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Erschienen in: Metabolic Brain Disease 6/2019

10.09.2019 | Original Article

Predictive value of induced hyperammonaemia and neuropsychiatric profiling in relation to the occurrence of post-TIPS hepatic encephalopathy

verfasst von: Marco Senzolo, Lisa Zarantonello, Chiara Formentin, Costanza Orlando, Raffaello Beltrame, Anna Vuerich, Paolo Angeli, Patrizia Burra, Sara Montagnese

Erschienen in: Metabolic Brain Disease | Ausgabe 6/2019

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Abstract

Hepatic encephalopathy (HE) occurs in 20–50% of patients after transjugular intrahepatic portosystemic shunt (TIPS) placement. Older age, HE history and severe liver failure have all been associated with post-TIPS HE but it remains difficult to identify patients at risk. The aim of the present pathophysiological, pilot study was to assess the role of induced hyperammonaemia and associated neuropsychological and neurophysiological changes as predictors of post-TIPS HE. Eighteen TIPS candidates with no overt HE history (56 ± 8 yrs., MELD 11 ± 3) underwent neurophysiological [Electroencephalography (EEG)], neuropsychological [Psychometric Hepatic Encephalopathy Score (PHES) and Scan tests], ammonia and sleepiness assessment at baseline and after the induction of hyperammonaemia by an oral amino acid challenge (AAC). Pre-AAC, 17% of patients had abnormal EEG, 5% abnormal PHES, and 33% abnormal Scan performance. Post-AAC, 17% had abnormal EEG, 0% abnormal PHES, and 17% abnormal Scan performance. Pre-AAC, ammonia concentrations were 201 ± 73 μg/dL and subjective sleepiness 2.5 ± 1.2 (1–9 scale). Post-AAC, patients exhibited the expected increase in ammonia/sleepiness. Six months post-TIPS, 3 patients developed an episode of HE requiring hospitalization; these showed significantly lower pre-AAC fasting ammonia concentrations compared to patients who did not develop HE (117 ± 63 vs. 227 ± 57 μg/dL p = 0.015). They also showed worse PHES/Scan performance pre-AAC, and worse Scan performance post-AAC. Findings at 12 months follow-up (n = 5 HE episodes) were comparable. In conclusion, baseline ammonia levels and both pre- and post-AAC neuropsychiatric indices hold promise in defining HE risk in TIPS candidates with no HE history.
Literatur
Zurück zum Zitat Åkerstedt T, Gillberg M (1990) Subjective and objective sleepiness in the active individual. Int J Neurosci 52:29–37PubMed Åkerstedt T, Gillberg M (1990) Subjective and objective sleepiness in the active individual. Int J Neurosci 52:29–37PubMed
Zurück zum Zitat Al Mardini H, Douglass H, Record C (2006) Amino acid challenge in patients with cirrhosis and control subjects: Ammonia, plasma amino acid and EEG changes. Metab Brain Dis 21:1–10PubMed Al Mardini H, Douglass H, Record C (2006) Amino acid challenge in patients with cirrhosis and control subjects: Ammonia, plasma amino acid and EEG changes. Metab Brain Dis 21:1–10PubMed
Zurück zum Zitat Amodio P, Marchetti P, Del Piccolo F et al (1998) Study on the Sternberg paradigm in cirrhotic patients without overt hepatic encephalopathy. Metab Brain Dis 13:159–172PubMed Amodio P, Marchetti P, Del Piccolo F et al (1998) Study on the Sternberg paradigm in cirrhotic patients without overt hepatic encephalopathy. Metab Brain Dis 13:159–172PubMed
Zurück zum Zitat Amodio P, Marchetti P, Del Piccolo F et al (1999) Spectral versus visual EEG analysis in mild hepatic encephalopathy. Clin Neurophysiol 110:1334–1344PubMed Amodio P, Marchetti P, Del Piccolo F et al (1999) Spectral versus visual EEG analysis in mild hepatic encephalopathy. Clin Neurophysiol 110:1334–1344PubMed
Zurück zum Zitat Amodio P, Montagnese S, Gatta A et al (2004) Characteristics of minimal hepatic encephalopathy. Metab Brain Dis 19:253–267PubMed Amodio P, Montagnese S, Gatta A et al (2004) Characteristics of minimal hepatic encephalopathy. Metab Brain Dis 19:253–267PubMed
