Advertisement

Treatment of Hepatic Encephalopathy

  • Kosuke KajiEmail author
  • Norihisa Nishimura
  • Kei Moriya
  • Hitoshi Yoshiji
Chapter

Abstract

Hepatic encephalopathy (HE) is predominantly induced by a portosystemic shunt as a complication of excessive portal hypertension. Initial treatments for HE involve the identification and improvement of the causal triggers, such as infection, constipation, dehydration, and gastrointestinal bleeding. A majority of the pharmacotherapies are aimed at decreasing the production of ammonia. Lactulose alters gastrointestinal pH by favoring lactobacilli over urease-containing bacteria and enhances the production of nonabsorbable ammonia. Furthermore, these laxatives enhance fecal nitrogen excretion. Although neomycin was the first antibiotic to be effective in the treatment of HE, its use has been limited because of ototoxicity and nephrotoxicity. Recently, rifaximin, a minimally absorbable oral antibiotic, which is available in many countries, has been used in lactulose resistance encephalopathy. When used in conjunction with lactulose, rifaximin has been shown to reduce recurrent encephalopathy and hospitalization. Supplementation of branched-chain amino acids is also beneficial for patients with HE because of their stimulatory effect on ammonia detoxification to glutamine. Balloon-occluded retrograde transvenous obliteration is recommended for patients with refractory HE especially caused by portosystemic shunt. Liver transplantation is eventually performed in patients who are resistant to the abovementioned pharmacological and interventional therapies.

