Treatment Options for Covert Hepatic Encephalopathy

  • Sahaj Rathi
  • Radha K. Dhiman


Hepatic encephalopathy, even in its mildest form, can lead to significant deterioration in quality of life, lower overall survival, and add to caregiver burden. However, due to a paucity of symptoms, covert hepatic encephalopathy (CHE) is often ignored or neglected by physicians as well as patients. The lack of consensus among experts for both diagnosis as well as treatment of CHE adds to this problem. Treatment options for CHE include lactulose, rifaximin, ammonia scavengers, branched-chain amino acids, and probiotics. In this chapter we review the existing evidence on these agents and explain treatment decisions using a case-based approach.


Covert hepatic encephalopathy Portosystemic shunt Psychometric hepatic encephalopathy score Minimal hepatic encephalopathy 



American Association for the Study of Liver Diseases


Branched-chain amino acids


Critical flicker frequency


Covert hepatic encephalopathy


European Association for the Study of the Liver


Hepatic encephalopathy


l-Ornithine l-aspartate


Model for end-stage liver disease


Mini-mental state examination


Overt hepatic encephalopathy


Psychometric hepatic encephalopathy score


Portosystemic shunt


Spontaneous bacterial peritonitis


  1. 1.
    Dhiman RK, Chawla YK. Minimal hepatic encephalopathy. Indian J Gastroenterol. 2009;28(1):5–16. Scholar
  2. 2.
    Dhiman RK, Kurmi R, Thumburu KK, et al. Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig Dis Sci. 2010;55(8):2381–90. Scholar
  3. 3.
    Ampuero J, Montoliú C, Simón-Talero M, et al. Minimal hepatic encephalopathy identifies patients at risk of faster cirrhosis progression. J Gastroenterol Hepatol. 2017.
  4. 4.
    Bajaj JS, Wade JB, Gibson DP, et al. The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol. 2011;106(9):1646–53. Scholar
  5. 5.
    Dhiman RK, Sawhney MS, Chawla YK, Das G, Ram S, Dilawari JB. Efficacy of lactulose in cirrhotic patients with subclinical hepatic encephalopathy. Dig Dis Sci. 2000;45(8):1549–52. Accessed 27 Oct 2017CrossRefPubMedGoogle Scholar
  6. 6.
    Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007;45(3):549–59. Scholar
  7. 7.
    Mittal VV, Sharma BC, Sharma P, Sarin SK. A randomized controlled trial comparing lactulose, probiotics, and L-ornithine L-aspartate in treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2011;23(8):725–32. Scholar
  8. 8.
    Bajaj JS, Pinkerton SD, Sanyal AJ, Heuman DM. Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor vehicle accidents: a cost-effectiveness analysis. Hepatology. 2012;55(4):1164–71. Scholar
  9. 9.
    Bajaj JS, Sanyal AJ, Bell D, Gilles H, Heuman DM. Predictors of the recurrence of hepatic encephalopathy in lactulose-treated patients. Aliment Pharmacol Ther. 2010;31(9):1012–7. Scholar
  10. 10.
    Sharma BC, Sharma P, Agrawal A, Sarin SK. Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo. Gastroenterology. 2009;137(3):885–91, 891.e1. Scholar
  11. 11.
    Rathi S, Fagan A, Wade J, et al. Lactulose acceptance varies between Indian and American covert HE patients: implications for comparing, designing and interpreting global HE trials. J Clin Exp Hepatol. 2017;7:S51–2. Scholar
  12. 12.
    Bajaj JS, Heuman DM, Sanyal AJ, et al. Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy. PLoS One. 2013;8(4):e60042. Scholar
  13. 13.
    Sidhu SS, Goyal O, Mishra BP, Sood A, Chhina RS, Soni RK. Rifaximin improves psychometric performance and health-related quality of life in patients with minimal hepatic encephalopathy (the RIME trial). Am J Gastroenterol. 2011;106(2):307–16. Scholar
  14. 14.
    Bajaj JS, Heuman DM, Wade JB, et al. Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology. 2011;140(2):478–487.e1. Scholar
  15. 15.
    Dhiman RK, Rana B, Agrawal S, et al. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology. 2014;147(6):1327–1337.e3. Scholar
  16. 16.
    Bajaj JS, Saeian K, Christensen KM, et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol. 2008;103(7):1707–15. Scholar
  17. 17.
    Dalal R, Mcgee RG, Riordan SM, Webster AC. Probiotics for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2017;(2).
  18. 18.
    Sharma K, Pant S, Misra S, et al. Effect of rifaximin, probiotics, and l-ornithine l-aspartate on minimal hepatic encephalopathy: a randomized controlled trial. Saudi J Gastroenterol. 2014;20(4):225. Scholar
  19. 19.
    Chadalavada R, Biyyani RSS, Maxwell J, Mullen K. Nutrition in hepatic encephalopathy. Nutr Clin Pract. 2010;25(3):257–64. Scholar
  20. 20.
    Vaisman N, Katzman H, Carmiel-Haggai M, Lusthaus M, Niv E. Breakfast improves cognitive function in cirrhotic patients with cognitive impairment. Am J Clin Nutr. 2010;92(1):137–40. Scholar
  21. 21.
    Maharshi S, Sharma BC, Sachdeva S, Srivastava S, Sharma P. Efficacy of nutritional therapy for patients with cirrhosis and minimal hepatic encephalopathy in a randomized trial. Clin Gastroenterol Hepatol. 2016;14(3):454–460.e3.; quiz e33. Scholar
  22. 22.
    Les I, Doval E, García-Martínez R, et al. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study. Am J Gastroenterol. 2011;106(6):1081–8. Scholar
  23. 23.
    Sharma P, Sharma BC, Puri V, Sarin SK. Natural history of minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction. Am J Gastroenterol. 2009;104(4):885–90. Scholar
  24. 24.
    Das K, Singh P, Chawla Y, Duseja A, Dhiman RK, Suri S. Magnetic resonance imaging of brain in patients with cirrhotic and non-cirrhotic portal hypertension. Dig Dis Sci. 2008;53(10):2793–8. Scholar
  25. 25.
    Kao D, Roach B, Park H, et al. Fecal microbiota transplantation in the management of hepatic encephalopathy. Hepatology. 2016;63(1):339–40. Scholar
  26. 26.
    Bajaj JS, Kassam Z, Fagan A, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology. 2017.
  27. 27.
    Thumburu KK, Dhiman RK, Chopra M, et al. Comparative effectiveness of different pharmacological interventions for the treatment of minimal hepatic encephalopathy: a systematic review with network meta-analysis. J Clin Exp Hepatol. 2017;7:S6–7. Scholar
  28. 28.
    Goyal O, Sidhu S, Kishore H. Minimal hepatic encephalopathy in cirrhosis—how long to treat? Ann Hepatol. 2017;16(1):115–22. Scholar
  29. 29.
    Rathi S, Dhiman RK. Managing encephalopathy in the outpatient setting. Clin Liver Dis. 2016;8(6):150–5. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Sahaj Rathi
    • 1
  • Radha K. Dhiman
    • 1
  1. 1.Department of HepatologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia

Personalised recommendations