Zurück zum Zitat Amodio P, Campagna F, Olianas S et al (2008) Detection of minimal hepatic encephalopathy: normalization and optimization of the psychometric hepatic encephalopathy score. A neuropsychological and quantified EEG study. J Hepatol 49:346–353PubMed Amodio P, Campagna F, Olianas S et al (2008) Detection of minimal hepatic encephalopathy: normalization and optimization of the psychometric hepatic encephalopathy score. A neuropsychological and quantified EEG study. J Hepatol 49:346–353PubMed
Zurück zum Zitat Amodio P, Montagnese S, Spinelli G et al (2017) Cognitive reserve is a resilience factor for cognitive dysfunction in hepatic encephalopathy. Metab Brain Dis 32:1287–1293PubMed Amodio P, Montagnese S, Spinelli G et al (2017) Cognitive reserve is a resilience factor for cognitive dysfunction in hepatic encephalopathy. Metab Brain Dis 32:1287–1293PubMed
Zurück zum Zitat Balata S, Damink SW, Ferguson K et al (2003) Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis. Hepatology 37:931–939PubMed Balata S, Damink SW, Ferguson K et al (2003) Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis. Hepatology 37:931–939PubMed
Zurück zum Zitat Berlioux P, Robic MA, Poirson H et al (2014) Pre-transjugular intrahepatic portosystemic shunts (TIPS) prediction of post-TIPS overt hepatic encephalopathy: the critical flicker frequency is more accurate than psychometric tests. Hepatology. 59:622–629PubMed Berlioux P, Robic MA, Poirson H et al (2014) Pre-transjugular intrahepatic portosystemic shunts (TIPS) prediction of post-TIPS overt hepatic encephalopathy: the critical flicker frequency is more accurate than psychometric tests. Hepatology. 59:622–629PubMed
Zurück zum Zitat Bersagliere A, Raduazzo ID, Nardi M et al (2012) Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis. Hepatology 55:869–878PubMed Bersagliere A, Raduazzo ID, Nardi M et al (2012) Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis. Hepatology 55:869–878PubMed
Zurück zum Zitat Bersagliere A, Raduazzo ID, Schiff S et al (2013) Ammonia-related changes in cerebral electrogenesis in healthy subjects and patients with cirrhosis. Clin Neurophysiol 124:492–646PubMed Bersagliere A, Raduazzo ID, Schiff S et al (2013) Ammonia-related changes in cerebral electrogenesis in healthy subjects and patients with cirrhosis. Clin Neurophysiol 124:492–646PubMed
Zurück zum Zitat Casado M, Bosch J, García-Pagán JC et al (1998) Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. Gastroenterology 114:1296–1303PubMed Casado M, Bosch J, García-Pagán JC et al (1998) Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. Gastroenterology 114:1296–1303PubMed
Zurück zum Zitat Casula EP, Bisiacchi PS, Corrias M et al (2015) Acute hyperammonaemia induces a sustained decrease in vigilance, which is modulated by caffeine. Metab Brain Dis 30:143–149PubMed Casula EP, Bisiacchi PS, Corrias M et al (2015) Acute hyperammonaemia induces a sustained decrease in vigilance, which is modulated by caffeine. Metab Brain Dis 30:143–149PubMed
Zurück zum Zitat Del Piccolo F, Sacerdoti D, Amodio P et al (2002) Central nervous system alterations in liver cirrhosis: the role of portal-systemic shunt and portal hypoperfusion. Metab Brain Dis 17:347–358PubMed Del Piccolo F, Sacerdoti D, Amodio P et al (2002) Central nervous system alterations in liver cirrhosis: the role of portal-systemic shunt and portal hypoperfusion. Metab Brain Dis 17:347–358PubMed
Zurück zum Zitat Douglass A, Al Mardini H, Record C (2001) Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy. J Hepatol 34:658–664PubMed Douglass A, Al Mardini H, Record C (2001) Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy. J Hepatol 34:658–664PubMed
