International Journal of Frontiers in Medicine, 2023, 5(10); doi: 10.25236/IJFM.2023.051003.
Miao Hao1, Wenjun Wang1, Juanjuan Shi1, Yaping Li1, Mei Li1, Guoying Pan1, Xiaoli Jia1, Jinhui Yang2, Shuangsuo Dang1, Xin Zhang1
1Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
2Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China
To investigate the efficacy and safety of glutargin versus arginine in the treatment of hyperammonemia in patients with chronic liver diseases, we screened consecutive patients aged 18 to 65 years with chronic liver diseases between February 2007 and October 2010 at two hepatology centers in China. The level of blood ammonia in eligible patients was at least 1.2 times the upper limit of normal. Enrolled patients were randomly assigned at a 1:1 ratio to receive either 20 g of glutargin or 20 g of arginine for 7 days. The primary outcome was the efficacy rate in lowering the levels of blood ammonia. Finally a total of 80 patients were enrolled in this study. In the intention-to-treat analysis, glutargin did not show a superior efficacy rate to arginine in lowering the levels of blood ammonia (75% in the glutargin group and 80% in the arginine group, P=0.57). The decrease in blood ammonia level was also similar in the glutargin group and the arginine group (41% versus 40%, P=0.59). Per-protocol analyses showed similar results. However, the overall symptom and sign scores decreased more in the glutargin group than in the arginine group (P=0.058 in the intention-to-treat analysis and P=0.014 in the per-protocol analysis, respectively). The incidence of adverse events was similar in the two groups. Conclusion: Glutargin shows similar efficacy to arginine in the treatment of hyperammonemia in patients with chronic liver diseases. However, glutargin is superior to arginine in improving symptoms and signs.
Glutargin; Arginine; Hyperammonemia; Chronic liver diseases
Miao Hao, Wenjun Wang, Juanjuan Shi, Yaping Li, Mei Li, Guoying Pan, Xiaoli Jia, Jinhui Yang, Shuangsuo Dang, Xin Zhang. Glutargin Versus Arginine for Hyperammonemia in Chronic Liver Diseases: A Randomized Controlled Trial. International Journal of Frontiers in Medicine (2023), Vol. 5, Issue 10: 17-22. https://doi.org/10.25236/IJFM.2023.051003.
[1] Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014; 60(2):715-735.
[2] Leger RF, Silverman MS, Hauck ES, Guvakova KD. Hyperammonemia Post Lung Transplantation: A Review. Clin Med Insights Circ Respir Pulm Med. 2020; 14:1179548420966234.
[3] Rose CF, Amodio P, Bajaj JS, et al. Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy. J Hepatol. 2020; 73(6):1526-1547.
[4] Kjærgaard K, Mikkelsen ACD, Wernberg CW, et al. Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease-Current Knowledge, Mechanisms and Perspectives. J Clin Med. 2021; 10(4):673.
[5] Shalimar, Sheikh MF, Mookerjee RP, Agarwal B, Acharya SK, Jalan R. Prognostic Role of Ammonia in Patients With Cirrhosis. Hepatology. 2019; 70(3):982-994.
[6] European Association for the Study of the Liver. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol. 2022; 77(3):807-824.
[7] Kim S, Paik WK, Cohen PP. Ammonia intoxication in rats: protection by N-carbamoyl-L-glutamate plus L-arginine. Proc Natl Acad Sci U S A. 1972; 69(12):3530-3533.
[8] Lee JH, Kim WH, Cho H, Kwak YS, Kim S, Paik WK. N-carbamoyl-L-glutamate plus L-arginine can protect ammonia intoxication in rats with reduced functional liver mass. Biochem Biophys Res Commun. 1998; 248(2):391-394.
[9] Kim WH, Park H, Yun C, et al. Mixture of N-carbamoyl-L-glutamate plus L-arginine can protect rats with liver cirrhosis from acute ammonia intoxication. J Hepatol. 2001; 35(6):719-725.
[10] Lauritsen, J.M. and Bruus, M. (2003) EpiData (Version 3). A Comprehensive Tool for Validated Entry and Documentation of Data. The EpiData Association, Odense.
[11] Sato T. A further look at the Cochran-Mantel-Haenszel risk difference. Control Clin Trials. 1995; 16(5):359-361.
[12] Shigesada K, Tatibana M. Role of acetylglutamate in ureotelism. I. Occurrence and biosynthesis of acetylglutamate in mouse and rat tissues. J Biol Chem. 1971; 246(18):5588-5595.
[13] Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000; 130(4S Suppl):1007S-15S.