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REVIEW

Pharmacological treatment of non-alcoholic steatohepatitis: The current evidence

, , , , & , FASA , MD , DSc , FRSH
Pages 139-147 | Received 29 May 2006, Published online: 08 Jul 2009

References

  • Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004; 114: 147–52
  • Guadrado A, Orive A, Garcia-Suarez C, Dominguez A, Fernandez-Escalante JC, Crespo J, et al. Non alcoholic steatohepatitis (NASH) and hepatocellular carcinoma. Obes Surg 2005; 15: 442–6
  • Gasparini O, Vero V, Miele L, Forgione A, Hernandez AP, Greco AV, et al. Non alcoholic fatty liver disease: defining a common problem. Eur Rev Pharmacol Sci 2005; 9: 253–9
  • Angelico F, Del Ben M, Conti R, Francioso S, Feole K, Fiorello S, et al. Insulin resistance, the metabolic syndrome, and non-alcoholic fatty liver disease. J Clin Endocrinol Metab 2005; 90: 1578–82
  • Marchesini G, Bugianesi E, Forlani G, Cerelli F, Lenzi M, Manini R, et al. Non alcoholic fatty liver, steatohepatitis and the metabolic syndrome. Hepatology 2003; 37: 917–23
  • Donati G, Stagni B, Piscaglia F, Venturoli N, Morselli-Labate AM, Rasciti L, et al. Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance. Gut 2004; 53: 1020–3
  • Choudhury J, Sanyal AJ. Insulin resistance in NASH. Front Biosci 2005; 10: 1520–33
  • Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, et al. NASH and insulin resistance: insulin secretion and specific association with the insulin resistance syndrome. Hepatology 2002; 35: 373–79
  • Day EP, James OFW. Steatohepatitis: a tale of two “hit”'?. Gastroenterology 1998; 114: 842–45
  • Diehl AM, Li ZP, Lin HZ, Yang SQ. Cytokines and the pathogenesis of non-alcoholic steatohepatitis. Gut 2005; 54: 303–6
  • Hui JM, Hogde A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF-a or adiponectin?. Hepatology 2004; 40: 46–54
  • Pagano C, Soardo G, Esposito W, Fallo F, Basan L, Donnini D, et al. Plasma adiponectin is decreased in non alcoholic fatty liver disease. Eur J Endocrinol 2005; 152: 113–8
  • Gaemers IC, Groen AK. New insights in the pathogenesis of non-alcoholic fatty liver disease. Curr Opin Lipidol 2006; 17: 268–73
  • Huang MA, Greenson JK, Chao C, Anderson L, Peterman D, Jacobson J, et al. One year intense nutritional counselling results in histological improvement in patients with non alcoholic steatohepatitis: a pilot study. Am J Gastroenterol 2005; 100: 1072–81
  • Stratopoulos C, Papakonstantinou A, Terzis I, Spiliadi C, Dimitriades G, Komesidou V, et al. Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity. Obes Surg 2005; 15: 1154–60
  • Luyckx FH, Lefebvre PJ, Scheen AJ. Non alcoholic steatohepatitis: association with obesity and insulin resistance and influence of weight loss. Diabetes Metab 2000; 26: 98–106
  • Luyckx FH, Desaive C, Thiry A, Dewe W, Scheen AJ, Gielen JE, et al. Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty. Int J Obes Relat Metab Disord 1998; 22: 222–6
  • Andersen T, Glund C, Franzmann MB, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol 1991; 12: 224–9
  • Mattar SG, Velcu LM, Rabinovitz M, Demetris AJ, Krasinskas AM, Barinas-Mitchell E, et al. Surgically-induced weight loss improves nonalcoholic fatty liver disease and the metabolic syndrome. Ann Surg 2005; 242: 610–7
  • Clarck JM, Alkhuraishi AR, Solga SF, Alli P, Diehl AM, Magnuson TH. Roux-en-Y gastric bypass improves liver histology in patients with non-alcoholic fatty liver disease. Obes Res 2005; 13: 1180–6
  • Brunt EM, Neuschwander-Tetri BA, Oliver D, Wehmeier KR, Bacon BR. Non alcoholic steatohepatitis: histologic features and clinical correlations with 30 blinded biopsy specimens. Hum Pathol 2004; 35: 1070–82
  • Van Ness MM, Diehl AM. Is liver biopsy useful in the evaluation of patients with chronically elevated liver enzymes?. Ann Intern Med 1989; 111: 473–8
  • Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology 2004; 40: 820–6