Zurück zum Zitat Guevara M, Baccaro ME, Ríos J et al (2010) Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration. Liver Int 30:1137–1142PubMed Guevara M, Baccaro ME, Ríos J et al (2010) Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration. Liver Int 30:1137–1142PubMed
Zurück zum Zitat Huizenga JR, Gips CH, Conn HO et al (1995) Determination of ammonia in ear-lobe capillary blood is an alternative to arterial blood ammonia. Clin Chim Acta 239:65–70PubMed Huizenga JR, Gips CH, Conn HO et al (1995) Determination of ammonia in ear-lobe capillary blood is an alternative to arterial blood ammonia. Clin Chim Acta 239:65–70PubMed
Zurück zum Zitat Irimia R, Stanciu C, Cojocariu C et al (2013) Oral glutamine challenge improves the performance of psychometric tests for the diagnosis of minimal hepatic encephalopathy in patients with liver cirrhosis. J Gastrointestin Liver Dis 22:277–281 Irimia R, Stanciu C, Cojocariu C et al (2013) Oral glutamine challenge improves the performance of psychometric tests for the diagnosis of minimal hepatic encephalopathy in patients with liver cirrhosis. J Gastrointestin Liver Dis 22:277–281
Zurück zum Zitat Maier KP, Talke H, Gerok W (1979) Activities of urea-cycle enzymes in chronic liver disease. Klin Wochenschr 13:661–665 Maier KP, Talke H, Gerok W (1979) Activities of urea-cycle enzymes in chronic liver disease. Klin Wochenschr 13:661–665
Zurück zum Zitat Mardini B, Saxby BK, Record CO (2008) Computerized psychometric testing in minimal encephalopathy and modulation by nitrogen challenge and liver transplant. Gastroenterology 135:1582–1590PubMed Mardini B, Saxby BK, Record CO (2008) Computerized psychometric testing in minimal encephalopathy and modulation by nitrogen challenge and liver transplant. Gastroenterology 135:1582–1590PubMed
Zurück zum Zitat Mardini H, Smith FE, Record CO et al (2011) Magnetic resonance quantification of water and metabolites in the brain of cirrhotics following induced hyperammonaemia. J Hepatol 54:1154–1160PubMed Mardini H, Smith FE, Record CO et al (2011) Magnetic resonance quantification of water and metabolites in the brain of cirrhotics following induced hyperammonaemia. J Hepatol 54:1154–1160PubMed
Zurück zum Zitat McDermott WV, Adams RD (1954) Episodic stupor associated with an Eck fistula in the human with particular reference to the metabolism of ammonia. J Clin Invest 33:1–9PubMedPubMedCentral McDermott WV, Adams RD (1954) Episodic stupor associated with an Eck fistula in the human with particular reference to the metabolism of ammonia. J Clin Invest 33:1–9PubMedPubMedCentral
Zurück zum Zitat Montagnese S, Biancardi A, Schiff S et al (2011) Different biochemical correlates for different neuropsychiatric abnormalities in patients with cirrhosis. Hepatology. 53:558–566PubMed Montagnese S, Biancardi A, Schiff S et al (2011) Different biochemical correlates for different neuropsychiatric abnormalities in patients with cirrhosis. Hepatology. 53:558–566PubMed
Zurück zum Zitat Montagnese S, Schiff S, Turco M et al (2012) Simple tools for complex syndromes: a three-level difficulty test for hepatic encephalopathy. Dig Liver Dis 44:957–960PubMed Montagnese S, Schiff S, Turco M et al (2012) Simple tools for complex syndromes: a three-level difficulty test for hepatic encephalopathy. Dig Liver Dis 44:957–960PubMed
Zurück zum Zitat Nardelli S, Gioia S, Pasquale C et al (2016) Cognitive impairment predicts the occurrence of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Am J Gastroenterol 111:523–528PubMed Nardelli S, Gioia S, Pasquale C et al (2016) Cognitive impairment predicts the occurrence of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Am J Gastroenterol 111:523–528PubMed
