Efficacy of L-ornithine-L-aspartate in the Treatment of Hepatic Encephalopathy: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 HU Wei ¹ , TANG Shaohui ²

1. Hospital of Wuhan University, Wuhan, China, 430072;2. Jinan University Qverseas Hospital;

Corresponding author：

HU Wei, Email: wiwine@sina.com

Keywords：

L-ornithine-L-aspartate; Hepatic encephalopathy; Systematic review; Meta -analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20120122

Video：

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Objective 　To evaluate the efficacy and safety of L-ornithine-L-aspartate (LOLA) in the treatment of hepatic encephalopathy (HE).
Methods 　Such databases as PubMed, EMbase, Web of Science, CENTRAL, Chinese Journals Full-text Database, CBM and WanFang Data were searched from the date of their establishment to November 30, 2011 to collect the randomized controlled trials (RCTs) on LOLA in treating HE. The quality of included studies was evaluated by two reviewers independently, data were extracted and cross-checked, and then meta-analysis was performed using Review Manager 5.0 software.
Results 　Among the total six included RCTs, 432 patients were diagnosed as type-C HE and 185 were diagnosed as type-A HE. Compared with the placebo group, for the patients with type-C HE, LOLA could significantly reduce the serum ammonia level (WMD=16.60, 95%CI 8.34 to 24.85, P lt;0.000 1) and the time of number connection test-A (NCT-A) (WMD=9.6, 95%CI 5.26 to 13.93, P lt;0.00 01), and it could also effectively improve the clinical remission rate (RR=1.36, 95%CI 1.06 to 1.73, P=0.01). However, no significant differences were found between the two groups for the patients with type-A HE (P gt;0.05).
Conclusion 　LOLA is effective for the patients with type-C hepatic encephalopathy, and it could be regarded as a choice in clinic. However, more high-quality RCTs are needed to further evaluate the effect of LOLA in treating type-A hepatic encephalopathy.

Citation： HU Wei,TANG Shaohui. Efficacy of L-ornithine-L-aspartate in the Treatment of Hepatic Encephalopathy: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2012, 12(7): 799-803. doi: 10.7507/1672-2531.20120122 Copy

1.	Ferenci P, Lockwood A, Mullen K, et al. 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(65):716-721.
2.	Sibae MR, Mc Guire BM. Current trends in the treatment of hepatic encephalopathy. Ther Clin Risk Manag, 2009, 5(7):617-626.
3.	Toris GT, Bikis CN, Tsourouflis GS, et al. Hepatic encephalopathy: an updated approach from pathogenesis to treatment. Med Sci Monit, 2011, 17(2): 53-63.
4.	Jadad AR, Moore, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(23): 1-12.
5.	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(76): 1351-1360.
6.	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(6): 856 -864.
7.	Ahmad I, Khan AA, Alam A, et al. L-ornithine-L-aspartate infusion efficacy in hepatic encephalopathy. J Coll Physicians Surg Pak, 2008, 18(3): 684-687.
8.	Acharya SK, Bhatia V, Sreenivas V, et al. Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology, 2009, 136(37): 2159-2168.
9.	Schmid M, Peck-Radosavljevic M, König F, et al. A double-blind, randomized, placebo-controlled trial of intravenous L-ornithine-L-aspartate on postural control in patients with cirrhosis. Liver Int, 2010, 30(17): 574-582.
10.	Abid S, Jafri W, Mumtaz K, et al. Efficacy of L-ornithine-L-aspartate as an Adjuvant Therapy in Cirrhotic Patients with Hepatic Encephalopathy. J Coll Physicians SurgPak, 2011, 21(7): 666-671.
11.	Haussinger D, Schliess F. Pathogenetic mechanisms of hepatic encephalopathy. Gut, 2008, 57(5): 1156 -1165.
12.	许建明. 肝性脑病诊治的难点与争议. 中华消化杂志, 2011, 31(1): 2-5.
13.	Perazzo JC, Tallis S, Delfante A, et al. Hepatic encephalopathy: An approach to its multiple pathophysiological features. World J Hepatol, 2012, 4(3): 50-65.
14.	Bajaj JS. Review article: the modern management of hepatic encephalopathy. Aliment Pharmacol Ther, 2010, 31(5): 537-547.
15.	Gillmann A, Gerharz CD, Müssig K. Diagnostics and treatment of hepatic encephalopathy. Dtsch Med Wochenschr, 2012, 137(1-2): 29-33.
16.	Jiang Q, Jiang XH, Zheng MH, et al. L-Ornithine-l-aspartate in the management of hepatic encephalopathy: a meta-analysis. J Gastroenterol Hepatol, 2009, 24(42): 9-14.
17.	Soárez PC, Oliveira AC, Padovan J, et al. A critical analysis of studies assessing L-ornithine-L-aspartate (LOLA) in hepatic encephalopathy treatment. Arq Gastroenterol, 2009, 46(12): 241-247.

