirrhosis, liver cancer, liver failure, cardiovascular disease, and mortality.[1]

What are the main signs and symptoms of NASH?

The majority of people with NASH exhibit no signs or symptoms. As NASH progresses and becomes more severe, people may experience vague symptoms, such as fatigue, weakness, or right upper quadrant abdominal pain. Blood tests may reveal elevated liver enzymes, but this isn’t found in all people with NASH.[2]

How is NASH diagnosed?

The gold standard for diagnosing NASH is through a liver biopsy, but this procedure is reserved for people at risk of advanced liver fibrosis. There’s no standard screening for NAFLD, so It’s more common for NASH to be diagnosed incidentally when being assessed for other health conditions. Imaging — specifically, an ultrasound, computed tomography (CT) scans, or certain types of magnetic resonance imaging (MRI) techniques — may be also used to look for signs of fat accumulation in the liver.[2][3]

What are some of the main medical treatments for NASH?

The main approach to managing NASH is weight loss, usually achieved via diet and exercise. Although no standard medications or treatments are approved for NASH, medications are prescribed to manage overall cardiometabolic risk from other comorbid conditions such as diabetes, hyperlipidemia or cardiovascular disease. In severe cases, liver transplantation may be needed if NASH has progressed to end stage liver disease.[2][4]

Hepatitis A and Hepatitis B vaccinations in unvaccinated individuals would reduce the risk of additional liver damage.

Have any supplements been studied for NASH?

Many supplements have been studied for the treatment of NASH, including vitamin E, L-carnitine, betaine, and melatonin. Other supplements studied for NASH include silymarin[5][6], which is found in milk thistle, and also various probiotic combinations.[7]

How could diet affect NASH?

Weight loss through a hypocaloric diet and lifestyle changes is recommended to manage other factors that contribute to the disease (e.g., obesity) and to prevent further complications (e.g., cirrhosis). Losing 5% or more of body weight can help reduce liver fat, losing 7% or more of body weight can lead to the resolution of NASH, and losing 10% or more of body weight can stabilize or regress fibrosis. It is also recommended that people with NASH reduce their consumption of saturated fat (particularly from processed red meat), commercially produced fructose, and alcohol consumption.[8]

Although there are fewer data on other dietary strategies for treating NASH, such as a low-carbohydrate/high-protein diet or intermittent fasting, these dietary strategies may be helpful if people find them easier to follow while still maintaining a caloric deficit.

Coffee consumption has been associated with a reduced risk of progression to cirrhosis in patients with NASH.[9]

Are there any other treatments for NASH?

Regular physical activity and exercise are recommended for people with NASH, to promote weight loss, reduce liver fat and improve overall health. When diet and exercise are insufficient to manage obesity in persons with NASH, then obesity pharmacotherapy and bariatric surgery might be considered.[4]

What causes NASH?

NASH results from excessive fat buildup in the liver which surpasses its capacity for secretion or metabolism, leading to liver damage and inflammation. This excess fat accumulation, also known as steatosis, is caused by an imbalance between energy intake and expenditure, with more energy consumed than expended.[10] People with obesity, metabolic syndrome, and type 2 diabetes are at the highest risk of developing NAFLD, which can then progress to NASH.[4]

