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Probiotics in management of hepatic encephalopathy

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Abstract

Gut microflora leads to production of ammonia and endotoxins which play important role in the pathogenesis of hepatic encephalopathy (HE). There is relationship between HE and absorption of nitrogenous substances from the intestines. Probiotics play a role in treatment of HE by causing alterations in gut flora by decreasing the counts of pathogen bacteria, intestinal mucosal acidification, decrease in production and absorption of ammonia, alterations in permeability of gut, decreased endotoxin levels and changes in production of short chain fatty acids. Role of gut microbiota using prebiotics, probiotics and synbiotics have been evaluated in the management of minimal hepatic encephalopathy (MHE), overt HE and prevention of HE. Many studies have shown efficacy of probiotics in reduction of blood ammonia levels, treatment of MHE and prevention of HE. However these trials have problems like inclusion of small number of patients, short treatment durations, variability in HE/MHE related outcomes utilized and high bias risk, errors of systematic and random types. Systematic reviews also have shown different results with one systematic review showing clinical benefits whereas another concluded that probiotics do not have any role in treatment of MHE or HE. Also practical questions on optimal dose, ideal combination of organisms, and duration of treatment and persistence of benefits on long term follow-up are still to be clarified. At present, there are no recommendations for use of probiotics in patients with HE.

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References

  • Agrawal A, Sharma BC, Sharma P, Sarin SK (2012) Secondary prophylaxis of hepatic encephalopathy in cirrhosis: an open-label randomized controlled trial of lactulose, probiotics and no therapy. Am J Gastroenterol 107:1043–1050

    Article  CAS  PubMed  Google Scholar 

  • Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, Uribe M, Vilstrup H, Morgan MY (2013) The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Heoatology 58:325–336

    CAS  Google Scholar 

  • Bajaj JS (2014) The role of microbiota in hepatic encephalopathy. Gut Microbes 5:1–7

    Article  Google Scholar 

  • Bajaj JS, Saeian K, Christensen KM, Hafeezullah M, Varma RR, Franco J, Pleuss JA, Krakower G, Hoffmann RG, Binion DG (2008) Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol 103:1707–1715

    Article  PubMed  Google Scholar 

  • Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM (2012) Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J PhysiolGastrointest Liver Physiol 302:G168–G175

    Article  CAS  Google Scholar 

  • Bauer TM, Schwacha H, Steinbrückner B, Brinkmann FE, Ditzen AK, Aponte JJ, Pelz K, Berger D, Kist M, Blum HE (2001) Small intestinal bacterial overgrowth in human cirrhosis is associated with systemic endotoxemia. Am J Gastroenterol 96:2962–2967

    Article  CAS  PubMed  Google Scholar 

  • Bauer TM, Schwacha H, Steinbrückner B, Brinkmann FE, Ditzen AK, Aponte JJ, Pelz K, Berger D, Kist M, Blum HE (2002) Small intestinal bacterial overgrowth in human cirrhosis is associated with systemic endotoxemia. Am J Gastroenterol 97:2364–2370

    Article  PubMed  Google Scholar 

  • Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, Wang Y, Zhu B, Li L (2011) Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54:562–572

    Article  PubMed  Google Scholar 

  • Chiva M, Soriano G, Rochat I, Peralta C, Rochat F, Llovet T, Mirelis B, Schiffrin EJ, Guarner C, Balanzó J (2002) Effect of lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis. J Hepatol 37:456–462

    Article  CAS  PubMed  Google Scholar 

  • Dhiman RK (2013) Gut microbiota and hepatic encephalopathy. Metab Brain Dis 28:321–326

    Article  CAS  PubMed  Google Scholar 

  • Dhiman RK, Rana B, Agrawal S, Garg A, Chopra M, Thumburu KK, Khattri A, Malhotra S, Duseja A, Chawla YK (2014) Probiotics VSL #3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized controlled trial. Gastroenterology 147:1327–1337

    Article  CAS  PubMed  Google Scholar 

  • Ding X, Zhang F, Wang Y (2014) Probiotics vs. lactulose for minimal hepatic encephalopathy therapy. Aliment Pharmacol Ther 39:1000–1001

    Article  CAS  PubMed  Google Scholar 

  • Gupta A, Dhiman RK, Kumari S, Rana S, Agarwal R, Duseja A, Chawla Y (2010) Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol 53:849–855

    Article  PubMed  Google Scholar 

  • Holte K, Krag A, Gluud LL (2012) Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy. Hepatol Res 42:1008–1015

    Article  PubMed  Google Scholar 

  • Jia L, Zhang MH (2005) Comparison of probiotics and lactulose in the treatment of minimal hepatic encephalopathy in rats. World J Gastroenterol 11:908–911

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM (2004) Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 39:1441–1449

    Article  PubMed  Google Scholar 

  • Loguercio C, Del Vecchio BC, Coltorti M (1987) Enterococcus lactic acid bacteria strain SF68 and lactulose in hepatic encephalopathy: a controlled study. J Int Med Res 15:335–343

