Effect of a Probiotic and Metformin on Liver Aminotransferases in Non-alcoholic Steatohepatitis: A Double Blind Randomized Clinical Trial

Ahmad Shavakhi, Mohammad Minakari, Hassan Firouzian, Raheleh Assali, Azita Hekmatdoost, Gordon Ferns, Ahmad Shavakhi, Mohammad Minakari, Hassan Firouzian, Raheleh Assali, Azita Hekmatdoost, Gordon Ferns

Abstract

Background: Non-alcoholic steatohepatitis (NASH) is a clinicopathological entity that is being recognized more frequently in recent years. This study aimed to evaluate the effects of Metformin, with and without a probiotic supplement on liver aminotransferases in patients with NASH.

Methods: Sixty four patients 18-75 years with NASH confirmed by biopsy and histological assessment were enrolled to study. Patients were randomized to one of the following treatments for 6 months: Group I, probiotic (Protexin two tablets per day) plus Metformin 500 mg two tablets per day (Met/Pro), or group II, Metformin 500 mg two tablets per day plus two placebo tablet (Met/P). After 6 month alanine aminotransferase (ALT), aspartate aminotransferase, and ultrasound grading of NASH were assessed.

Results: IN GROUP I, SERUM ALANINE AMINOTRANSFERASE (ALT: 133.7 ± 70 vs. 45.2 ± 32.5; P < 0.00), and aspartate aminotransferase activity (AST: 123.1 ± 72 vs. 44.2 ± 33.9; P < 0.001), and ultrasound grading of NASH (P < 0.001) all decreased significantly by the end of the treatment period. In group II, while serum alanine aminotransferase (ALT) was not significantly reduced (118.4 ± 67.9 vs. 112.5 ± 68.7; P < 0.064), aspartate aminotransferase activity (AST: 125.3 ± 71 vs. 113.4 ± 71; P < 0.001), and ultrasound grading of NASH did fall significantly (P < 0.01). Body mass index (BMI), fasting blood sugar (FBS), cholesterol, and triglyceride fell significantly in both groups.

Conclusions: Probiotic combination with Metformin improves liver aminotransferases better than metformin alone in patients with NASH.

Keywords: Aminotransferase; insulin resistance; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; probiotic; randomized clinical trial.

Conflict of interest statement

Conflict of Interest: None declared

Figures

Figure 1
Figure 1
Participation flow chart
Figure 2
Figure 2
Ultrasound grade steatosis before intervention (M0). None of patients had normal grade ultrasound
Figure 3
Figure 3
Ultrasound grade steatosis after six month treatment.38.7% patients had normal grade ultrasound in metformin/probiotic group and 61.3% patients had grade 1 and none of patient had grade 2, 3. Wilcoxon signed ranks test showed significant decrease in ultrasound grade steatosis (P = 0.01) in groups

References

    1. Medina J, Fern’andez-Salazar JI, Garc′ia-Buey L, Moreno-Oteror Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care. 2004;27:2057–66.
    1. Ruhl CE, Everhart JE. Epidemiology of nonalcoholic fatty liver. Clin Liver Dis. 2004;8:501–19.
    1. Preiss D, Sattar N. Non-alcoholic fatty liver disease: An overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci. 2008;115:141–50.
    1. Neuschwander-Tetri B, Caldwell S. Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference. Hepatology. 2003;37:1202–19.
    1. Torres DM, Harrison SA. Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology. 2008;134:1682–98.
    1. Heidari K, Sajjadi SA, Hadian R, Hadi S, Hosseinkhani R, Amini S, et al. Establishment of health clinics as mass screening and referral systems for chronic non-communicable diseases in primary health care. Int J Prev Med. 2012;3:173–80.
    1. Guarner F, Khan AG, Garisch J, Eliakim R, Gangl A, Thomson A, et al. World gastroenterology organisation global guidelines: Probiotics and prebiotics October 2011. J Clin Gastroenterol. 2012;46:468–81.
    1. Lata J, Jurankova J, Kopacova M, Vitek P. Probiotics in hepatology. World J Gastroenterol. 2011;17:2890–6.
    1. Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor á in the pathogenesis of non-alcoholic steatohepatitis. Gut. 2001;48:206–11.
    1. Abu-Shanab A, Quigley EM. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7:691–701.
    1. Shanab AA, Scully P, Crosbie O, Buckley M, O’Mahony L, Shanahan F, et al. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: Association with toll-like receptor 4 expression and plasma levels of interleukin 8. Dig Dis Sci. 2011;56:1524–34.
    1. Gratz SW, Mykkanen H, El-Nezami HS. Probiotics and gut health: A special focus on liver diseases. World J Gastroenterol. 2010;16:403–10.
    1. Karahan N, Işler M, Koyu A, Karahan AG, Başyığıt Kiliç G, Cırış IM, et al. Effects of probiotics on methionine cholinedeficient diet-induced steatohepatitis in rats. Turk J Gastroenterol. 2012;23:110–21.
    1. Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, et al. Probiotics and Antibodies to TNF Inhibit Inflammatory Activity and Improve Nonalcoholic Fatty Liver Disease. Hepatology. 2003;37:343–50.
    1. Loguercio C, Federico A, Tuccillo C, Terracciano F, D’Auria MV, De Simone C, et al. Beneficial effects of a probiotic VS. L#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol. 2005;39:540–3.
    1. Aller R, De Luis DA, Izaola O, Conde R, Gonzalez Sagrado M, Primo D, et al. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: A double blind randomized clinical trial. Eur Rev Med Pharmacol Sci. 2011;15:1090–5.
    1. Wong VW, Wong GL, Tse CH, Chan HL. The International Liver Congress 2011. Berlin, Germany: 2011. Mar 30, Treatment of nonalcoholic steatohepatitis with probiotics-A proof-of-concept study with serial gut microbiota analysis by ultra-deep sequencing.
    1. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: The TONIC randomized controlled trial. JAMA. 2011;305:1659–68.
    1. Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, 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.
    1. Haukeland JW, Konopski Z, Eggesbø HB, von Volkmann HL, Raschpichler G, Bjøro K, et al. Metformin in patients with non-alcoholic fatty liver disease: A randomized, controlled trial. Scand J Gastroenterol. 2009;44:853–60.
    1. Aithal GP, Thomas JA, Kaye PV, Lawson A, Ryder SD, Spendlove I, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic Steatohepatitis. Gastroenterology. 2008;135:1176–84.
    1. Rogha M, Najafi N, Azari A, Kaji M, Pourmoghad Z, Rezaee M. Non-alcoholic Steatohepatitis in a sample of Iranian adult population: Age is a Risk Factor. Int J Prev Med. 2011;2:24–7.

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