Digestive Diseases and Sciences

, Volume 53, Issue 9, pp 2330–2333 | Cite as

Is Oral l-Acyl-Carnitine an Effective Therapy for Hepatic Encephalopathy? Review of the Literature

  • Nathan J. Shores
  • Emmet B. Keeffe
Review Paper


Hepatic encephalopathy (HE) is a significant cause of morbidity and mortality in patients with advanced chronic liver disease. Current therapies are associated with inconvenient side-effects, high cost, and incomplete efficacy. The quanternary ammonium compound l-acyl-carnitine has been suggested as a potent, low-cost, and safe alternative therapy for patients with cirrhosis and HE. A systematic review of the literature assessing the use of carnitine in the treatment of HE identified three high-quality human trials for review. Analysis of the selected carnitine trials compared to currently accepted therapies suggests that l-acyl-carnitine is promising as a safe and effective treatment for HE, and further trials of this drug are warranted.


Carnitine Hepatic encephalopathy Cirrhosis Portal hypertension 



Thanks are due to Drs. John Baillie, MB, ChB, FRCP and Girish Mishra, MD, MS for their assistance in reviewing this article before submission.


  1. 1.
    Mas A (2006) Hepatic encephalopathy: from pathophysiology to treatment. Digestion 73(Suppl 1):86–93PubMedCrossRefGoogle Scholar
  2. 2.
    Blei AT, Cordoba J (2001) Hepatic encephalopathy. Am J Gastroenterol 96:1968–1976PubMedCrossRefGoogle Scholar
  3. 3.
    Brown JK, Imam H (1991) Interrelationships of liver and brain with special reference to Reye syndrome. J Inherit Metab Dis 14:436–458PubMedCrossRefGoogle Scholar
  4. 4.
    Kilpatrick-Smith L, Hale DE, Douglas SD (1989) Progress in Reye syndrome: epidemiology, biochemical mechanisms and animal models. Dig Dis 7:135–146PubMedCrossRefGoogle Scholar
  5. 5.
    Qureshi K, Rao KV, Qureshi IA (1998) Differential inhibition by hyperammonemia of the electron transport chain enzymes in synaptosomes and non-synaptic mitochondria in ornithine transcarbamylase-deficient spf-mice: restoration by acetyl-l-carnitine. Neurochem Res 23:855–861PubMedCrossRefGoogle Scholar
  6. 6.
    Virmani A, Binienda Z (2004) Role of carnitine esters in brain neuropathology. Mol Aspects Med 25:533–549PubMedCrossRefGoogle Scholar
  7. 7.
    Russell S (2007) Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr 19:206–210PubMedCrossRefGoogle Scholar
  8. 8.
    Therrien G, Rose C, Butterworth J, Butterworth RF (1997) Protective effect of l-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat. Hepatology 25:551–556PubMedCrossRefGoogle Scholar
  9. 9.
    Hearn TJ, Coleman AE, Lai JC, Griffith OW, Cooper AJ (1989) Effect of orally administered l-carnitine on blood ammonia and l-carnitine concentrations in portacaval-shunted rats. Hepatology 10:822–828PubMedCrossRefGoogle Scholar
  10. 10.
    del Olmo JA, Castillo M, Rodrigo JM, Aparisi L, Serra MA, Wassel A, Bixquert M (1990) Effect of l-carnitine upon ammonia tolerance test in cirrhotic patients. Adv Exp Med Biol 272:197–208PubMedGoogle Scholar
  11. 11.
    Cecere A, Ciaramella F, Tancredi L, Romano C, Gattoni A (2002) Efficacy of l-carnitine in reducing hyperammonaemia and improving neuropsychological test performance in patients with hepatic cirrhosis. Clin Drug Investig 22:7–14CrossRefGoogle Scholar
  12. 12.
    Malaguarnera M, Pistone G, Astuto M, Dell’Arte S, Finocchiaro G, Lo Giudice E, Pennisi G (2003) l-Carnitine in the treatment of mild or moderate hepatic encephalopathy. Dig Dis 21:271–275PubMedCrossRefGoogle Scholar
  13. 13.
    Malaguarnera M, Pistone G, Astuto M, Vecchio I, Raffaele R, Lo Giudice E, Rampello L (2006) Effects of l-acetylcarnitine on cirrhotic patients with hepatic coma: randomized double-blind, placebo-controlled trial. Dig Dis Sci 51:2242–2247PubMedCrossRefGoogle Scholar
  14. 14.
    Malaguarnera M, Pistone G, Elvira R, Leotta C, Scarpello L, Liborio R (2005) Effects of l-carnitine in patients with hepatic encephalopathy. World J Gastroenterol 11:7197–7202PubMedGoogle Scholar
  15. 15.
    Siciliano M, Annicchiarico BE, Lucchese F, Bombardieri G (2006) Effects of a single, short intravenous dose of acetyl-l-carnitine on pattern-reversal visual-evoked potentials in cirrhotic patients with hepatic encephalopathy. Clin Exp Pharmacol Physiol 33:76–80PubMedCrossRefGoogle Scholar
  16. 16.
    Tempesta E, Troncon R, Janiri L, Colusso L, Riscica P, Saraceni G, Gesmundo E et al (1990) Role of acetyl-l-carnitine in the treatment of cognitive deficit in chronic alcoholism. Int J Clin Pharmacol Res 10:101–107PubMedGoogle Scholar
  17. 17.
    Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12PubMedCrossRefGoogle Scholar
  18. 18.
    Conn HO (1977) Trailmaking and number-connection tests in the assessment of mental state in portal systemic encephalopathy. Am J Dig Dis 22:541–550PubMedCrossRefGoogle Scholar
  19. 19.
    Conn HO, Leevy CM, Vlahcevic ZR, Rodgers JB, Maddrey WC, Seeff L, Levy LL (1977) Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology 72:573–583PubMedGoogle Scholar
  20. 20.
    Mas A, Rodes J, Sunyer L, Rodrigo L, Planas R, Vargas V, Castells L et al (2003) 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 38:51–58PubMedCrossRefGoogle Scholar
  21. 21.
    Paik YH, Lee KS, Han KH, Song KH, Kim MH, Moon BS, Ahn SH et al (2005) Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study. Yonsei Med J 46:399–407PubMedCrossRefGoogle Scholar
  22. 22.
    Kharbanda PS, Saraswat VA, Dhiman RK (2003) Minimal hepatic encephalopathy: diagnosis by neuropsychological and neurophysiologic methods. Indian J Gastroenterol 22(Suppl 2):S37–S41PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Division of Gastroenterology, Department of MedicineWake Forest University Health SystemWinston-SalemUSA
  2. 2.Department of Internal Medicine, Section on Gastroenterology, Medical Center BoulevardWake Forest University Baptist Medical CenterWinston-SalemUSA
  3. 3.Division of Gastroenterology and Hepatology, Department of MedicineStanford University School of MedicineStanfordUSA

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