What Is the Best Therapy for Acute Hepatic Encephalopathy?

Sodium benzoate might be beneficial in the treatment of acute HE; it increases urinary excretion of ammonia. A prospective, randomized, double-blind study of 74 patients with acute HE found that treatment with sodium benzoate 5 g twice daily, compared with lactulose, resulted in equivalent improvements in encephalopathy. There was no placebo group.11 Routine use has been limited due to concerns regarding sodium load and increased frequency of adverse gastrointestinal symptoms, particularly nausea.

Flumazenil, a short-acting benzodiazepine receptor antagonist, has been utilized on the basis of observed increases in benzodiazepine receptor activation among cirrhotic HE patients. In a systematic review of 12 controlled trials (765 patients), Als-Nielsen and colleagues found flumazenil to be associated with significant improvement.12 Flumazenil is not used routinely as an HE therapy because of significant side effects, namely seizures, nausea, vomiting, dizziness, and agitation.

Such therapies as L-carnitine, branched amino acids (BCAA), probiotics, bromocriptine, acarbose, and zinc are among the many experimental agents currently under evaluation. Few have been tested in clinical trials.

Back to the Case

Our patient has severe HE manifested by worsening somnolence. It is postulated that ongoing alcohol abuse led to medication nonadherence, precipitating his HE, but as HE has many causes, a complete workup for infection and metabolic derangement is performed. However, it is unrevealing.

The best initial action is the prescription of lactulose, the mainstay of HE therapy. Given concern for aspiration in patients with somnolence, a feeding tube is placed for administration. The lactulose dosage will be titrated to achieve two to three soft stools per day. If the patient remains symptomatic or develops significant side effects on lactulose, the addition of an antibiotic is recommended. Neomycin, a low-cost medicine approved by the FDA for HE treatment, is a good choice. The patient will be maintained on a normal protein diet.

Bottom Line

The first-line agents used to treat episodes of acute HE are the nonabsorbable disaccharides, lactulose or lactitol. TH

Dr. Shoeb is a resident in the Department of Medicine at the University of Washington in Seattle. Dr. Best is assistant professor of medicine in the Division of General Internal Medicine at the University of Washington.

References

1. Als-Nielsen B, Gluud L, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004;2:CD003044.
2. Morgan MY, Hawley KE. Lactitol v. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind, randomized trial. Hepatology. 1987; 7(6):1278-1284.
3. Blanc P, Daurès JP, Liautard J, et al. Lactulose-neomycin combination versus placebo in the treatment of acute hepatic encephalopathy. Results of a randomized controlled trial. Gastroenterol Clin Biol. 1994;18(12):1063-1068.
4. Mas A, Rodés J, Sunyer L, et al. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. 2003;38(1):51-58.
5. Paik YH, Lee KS, Han KH, et al. Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study. Yonsei Med J. 2005;46(3):399-407.
6. Massa P, Vallerino E, Dodero M. Treatment of hepatic encephalopathy with rifaximin: double blind, double dummy study versus lactulose. Eur J Clin Res. 1993;4:7-18.
7. Williams R, James OF, Warnes TW, Morgan MY. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol. 2000;12(2):203-208.
8. Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut. 1982;23(1):1-7.
9. Córdoba J, López-Hellín J, Planas M, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41(1):38-43.
10. Poo JL, Gongora J, Sánchez-Avila F, et al. Efficacy of oral L-ornithine-L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Results of a randomized, lactulose-controlled study. Ann Hepatol. 2006;5(4):281-288.
11. Sushma S, Dasarathy S, Tandon RK, Jain S, Gupta S, Bhist MS. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. 1992;16(16):138-144.
12. Als-Nielsen B, Kjaergard LL, Gluud C. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy. Cochrane Database Syst Rev. 2001;4:CD002798.