Gastroenterology
Volume 136, Issue 7 , Pages 2159-2168 , June 2009

Efficacy of L-Ornithine L-Aspartate in Acute Liver Failure: A Double-Blind, Randomized, Placebo-Controlled Study

  • Subrat Kumar Acharya

      Affiliations

    • Department of Gastroenterology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
    • Corresponding Author InformationReprint requests Address requests for reprints to: Subrat Kumar Acharya, Professor and Head, Department of Gastroenterology, Room 3105, 3rd floor, Teaching block, All India Institute of Medical Sciences, New Delhi 110029, India
    • ,
  • Vikram Bhatia

      Affiliations

    • Department of Gastroenterology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
    • ,
  • Vishnubhatla Sreenivas

      Affiliations

    • Department of Biostatistics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
    • ,
  • Shankar Khanal

      Affiliations

    • Department of Biostatistics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
    • ,
  • Subrat Kumar Panda

      Affiliations

    • Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Received 30 October 2008 ,Accepted 10 February 2009.

References 

  1. Strauss GI, Knudsen GM, Kondrup J, et al. Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure. Gastroenterology. 2001;121:1109–1119
  2. Chatauret N, Butterworth R. Effects of liver failure on inter-organ trafficking of ammonia: implications for the treatment of hepatic encephalopathy. J Gastroenterol Hepatol. 2004;19:S219–S223
  3. Jones EA. Ammonia, the GABA neurotransmitter system, and hepatic encephalopathy. Metab Brain Dis. 2002;17:275–281
  4. Clemmesen JO, Larsen FS, Kondrup J, et al. Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology. 1999;29:648–653
  5. Kundra A, Jain A, Banga A, et al. Evaluation of plasma ammonia levels in patients with acute liver failure and chronic liver disease and its correlation with the severity of hepatic encephalopathy and clinical features of raised intracranial tension. Clin Biochem. 2005;38:696–699
  6. Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut. 2006;55:98–104
  7. Bernal W, Hall C, Karvellas CJ, et al. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology. 2007;46:1844–1852
  8. Zieve L, Lyftogt C, Raphael D. Ammonia toxicity: comparative protective effect of various arginine and ornithine derivatives, aspartate, benzoate and carbamyl glutamate. Metab Brain Dis. 1986;1:25–35
  9. Albrecht J, Hilgier W, Januszewski S, et al. Increase of the brain uptake index for L-ornithine in rats with hepatic encephalopathy. Neuroreport. 1994;5:671–673
  10. Rose C, Michalak A, Pannunzio P, et al. L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action. Metab Brain Dis. 1998;13:147–157
  11. Kircheis G, Wettstein M, Dahl S, et al. Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy. Metab Brain Dis. 2002;17:453–462
  12. Rose C, Michalak A, Rao KV, et al. L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology. 1999;30:636–640
  13. Tandon BN, Bernauau J, Grady J, et al. Recommendations of the International Association for the Study of the Liver Subcommittee on nomenclature of acute and sub acute liver failure. J Gastroenterol Hepatol. 1999;14:403–404
  14. Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001;134:663–694
  15. Acharya SK, Dasarathy S, Kumer TL, et al. Fulminant hepatitis in a tropical population: clinical course, cause and early predictors of outcome. Hepatology. 1996;23:1448–1455
  16. Jameel S, Durgapal H, Habibullah CM, et al. Enteric non-A, non-B hepatitis: epidemics, animal transmission, and hepatitis E virus detection by the polymerase chain reaction. J Med Virol. 1992;37:263–270
  17. Riegler JL, Lake JR. Fulminant hepatic failure. Med Clin North Am. 1993;77:1057–1083
  18. Staedt U, Leweling H, Gladisch R, et al. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis (A double-blind, randomized study using a four-fold crossover design). J Hepatol. 1993;19:424–430
  19. Kircheis G, Nilius R, Held C, et al. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology. 1997;25:1351–1360
  20. Stauch S, Kircheis G, Adler G, et al. Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study. J Hepatol. 1998;28:856–864
  21. Poo JL, Góngora 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;5:281–288
  22. Clemmesen JO, Kondrup J, Ott P. Splanchnic and leg exchange of amino acids and ammonia in acute liver failure. Gastroenterology. 2000;118:1131–1139
  23. Rosen HM, Yoshimura N, Hodgman JM, et al. Plasma amino acid patterns in hepatic encephalopathy of differing etiology. Gastroenterology. 1977;72:483–487
  24. Clemmesen JO, Kondrup J, Nielsen LB, et al. Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure. Am J Gastroenterol. 2001;96:1217–1223
  25. Rees CJ, Oppong K, Al Mardini H, et al. Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial. Gut. 2000;47:571–574
  26. Alba L, Hay JE, Angulo P, et al. Lactulose therapy in acute liver failure. J Hepatol. 2002;36:33A
  27. Polson J, Lee WM. AASLD position paper: the management of acute liver failure. Hepatology. 2005;41:1179–1197
  28. Sushma S, Dasarathy S, Tandon RK, et al. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. 1992;16:138–144
  29. Efrati C, Masini A, Merli M, et al. Effect of sodium benzoate on blood ammonia response to oral glutamine challenge in cirrhotic patients: a note of caution. Am J Gastroenterol. 2000;95:3574–3578
  30. Palekar AG, Canas JA, Kalbag SS, et al. Failure of sodium benzoate to alleviate plasma and liver ammonia in rats. Biochem Med Metab Biol. 1989;41:64–69

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by the Indian Council of Medical Research (ICMR), New Delhi, India, through the project: ‘Advanced Center for Liver Diseases,' sanctioned by the Department of Gastroenterology, AIIMS, New Delhi.

PII: S0016-5085(09)00294-7

doi: 10.1053/j.gastro.2009.02.050

Gastroenterology
Volume 136, Issue 7 , Pages 2159-2168 , June 2009

Article Tools

* Image Usage & Resolution