  • Lee RG. Non alcoholic steatohepatitis: a study of 49 patients. Hum Pathol 1989; 20: 594–8
  • Das K, Kar P. Non alcoholic steatohepatitis. J Assoc Physicians India 2005; 53: 195–9
  • Mardini H, Record C. Detection assessment and monitoring of hepatic fibrosis: biochemistry or biopsy. Ann Clin Biochem 2005; 42: 441–7
  • Uygun A, Kadayifci A, Isik AT, Ozgurtas T, Deveci S, Tuzun A, et al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2004; 19: 537–44
  • Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 2005; 100: 1082–90
  • Nair S, Diehl AM, Wiseman M, Farr GH, Perrillo RP. Metformin in the treatment of non alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther 2004; 20: 23–8
  • Tiikkainen, M, Hakkinen, AM, Korsheninnikova, E, Nyman, T, Makimattila, S, Yki-Jarvinen. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 2004;53:2169–76.
  • Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N. Metformin in nonalcoholic steatohepatitis. Lancet 2001; 358: 893–4
  • Schwimmer JB, Middleton MS, Deutsch R, Lavine JE. A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005; 21: 871–9
  • Caldwell SH, Hespenheide EE, Redick JA, Iezzoni JC, Bettle EH, Sheppard BL. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastroenterol 2001; 96: 519–25
  • Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved non-alcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone. Hepatology 2003; 38: 1008–17
  • Sanyal AJ, Mofrad PS, Contos MJ, Sargeant C, Luketic VA, Sterling RK, et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of non alcoholic steatohepatitis. Clin Gastroenterol Hepatol 2004; 2: 1107–15
  • Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004; 39: 188–96
  • Harrison SA, Torgerson S, Hayashi P, Ward J, Shenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003; 98: 2485–90
  • Hasegawa T, Yoneda M, Makamura K, Makino I, Terano A. Plasma transforming growth factor-beta 1 level and efficacy of alpha tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther 2001; 15: 1667–72
  • Lavine JE. Vitamin E treatment of non alcoholic steatohepatitis in children: a pilot study. J Pediatr 2000; 136: 734–8
  • Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, et al. Ursodeoxycholic acid for the treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004; 39: 770–8
  • Laurin J, Lindor KD, Crippin JS, Gossard A, Gores GJ, Ludwig J, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcoholic-induced steatohepatitis: a pilot study. Hepatology 1996; 23: 1464–7
  • Kiyici M, Gulten M, Nak SG, Dolar E, Savci G, et al. Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis. Can J Gastroenterol 2003; 17: 713–8
  • Santos VN, Lanzoni VP, Szejnfeld J, Shigneoka D, Parise ER. A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid. Braz J Med Biol Res 2003; 36: 723–9
  • Abdelmalek MF, Angulo P, Jorgensen RA, Sylvestre PB, Lindor KD. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol 2001; 96: 2711–7
  • Adams LA, Zein CO, Angulo P, Lindor KD. A pilot trial of pentoxifylline in nonalcoholic steatohepatitis. Am J Gastroentrol 2004; 99: 2365–8
  • Yokohama S, Yoneda M, Haneda M, Okamoto S, Okada M, Aso K, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 2004; 40: 1222–5
  • Zelber-Sagi S, Kessler A, Brazowsky E, Webb M, Lurie Y, Santo M, et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006; 4: 639–44
  • Harrison SA, Fincke C, Helinski D, Torgerson S, Hayashi P. A pilot study of orlistat treatment in obese nonalcoholic steatohepatitis patients. Aliment Pharmacol Ther 2004; 20: 623–8
  • Sabuncu T, Nzligul Y, Karaoglanoglu M, Ucar E, Kilic FB. 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: 189–92
  • Hatzitolios A, Savopoulos C, Lazaraki G, Sidiropoulos I, Haritanti P, Lefkopoulos A, et al. Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia. Indian J Gastroenterol 2004; 23: 131–4
  • Rallidis LS, Drakoulis CK, Parasi AS. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis 2004; 174: 193–6
