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Gastroenterologie up2date 2023; 19(04): 357-372
DOI: 10.1055/a-2039-9694
Leber/Galle/Pankreas

Hepatische Enzephalopathie Teil 2: Therapie

Axel Holstege
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Die Therapie der hepatischen Enzephalopathie (HE) wird bestimmt von HE-Typ, Schweregrad der kognitiven und neuropsychiatrischen Störungen und möglichen HE-Auslösern – Letztere stehen in der akuten Situation im Vordergrund. Wichtig für Akutbehandlung und Sekundärprophylaxe ist auch die richtige Ernährung bei Leberzirrhose. Die Therapieempfehlungen dieses Beitrags leiten sich in erster Linie von der deutschen und europäischen Leitlinie zur HE ab.
Kernaussagen

  • HE-Typ (A, B, C), Schweregrad (klinisch, subklinisch) und Vorliegen eines HE-Auslösers bestimmen das therapeutische Vorgehen. Bei HE-Schweregrad 3 und 4 ist eine intensivmedizinische Betreuung indiziert.

  • Die Therapie einer akuten HE-Episode erfolgt ebenso wie die Sekundärprophylaxe nach einer durchgemachten HE primär mit Lactulose.

  • Bei Unverträglichkeit oder Unwirksamkeit von nicht resorbierbaren Disacchariden kann auf Rifaximin allein bzw. in Kombination mit Lactulose umgestellt werden.

  • Die Evidenz für die Wirksamkeit von L-Ornithin-L-Aspartat bei oHE ist gering und unsicher.

  • Die Sekundärprophylaxe nach einer HE-Episode kann beendet werden, wenn ein Auslöser der HE vorlag und erfolgreich therapiert wurde oder sich Ernährungszustand und Leberfunktion gebessert haben.

  • Die Primärprophylaxe der HE ist immer nach gastrointestinaler Blutung indiziert. Nach TIPS-Implantation ist sie nur bei früher durchgemachter oHE-Episode angezeigt.

  • Eine Proteinrestriktion ist bei Leberzirrhose und HE nicht indiziert.

  • Ausreichende Kalorien- und Proteinzufuhr und die Verhinderung längerer Nüchternphasen wirken einer Sarkopenie und dem damit einhergehenden HE-Risiko entgegen.

Schlüsselwörter

hepatische Enzephalopathie - Therapie und Prophylaxe - Lactulose - Rifaximin - L-Ornithin-L-Aspartat


Publication History

Article published online:
12 December 2023

© 2023. Thieme. All rights reserved.

