medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-14-34-42medsovet-2649Research ArticleЗАБОЛЕВАНИЯ ПЕЧЕНИLIVER DISEASEРазличные варианты гипераммониемии в клинической практикеDifferent types of hyperammonemia in clinical practiceПлотниковаЕ. Ю.PlotnikovaE. Yu.

д.м.н., профессор кафедры подготовки врачей первичного звена здравоохранения, руководитель курса клинической гастроэнтерологии

eka-pl@rambler.ruСухихА. С.SukhikhA. S.

к.м.н., доцент ЦНИЛ

ФГБОУ ВО «Кемеровский государственный медицинский университет» (КемГМУ) Минздрава РоссииРоссияKemerovo State Medical University (KemGMU) of the Ministry of Health of RussiaRussian Federation2018091020180143442Copyright © Плотникова Е.Ю., Сухих А.С., 20182018Плотникова Е.Ю., Сухих А.С.Plotnikova E.Y., Sukhikh A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2649

Гипераммониемия  – это метаболическое нарушение, вызванное избыточным количеством аммиака в крови. Гипераммониемия связана с тяжелыми заболеваниями печени, прежде всего с циррозом, в 90% случаев. В остальных 10% следует учитывать нецирротические причины. В статье описаны различные причины и клинические особенности гипераммониемии, связанной с доцирротическими стадиями заболевания печени, особенно с неалкогольной жировой дистрофией. Также приводятся другие этиологические факторы, которые вызывают гипераммониемию различной степени тяжести, от минимальной до очень тяжелой, приводящей к фатальному исходу. Проводится анализ эффективности L-орнитин-Lаспартата при гипераммониемии, а также собственное оригинальное авторское исследование по фармацевтической эквивалентности оригинального и дженерического препаратов L-орнитин-L-аспартата.

Hyperammonemia is a metabolic disorder, which is caused as a result of high levels of ammonia present in the blood. Hyperammonemia is related to severe liver diseases, primarily to cirrhosis in 90% of cases. Non-cirrhotic causes should be considered in the remaining 10%. The article describes various causes and clinical features of hyperammonemia related to the pre-cirrhotic stages of liver disease, especially to non-alcoholic fatty dystrophy. The authors also provide other etiologies that cause hyperammonemia of varying severity, from minimal to very severe, leading to fatal outcome. The paper provides an analysis of the efficacy of L-ornithine-L-aspartate in hyperammonemia, and the results of own original author’s pharmaceutical equivalence study of the original and generic drug L-ornithine-L-aspartate.

гипераммониемиязаболевания печенинеалкогольная жировая болезнь печенистеатозфибрознецирротическая гипераммониемияL-орнитин-L-аспартатhyperammonemialiver diseasesnon-alcoholic fatty liver diseasesteatosisfibrosisnon-cirrhotic hyperammonemiaL-ornithine-L-aspartateReferencesCichoż-Lach H, Michalak A. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. World J Gastroenterol, 2013 Jan 7, 19(1): 26–34.Cichoż-Lach H, Michalak A. