Review Article
Nonalcoholic Steatohepatitis: A Review of the Literature and Updates in Management
Abstract
Nonalcoholic steatohepatitis is a common cause of liver inflammation and is associated with obesity, insulin resistance, and hyperlipidemia. There are concerns that it may turn out to be the most common cause of liver failure as prevalence of obesity increases. It leads to increased morbidity and mortality. Other causes of liver inflammation, especially alcoholic liver disease, must be ruled out. The diagnosis is suggested by abnormalities in the blood work and metabolic panel in an obese patient. Despite advances made in our understanding regarding the pathogenesis and trials with multiple drugs targeting mechanisms in pathogenesis, there are no consistent guidelines regarding treatment. However, multiple sources advocate weight reduction, optimum blood glucose control, and elimination of medications that cause fatty infiltration. The purpose of our article is to detail advances made in identifying disease mechanisms and treatment modalities, including surgery to promote weight loss.This content is limited to qualifying members.
Existing members, please login first
If you have an existing account please login now to access this article or view purchase options.
Purchase only this article ($25)
Create a free account, then purchase this article to download or access it online for 24 hours.
Purchase an SMJ online subscription ($75)
Create a free account, then purchase a subscription to get complete access to all articles for a full year.
Purchase a membership plan (fees vary)
Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.
References
1.Ludwig J, Viggiano TR, McGill DB, et al. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980;55:434–438.
2.Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003;98:960–967.
3.Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003;124:71–79.
4.Ekstedt M, Franzén L, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865–873.
5.Edmison J, McCullough AJ. Pathogenesis of non-alcoholic steatohepatitis: human data. Clin Liver Dis 2007;11:75–104, ix.
6.Ryan MW, Harrison SA, Neuschwander-Tetri BA. Serum amyloid A and C-reactive protein diminish after treatment of NASH with rosiglitazone (abstract). Gastroenterology 2003;124:A747.
7.Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 2000;343:1467–1476.
8.Harrison SA, Torgerson S, Hayashi P, et al. Vitamin E and vitamin C in the treatment of nonalcoholic steatohepatitis. Am J Gastroenterol 2003;98:2485–2490.
9.Musso G, Gambino R, De Michieli F, et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003;37:909–916.
10.Koteish A, Diehl AM. Animal models of steatosis. Semin Liver Dis 2001;21:089–104.
11.Ikejima K, Takei Y, Honda H, et al. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 2002;122:1399–1410.
12.Jonsson JR, Clouston AD, Ando Y, et al. Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology 2001;121:148–155.
13.Powell EE, Cooksley WG, Hanson R, et al. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990;11:74–80.
14.Falck-Ytter Y, Younossi ZM, Marchesini G, et al. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 2001;21:17–26.
15.Oh MK, Winn J, Poordad F. Review article: diagnosis and treatment of non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008;28:503–522.
16.Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45:846–854.
17.Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999;30:1356–1362.
18.Gressner AM, Gao CF, Gressner OA. Non-invasive biomarkers for monitoring the fibrogenic process in liver: a short survey. World J Gastroenterol 2009;15:2433–2440.
19.Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004;24:3–20.
20.Ratziu V, Charlotte F, Heurtier A, et al; LIDO Study Group. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128:1898–1906.
21.Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002;123:745–750.
22.Dixon JB, Bhathal PS, Hughes NR, et al. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology 2004;39:1647–1654.
23.Sabuncu T, Nazligul Y, Karaoglanoglu M, et al. The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis. Rom J Gastroenterol 2003;12:189–192.
24.Lavine, JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr 2000;136:734–738.
25.Sanyal AJ, Mofrad PS, Contos MJ, et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2004;2:1107–1115.
26.Uygun A, Kadayifci A, Isik AT, et al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2004;19:537–544.
27.Bugianesi E, Gentilcore E, Manini R, et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 2005;100:1082–1090.
28.Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, et al. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 2003;38:1008–1017.
29.Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006;355:2297–2307.
30.Basaranoglu M, Acbay O, Sonsuz A. A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J Hepatol 1999;31:384.
31.Rallidis LS, Drakoulis CK, Parasi AS. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis 2004;174:193–196.
32.Gómez-Domínguez E, Gisbert JP, Moreno-Monteagudo JA, et al. A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 2006;23:1643–1647.
33.Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 2005;41:690–695.
34.Abdelmalek MF, Angulo P, Jorgensen RA, et al. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol 2001;96:2711–2717.
35.Adams LA, Zein CO, Angulo P, et al. A pilot trial of pentoxifylline in nonalcoholic steatohepatitis. Am J Gastroenterol 2004;99:2365–2368.
36.Laurin J, Lindor KD, Crippin JS, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology 1996;23:1464–1467.
37.Yokohama S, Yoneda M, Haneda M, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 2004;40:1222–1225.