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  • Literatur

  • 1 European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol 2022; 77: 807-824
    CrossrefPubMedSearch in Google Scholar
  • 2 Gerbes AL, Labenz J, Appenrodt B. et al. Aktualisierte S2k-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) „Komplikationen der Leberzirrhose“. Z Gastroenterol 2019; 57: 611-680
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Wijdicks E. Hepatic encephalopathy. N Engl J Med 2016; 375: 1660-1670
    CrossrefPubMedSearch in Google Scholar
  • 4 Tujios S, Stravitz RT, Lee WM. Management of Acute liver failure: Update 2022. Semin Liver Dis 2022; 42: 362-378
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Montrief T, Koyfman A, Long B. Acute liver failure: A review for emergency physicians. Am J Emerg Med 2019; 37: 329-337
    CrossrefPubMedSearch in Google Scholar
  • 6 Gyr N, Meier R, Häussler J. et al. Evaluation of the efficacy and safety of flumazenil in the treatment of portalsystemic encephalopathy – a double blind, randomized, placebo-controlled multicentre study. Gut 1996; 39: 319-324
    CrossrefPubMedSearch in Google Scholar
  • 7 Bischoff SC, Bernal W, Dasarathy S. et al. ESPEN practical guideline: Clinical nutrition in liver disease. Clin Nutr 2020; 39: 3533-3562
    CrossrefPubMedSearch in Google Scholar
  • 8 Koretz RL, Avenell A, Lipman TO. Nutritional support for liver disease. Cochrane Database Syst Rev 2012; (05) CD008344
    CrossrefPubMedSearch in Google Scholar
  • 9 Ahuja H, Sharma BC, Sachdeva S. et al. A double blind randomized controlled trial to assess efficacy of nutritional therapy for prevention of recurrence of hepatic encephalopathy in patients with cirrhosis. J Gastroenterol Hepatol 2023; 38: 433-440
    CrossrefPubMedSearch in Google Scholar
  • 10 Fritz MK, Mangino AA, Hunt TV. et al. Clinical outcomes of oral zinc therapy in hepatic encephalopathy treatment. Ann Pharmacother 2023; 57: 899-906
    CrossrefPubMedSearch in Google Scholar
  • 11 Maharshi S, Sharma BC, Sachdeva S. et al. Efficacy of nutritional therapy for patients with cirrhosis and minimal hepatic encephalopathy in a randomized trial. Clin Gastroenterol Hepatol 2016; 14: 454-460
    CrossrefPubMedSearch in Google Scholar
  • 12 Allen SL, Quinlan JI, Dhaliwal A. et al. Sarcopenia in chronic liver disease: mechanisms and countermeasures. Am J Physiol Gastrointest Liver Physiol 2021; 320: G241-G257
    CrossrefPubMedSearch in Google Scholar
  • 13 Carey EJ, Lai JC, Wang CW. et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl 2017; 23: 625-633
    CrossrefPubMedSearch in Google Scholar
  • 14 Gil-Gómez A, Ampuero J, Rojas Á. et al. Development and validation of a clinical-genetic risk score to predict hepatic encephalopathy in patients with liver cirrhosis. Am J Gastroenterol 2021; 116: 1238-1247
    CrossrefPubMedSearch in Google Scholar
  • 15 Gluud LL, Vilstrup H, Morgan MY. Nonabsorbable disaccharides for hepatic encephalopathy: A systematic review and meta-analysis. Hepatology 2016; 64: 908-922
    CrossrefPubMedSearch in Google Scholar
  • 16 Won SM, Oh KK, Gupta H. et al. The link between gut microbiota and hepatic encephalopathy. Int J Mol Sci 2022; 23: 8999
    CrossrefPubMedSearch in Google Scholar
  • 17 Kimer N, Krag A, Møller S. et al. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther 2014; 40: 123-132
    CrossrefPubMedSearch in Google Scholar
  • 18 Cheng J, Chen Y, Cao W. et al. Is rifaximin better than nonabsorbable disaccharides in hepatic encephalopathy? A meta-analysis. Medicine (Baltimore) 2021; 100: e28232
    CrossrefPubMedSearch in Google Scholar
  • 19 Dhiman RK, Thumburu KK, Verma N. et al. Comparative efficacy of treatment options for minimal hepatic encephalopathy: a systematic review and network meta-analysis. Clin Gastroenterol Hepatol 2020; 18: 800-812.e25
    CrossrefPubMedSearch in Google Scholar
  • 20 Bass NM, Mullen KD, Sanyal A. et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010; 362: 1071-1081
    CrossrefPubMedSearch in Google Scholar
  • 21 Dimick L. Center for Drug Evaluation and Research. Application Number: 22–554. Rifaximin. 2010 Accessed May 13, 2023 at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000MedR.pdf
    PubMedSearch in Google Scholar
  • 22 Zullo A, Hassan C, Ridola L. et al. Rifaximin therapy and hepatic encephalopathy: Pros and cons. World J Gastrointest Pharmacol Ther 2012; 3: 62-67
    CrossrefPubMedSearch in Google Scholar
  • 23 Reigadas E, Alcalá L, Gómez J. et al. Breakthrough Clostridium difficile infection in cirrhotic patients receiving rifaximin. Clin Infect Dis 2018; 66: 1086-1091
    CrossrefPubMedSearch in Google Scholar
  • 24 Royer G, Fourreau F, Gomart C. et al. Outbreak of an uncommon rifampin-resistant blaNDM-1Citrobacter amalonaticus strain in a digestive rehabilitation center: the putative role of rifaximin. Clin Infect Dis 2020; 71: 1331-1333
    CrossrefPubMedSearch in Google Scholar