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. World J Gastroenterol, 2013 Jan 7, 19(1): 26–34.Hahn M, Massen O, Nencki M, Pawlow J. Die Eck’sche Fistel zwischen der unteren Hohlvene und der Pfortader und ihre Folgen für den Organismus. Arch Exp Pathol Pharmakol, 1893, 32(3–4): 161–210.Hahn M, Massen O, Nencki M, Pawlow J. Die Eck’sche Fistel zwischen der unteren Hohlvene und der Pfortader und ihre Folgen für den Organismus. Arch Exp Pathol Pharmakol, 1893, 32(3–4): 161–210.Shawcross DL, Damink SW, Butterworth RF, Jalan R. Ammonia and hepatic encephalopathy: the more things change, the more they remain the same. Metab Brain Dis, 2005, 20(3): 169–179.Shawcross DL, Damink SW, Butterworth RF, Jalan R. Ammonia and hepatic encephalopathy: the more things change, the more they remain the same. Metab Brain Dis, 2005, 20(3): 169–179.Rose CF. Ammonia-lowering strategies for the treatment of hepatic encephalopathy. Clin Pharmacol Ther, 2012, 92(3): 321–331.Rose CF. Ammonia-lowering strategies for the treatment of hepatic encephalopathy. Clin Pharmacol Ther, 2012, 92(3): 321–331.Liere V, Sandhu G, DeMorrow S. Recent advances in hepatic encephalopathy. F1000Res, 2017, 6: 1637.Liere V, Sandhu G, DeMorrow S. Recent advances in hepatic encephalopathy. F1000Res, 2017, 6: 1637.McDermott WV, Jr, Victor M, Point WW. Exclusion of the colon in the treatment of hepatic encephalo pathy. N Engl J Med, 1962, 267(17): 850–854.McDermott WV, Jr, Victor M, Point WW. Exclusion of the colon in the treatment of hepatic encephalo pathy. N Engl J Med, 1962, 267(17): 850–854.McDermott WV, Jr. Treatment of ammonia intoxication by exclusion of the colon. Gastroenterology, 1966, 51(5): 721–723.McDermott WV, Jr. Treatment of ammonia intoxication by exclusion of the colon. Gastroenterology, 1966, 51(5): 721–723.Gluud LL, Dam G, Borre M, et al. Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: what is the evidence? Metab Brain Dis, 2013, 28(2): 221–225.Gluud LL, Dam G, Borre M, et al. Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: what is the evidence? Metab Brain Dis, 2013, 28(2): 221–225.Bates RG, Pinching GD. Acidic dissociation constant of ammonium ion at 0° to 50°C, and the base strength of ammonia. J Res Natl Bur Stand (1977), 1949, 42: 419–430.Bates RG, Pinching GD. Acidic dissociation constant of ammonium ion at 0° to 50°C, and the base strength of ammonia. J Res Natl Bur Stand (1977), 1949, 42: 419–430.Hagenfeldt L, Eriksson S, Wahren J. Influence of leucine on arterial concentrations and regional exchange of amino acids in healthy subjects. Clin Sci (Lond), 1980, 59(3): 173–181.Hagenfeldt L, Eriksson S, Wahren J. Influence of leucine on arterial concentrations and regional exchange of amino acids in healthy subjects. Clin Sci (Lond), 1980, 59(3): 173–181.Tizianello A, De Ferrari G, Garibotto G, Gurreri G. Effects of chronic renal insufficiency and metabolic acidosis on glutamine metabolism in man. Clin Sci Mol Med, 1978, 55(4): 391–397.Tizianello A, De Ferrari G, Garibotto G, Gurreri G. Effects of chronic renal insufficiency and metabolic acidosis on glutamine metabolism in man. Clin Sci Mol Med, 1978, 55(4): 391–397.Cooper AJ, Plum F. Biochemistry and physiology of brain ammonia. Physiol Rev, 1987, 67(2): 440–519.Cooper AJ, Plum F. Biochemistry and physiology of brain ammonia. Physiol Rev, 1987, 67(2): 440–519.Meyer JS, Gotoh F, Akiyama M, Toshitake S. Monitoring cerebral blood flow and oxygen, glucose, lactate and ammonia metabolism. Circ Res, 1967, 21(5): 649–660.Meyer JS, Gotoh F, Akiyama M, Toshitake S. Monitoring cerebral blood flow and oxygen, glucose, lactate and ammonia metabolism. Circ Res, 1967, 21(5): 649–660.van de Poll MC, Ligthart-Melis GC, Damink SW, et al. The gut does not contribute to systemic ammonia release in humans without