Zurück zum Zitat Nolte W, Wiltfang J, Schindler C et al (1998) Portosystemic hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis: clinical, laboratory, psychometric, and electroencephalographic investigations. Hepatology 28:1215–1225PubMed Nolte W, Wiltfang J, Schindler C et al (1998) Portosystemic hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis: clinical, laboratory, psychometric, and electroencephalographic investigations. Hepatology 28:1215–1225PubMed
Zurück zum Zitat Ong JP, Aggarwal A, Krieger D et al (2003) Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 114:188–193PubMed Ong JP, Aggarwal A, Krieger D et al (2003) Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 114:188–193PubMed
Zurück zum Zitat Oppong KNW, Al-Mardini H, Thick M et al (1997) Oral glutamine challenge in cirrhotics pre- and post-liver transplantation: a psychometric and analyzed EEG study. Hepatology 26:870–876PubMed Oppong KNW, Al-Mardini H, Thick M et al (1997) Oral glutamine challenge in cirrhotics pre- and post-liver transplantation: a psychometric and analyzed EEG study. Hepatology 26:870–876PubMed
Zurück zum Zitat Parsons-Smith BG, Summerskill WH, Dawson AM et al (1957) The electroencephalograph in liver disease. Lancet 273:867–871PubMed Parsons-Smith BG, Summerskill WH, Dawson AM et al (1957) The electroencephalograph in liver disease. Lancet 273:867–871PubMed
Zurück zum Zitat Phillips GB, Schwartz R, Gabuzda GJ et al (1952) The syndrome of impending hepatic coma in patients with cirrhosis of the liver given certain nitrogenous substances. N Engl J Med 247:239–246PubMed Phillips GB, Schwartz R, Gabuzda GJ et al (1952) The syndrome of impending hepatic coma in patients with cirrhosis of the liver given certain nitrogenous substances. N Engl J Med 247:239–246PubMed
Zurück zum Zitat Riggio O, Merlli M, Pedretti G et al (1996) Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Incidence and risk factors. Dig Dis Sci 41:578–584PubMed Riggio O, Merlli M, Pedretti G et al (1996) Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Incidence and risk factors. Dig Dis Sci 41:578–584PubMed
Zurück zum Zitat Riggio O, Masini A, Efrati C et al (2005) Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled study. J Hepatol 42:674–679PubMed Riggio O, Masini A, Efrati C et al (2005) Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled study. J Hepatol 42:674–679PubMed
Zurück zum Zitat Riggio O, Angeloni S, Salvatori FM et al (2008) Incidence, natural history, and risk factors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stent grafts. Am J Gastroenterol 103:2738–2746PubMed Riggio O, Angeloni S, Salvatori FM et al (2008) Incidence, natural history, and risk factors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stent grafts. Am J Gastroenterol 103:2738–2746PubMed
Zurück zum Zitat Riggio O, Ridola L, Lucidi C et al (2010) Emerging issues in the use of transjugular intrahepatic portosystemic shunt (TIPS) for management of portal hypertension: time to update the guidelines? Dig Liver Dis 42:462–467PubMed Riggio O, Ridola L, Lucidi C et al (2010) Emerging issues in the use of transjugular intrahepatic portosystemic shunt (TIPS) for management of portal hypertension: time to update the guidelines? Dig Liver Dis 42:462–467PubMed
Zurück zum Zitat Rikkers L, Jenko P, Rudman D et al (1978) Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism. Gastroenterology 75:462–469PubMed Rikkers L, Jenko P, Rudman D et al (1978) Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism. Gastroenterology 75:462–469PubMed
Zurück zum Zitat Romero-Gómez M, Grande L, Camacho I et al (2002) Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. J Hepatol 37:781–787PubMed Romero-Gómez M, Grande L, Camacho I et al (2002) Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. J Hepatol 37:781–787PubMed
