Makoto Shiraki1, Masahito Shimizu1, Hisataka Moriwaki1, Kiwamu Okita2, Kazuhiko Koike3. 1. The First Department of Internal Medicine, Gifu University School of Medicine, Gifu. 2. Shunan Memorial Hospital, Kudamatsu, Yamaguchi. 3. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan.
Abstract
AIM: Supplementation with levocarnitine preparations has been reported to improve hepatic encephalopathy, but no detailed investigations have addressed the dynamics of carnitine or its supplementation indication in cirrhosis patients. We studied carnitine dynamics in cirrhotic patients by measuring serum and liver tissue carnitine levels and tested the effects of levocarnitine supplementation on concurrent hyperammonemia. METHODS: In a pilot cohort of seven patients with liver cirrhosis and five patients without cirrhosis, the serum and liver carnitine concentrations were measured. Then the serum carnitine fractions were analyzed in 70 liver cirrhosis patients. Among them, a levocarnitine preparation (1800 mg/day) was supplemented orally for 3 months in 27 patients with refractory hyperammonemia, and the effects were evaluated. RESULTS: A significant correlation was observed between serum and liver tissue carnitine concentrations (r = 0.69, P < 0.05). The serum total carnitine concentration was 68.4 ± 4.7 μmol/L, the free carnitine concentration was 53.2 ± 2.6 μmol/L, and the acylcarnitine concentration was 13.2 ± 1.1 μmol/L in 70 cirrhotic patients (reference values are 45-91, 36-74, 6-23 μmol/L, respectively). There was no correlation between blood ammonia and serum carnitine concentrations. The serum carnitine concentration rose with levocarnitine supplementation, reaching steady state after 1 month and, in parallel, refractory hyperammonemia was significantly improved. The cut-off level for a 20% decrease in blood ammonia was identified as 62.0 μmol/L total carnitine concentration by receiver-operating characteristic curve analysis, with an area under the curve of 0.69. CONCLUSION: Serum carnitine concentrations were within standard levels in the majority of liver cirrhosis patients. In patients with concurrent hyperammonemia, the levocarnitine supplementation reduced blood ammonia levels.
AIM: Supplementation with levocarnitine preparations has been reported to improve hepatic encephalopathy, but no detailed investigations have addressed the dynamics of carnitine or its supplementation indication in cirrhosispatients. We studied carnitine dynamics in cirrhotic patients by measuring serum and liver tissue carnitine levels and tested the effects of levocarnitine supplementation on concurrent hyperammonemia. METHODS: In a pilot cohort of seven patients with liver cirrhosis and five patients without cirrhosis, the serum and liver carnitine concentrations were measured. Then the serum carnitine fractions were analyzed in 70 liver cirrhosispatients. Among them, a levocarnitine preparation (1800 mg/day) was supplemented orally for 3 months in 27 patients with refractory hyperammonemia, and the effects were evaluated. RESULTS: A significant correlation was observed between serum and liver tissue carnitine concentrations (r = 0.69, P < 0.05). The serum total carnitine concentration was 68.4 ± 4.7 μmol/L, the free carnitine concentration was 53.2 ± 2.6 μmol/L, and the acylcarnitine concentration was 13.2 ± 1.1 μmol/L in 70 cirrhotic patients (reference values are 45-91, 36-74, 6-23 μmol/L, respectively). There was no correlation between blood ammonia and serum carnitine concentrations. The serum carnitine concentration rose with levocarnitine supplementation, reaching steady state after 1 month and, in parallel, refractory hyperammonemia was significantly improved. The cut-off level for a 20% decrease in blood ammonia was identified as 62.0 μmol/L total carnitine concentration by receiver-operating characteristic curve analysis, with an area under the curve of 0.69. CONCLUSION: Serum carnitine concentrations were within standard levels in the majority of liver cirrhosispatients. In patients with concurrent hyperammonemia, the levocarnitine supplementation reduced blood ammonia levels.
Authors: Sophie L Allen; Jonathan I Quinlan; Amritpal Dhaliwal; Matthew J Armstrong; Ahmed M Elsharkawy; Carolyn A Greig; Janet M Lord; Gareth G Lavery; Leigh Breen Journal: Am J Physiol Gastrointest Liver Physiol Date: 2020-11-25 Impact factor: 4.052