L-ornithine L-aspartate for the Treatment of Sarcopenia in Cirrhosis: Potential Impact on the Outcome of Liver Transplantation
Keywords:
L-ornithine L-aspartate, Sarcopenia, Liver transplantation, Ammonia, Cirrhosis, Running Head: LOLA for Sarcopenia and TransplantationAbstract
References
Dasarathy, S., Merli, M. (2016) Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol, 65(6): 1232-1244.
Englesbe, MJ., Patel, SP., He, K., Lynch, RJ., Schaubel, DE., Harbaugh, C., et al. (2010) Sarcopenia and mortality after liver transplantation. J Am Coll Surg, 211(2): 271-278.
Masuda, T., Shirabe, K., Ikegami, T., Harimoto, N., Yoshizumi, T., Soejima, Y., et al. (2014) Soarcopenia is a prognostic factor in living donor liver transplantation. Liver Transpl, 20(4): 401-407.
Nardelli, S., Lattanzi, B., Torrisi, S., Greco, F., Farcomenia, A., Gioia, S., et al. (2017) Sarcopenia is risk factor for development of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt placement. Clin Gastroenterol Hepatol, 15(6): 934-936.
Lockwood, AH., McDonald, JM., Reiman, RE., Gelbard, AS., Laughlin, JS., Duffy, TE., et al. (1979) The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest, 63(3): 449-460.
Desjardins, P., Rao, KVR., Michalak, A., Rose, C., Butterworth, RF. (1999) Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle. Metab Brain Dis, 14(4): 273-280.
Takeda, K., Takemasa, T. (2015) Expression of ammonia transporters Rhbg and RHcg in mouse skeletal muscle and the effects of 6-week training on these proteins. Physiol Rep, 3(10): e12596.
Kumar, A., Davuluri, G., Nascimento e Silva, R., Engelen, MPKJ., Gabrie, AM., et al. (2017) Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis. Hepatology, 65(6): 2045- 2058.
Qiu, J., Tsien, C., Thapalaya, S., Narayanan, A., Weihl, CC., Ching, JK., et al. (2012) Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab, 303(8): E983-E993.
Butterworth, RF. (2019) L-ornithine L-aspartate for the treatment of sarcopenia in chronic liver disease: the taming of a vicious cycle. Can J Gastroenterol Heptol, in press.
Rose, C., Michalak, A., Pannunzio, P., Therrien, G., Quack, G., Kircheis, G. (1998) L-ornithine L-aspartate in experimental portosystemic encephalopathy: therapeutic efficacy and mechanism of action. Metab Brain Dis, 13(2): 147-157.
Staedt, U., Leweling, H., Gladisch, R., Kortsik, C., Hagmuller, E., Holm, E. (1993) Treatment of cirrhotic rats with L-ornithine L-aspartate lowers serum ammonia levels. J Pharmacol Exp Ther, 283(1): 1-6.
Butterworth, RF., Kircheis, G., Hilger, N., McPhail, MJW. (2018) Efficacy of L-ornithine L-aspartate for the treatment of hepatic encephalopathy and hyperammonemia in cirrhosis: systematic review and metaanalysis of randomized controlled trials. J Clin Exp Hepatol, 8(3): 301- 313.
Reynolds, N., Downie, S., Smith, K., Kircheis, G., Rennie, MJ., et al. (1999) Treatment with L-ornithine L-aspartate (LOLA) infusion restores muscle protein synthesis responsiveness to feeding in patients with cirrhosis. Journal of Hepatology, 1: 30(7).
Pasha, Y., Taylor-Robinson, SD., Leech, R., Ribero, I., Cook, N., Crossey, M., et al. (2018) L-ornithine L-aspartate in minimal hepatic encephalopathy: possible effects on the brain-muscle axis. Gut, 67: A117.
Wolfe, RA., McCullough, KP., Leichtman, AB. (2009) Predictability of survival models for waiting list and transplant patients: calculating LYFT. Am J Transplant, 9(7): 1523-1527.
Tandon, P., Ney, M., Irwin, I., Ma, MM., Gramlich, L., Bain, VG., et al. (2012) Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl, 18(10): 1209-1216.
Butterworth, RF., Gruengreiff, K. (2018) L-ornithine L-aspartate (LOLA) for the treatment of hepatic encephalopathy in cirrhosis: evidence for novel hepatoprotective mechanisms. Journal of Liver Clinical Research, 5: 1044.
Alvares-da-Silva, MR., De Arujo, A., Vicienzi, R., Da Silva, GV, Oliviera, FB., Schacher, F., et al. (2011) L-ornithine L-aspartate in minimal hepatic encephalopathy: randomized double-blind placebo-controlled trial. Hepatol Res, 44(9): 956-963.
Abid, S., Jafri, W., Muntaz, K., Islam, M., Abbas, Z., Shah, A., et al. (2011) Efficacy of L-ornithine L-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy. J Coll Physicians Surg Pak, 21(11): 666-671.
Bai, M., He, C., Yin, Z., Niu, J., Wang, Z., Qi, X., et al. (2014) Randomized clinical trial: L-ornithine L-aspartate reduces significantly the increase of venous ammonia concentration after TIPSS. Aliment Pharmacol Ther, 40(1): 63-71.
Ijaz, S., Yang, W., Winslet, MC., Seifalian, AM. (2005) The role of nitric oxide in the regulation and tissue oxygenation in an experimental model of hepatic steatosis. Microvascular Research, 70(3): 129-136.
Butterworth, RF., Canbay, A. (2019) Hepatoprotection by L-ornithine L-aspartate in non-alcoholic fatty liver disease. Dig Dis; 37(1): 63-68.
Samengo, G., Avik, A., Fedor, B., Whittaker, D., Myung, KH., Wehling- Henricks, M., et al. (2012) Age-related loss of nitric oxide synthase in skeletal muscle causes reductions in calpain S-nitrosylation that increase myofibril degradation and sarcopenia. Aging Cell, 11(6): 1036-1045.
