Abstract
The aim of this study was to clarify the relationships among psychometric testing results, blood ammonia (NH3) levels, electrolyte abnormalities, and degree of inflammation, and their associations with the development of overt hepatic encephalopathy (HE) in liver cirrhosis (LC) patients. The relationships between covert HE and blood NH3, sodium (Na), and C-reactive protein (CRP) were examined in 40 LC patients. The effects of elevated NH3, hyponatremia, and elevated CRP on the development of overt HE were also investigated. The covert HE group had significantly lower serum Na levels and significantly higher serum CRP levels. During the median observation period of 11 months, 10 patients developed overt HE, and the results of multivariate analysis showed that covert HE and elevated blood NH3 were factors contributing to the development of overt HE. Electrolyte abnormalities and mild inflammation are involved in the pathogenesis of HE. Abnormal psychometric testing results and hyperammonemia are linked to subsequent development of overt HE.
Similar content being viewed by others
References
Ahluwalia V, Heuman DM, Feldman G, Wade JB, Thacker LR, Gavis E, Gilles H, Unser A, White MB, Bajaj JS (2015a) Correction of hyponatraemia improves cognition, quality of life, and brain oedema in cirrhosis. J Hepatol 62:75–82
Ahluwalia V, Heuman DM, Feldman G, Wade JB, Thacker LR, Gavis E, Gilles H, Unser A, White MB, Bajaj JS (2015b) Correction of hyponatraemia improves cognition, quality of life, and brain oedema in cirrhosis. J Hepatol 62:75–82
Amodio P, Del Piccolo F, Pettenò E, Mapelli D, Angeli P, Iemmolo R, Muraca M, Musto C, Gerunda G, Rizzo C, Merkel C, Gatta A (2001) Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients. J Hepatol 35:37–45
Bajaj JS (2010) Review article: the modern management of hepatic encephalopathy. Aliment Pharmacol Ther 31:537–547
Bajaj JS, Cordoba J, Mullen KD, Amodio P, Shawcross DL, Butterworth RF, Morgan MY (2011) International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN). Review article: the design of clinical trials in hepatic encephalopathy--an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Aliment Pharmacol Ther 33:739–747
Dhiman RK, Rana B, Agrawal S, Garg A, Chopra M, Thumburu KK, Khattri A, Malhotra S, Duseja A, Chawla YK (2014) Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology 147:1327–1337
Häussinger D, Schliess F (2005) Astrocyte swelling and protein tyrosine nitration in hepatic encephalopathy. Neurochem Int 47:64–70
Heuman DM, Abou-Assi SG, Habib A, Williams LM, Stravitz RT, Sanyal AJ, Fisher RA, Mihas AA (2004) Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death. Hepatology 40:802–810
Iwasa M, Takei Y (2015) Pathophysiology and management of hepatic encephalopathy 2014 update: ammonia toxicity and hyponatremia. Hepatol Res 45:1155–1162
Iwasa M, Sugimoto R, Takei Y (2014) Patients with hyponatremic cirrhosis have low-grade cerebral edema and poor quality-of-life. Ann Hepatol 13:407–408
Jain L, Sharma BC, Srivastava S, Puri SK, Sharma P, Sarin S (2013) Serum endotoxin, inflammatory mediators, and magnetic resonance spectroscopy before and after treatment in patients with minimal hepatic encephalopathy. J Gastroenterol Hepatol 28:1187–1193
Kappus MR, Bajaj JS (2012) Covert hepatic encephalopathy: not as minimal as you might think. Clin Gastroenterol Hepatol 10:1208–1219
Kato A, Kato M, Ishii H, Ichimiya Y, Suzuki K, Kawasaki H, Yamamoto SI, Kumashiro R, Yamamoto K, Kawamura N, Hayashi N, Matsuzaki S, Terano A, Okita K, Watanabe A (2004) Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese. Hepatol Res 30:71–78
Luo M, Guo JY, Cao WK (2015) Inflammation: a novel target of current therapies for hepatic encephalopathy in liver cirrhosis. World J Gastroenterol 21:11815–11824
Mardini H, Smith FE, Record CO, Blamire AM (2011) Magnetic resonance quantification of water and metabolites in the brain of cirrhotics following induced hyperammonaemia. J Hepatol 54:1154–1160
Montagnese S, Biancardi A, Schiff S, Carraro P, Carlà V, Mannaioni G, Moroni F, Tono N, Angeli P, Gatta A, Amodio P (2011) Different biochemical correlates for different neuropsychiatric abnormalities in patients with cirrhosis. Hepatology 53:558–566
Reinehr R, Görg B, Becker S, Qvartskhava N, Bidmon HJ, Selbach O, Haas HL, Schliess F, Häussinger D (2007) Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Glia 55:758–771
Romero-Gómez M, Grande L, Camacho I (2004) Prognostic value of altered oral glutamine challenge in patients with minimal hepatic encephalopathy. Hepatology 39:939–943
Romero-Gómez M, Montagnese S, Jalan R (2015) Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol 62:437–447
Rovira A, Grivé E, Pedraza S, Rovira A, Alonso J (2001) Magnetization transfer ratio values and proton MR spectroscopy of normal-appearing cerebral white matter in patients with liver cirrhosis. AJNR Am J Neuroradiol 22:1137–1142
Shawcross DL, Wright G, Olde Damink SW, Jalan R (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138
Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA (2011) Infection and systemic inflammation, not ammonia, are associated with grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol 54:640–649
Solà E, Watson H, Graupera I, Turón F, Barreto R, Rodríguez E, Pavesi M, Arroyo V, Guevara M, Ginès P (2012) Factors related to quality of life in patients with cirrhosis and ascites: relevance of serum sodium concentration and leg edema. J Hepatol 57:1199–1206
Sugimoto R, Iwasa M, Maeda M, Urawa N, Tanaka H, Fujita N, Kobayashi Y, Takeda K, Kaito M, Takei Y (2008) Value of the apparent diffusion coefficient for quantification of low-grade hepatic encephalopathy. Am J Gastroenterol 103:1413–1420
Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P (2014) 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 60:715–735
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
No external financial support was received.
Conflict of interest
There are no conflicts of interest.
Electronic supplementary material
Supplementary Figure 1
Receiver operating characteristic (ROC) curves to determine the optimum cut-off of blood NH3, sodium (Na), and C-reactive protein (CRP) for predicting overt hepatic encephalopathy (HE) onset. TPF, true positive fraction; FPF, false positive fraction (PDF 106 kb)
Rights and permissions
About this article
Cite this article
Iwasa, M., Sugimoto, R., Mifuji-Moroka, R. et al. Factors contributing to the development of overt encephalopathy in liver cirrhosis patients. Metab Brain Dis 31, 1151–1156 (2016). https://doi.org/10.1007/s11011-016-9862-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-016-9862-6