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Factors contributing to the development of overt encephalopathy in liver cirrhosis patients

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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.

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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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Bajaj JS (2010) Review article: the modern management of hepatic encephalopathy. Aliment Pharmacol Ther 31:537–547

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Häussinger D, Schliess F (2005) Astrocyte swelling and protein tyrosine nitration in hepatic encephalopathy. Neurochem Int 47:64–70

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Iwasa M, Takei Y (2015) Pathophysiology and management of hepatic encephalopathy 2014 update: ammonia toxicity and hyponatremia. Hepatol Res 45:1155–1162

    Article  CAS  PubMed  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Kappus MR, Bajaj JS (2012) Covert hepatic encephalopathy: not as minimal as you might think. Clin Gastroenterol Hepatol 10:1208–1219

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

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Correspondence to Motoh Iwasa.

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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)

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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

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  • DOI: https://doi.org/10.1007/s11011-016-9862-6

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