  • 25 Hoilat GJ, Ayas MF, Hoilat JN. et al. Polyethylene glycol versus lactulose in the treatment of hepatic encephalopathy: a systematic review and meta-analysis. BMJ Open Gastroenterol 2021; 8: e000648
    CrossrefPubMedSearch in Google Scholar
  • 26 Bajaj JS, Fagan A, Gavis EA. et al. Long-term outcomes of fecal microbiota transplantation in patients with cirrhosis. Gastroenterology 2019; 156: 1921-1923.e3
    CrossrefPubMedSearch in Google Scholar
  • 27 Horvath A, Traub J, Aliwa B. et al. Oral intake of L-ornithine-L-aspartate is associated with distinct microbiome and metabolome changes in cirrhosis. Nutrients 2022; 14: 748
    CrossrefPubMedSearch in Google Scholar
  • 28 Goh ET, Stokes CS, Sidhu SS. et al. L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev 2018; (05) CD012410
    CrossrefPubMedSearch in Google Scholar
  • 29 Sidhu SS, Sharma BC, Goyal O. et al. L-ornithine L-aspartate in bouts of overt hepatic encephalopathy. Hepatology 2018; 67: 700-710
    CrossrefPubMedSearch in Google Scholar
  • 30 Jain A, Sharma BC, Mahajan B. et al. L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial. Hepatology 2022; 75: 1194-1203
    CrossrefPubMedSearch in Google Scholar
  • 31 Tranah TH, Shawcross DL. The rise and fall and rise again of ammonia as a therapeutic target in HE. Hepatology 2022; 75: 1078-1080
    CrossrefPubMedSearch in Google Scholar
  • 32 Varakanahalli S, Sharma BC, Srivastava S. et al. Secondary prophylaxis of hepatic encephalopathy in cirrhosis of liver: a double-blind randomized controlled trial of L-ornithine L-aspartate versus placebo. Eur J Gastroenterol Hepatol 2018; 30: 951-958
    CrossrefPubMedSearch in Google Scholar
  • 33 Safadi R, Rahimi RS, Thabut D. et al. Pharmacokinetics/pharmacodynamics of L-ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes. Clin Transl Sci 2022; 15: 1449-1459
    CrossrefPubMedSearch in Google Scholar
  • 34 Rahimi RS, Safadi R, Thabut D. et al. Efficacy and safety of ornithine phenylacetate for treating overt hepatic encephalopathy in a randomized trial. Clin Gastroenterol Hepatol 2021; 19: 2626-2635.e7
    CrossrefPubMedSearch in Google Scholar
  • 35 Zacharias HD, Zacharias AP, Gluud LL. et al. Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis. Cochrane Database Syst Rev 2019; (06) CD012334
    CrossrefPubMedSearch in Google Scholar
  • 36 Gluud LL, Dam G, Les I. et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev 2017; (05) CD001939
    CrossrefPubMedSearch in Google Scholar
  • 37 Tsipotis E, Shuja A, Jaber BL. Albumin dialysis for liver failure: a systematic review. Adv Chronic Kidney Dis 2015; 22: 382-390
    CrossrefPubMedSearch in Google Scholar
  • 38 Bañares R, Nevens F, Larsen FS. et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: The RELIEF trial. Hepatology 2013; 57: 1153-1162
    CrossrefPubMedSearch in Google Scholar
  • 39 Simón-Talero M, Roccarina D, Martínez J. et al. Association between portosystemic shunts and increased complications and mortality in patients with cirrhosis. Gastroenterology 2018; 154: 1694-1705.e4
    CrossrefPubMedSearch in Google Scholar
  • 40 An J, Kim KW, Han S. et al. Improvement in survival associated with embolisation of spontaneous portosystemic shunt in patients with recurrent hepatic encephalopathy. Aliment Pharmacol Ther 2014; 39: 1418-1426
    CrossrefPubMedSearch in Google Scholar
  • 41 Nardelli S, Bellafante D, Ridola L. et al. Prevention of post-tips hepatic encephalopathy: The search of the ideal candidate. Metab Brain Dis 2023; 38: 1729-1736
    CrossrefPubMedSearch in Google Scholar
  • 42 Riggio O, Masini A, Efrati C. et al. Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled study. J Hepatol 2005; 42: 674-679
    CrossrefPubMedSearch in Google Scholar
  • 43 Bureau C, Thabut D, Jezequel C. et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled trial. Ann Intern Med 2021; 174: 633-640
    CrossrefPubMedSearch in Google Scholar
  • 44 Seifert LL, Schindler P, Schoster M. et al. Recurrence of hepatic encephalopathy after TIPS: Effective prophylaxis with combination of lactulose and rifaximin. J Clin Med 2021; 10: 4763
    CrossrefPubMedSearch in Google Scholar
  • 45 Pereira K, Carrion AF, Salsamendi J. et al. Endovascular management of refractory hepatic encephalopathy complication of transjugular intrahepatic portosystemic shunt (TIPS): Comprehensive review and clinical practice algorithm. Cardiovasc Intervent Radiol 2016; 39: 170-182
    CrossrefPubMedSearch in Google Scholar
  • 46 Warrillow S, Fisher C, Tibballs H. et al. Continuous renal replacement therapy and its impact on hyperammonaemia in acute liver failure. Crit Care Resusc 2020; 22: 158-165
    PubMedSearch in Google Scholar
  • 47 Cardoso FS, Gottfried M, Tujios S. et al. Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Hepatology 2018; 67: 711-720
    CrossrefPubMedSearch in Google Scholar
  • 48 Maharshi S, Sharma BC, Srivastava S. et al. Randomised controlled trial of lactulose versus rifaximin for prophylaxis of hepatic encephalopathy in patients with acute variceal bleed. Gut 2015; 64: 1341-1342
    CrossrefPubMedSearch in Google Scholar