Keywords

Lactulose Rifaximin BCAAs B-RTO 

References

  1. 1.
    Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35(3):716–21.CrossRefGoogle Scholar
  2. 2.
    American Association for the Study of Liver D, European Association for the Study of the L. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014;61(3):642–59.CrossRefGoogle Scholar
  3. 3.
    Fukui H, Saito H, Ueno Y, Uto H, Obara K, Sakaida I, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51(7):629–50.CrossRefGoogle Scholar
  4. 4.
    Plauth M, Cabre E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, et al. ESPEN guidelines on enteral nutrition: liver disease. Clin Nutr. 2006;25(2):285–94.CrossRefGoogle Scholar
  5. 5.
    Okita M. Chronic hepatic disease and dietary instruction. Hepatol Res. 2004;30S:92–5.CrossRefGoogle Scholar
  6. 6.
    Patel VC, White H, Stoy S, Bajaj JS, Shawcross DL. Clinical science workshop: targeting the gut-liver-brain axis. Metab Brain Dis. 2016;31(6):1327–37.CrossRefGoogle Scholar
  7. 7.
    Weber FL Jr, Banwell JG, Fresard KM, Cummings JH. Nitrogen in fecal bacterial, fiber, and soluble fractions of patients with cirrhosis: effects of lactulose and lactulose plus neomycin. J Lab Clin Med. 1987;110(3):259–63.PubMedGoogle Scholar
  8. 8.
    van Leeuwen PA, van Berlo CL, Soeters PB. New mode of action for lactulose. Lancet. 1988;1(8575–6):55–6.CrossRefGoogle Scholar
  9. 9.
    Blanc P, Daures JP, Rouillon JM, Peray P, Pierrugues R, Larrey D, et al. Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: results of a meta-analysis. Hepatology. 1992;15(2):222–8.CrossRefGoogle Scholar
  10. 10.
    Gluud LL, Vilstrup H, Morgan MY. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2016;4:CD003044.PubMedGoogle Scholar
  11. 11.
    Strauss E, Tramote R, Silva EP, Caly WR, Honain NZ, Maffei RA, et al. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepato-gastroenterology. 1992;39(6):542–5.PubMedGoogle Scholar
  12. 12.
    Jiang ZD, DuPont HL. Rifaximin: in vitro and in vivo antibacterial activity—a review. Chemotherapy. 2005;51(Suppl 1):67–72.CrossRefGoogle Scholar
  13. 13.
    Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071–81.CrossRefGoogle Scholar
  14. 14.
    Bajaj JS, Heuman DM, Wade JB, Gibson DP, Saeian K, Wegelin JA, et al. Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology. 2011;140(2):478–87.e1.CrossRefGoogle Scholar
  15. 15.
    Eltawil KM, Laryea M, Peltekian K, Molinari M. Rifaximin vs. conventional oral therapy for hepatic encephalopathy: a meta-analysis. World J Gastroenterol. 2012;18(8):767–77.CrossRefGoogle Scholar
  16. 16.
    Sharma BC, Sharma P, Lunia MK, Srivastava S, Goyal R, Sarin SK. A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol. 2013;108(9):1458–63.CrossRefGoogle Scholar
  17. 17.
    Kimer N, Krag A, Moller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014;40(2):123–32.CrossRefGoogle Scholar
  18. 18.
    Dam G, Ott P, Aagaard NK, Vilstrup H. Branched-chain amino acids and muscle ammonia detoxification in cirrhosis. Metab Brain Dis. 2013;28(2):217–20.CrossRefGoogle Scholar
  19. 19.
    Gluud LL, Dam G, Les I, Cordoba J, Marchesini G, Borre M, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2015;2:CD001939.Google Scholar
  20. 20.
    Riggio O, Merli M, Capocaccia L, Caschera M, Zullo A, Pinto G, et al. Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis. Hepatology. 1992;16(3):785–9.CrossRefGoogle Scholar
  21. 21.
    Yoshida Y, Higashi T, Nouso K, Nakatsukasa H, Nakamura SI, Watanabe A, et al. Effects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis. Acta Med Okayama. 2001;55(6):349–55.PubMedGoogle Scholar
  22. 22.
    Krahenbuhl S, Reichen J. Carnitine metabolism in patients with chronic liver disease. Hepatology. 1997;25(1):148–53.PubMedGoogle Scholar
  23. 23.
    Shiraki M, Shimizu M, Moriwaki H, Okita K, Koike K. The carnitine dynamics and their effects on hyperammonemia in cirrhotic Japanese patients. Hepatol Res. 2017;47(4):321–7.CrossRefGoogle Scholar
  24. 24.
    Hassanein TI, Tofteng F, Brown RS Jr, McGuire B, Lynch P, Mehta R, et al. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology. 2007;46(6):1853–62.CrossRefGoogle Scholar
  25. 25.
    Kanagawa H, Mima S, Kouyama H, Gotoh K, Uchida T, Okuda K. Treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration. J Gastroenterol Hepatol. 1996;11(1):51–8.CrossRefGoogle Scholar
  26. 26.
    Kato T, Uematsu T, Nishigaki Y, Sugihara J, Tomita E, Moriwaki H. Therapeutic effect of balloon-occluded retrograde transvenous obliteration on portal-systemic encephalopathy in patients with liver cirrhosis. Intern Med. 2001;40(8):688–91.CrossRefGoogle Scholar
  27. 27.
    Ohmoto K, Miyake I, Tsuduki M, Ohno S, Yamamoto S. Control of solitary gastric fundal varices and portosystemic encephalopathy accompanying liver cirrhosis by balloon-occluded retrograde transvenous obliteration (B-RTO): a case report. Hepato-Gastroenterology. 1999;46(26):1249–52.PubMedGoogle Scholar
  28. 28.
    Uehara H, Akahoshi T, Tomikawa M, Kinjo N, Hashimoto N, Nagao Y, et al. Prediction of improved liver function after balloon-occluded retrograde transvenous obliteration: relation to hepatic vein pressure gradient. J Gastroenterol Hepatol. 2012;27(1):137–41.CrossRefGoogle Scholar
  29. 29.
    Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426–37, 37.e1–9.CrossRefGoogle Scholar
  30. 30.
    Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715–35.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Kosuke Kaji
    • 1
    Email author
  • Norihisa Nishimura
    • 1
  • Kei Moriya
    • 1
  • Hitoshi Yoshiji
    • 1
  1. 1.Division of Gastroenterology and Hepatology, Third Department of Internal MedicineNara Medical UniversityKashiharaJapan

Personalised recommendations