Treatment of Nonalcoholic Fatty Liver Disease With Probiotics and Prebiotics

Summary

The investigators' aim is to determine whether probiotic and prebiotic treatment plus lifestyle advice is more effective in reducing hepatic fat content than lifestyle advice alone in patients with Nonalcoholic Fatty Liver Disease (NAFLD).

Timeline

Start

2009-02

Primary completion

2012-01

Completion

2012-01

Publications

• Background Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006 Feb;43(2 Suppl 1):S99-S112. doi: 10.1002/hep.20973.
• Background Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002 Jul;123(1):134-40. doi: 10.1053/gast.2002.34168.
• Background Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004 Oct;40(4):820-6. doi: 10.1002/hep.20410.
• Background Hui AY, Wong VW, Chan HL, Liew CT, Chan JL, Chan FK, Sung JJ. Histological progression of non-alcoholic fatty liver disease in Chinese patients. Aliment Pharmacol Ther. 2005 Feb 15;21(4):407-13. doi: 10.1111/j.1365-2036.2005.02334.x.
• Background Villanova N, Moscatiello S, Ramilli S, Bugianesi E, Magalotti D, Vanni E, Zoli M, Marchesini G. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005 Aug;42(2):473-80. doi: 10.1002/hep.20781.
• Background Wong VW, Hui AY, Tsang SW, Chan JL, Tse AM, Chan KF, So WY, Cheng AY, Ng WF, Wong GL, Sung JJ, Chan HL. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006 Sep;4(9):1154-61. doi: 10.1016/j.cgh.2006.06.011. Epub 2006 Aug 14.
• Background Targher G, Bertolini L, Rodella S, Tessari R, Zenari L, Lippi G, Arcaro G. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care. 2007 Aug;30(8):2119-21. doi: 10.2337/dc07-0349. Epub 2007 May 22. No abstract available.
• Background Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006 Nov 30;355(22):2297-307. doi: 10.1056/NEJMoa060326.
• Background Lutchman G, Modi A, Kleiner DE, Promrat K, Heller T, Ghany M, Borg B, Loomba R, Liang TJ, Premkumar A, Hoofnagle JH. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology. 2007 Aug;46(2):424-9. doi: 10.1002/hep.21661.
• Background Balas B, Belfort R, Harrison SA, Darland C, Finch J, Schenker S, Gastaldelli A, Cusi K. Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis. J Hepatol. 2007 Oct;47(4):565-70. doi: 10.1016/j.jhep.2007.04.013. Epub 2007 May 24.
• Background Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003 May 22;348(21):2074-81. doi: 10.1056/NEJMoa022637.
• Background Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3. doi: 10.1038/4441022a.
• Background Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23. doi: 10.1073/pnas.0407076101. Epub 2004 Oct 25.
• Background Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5. doi: 10.1073/pnas.0504978102. Epub 2005 Jul 20.
• Background Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31. doi: 10.1038/nature05414.
• Background Lichtman SN, Sartor RB, Keku J, Schwab JH. Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology. 1990 Feb;98(2):414-23. doi: 10.1016/0016-5085(90)90833-m.
• Background Bigorgne AE, Bouchet-Delbos L, Naveau S, Dagher I, Prevot S, Durand-Gasselin I, Couderc J, Valet P, Emilie D, Perlemuter G. Obesity-induced lymphocyte hyperresponsiveness to chemokines: a new mechanism of Fatty liver inflammation in obese mice. Gastroenterology. 2008 May;134(5):1459-69. doi: 10.1053/j.gastro.2008.02.055. Epub 2008 Mar 4.
• Background Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002 Jul 2;137(1):1-10. doi: 10.7326/0003-4819-137-1-200207020-00006.
• Background Canani RB, Cirillo P, Terrin G, Cesarano L, Spagnuolo MI, De Vincenzo A, Albano F, Passariello A, De Marco G, Manguso F, Guarino A. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ. 2007 Aug 18;335(7615):340. doi: 10.1136/bmj.39272.581736.55. Epub 2007 Aug 9.
• Background Hickson M, D'Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C, Bulpitt CJ. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ. 2007 Jul 14;335(7610):80. doi: 10.1136/bmj.39231.599815.55. Epub 2007 Jun 29.
• Background Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389-402. doi: 10.1093/nar/25.17.3389.
• Background Cole JR, Chai B, Farris RJ, Wang Q, Kulam SA, McGarrell DM, Garrity GM, Tiedje JM. The Ribosomal Database Project (RDP-II): sequences and tools for high-throughput rRNA analysis. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D294-6. doi: 10.1093/nar/gki038.
• Background Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005 Jun 10;308(5728):1635-8. doi: 10.1126/science.1110591. Epub 2005 Apr 14.
• Wong VW, Won GL, Chim AM, Chu WC, Yeung DK, Li KC, Chan HL. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann Hepatol. 2013 Mar-Apr;12(2):256-62.

Drugs

Indications