1. Ferenci P, Lockwood A, Mullen K, et al. 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(65):716-721.
2. Sibae MR, Mc Guire BM. Current trends in the treatment of hepatic encephalopathy. Ther Clin Risk Manag, 2009, 5(7):617-626.
3. Toris GT, Bikis CN, Tsourouflis GS, et al. Hepatic encephalopathy: an updated approach from pathogenesis to treatment. Med Sci Monit, 2011, 17(2): 53-63.
4. Jadad AR, Moore, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(23): 1-12.
5. 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(76): 1351-1360.
6. 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(6): 856 -864.
7. Ahmad I, Khan AA, Alam A, et al. L-ornithine-L-aspartate infusion efficacy in hepatic encephalopathy. J Coll Physicians Surg Pak, 2008, 18(3): 684-687.
8. Acharya SK, Bhatia V, Sreenivas V, et al. Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology, 2009, 136(37): 2159-2168.
9. Schmid M, Peck-Radosavljevic M, König F, et al. A double-blind, randomized, placebo-controlled trial of intravenous L-ornithine-L-aspartate on postural control in patients with cirrhosis. Liver Int, 2010, 30(17): 574-582.
10. Abid S, Jafri W, Mumtaz K, et al. Efficacy of L-ornithine-L-aspartate as an Adjuvant Therapy in Cirrhotic Patients with Hepatic Encephalopathy. J Coll Physicians SurgPak, 2011, 21(7): 666-671.
11. Haussinger D, Schliess F. Pathogenetic mechanisms of hepatic encephalopathy. Gut, 2008, 57(5): 1156 -1165.
12. 许建明. 肝性脑病诊治的难点与争议. 中华消化杂志, 2011, 31(1): 2-5.
13. Perazzo JC, Tallis S, Delfante A, et al. Hepatic encephalopathy: An approach to its multiple pathophysiological features. World J Hepatol, 2012, 4(3): 50-65.
14. Bajaj JS. Review article: the modern management of hepatic encephalopathy. Aliment Pharmacol Ther, 2010, 31(5): 537-547.
15. Gillmann A, Gerharz CD, Müssig K. Diagnostics and treatment of hepatic encephalopathy. Dtsch Med Wochenschr, 2012, 137(1-2): 29-33.
16. Jiang Q, Jiang XH, Zheng MH, et al. L-Ornithine-l-aspartate in the management of hepatic encephalopathy: a meta-analysis. J Gastroenterol Hepatol, 2009, 24(42): 9-14.
17. Soárez PC, Oliveira AC, Padovan J, et al. A critical analysis of studies assessing L-ornithine-L-aspartate (LOLA) in hepatic encephalopathy treatment. Arq Gastroenterol, 2009, 46(12): 241-247.

Chinese Journal of Evidence-Based Medicine

Efficacy of L-ornithine-L-aspartate in the Treatment of Hepatic Encephalopathy: A Systematic Review

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