portosystemic shunting. Am J Physiol Gastrointest Liver Physiol, 2008, 295(4): G760–G765.van de Poll MC, Ligthart-Melis GC, Damink SW, et al. The gut does not contribute to systemic ammonia release in humans without portosystemic shunting. Am J Physiol Gastrointest Liver Physiol, 2008, 295(4): G760–G765.Levitt DG. PKQuest Java: free, interactive physiologically based pharmacokinetic software package and tutorial. BMC Res Notes, 2009, 2: 158.Levitt DG. PKQuest Java: free, interactive physiologically based pharmacokinetic software package and tutorial. BMC Res Notes, 2009, 2: 158.Damink SW, Jalan R, Redhead DN, Hayes PC, Deutz NE, Soeters PB. Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS. Hepatology, 2002, 36(5): 1163–1171.Damink SW, Jalan R, Redhead DN, Hayes PC, Deutz NE, Soeters PB. Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS. Hepatology, 2002, 36(5): 1163–1171.Katz A, Broberg S, Sahlin K, Wahren J. Muscle ammonia and amino acid metabolism during dynamic exercise in man. Clin Physiol, 1986, 6(4): 365–379.Katz A, Broberg S, Sahlin K, Wahren J. Muscle ammonia and amino acid metabolism during dynamic exercise in man. Clin Physiol, 1986, 6(4): 365–379.Nomura F, Ohnishi K, Terabayashi H, et al. Effect of intrahepatic portal-systemic shunting on hepatic ammonia extraction in patients with cirrhosis. Hepatology, 1994, 20(6): 1478–1481.Nomura F, Ohnishi K, Terabayashi H, et al. Effect of intrahepatic portal-systemic shunting on hepatic ammonia extraction in patients with cirrhosis. Hepatology, 1994, 20(6): 1478–1481.McDermott WV, Adams RD, Riddell AG. Ammonia metabolism in man. Ann Surg, 1954, 140(4): 539–556.McDermott WV, Adams RD, Riddell AG. Ammonia metabolism in man. Ann Surg, 1954, 140(4): 539–556.Tizianello A, De Ferrari G, Garibotto G, Gurreri G. Effects of chronic renal insufficiency and metabolic acidosis on glutamine metabolism in man. Clin Sci Mol Med, 1978, 55(4): 391–397.Tizianello A, De Ferrari G, Garibotto G, Gurreri G. Effects of chronic renal insufficiency and metabolic acidosis on glutamine metabolism in man. Clin Sci Mol Med, 1978, 55(4): 391–397.Fulgoni VL, 3rd Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003–2004. Am J Clin Nutr,2008, 87(5): 1554S–1557S.Fulgoni VL, 3rd Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003–2004. Am J Clin Nutr,2008, 87(5): 1554S–1557S.Mariotti F, Tomé D, Mirand PP. Converting nitrogen into protein: beyond 6.25 and Jones’ factors. Crit Rev Food Sci Nutr, 2008, 48(2): 177–184.Mariotti F, Tomé D, Mirand PP. Converting nitrogen into protein: beyond 6.25 and Jones’ factors. Crit Rev Food Sci Nutr, 2008, 48(2): 177–184.Matthews DE, Campbell RG. The effect of dietary protein intake on glutamine and glutamate nitrogen metabolism in humans. Am J Clin Nutr, 1992, 55(5): 963–970.Matthews DE, Campbell RG. The effect of dietary protein intake on glutamine and glutamate nitrogen metabolism in humans. Am J Clin Nutr, 1992, 55(5): 963–970.Rudman D, DiFulco TJ, Galambos JT, Smith RB, 3rd, Salam AA, Warren WD. Maximal rates of excretion and synthesis of urea in normal and cirrhotic subjects. J Clin Invest, 1973, 52(9): 2241–2249.Rudman D, DiFulco TJ, Galambos JT, Smith RB, 3rd, Salam AA, Warren WD. Maximal rates of excretion and synthesis of urea in normal and cirrhotic subjects. J Clin Invest, 1973, 52(9): 2241–2249.Levitt DG, Levitt MD. A model of