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Higher Grades and Repeated Recurrence of Hepatic Encephalopathy May Be Related to High Serum Manganese Levels

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Abstract

Hepatic encephalopathy is a serious complication of liver failure. Until now, the precise pathophysiologic mechanisms are not fully determined. It has been demonstrated that manganese plays an important role in the pathogenesis of hepatic encephalopathy. Therefore, we studied manganese levels in serum of cirrhotic patients with hepatic encephalopathy in relation to grading and recurrence of hepatic encephalopathy. One hundred persons were enrolled in the study, 80 cirrhotic patients with or without encephalopathy and 20 healthy controls. Hepatic encephalopathy was diagnosed clinically and by laboratory findings. Serum manganese levels were measured in all participants. The grading of hepatic encephalopathy was significantly correlated to the severity of liver dysfunction. The mean serum manganese level was significantly higher in cirrhotic patients than in controls and in cirrhotic patients with encephalopathy than in those without encephalopathy. It was also significantly higher in patients with advanced grading of hepatic encephalopathy. Serum manganese level was positively correlated to number of recurrences of encephalopathy during a 6-month follow-up period. Serum manganese levels were able to predict recurrence of hepatic encephalopathy within 6 months following the episode. Serum manganese levels are positively correlated to the modified Child-Pugh score of cirrhosis as well as grading and number of recurrences of hepatic encephalopathy. Higher manganese levels seem to be related to worsening of the condition, and its measurement may be used as a predictor of repeated recurrences.

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References

  1. Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P (2014) Hepatic encephalopathy in chronic liver disease: practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 60(2):715–735

    Article  PubMed  Google Scholar 

  2. Ahboucha S. (2011). Neurosteroids and hepatic encephalopathy: an update on possible pathophysiologic mechanisms. Curr Mol Pharmacol 4(1):1-13.

  3. Bajaj JS, Wade JB, Sanyal AJ (2009) Spectrum of neurocognitive impairment in cirrhosis: implications for the assessment of hepatic encephalopathy. Hepatology 50:2014–2021

    Article  PubMed  Google Scholar 

  4. Romero-Gόmez M, Ramos-Guerrero R, Grande L, de Teran LC, Corpas R, Camacho I, Bautista JD (2004) Intestinal glutaminase activity is increased in liver cirrhosis and correlates with minimal hepatic encephalopathy. J Hepatol 41:49–54

    Article  Google Scholar 

  5. Mas A (2006) Hepatic encephalopathy: from pathophysiology to treatment. Digestion 73(Suppl 1):86–93

    Article  PubMed  CAS  Google Scholar 

  6. Ciećko-Michalska I, Szczepanek M, Słowik A, Mach T. (2012). Pathogenesis of hepatic encephalopathy.Gastroenterology Res Practice 2012: Article ID 642108, 7 pages doi:10.1155/2012/642108

  7. Hazell AS, Desjardins P, Butterworth RF (1999) Chronic exposure of rat primary astrocyte cultures to manganese results in increased binding sites for the ‘peripheral-type’ benzodiazepine receptor ligand 3H-PK 11195. Neurosci Lett 271(1):5–8

    Article  PubMed  CAS  Google Scholar 

  8. Pomier-Layrargues G, Spahr L, Butterworth RF (1995) Increased manganese concentrations in pallidum of cirrhotic patients. The Lancet 345(8951):735

    Article  CAS  Google Scholar 

  9. Pomier-Layrargues G, Shapcott D, Spahr L, Butterworth RF (1995) Accumulation of manganese and copper in pallidum of cirrhotic patients: role in the pathogenesis of hepatic encephalopathy? Metab Brain Dis 10(4):353–356

    Article  Google Scholar 

  10. Barron TF, Devenyi AG, Mamourian AC (1994) Symptomatic manganese neurotoxicity in a patient with chronic liver disease: correlation of clinical symptoms with MRI findings. Pediatr Neurol 10(2):145–148

    Article  PubMed  CAS  Google Scholar 

  11. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60(8):646–649

    Article  PubMed  CAS  Google Scholar 

  12. Conn HO, Leevy CM, Vlahcevic ZR, Rodgers JB, Maddrey WC, Seeff L, Levy LL (1977) Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology 72:573–583

    PubMed  CAS  Google Scholar 

  13. Weissenborn K, Ennen JC, Schomerus H, Rückert N, Hecker H (2001) Neuropsychological characterization of hepatic encephalopathy. J Hepatol 34(5):768–773

    Article  PubMed  CAS  Google Scholar 

  14. Li YY, Nie YQ, Sha WH, Zheng Z, Yang FY, Ping L, Jia L (2004) Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China. World J Gastroenterol 10(16):2397–2401

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hartmann IJ, Groeneweg M, Quero JC, Beijeman, S.J., de Man, R.A., Hop, W.C. et al. (2000). The prognostic significance of subclinical hepatic encephalopathy. Am J Gastroenterol 95(8):2029-2034.