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  1. ^Sheka AC, Adeyi O, Thompson J, Hameed B, Crawford PA, Ikramuddin SNonalcoholic Steatohepatitis: A Review.JAMA.(2020-Mar-24)
  2. ^Kenneth Cusi, Scott Isaacs, Diana Barb, Rita Basu, Sonia Caprio, W Timothy Garvey, Sangeeta Kashyap, Jeffrey I Mechanick, Marialena Mouzaki, Karl Nadolsky, Mary E Rinella, Miriam B Vos, Zobair YounossiAmerican Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD)Endocr Pract.(2022 May)
  3. ^Gosalia D, Ratziu V, Stanicic F, Vukicevic D, Zah V, Gunn N, Halegoua-DeMarzio D, Tran TAccuracy of Noninvasive Diagnostic Tests for the Detection of Significant and Advanced Fibrosis Stages in Nonalcoholic Fatty Liver Disease: A Systematic Literature Review of the US Studies.Diagnostics (Basel).(2022-Oct-27)
  4. ^Westfall E, Jeske R, Bader ARNonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management.Am Fam Physician.(2020-Nov-15)
  5. ^Victor J Navarro, Steven H Belle, Massimo D'Amato, Nezam Adfhal, Elizabeth M Brunt, Michael W Fried, K Rajender Reddy, Abdus S Wahed, Stephen Harrison, Silymarin in NASH and C Hepatitis (SyNCH) Study GroupSilymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trialPLoS One.(2019 Sep 19)
  6. ^Chan Wah Kheong, Nik Raihan Nik Mustapha, Sanjiv MahadevaA Randomized Trial of Silymarin for the Treatment of Nonalcoholic SteatohepatitisClin Gastroenterol Hepatol.(2017 Dec)
  7. ^Carpi RZ, Barbalho SM, Sloan KP, Laurindo LF, Gonzaga HF, Grippa PC, Zutin TLM, Girio RJS, Repetti CSF, Detregiachi CRP, Bueno PCS, Mazuqueli Pereira ESB, Goulart RA, Haber JFDSThe Effects of Probiotics, Prebiotics and Synbiotics in Non-Alcoholic Fat Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Systematic Review.Int J Mol Sci.(2022-Aug-08)
  8. ^Younossi ZM, Corey KE, Lim JKAGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review.Gastroenterology.(2021-02)
  9. ^Jeffrey W Molloy, Christopher J Calcagno, Christopher D Williams, Frances J Jones, Dawn M Torres, Stephen A HarrisonAssociation of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosisHepatology.(2012 Feb)
  10. ^Machado MV, Diehl AMPathogenesis of Nonalcoholic Steatohepatitis.Gastroenterology.(2016-Jun)
  11. ^Spengler EK, Loomba RRecommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic SteatohepatitisMayo Clin Proc.(2015 Sep)
Examine Database References
  1. Ghrelin - Gonciarz M, Bielański W, Partyka R, Brzozowski T, Konturek PC, Eszyk J, Celiński K, Reiter RJ, Konturek SJPlasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatoninJ Pineal Res.(2012 Jun 13)
  2. Liver Enzymes - Chitapanarux T, Tienboon P, Pojchamarnwiputh S, Leelarungrayub DOpen-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patientsJ Gastroenterol Hepatol.(2009 Jun)
  3. Liver Enzymes - T Hasegawa, M Yoneda, K Nakamura, I Makino, A TeranoPlasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot studyAliment Pharmacol Ther.(2001 Oct)
  4. Liver Enzymes - Sumida Y, Naito Y, Tanaka S, Sakai K, Inada Y, Taketani H, Kanemasa K, Yasui K, Itoh Y, Okanoue T, Yoshikawa TLong-term (>=2 yr) efficacy of vitamin E for non-alcoholic steatohepatitisHepatogastroenterology.(2013 Sep)
  5. Liver Enzymes - Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR, NASH CRNPioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitisN Engl J Med.(2010 May 6)
  6. Liver Enzymes - Miwa Kawanaka, Sabina Mahmood, Gouichi Niiyama, Akiyoshi Izumi, Ayumi Kamei, Hideji Ikeda, Mitsuhiko Suehiro, Kazumi Togawa, Takayo Sasagawa, Misako Okita, Hajime Nakamura, Junji Yodoi, Gotaro YamadaControl of oxidative stress and reduction in biochemical markers by Vitamin E treatment in patients with nonalcoholic steatohepatitis: a pilot studyHepatology Research.()
  7. Liver Enzymes - Abdelmalek MF, Angulo P, Jorgensen RA, Sylvestre PB, Lindor KDBetaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot studyAm J Gastroenterol.(2001 Sep)
  8. Liver Enzymes - Sandeep Mukherjee, Tamara Bernard, Kusum Kharbanda, Anthony J. Barak, Michael F. Sorrell, Dean J. TumaImpact of Betaine on Hepatic Fibrosis and Homocysteine in Nonalcoholic Steatohepatitis - A Prospective, Cohort StudyThe Open Translational Medicine Journal.()
  9. Liver Enzymes - Zhong S, Fan Y, Yan Q, Fan X, Wu B, Han Y, Zhang Y, Chen Y, Zhang H, Niu JThe therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trialsMedicine (Baltimore).(2017 Dec)
  10. Liver Enzymes - de Avelar CR, Pereira EM, de Farias Costa PR, de Jesus RP, de Oliveira LPMEffect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis.World J Gastroenterol.(2017-Jul-21)
  11. Liver Enzymes - Malaguarnera M, Gargante MP, Russo C, Antic T, Vacante M, Malaguarnera M, Avitabile T, Li Volti G, Galvano FL-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis--a randomized and controlled clinical trialAm J Gastroenterol.(2010 Jun)
  12. Weight - Amiri-Moghadam S, et alEffects of L-carnitine supplementation on body composition in patients with nonalcoholic steatohepatitis (NASH)CURR TOP NUTRACEUT R.()
  13. Oxidative Stress Biomarkers - Amiri-Moghadam s, et alEffects of L-carnitine supplementation on inflammatory factors and malondialdehyde in patients with nonalcoholic steatohepatitis (NASH)CURR TOP NUTRACEUT R.()
  14. Liver Enzymes - Jingwen Zhou, Yidi Chen, Jun Yu, Tianci Li, Ziyu Lu, Yan Chen, Xiaolong Zhang, Fang YeThe efficacy of novel metabolic targeted agents and natural plant drugs for nonalcoholic fatty liver disease treatment: A PRISMA-compliant network meta-analysis of randomized controlled trialsMedicine (Baltimore).(2021 Mar 26)