Hepatische Enzephalopathie Teil 2: Therapie

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.

Schlüsselwörter

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

• 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
• 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
• 3 Wijdicks E. Hepatic encephalopathy. N Engl J Med 2016; 375: 1660-1670
• 4 Tujios S, Stravitz RT, Lee WM. Management of Acute liver failure: Update 2022. Semin Liver Dis 2022; 42: 362-378
• 5 Montrief T, Koyfman A, Long B. Acute liver failure: A review for emergency physicians. Am J Emerg Med 2019; 37: 329-337
• 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
• 7 Bischoff SC, Bernal W, Dasarathy S. et al. ESPEN practical guideline: Clinical nutrition in liver disease. Clin Nutr 2020; 39: 3533-3562
• 8 Koretz RL, Avenell A, Lipman TO. Nutritional support for liver disease. Cochrane Database Syst Rev 2012; (05) CD008344
• 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
• 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
• 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
• 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
• 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
• 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
• 15 Gluud LL, Vilstrup H, Morgan MY. Nonabsorbable disaccharides for hepatic encephalopathy: A systematic review and meta-analysis. Hepatology 2016; 64: 908-922
• 16 Won SM, Oh KK, Gupta H. et al. The link between gut microbiota and hepatic encephalopathy. Int J Mol Sci 2022; 23: 8999
• 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
• 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
• 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
• 20 Bass NM, Mullen KD, Sanyal A. et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010; 362: 1071-1081
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 29 Sidhu SS, Sharma BC, Goyal O. et al. L-ornithine L-aspartate in bouts of overt hepatic encephalopathy. Hepatology 2018; 67: 700-710
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 37 Tsipotis E, Shuja A, Jaber BL. Albumin dialysis for liver failure: a systematic review. Adv Chronic Kidney Dis 2015; 22: 382-390
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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