  16. Sexana N, Bhatia M, Yoshi YK, Garq PK, Tandon RK (2001) Utility of P300 auditory event related potential in detecting cognitive dysfunction in patients with cirrhosis of the liver. Neurol India 49:350

    Google Scholar 

  17. Zeng Z, Li YY, Nie YQ (2003) An epidemiological survey of subclinical hepatic encephalopathy. Zhonghua Gan Zang Bing Za Zhi 11(11):680–682

    PubMed  Google Scholar 

  18. Quero JC, Schalm SW (1996) Subclinical hepatic encephalopathy. Semin Liver Dis 16(3):321–328

    Article  PubMed  CAS  Google Scholar 

  19. Krieger D, Krieger S, Jansen O, Gass P, Theilmann L, Lichtnecker H (1995) Manganese and chronic hepatic encephalopathy. Lancet 346(8970):270–274

    Article  PubMed  CAS  Google Scholar 

  20. Rahelic D, Kujundzic M, Romic Z, Brkic K, Petrovecki M (2006) Serum concentration of zinc, copper, manganese and magnesium in patients with liver cirrhosis. Coll Antropol 30(3):523–528

    PubMed  CAS  Google Scholar 

  21. Keen CL, Ensunsa JL, Watson MH, Baly DL, Donovan SM, Monaco MH, Cleqq MS (1999) Nutritional aspects of manganese from experimental studies. Neurotoxicology 20(2–3):213–223

    PubMed  CAS  Google Scholar 

  22. Spahr L, Butterworth RF, Fontaine S, Bui L, Therrien G, Milette PC, et al. (1996) Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms. Hepatology 24(5):1116–1120

    Article  PubMed  CAS  Google Scholar 

  23. Zeron HM, Rodriguez MR, Montes S, Castaneda CR (2011) Blood manganese levels in patients with hepatic encephalopathy. J Trace Elem Med Biol 25(4):225–229

    Article  PubMed  Google Scholar 

  24. Hauser RA, Zesiewicz TA, Martinez C, Rosemurgy AS, Olanow CW (1996) Blood manganese correlates with brain magnetic resonance imaging changes in patients with liver disease. Can J Neurol Sci 23(2):95–98

    PubMed  CAS  Google Scholar 

  25. Grande L, Romero-Gómez M, López-Artigues M, García-Díaz E, Castro M (2000) Manganese level in patients with subclinical hepatic encephalopathy (SHE). J Hepatol 32(Supplement 2):150

    Article  Google Scholar 

  26. Milne D, Sims R, Ralston N (1990) Manganese content of the cellular components of blood. Clin Chem 36(3):450–452

    PubMed  CAS  Google Scholar 

  27. Takagi Y, Okada A, Sando K, Wasa M, Yoshida H, Hirabuki N (2002) Evaluation of indexes of in vivo manganese status and the optimal intravenous dose for adult patients undergoing home parenteral nutrition. Am J Clin Nutr 75:112–118

    PubMed  CAS  Google Scholar 

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University , 1Algeish St., Tanta, Gharbiyah Governorate, 31111, Egypt

    Abdelrahman A. Kobtan, Ferial S. El-Kalla & Hanan H. Soliman

  2. Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt

    Soha S. Zakaria

  3. Emergency Department, Senbelawein Central Hospital, Egyptian Ministry of Health, Senbelawein, Egypt

    Mohamed A. Goda

Authors
  1. Abdelrahman A. Kobtan
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  2. Ferial S. El-Kalla
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  3. Hanan H. Soliman
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  4. Soha S. Zakaria
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  5. Mohamed A. Goda
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Correspondence to Abdelrahman A. Kobtan.

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Kobtan, A.A., El-Kalla, F.S., Soliman, H.H. et al. Higher Grades and Repeated Recurrence of Hepatic Encephalopathy May Be Related to High Serum Manganese Levels. Biol Trace Elem Res 169, 153–158 (2016). https://doi.org/10.1007/s12011-015-0405-5

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  • DOI: https://doi.org/10.1007/s12011-015-0405-5

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