blood-ammonia homeostasis based on a quantitative analysis of nitrogen metabolism in the multiple organs involved in the production, catabolism, and excretion of ammonia in humans. Clin Exp Gastroenterol, 2018, 11: 193–215.Levitt DG, Levitt MD. A model of blood-ammonia homeostasis based on a quantitative analysis of nitrogen metabolism in the multiple organs involved in the production, catabolism, and excretion of ammonia in humans. Clin Exp Gastroenterol, 2018, 11: 193–215.Vela CI, Padilla FJ. Determination of ammonia concentrations in cirrhosis patients: still confusing after all these years? Ann Hepatol, 2011, 10(Suppl 2): S60–S65.Vela CI, Padilla FJ. Determination of ammonia concentrations in cirrhosis patients: still confusing after all these years? Ann Hepatol, 2011, 10(Suppl 2): S60–S65.Walker MC, Hill RC, Guilford WG, Scott KC, Jones GL, Buergelt CD. Postprandial venous ammonia concentrations in the diagnosis of hepatobiliary disease in dogs. J Vet Intern Med, 2001, 15(5): 463–466.Walker MC, Hill RC, Guilford WG, Scott KC, Jones GL, Buergelt CD. Postprandial venous ammonia concentrations in the diagnosis of hepatobiliary disease in dogs. J Vet Intern Med, 2001, 15(5): 463–466.Deutz NE, Reijven PL, Athanasas G, Soeters PB. Post-operative changes in hepatic, intestinal, splenic and muscle fluxes of amino acids and ammonia in pigs. Clin Sci (Lond), 1992, 83(5): 607–614.Deutz NE, Reijven PL, Athanasas G, Soeters PB. Post-operative changes in hepatic, intestinal, splenic and muscle fluxes of amino acids and ammonia in pigs. Clin Sci (Lond), 1992, 83(5): 607–614.Wolpert E, Phillips SF, Summerskill WH. Ammonia production in the human colon: effects of cleansing, neomycin and acetohydroxamic acid. N Engl J Med, 1970, 283(4): 159–164.Wolpert E, Phillips SF, Summerskill WH. Ammonia production in the human colon: effects of cleansing, neomycin and acetohydroxamic acid. N Engl J Med, 1970, 283(4): 159–164.Nevah MI, Fallon MB. Hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome and systemic complications of liver disease. In: Feldman M, Friedman LS, Brandt LJ, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Diseases: Pathophysiology/ Diagnosis/Management. 10th ed. Philadelphia, PA: Saunders, 2016: 1577–1590.Nevah MI, Fallon MB. Hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome and systemic complications of liver disease. In: Feldman M, Friedman LS, Brandt LJ, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Diseases: Pathophysiology/ Diagnosis/Management. 10th ed. Philadelphia, PA: Saunders, 2016: 1577–1590.van Berlo CL, van Leeuwen PA, Soeters PB. Porcine intestinal ammonia liberation: influence of food intake, lactulose and neomycin treatment. J Hepatol, 1988, 7(2): 250–257.van Berlo CL, van Leeuwen PA, Soeters PB. Porcine intestinal ammonia liberation: influence of food intake, lactulose and neomycin treatment. J Hepatol, 1988, 7(2): 250–257.van der Hulst RR, von Meyenfeldt MF, Deutz NE, Soeters PB. Glutamine extraction by the gut is reduced in depleted [corrected] patients with gastrointestinal cancer. Ann Surg, 1997, 225(1): 112–121.van der Hulst RR, von Meyenfeldt MF, Deutz NE, Soeters PB. Glutamine extraction by the gut is reduced in depleted [corrected] patients with gastrointestinal cancer. Ann Surg, 1997, 225(1): 112–121.Delaney JP, Custer J. Gastrointestinal blood flow in the