Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy.
ammonia
ammonia-lowering drugs
cirrhosis
inflammation
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
26
06
2019
revised:
22
10
2019
accepted:
25
10
2019
pubmed:
16
11
2019
medline:
22
6
2021
entrez:
16
11
2019
Statut:
ppublish
Résumé
The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE. We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60 minutes post-load ammonia levels. Combined evaluation of baseline hyperammonemia (>78 mcg/dL) and impaired OGC (Δ >32 mcg/dL) defined low-, intermediate- and high-risk groups. Patients were censored at HE, liver transplantation and death or 6 years of follow-up. The 28.3% (56/198) of the main cohort suffered from HE during the follow-up. In the competing risk analysis, both intermediate- (subhazard ratio (sHR) 2.01 (95% CI 1.00-4.14); P = .048) and high-risk groups (sHR 4.67 (95% CI 2.19-9.98); P = .0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high-risk group was two and four times greater than the intermediate- and low-risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P = .035). The most common precipitant factor was diuretics in the high-risk group, while infections and electrolyte imbalance predominated in the rest of patients. Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision-making process for the adequate management of HE.
Sections du résumé
BACKGROUND
The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE.
METHODS
We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60 minutes post-load ammonia levels. Combined evaluation of baseline hyperammonemia (>78 mcg/dL) and impaired OGC (Δ >32 mcg/dL) defined low-, intermediate- and high-risk groups. Patients were censored at HE, liver transplantation and death or 6 years of follow-up.
RESULTS
The 28.3% (56/198) of the main cohort suffered from HE during the follow-up. In the competing risk analysis, both intermediate- (subhazard ratio (sHR) 2.01 (95% CI 1.00-4.14); P = .048) and high-risk groups (sHR 4.67 (95% CI 2.19-9.98); P = .0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high-risk group was two and four times greater than the intermediate- and low-risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P = .035). The most common precipitant factor was diuretics in the high-risk group, while infections and electrolyte imbalance predominated in the rest of patients.
CONCLUSION
Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision-making process for the adequate management of HE.
Substances chimiques
Glutamine
0RH81L854J
Ammonia
7664-41-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
921-930Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Bustamante J, Rimola A, Ventura P-J, et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;30:890-895.
Ampuero J, Simón M, Montoliú C, et al. Minimal hepatic encephalopathy and critical flicker frequency are associated with survival of patients with cirrhosis. Gastroenterology. 2015;149:1483-1489.
Bajaj JS, Hafeezullah M, Hoffmann RG, et al. Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations. Am J Gastroenterol. 2007;102:1903-1909.
Montagnese S, De Pittà C, De Rui M, et al. Sleep-wake abnormalities in patients with cirrhosis. Hepatology. 2014;59:705-712.
Román E, Córdoba J, Torrens M, et al. Minimal hepatic encephalopathy is associated with falls. Am J Gastroenterol. 2011;106:476-482.
Romero-Gómez M, Ramos-Guerrero R, Grande L, et al. Intestinal glutaminase activity is increased in liver cirrhosis and correlates with minimal hepatic encephalopathy. J Hepatol. 2004;41:49-54.
Oppong KN, Al-Mardini H, Thick M, Record CO. Oral glutamine challenge in cirrhotics pre- and post-liver transplantation: a psychometric and analyzed EEG study. Hepatology. 1997;26:870-876.
Romero-Gómez M, Grande L, Camacho I, Benitez S, Irles JA, Castro M. Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. J Hepatol. 2002;37:781-787.
Masini A, Efrati C, Merli M, et al. Effect of lactitol on blood ammonia response to oral glutamine challenge in cirrhotic patients: evidence for an effect of nonabsorbable disaccharides on small intestine ammonia generation. Am J Gastroenterol. 1999;94:3323-3327.
Rees CJ, Oppong K, Al MH, et al. Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial. Gut. 2000;47:571-574.