  • Gomez-Dominguez E, Gisbert JP, Moreno-Monteagudo JA, Garcia-Buey L, Moreno-Otero R. A pilot study of atorvastatin treatment in dyslipidemia, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 2006; 23: 1643–7
  • Basaranoglu M, Acbay O, Sonsuz A. A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J Hepatol 1999; 31: 384
  • Merat S, Malekzadeh R, Sohrabi MR, Sotoudeh M, Rakhshani N, Sohrabpour AA, et al. Probucol in the treatment of nonalcoholic steatohepatitis: an open-labelled study. J Hepatol 2003; 36: 266–8
  • Capanni M, Calella F, Biagini MR, Genise S, Raimondi L, Bedogni G, et al. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 2006; 23: 1143–51
  • Cholongitas, E, Quaglia, A, Samonahis, D, Senzolo, M, Triantos, C, Patch, D, , et al.Transjugular liver biopsy: how good is it for accurate histological interpretation?. Gut 2006; Epub ahead of print.
  • Cholongitas E, Senzolo M, Standish R, Marelli L, Quaglia A, Patch D, et al. A systematic review of the quality of liver biopsy specimens. Am J Clin Pathol 2006; 125: 710–21
  • Filippatos TD, Kiortsis DN, Liberopoulos EN, Georgoula M, Mikhailidis DP, Elisaf MS. Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study. Curr Med Res Op 2005; 21: 1997–2006
  • Athyros AG, Mikhailidis DP, Didangelos TP, Giouleme OI, Liberopoulos EN, Karagiannis A, et al. Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study. Curr Med Res Opin 2006; 22: 873–83
  • Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005; 353: 2121–34
  • Ahmed MH. Rosuvastatin as treatment for non alcoholic steatohepatitis (NASH) and highly active antiretroviral therapy (HAART)-dyslipidaemia: New treatment for global dangers. Med Hypotheses 2006; 66: 440–1
  • Antonopoulos S, Mikros S, Mylonopoulou M, Kokkoris S, Giannoulis G. Rosuvastatin as a novel treatment of non-alcoholic fatty liver disease in hyperlipidemic patients. Atherosclerosis 2006; 184: 233–4
  • Ahmed MH. Rosuvastatin: a safe and effective treatment for dyslipidaemia associated with non-alcoholic steatohepatitis (NASH). Scand J Gastroenterol 2006; 41: 631
  • Liberopoulos EN, Athyros VG, Mikhailidis DP, Elisaf MS. Statins for non-alcoholic fatty liver disease: a new indication?. Aliment Pharmacol Ther 2006; 24: 698–9
  • Yamagishi S, Nakamura K, Matsui T, Sato T, Takeuchi M. Inhibition of intestinal cholesterol absorption by ezetimibe is a novel therapeutic target for fatty liver. Med Hypotheses 2006; 66: 844–6
  • Yamagishi S, Nakamura K, Inoue H. Acarbose is a promising therapeutic strategy for the treatment of patients with nonalcoholic steatohepatitis (NASH). Med Hypotheses 2005; 65: 377–9
  • Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H. Gamma-glutamyl transferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation 2005; 112: 2130–7
  • Meisinger, C, Löwel, H, Heier, M, Schneider, A, Thorand, B, for the KORA study group. Serum γ-glutamyltransferase and risk of type 2 diabetes in men and women from the general population. J Intern Med 2005;258:527–35.
  • Hamagushi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, et al. The metabolic syndrome as a predictor of non-alcoholic fatty liver disease. Ann Intern Med 2005; 143: 722–8
  • Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with non alcoholic steatohepatitis. Hepatology 1999; 30: 1356–62
  • Clark JM, Brancati FI. Negative trials in nonalcoholic steatohepatitis. Why they happen and what they teach us. Hepatology 2004; 39: 602–3
  • Comar KM, Sterling RK. Review article: drug therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2006; 23: 207–15
  • Adams LA, Angulo P. Treatment of non-alcoholic fatty liver disease. Postgrad Med J 2006; 82: 315–22
  • Brea A, Mosquera D, Martin E, Arizti A, Cordero JL, Ros E. Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study. Arterioscler Thromb Vasc Biol 2005; 25: 1045–50
  • Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005; 54: 3541–6

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