dog. Circ Res, 1965, 17(5): 394–402.Delaney JP, Custer J. Gastrointestinal blood flow in the dog. Circ Res, 1965, 17(5): 394–402.Butterworth RF, Giguère J-F, Michaud J, Lavoie J, Layrargues GP. Ammonia: Key factor in the pathogenesis of hepatic encephalopathy. Mol Chem Neuropathol, 1987, 6: 1–12.Butterworth RF, Giguère J-F, Michaud J, Lavoie J, Layrargues GP. Ammonia: Key factor in the pathogenesis of hepatic encephalopathy. Mol Chem Neuropathol, 1987, 6: 1–12.Thomsen KL, De Chiara F, Rombouts K, Vilstrup H, Andreola F, Mookerjee RP, Jalan R. Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis. Med Hypotheses. 2018 Apr, 113: 91-97.Thomsen KL, De Chiara F, Rombouts K, Vilstrup H, Andreola F, Mookerjee RP, Jalan R. Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis. Med Hypotheses. 2018 Apr, 113: 91-97.Jalan R., De Chiara F., Balasubramaniyan V. et al. Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension. J Hepatol, 2016, 64(4): 823–833.Jalan R., De Chiara F., Balasubramaniyan V. et al. Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension. J Hepatol, 2016, 64(4): 823–833.De Chiara, Habtension A, Davies N, Andreola F, Rombouts K, Arias N, Thomsen KL, Jalan R. Early increase in ammonia is a feature of nonalcoholic fatty liver disease and the ammonia lowering drug, ornithine phenylacetate (OCR002) prevents progression of fibrosis in a rodent model F. J Hepatol, 2017, 66(1): S170.De Chiara, Habtension A, Davies N, Andreola F, Rombouts K, Arias N, Thomsen KL, Jalan R. Early increase in ammonia is a feature of nonalcoholic fatty liver disease and the ammonia lowering drug, ornithine phenylacetate (OCR002) prevents progression of fibrosis in a rodent model F. J Hepatol, 2017, 66(1): S170.Gutiérrez-de-Juan V, de Davalillo SL, FernándezRamos D, Barbier-Torres L et al. A morphological method for ammonia detection in liver. PLoS One, 2017, 12(3): e0173914.Gutiérrez-de-Juan V, de Davalillo SL, FernándezRamos D, Barbier-Torres L et al. A morphological method for ammonia detection in liver. PLoS One, 2017, 12(3): e0173914.Felipo V, Urios A, Montesinos E, Molina I, Garcia-Torres ML, Civera M, Olmo JA, Ortega J, Martinez-Valls J, Serra MA, Cassinello N, Wassel A, Jordá E, Montoliu C. Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy. Metab Brain Dis, 2012 Mar, 27(1): 51-8.Felipo V, Urios A, Montesinos E, Molina I, Garcia-Torres ML, Civera M, Olmo JA, Ortega J, Martinez-Valls J, Serra MA, Cassinello N, Wassel A, Jordá E, Montoliu C. Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy. Metab Brain Dis, 2012 Mar, 27(1): 51-8.Агеева Е.А., Алексеенко С.А. Гипераммониемия встречается у больных с хроническими заболеваниями печени на доцирротической стадии, у 32,4% пациентов наблюдалось рецидивирующее течение гипераммониемии. Клинические перспективы в гастроэнтерологии, гепатологии, 2015, 6: 24-26.Ageeva EA, Alekseenko SA. Hyperammonemia occurs in patients with chronic liver disease at the pre-cirrhotic stage, 32.4% of patients had recurring, reversible elevations in ammonia levels. Klinicheskie Perspektivy Gastroehnterologii Gepatologii, 2015, 6: 24-26.Богомолов П.О., Буеверов А.О., Уварова О.В., Мациевич М.