Masini A, Efrati C, Merli M, et al. Effect of blood ammonia elevation following oral glutamine load on the psychometric performance of cirrhotic patients. Metab Brain Dis. 2003;18:27-35.
Ditisheim S, Giostra E, Burkhard PR, et al. A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis. BMC Gastroenterol. 2011;11:134.
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;60:715-735.
Hilden J, Glasziou P. Regret graphs, diagnostic uncertainty and Youden's Index. Stat Med. 1996;15:969-986.
Stepanova M, Aquino R, Alsheddi A, et al. Clinical predictors of fibrosis in patients with chronic liver disease. Aliment Pharmacol Ther. 2010;31:1085-1094.
Janssen KJM, Donders ART, Harrell FE, et al. Missing covariate data in medical research: to impute is better than to ignore. J Clin Epidemiol. 2010;63:721-727.
Tapper EB, Halbert B, Mellinger J. Rates of and reasons for hospital readmissions in patients with cirrhosis: a multistate population-based cohort study. Clin Gastroenterol Hepatol. 2016;14:1181-1188.
Ampuero J, Montoliú C, Simón-Talero M, et al. Minimal hepatic encephalopathy identifies patients at risk of faster cirrhosis progression. J Gastroenterol Hepatol. 2018;33(3):718-725.
Romero-Gómez M, Córdoba J, Jover R, et al. Value of the critical flicker frequency in patients with minimal hepatic encephalopathy. Hepatology. 2007;45:879-885.
Goldbecker A, Weissenborn K, Hamidi Shahrezaei G, et al. Comparison of the most favoured methods for the diagnosis of hepatic encephalopathy in liver transplantation candidates. Gut. 2013;62:1497-1504.
Riggio O, Amodio P, Farcomeni A, et al. A model for predicting development of overt hepatic encephalopathy in patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13:1346-1352.
Tapper EB, Parikh N, Sengupta N, et al. A risk score to predict the development of hepatic encephalopathy in a population-based cohort of patients with cirrhosis. Hepatology. 2018;68:1498-1507.
Ridola L, Riggio O. Prediction of hepatic encephalopathy: why disregard well known risk factors? Hepatology. 2018;67(4):1637.
Ruiz-Margáin A, Macías-Rodríguez RU, Ampuero J, et al. Low phase angle is associated with the development of hepatic encephalopathy in patients with cirrhosis. World J Gastroenterol. 2016;22:10064.
Ampuero J, Ranchal I, del Mar Díaz-Herrero M, del Campo JA, Bautista JD, Romero-Gómez M. Role of diabetes mellitus on hepatic encephalopathy. Metab Brain Dis. 2013;28:277-279.
Jepsen P, Watson H, Andersen PK, Vilstrup H. Diabetes as a risk factor for hepatic encephalopathy in cirrhosis patients. J Hepatol. 2015;63:1133-1138.
Nicolao F, Efrati C, Masini A, Merli M, Attili AF, Riggio O. Role of determination of partial pressure of ammonia in cirrhotic patients with and without hepatic encephalopathy. J Hepatol. 2003;38:441-446.
Ong JP, Aggarwal A, Krieger D, et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003;114:188-193.
Luo M, Li L, Yang E-N, et al. Correlation between interleukin-6 and ammonia in patients with overt hepatic encephalopathy due to cirrhosis. Clin Res Hepatol Gastroenterol. 2013;37:384-390.
Ventura-Cots M, Carmona I, Moreno C, et al. Duration of the acute hepatic encephalopathy episode determines survival in cirrhotic patients. Therap Adv Gastroenterol. 2018;11:1756283X1774341.
Romero-Gómez M, Jover M, Del CJA, et al. Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis. Ann Intern Med. 2010;153:281.
Mayer LB, Krawczyk M, Grünhage F, Lammert F, Stokes CS. A genetic variant in the promoter of phosphate-activated glutaminase is associated with hepatic encephalopathy. J Intern Med. 2015;278:313-322.