Zurück zum Zitat Rossle M, Haag K, Ochs A et al (1994) The transjugular intrahepatic portosystemic stent-shunt procedure for variceal bleeding. N Engl J Med 330:165–171PubMed Rossle M, Haag K, Ochs A et al (1994) The transjugular intrahepatic portosystemic stent-shunt procedure for variceal bleeding. N Engl J Med 330:165–171PubMed
Zurück zum Zitat Rössle M, Deibert P, Haag K et al (1997) Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding. Lancet 349:1043–1049PubMed Rössle M, Deibert P, Haag K et al (1997) Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding. Lancet 349:1043–1049PubMed
Zurück zum Zitat Sanyal AJ, Freedman AM, Shiffman ML et al (1994) Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt: results of a prospective controlled study. Hepatology 20:46–55PubMed Sanyal AJ, Freedman AM, Shiffman ML et al (1994) Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt: results of a prospective controlled study. Hepatology 20:46–55PubMed
Zurück zum Zitat Shawcross DL, Wright G, Olde Damink SWM et al (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138PubMed Shawcross DL, Wright G, Olde Damink SWM et al (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138PubMed
Zurück zum Zitat Sherlock S, Summerskill WH, White LP et al (1954) Portal- systemic encephalopathy; neurological complications of liver disease. Lancet 267:454–457PubMed Sherlock S, Summerskill WH, White LP et al (1954) Portal- systemic encephalopathy; neurological complications of liver disease. Lancet 267:454–457PubMed
Zurück zum Zitat Somberg KA, Riegler JL, LaBerge JM et al (1995) Hepatic encephalopathy after transjugular intrahepatic portosystemic shunts: incidence and risk factors. Am J Gastroenterol 90:549–555PubMed Somberg KA, Riegler JL, LaBerge JM et al (1995) Hepatic encephalopathy after transjugular intrahepatic portosystemic shunts: incidence and risk factors. Am J Gastroenterol 90:549–555PubMed
Zurück zum Zitat Sternberg S (1969) Memory-scanning: mental processes revealed by reaction-time experiments. Am Sci 57:421–457PubMed Sternberg S (1969) Memory-scanning: mental processes revealed by reaction-time experiments. Am Sci 57:421–457PubMed
Zurück zum Zitat Van der Rijt CC, Schalm SW, De Groot GH et al (1984) Objective measurement of hepatic encephalopathy by means of automated EEG analysis. Electroencephalogr Clin Neurophysiol 57:423–426PubMed Van der Rijt CC, Schalm SW, De Groot GH et al (1984) Objective measurement of hepatic encephalopathy by means of automated EEG analysis. Electroencephalogr Clin Neurophysiol 57:423–426PubMed
Zurück zum Zitat Vilstrup H, Amodio P, Bajaj J et al (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 60:715–735PubMed Vilstrup H, Amodio P, Bajaj J et al (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 60:715–735PubMed
Zurück zum Zitat Watson H, Guevara M, Vilstrup H, Ginès P (2019) Improvement of hyponatremia in cirrhosis is associated with improved complex information processing. J Gastroenterol Hepatol Watson H, Guevara M, Vilstrup H, Ginès P (2019) Improvement of hyponatremia in cirrhosis is associated with improved complex information processing. J Gastroenterol Hepatol
Zurück zum Zitat Weissenborn K, Ennen JC, Schomerus H et al (2001) Neuropsychological characterization of hepatic encephalopathy. J Hepatol 34:768–773PubMed Weissenborn K, Ennen JC, Schomerus H et al (2001) Neuropsychological characterization of hepatic encephalopathy. J Hepatol 34:768–773PubMed
Metadaten
Titel
Predictive value of induced hyperammonaemia and neuropsychiatric profiling in relation to the occurrence of post-TIPS hepatic encephalopathy
verfasst von
Marco Senzolo
Lisa Zarantonello
Chiara Formentin
Costanza Orlando
Raffaello Beltrame
Anna Vuerich
Paolo Angeli
Patrizia Burra
Sara Montagnese
Publikationsdatum
10.09.2019
Verlag
Springer US
Erschienen in
Metabolic Brain Disease / Ausgabe 6/2019
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-019-00490-5

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