В. Гипераммониемия у пациентов с заболеваниями печени на доцирротической стадии: возможно ли это? (Предваритель ные результаты исследования «СМАРТ РАДАР»). Клинические перспективы в гастроэнтерологии, гепатологии, 2013, 5: 3-8.Bogomolov PO, Bueverov AO, Uvarova OV, Matzievich MV. Hyperammonemia in patients with hepatic disease at the pre-cirrhotic stage: is this possible? (Preliminary results of SMART RADAR study). Klinicheskie Perspektivy Gastroehnterologii Gepatologii, 2013, 5: 3-8.Summar ML, Barr F, Dawling S, Smith W, Lee B, Singh RH, Rhead WJ, Sniderman King L, Christman BW. Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin, 2005, 21: S1–S8.Summar ML, Barr F, Dawling S, Smith W, Lee B, Singh RH, Rhead WJ, Sniderman King L, Christman BW. Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin, 2005, 21: S1–S8.Panlaqui OM, Tran K, Johns A, McGill J, White H. Acute hyperammonemic encephalopathy in adult onset ornithine transcarbamylase deficiency. Intensive Care Med, 2008, 34: 1922–1924.Panlaqui OM, Tran K, Johns A, McGill J, White H. Acute hyperammonemic encephalopathy in adult onset ornithine transcarbamylase deficiency. Intensive Care Med, 2008, 34: 1922–1924.Schultz RE, Salo MK. Under recognition of late onset ornithine transcarbamylase deficiency. Arch Dis Child, 2000, 82: 390–391.Schultz RE, Salo MK. Under recognition of late onset ornithine transcarbamylase deficiency. Arch Dis Child, 2000, 82: 390–391.Yoshino M, Nishiyori J, Yamashita F, Kumashiro R, Abe H, Tanikawa K, Ohno T, Nakao K, Kaku N, Fukushima H. Ornithine transcarbamylase deficiency in male adolescence and adulthood. Enzyme. 1990, 43: 160–168.Yoshino M, Nishiyori J, Yamashita F, Kumashiro R, Abe H, Tanikawa K, Ohno T, Nakao K, Kaku N, Fukushima H. Ornithine transcarbamylase deficiency in male adolescence and adulthood. Enzyme. 1990, 43: 160–168.Ghatak T, Azim A, Mahindra S, Ahmed A. Can Klebsiella sepsis lead to hyperammonemic encephalopathy with normal liver function? J Anaesthesiol Clin Pharmacol, 2013 Jul-Sep, 29(3): 415–416.Ghatak T, Azim A, Mahindra S, Ahmed A. Can Klebsiella sepsis lead to hyperammonemic encephalopathy with normal liver function? J Anaesthesiol Clin Pharmacol, 2013 Jul-Sep, 29(3): 415–416.Nott L, Price TJ, Pittman K, Patterson K, Fletcher J. Hyperammonemia encephalopathy: an important cause of neurological deterioration following chemotherapy. Leuk Lymphoma, 2007 Sep, 48(9): 1702-11.Nott L, Price TJ, Pittman K, Patterson K, Fletcher J. Hyperammonemia encephalopathy: an important cause of neurological deterioration following chemotherapy. Leuk Lymphoma, 2007 Sep, 48(9): 1702-11.Samuel I, Mason EE, Renquist KE, Huang YH, Zimmerman MB, Jamal M. Bariatric surgery trends: An 18‐year report from the Inter national Bariatric Surgery Registry. Am J Surg, 2006, 192: 657‐662.Samuel I, Mason EE, Renquist KE, Huang YH, Zimmerman MB, Jamal M. Bariatric surgery trends: An 18‐year report from the Inter national Bariatric Surgery Registry. Am J Surg, 2006, 192: 657‐662.Consortium TLAoBSL. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med, 2009, 361: 445‐454.Consortium TLAoBSL. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med, 2009, 361: 445‐454.Limketkai BN, Zucker SD. Hyperammonemic Encephalopathy Caused by Carnitine Deficiency. J Gen Intern Med, 2008 Feb, 23(2): 210–213.Limketkai BN, Zucker SD. Hyperammonemic Encephalopathy Caused by Carnitine Deficiency. J Gen Intern Med, 2008 Feb, 23(2): 210–213.Juhasz‐Pocsine K, Rudnicki SA, Archer RL, Harik SI. Neurologic complications of gastric bypass surgery for morbid obesity. Neurology, 2007, 68: 1843‐1850.Juhasz‐Pocsine K, Rudnicki SA, Archer RL, Harik SI. Neurologic complications of gastric bypass surgery for morbid obesity. Neurology, 2007, 68: 1843‐1850.Summar ML, Barr F, Dawling S, et al. Unmasked adult‐onset urea cycle disorders in the critical care setting. Crit Care Clin, 2005, 21: S1‐S8.Summar ML, Barr F, Dawling S, et al. Unmasked adult‐onset urea cycle disorders in the critical care setting. Crit Care Clin, 2005, 21: S1‐S8.Hu WT, Kantarci OH, Merritt JL, 2nd, et al. Ornithine transcarbamylase deficiency presenting as encephalopathy during adulthood following bariatric surgery. Arch Neurol, 2007, 64: 126‐128.Hu WT, Kantarci OH, Merritt JL, 2nd, et al. Ornithine transcarbamylase deficiency presenting as encephalopathy during adulthood following bariatric surgery. Arch Neurol, 2007, 64: 126‐128.Limketkai BN, Zucker SD. Hyperammonemic encephalopathy caused by carnitine deficiency. J Gen Intern Med, 2008, 23: 210‐213.Limketkai BN, Zucker SD. Hyperammonemic encephalopathy caused by carnitine deficiency. J Gen Intern Med, 2008, 23: 210‐213.Goodin KM PD, Platky K, Gowans G, et al. Asymptomatic carrier of Ornithine transcarbamylase deficiency unmasked by bariatric surgery. Annual Clinical Genetics Meeting: University of Louisville, Louisville, KY, 2010.Goodin KM PD, Platky K, Gowans G, et al. Asymptomatic carrier of Ornithine transcarbamylase deficiency unmasked by bariatric surgery. Annual Clinical Genetics Meeting: University of Louisville, Louisville, KY, 2010.Estrella J, Yee G, Wilcken B, Tchan M, Talbot M. Hyperammonemic encephalopathy complicating bariatric surgery: A case study and review of the literature. Surg Obes Relat Dis, 2013, 10: e35‐e38.Estrella J, Yee G, Wilcken B, Tchan M, Talbot M. Hyperammonemic encephalopathy complicating bariatric surgery: A case study and review of the literature. Surg Obes Relat Dis, 2013, 10: e35‐e38.Rogal SS, Hu A, Bandi R, Shaikh O. Novel therapy for non‐cirrhotic hyperammonemia due to a spontaneous splenorenal shunt. World J Gastroenterol, 2014, 20: 8288‐8291.Rogal SS, Hu A, Bandi R, Shaikh O. Novel therapy for non‐cirrhotic hyperammonemia due to a spontaneous splenorenal shunt. World J Gastroenterol, 2014, 20: 8288‐8291.Fenves A, Boland CR, Lepe R, Rivera‐Torres P, Spechler SJ. Fatal hyperammonemic encephalopathy after gastric bypass surgery. Am J Med, 2008, 121: e1‐e2.Fenves A, Boland CR, Lepe R, Rivera‐Torres P, Spechler SJ. Fatal hyperammonemic encephalopathy after gastric bypass surgery. Am J Med, 2008, 121: e1‐e2.Acharya G, Mehra S, Patel R, Frunza-Stefan S, Kaur H. Fatal Nonhepatic Hyperammonemia in ICU Setting: A Rare but Serious Complication following Bariatric Surgery. Case Rep Crit Care, 2016, 2016: 8531591.Acharya G, Mehra S, Patel R, Frunza-Stefan S, Kaur H. Fatal Nonhepatic Hyperammonemia in ICU Setting: A Rare but Serious Complication following Bariatric Surgery. Case Rep Crit Care, 2016, 2016: 8531591.Kromas ML, Mousa OY, John S. Hyperammonemia-induced encephalopathy: A rare devastating complication of bariatric surgery. World J Hepatol, 2015 May 8, 7(7): 1007–1011.Kromas ML, Mousa OY, John S. Hyperammonemia-induced encephalopathy: A rare devastating complication of bariatric surgery. World J Hepatol, 2015 May 8, 7(7): 1007–1011.Fenves AZ, Shchelochkov OA, Mehta A. Hyperammonemic syndrome after