    CAS  PubMed  Google Scholar 

  • Loguercio C, Abbiati R, Rinaldi M, Romano A, Del Vecchio BC, Coltorti M (1995) Long-term effects of enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy. J Hepatol 23:39–46

    Article  CAS  PubMed  Google Scholar 

  • Lunia MK, Sharma BC, Sachdeva S (2013) Small intestinal bacterial overgrowth and delayed orocecal transit time in patients with cirrhosis and low-grade hepatic encephalopathy. Hepatol Int 7:268–273

    Article  PubMed  Google Scholar 

  • Lunia MK, Sharma BC, Sharma P, Sachdeva S, Srivastava S (2014) Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial. Clin Gastroenterol Hepatol 12:1003–1008

    Article  PubMed  Google Scholar 

  • Malaguarnera M, Greco F, Barone G, Gargante MP, Toscano MA (2007) Bifidobacte-riumlongumwithfructo-oligosaccharide (FOS) treatment in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Dig Dis Sci 52:3259–3265

    Article  PubMed  Google Scholar 

  • Malaguarnera M, Gargante MP, Malaguarnera G, Salmeri M, Mastrojeni S, Rampello L, Pennisi G, Li Volti G, Galvano F (2010) Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. Eur J Gastroenterol Hepatol 22:199–206

    Article  PubMed  Google Scholar 

  • McGee RG, Bakens A, Wiley K, Riordan SM, Webster AC (2011) Probiotics for patients with hepatic encephalopathy. Cochrane Database Syst Rev 9(11):CD008716

    Google Scholar 

  • Mittal VV, Sharma BC, Sharma P, Sarin SK (2011) A randomized controlled trial comparing lactulose, probiotics, and L-ornithine L-aspartate in treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol 23:725–732

    Article  CAS  PubMed  Google Scholar 

  • Mouli VP, Benjamin J, Singh MB, Mani K, Garg SK, Saraya A (2014) Effects of probiotic VSL#3 in the treatment of minimal hepatic encephalopathy: A non-inferiority randomized controlled trial. Hepatol Res. doi:10.11111/hepr12429

    Google Scholar 

  • Pereg D, Kotliroff A, Gadoth N, Hadary R, Lishner M, Kitay-Cohen Y (2011) Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study. Nutrition 27:177–181

    Article  CAS  PubMed  Google Scholar 

  • Saji S, Kumar S, Thomas V (2011) A randomized double blind placebo controlled trial of probiotics in minimal hepatic encephalopathy. Trop Gastroenterol 32:128–132

    PubMed  Google Scholar 

  • Sharma P, Sharma BC, Puri V, Sarin SK (2008) An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol 20:506–511

    Article  CAS  PubMed  Google Scholar 

  • Shukla S, Shukla A, Mehboob S, Guha S (2011) Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment PharmacolTher 33:662–671

    Article  CAS  Google Scholar 

  • Solga SF (2003) Probiotics can treat hepatic encephalopathy. Med Hypotheses 61:307–313

    Article  CAS  PubMed  Google Scholar 

  • Wiest R, Chen F, Cadelina G, Groszmann RJ, Garcia-Tsao G (2003) Effect of lactobacillus-fermented diets on bacterial translocation and intestinal flora in experimental prehepatic portal hypertension. Dig Dis Sci 48:1136–1141

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Ma R, Chen LF, ZhaoLJ CK, Zhang RB (2014) Effects of probiotic therapy on hepatic encephalopathy in patients with liver cirrhosis: an updated meta-analysis of six randomized controlled trials. Hepatobiliary Pancreat Dis Int 13:354–360

    Article  PubMed  Google Scholar 

  • Zhang Z, Zhai H, Geng J, Yu R, Ren H, Fan H, Shi P (2013) Large-scale survey of gut microbiota associated with MHE via 16S rRNA-based pyrosequencing. Am J Gastroenterol 108:1601–1611

    Article  CAS  PubMed  Google Scholar 

  • Ziada DH, Soliman HH, El Yamani SA, Hamisa MF, Hasan AM (2013) Can lactobacillus acidophilus improve minimal hepatic encephalopathy? A neurometabolite study using magnetic resonance spectroscopy. Arab Journal of Gastroenterology 14:116–122

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, Room No. 203, Academic Block, New Delhi, 110002, India

    Barjesh Chander Sharma & Jatinderpal Singh

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  1. Barjesh Chander Sharma
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  2. Jatinderpal Singh
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Correspondence to Barjesh Chander Sharma.

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Sharma, B.C., Singh, J. Probiotics in management of hepatic encephalopathy. Metab Brain Dis 31, 1295–1301 (2016). https://doi.org/10.1007/s11011-016-9826-x

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  • DOI: https://doi.org/10.1007/s11011-016-9826-x

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