Roux-en-Y gastric bypass. Obesity (Silver Spring), 2015 Apr, 23(4): 746-9.Fenves AZ, Shchelochkov OA, Mehta A. Hyperammonemic syndrome after Roux-en-Y gastric bypass. Obesity (Silver Spring), 2015 Apr, 23(4): 746-9.Nagarur A, Fenves AZ. Late presentation of fatal hyperammonemic encephalopathy after Roux-en-Y gastric bypass. Proc (Bayl Univ Med Cent), 2017 Jan, 30(1): 41–43.Nagarur A, Fenves AZ. Late presentation of fatal hyperammonemic encephalopathy after Roux-en-Y gastric bypass. Proc (Bayl Univ Med Cent), 2017 Jan, 30(1): 41–43.Singh S, Suresh S, McClave SA, Cave M. Treating Every Needle in the Haystack: Hyperammone mic Encephalopathy and Severe Malnutrition After Bariatric Surgery-A Case Report and Review of the Literature. JPEN J Parenter Enteral Nutr, 2015 Nov, 39(8): 977-85.Singh S, Suresh S, McClave SA, Cave M. Treating Every Needle in the Haystack: Hyperammone mic Encephalopathy and Severe Malnutrition After Bariatric Surgery-A Case Report and Review of the Literature. JPEN J Parenter Enteral Nutr, 2015 Nov, 39(8): 977-85.Matoori S, Leroux J-C. Recent advances in the treatment of hyperammonemia. Adv Drug Deliv Rev, 2015, 90: 55–68.Matoori S, Leroux J-C. Recent advances in the treatment of hyperammonemia. Adv Drug Deliv Rev, 2015, 90: 55–68.Плотникова Е.Ю. Роль L-орнитина-L-аспартата в комплексном лечении больных с гипераммониемией. Клинические перспективы гастро энтерологии, гепатологии, 2013, 2: 41-50.Plotnikova EYu. The role of L-ornithineL-aspartate in the complex treatment of patients with hyperammonemia. Klinicheskie Perspektivy Gastroehnterologii Gepatologii, 2013, 2: 41-50.Sikorska H, Cianciara J, Wiercińska-Drapało A. Physiological functions of L-ornithine and L-aspartate in the body and the efficacy of administration of L-ornithine-L-aspartate in conditions of relative deficiency. Pol Merkur Lekarski, 2010 Jun, 28(168): 490-5.Sikorska H, Cianciara J, Wiercińska-Drapało A. Physiological functions of L-ornithine and L-aspartate in the body and the efficacy of administration of L-ornithine-L-aspartate in conditions of relative deficiency. Pol Merkur Lekarski, 2010 Jun, 28(168): 490-5.Pérez Hernández JL, Higuera de la Tijera F, Serralde-Zúñiga AE, Abdo Francis JM. Critical analysis of studies evaluating the efficacy of infusion of L-ornithine L-aspartate in clinical hepatic encephalopathy in patients with liver failure. Ann Hepatol, 2011 Jun, 10(Suppl 2): S66-9.Pérez Hernández JL, Higuera de la Tijera F, Serralde-Zúñiga AE, Abdo Francis JM. Critical analysis of studies evaluating the efficacy of infusion of L-ornithine L-aspartate in clinical hepatic encephalopathy in patients with liver failure. Ann Hepatol, 2011 Jun, 10(Suppl 2): S66-9.Goh ET, Stokes CS, Sidhu SS, Vilstrup H, Gluud LL, Morgan MY. L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev, 2018 May 15, 5: CD012410. doi: 10.1002/14651858.CD012410.pub2.Goh ET, Stokes CS, Sidhu SS, Vilstrup H, Gluud LL, Morgan MY. L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev, 2018 May 15, 5: CD012410. doi: 10.1002/14651858.CD012410.pub2.Butterworth RF. Pathophysiology of hepatic encephalopathy: a new look at ammonia. Metab Brain Dis 2002, 17: 221–7.Butterworth RF. Pathophysiology of hepatic encephalopathy: a new look at ammonia. Metab Brain Dis 2002, 17: 221–7.

The authors declare that there are no conflicts of interest present.