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Dekompensierte Leberzirrhose und akut-auf-chronisches Leberversagen

Decompensated liver cirrhosis and acute-on-chronic liver failure

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Zusammenfassung

Patienten mit Leberzirrhose, die auf der Intensivstation behandelt werden, haben eine hohe Letalität. Man unterscheidet die dekompensierte Leberzirrhose, d. h. typische Komplikationen der Zirrhose, wie Ösophagusvarizenblutung, hepatische Enzephalopathie, hepatorenales Syndrom oder Aszites, vom akut-auf-chronischen Leberversagen (ACLF), bei dem begleitend zur vorbestehenden chronischen Lebererkrankung ein oder mehrere Organversagen vorliegen. In beiden Fällen ist ein strukturiertes intensivmedizinisches Management zur zielgerechten Behandlung der Ursachen der Dekompensation (z. B. Blutungen, Infektionen, Exsikkose, Medikamente) und der begleitenden Organversagen (z. B. Nierenversagen, Enzephalopathie) essenziell. Für Organversagen sind Kriterien definiert, die die Diagnose eines ACLF ermöglichen. Eine besondere Bedeutung kommt der schnellen und adäquaten (antibiotischen und antimykotischen) Infekttherapie zu. Für typische Komplikationen der Leberzirrhose, wie Nierenversagen/hepatorenales Syndrom, hepatische Enzephalopathie, Aszites oder Varizenblutungen, existieren klare Behandlungspfade. Bei ACLF oder dekompensierter Leberzirrhose sollte immer die Möglichkeit einer Lebertransplantation bedacht und im interdisziplinären Team diskutiert werden. Neue Behandlungsansätze beim ACLF adressieren in klinischen Studien Mechanismen der Inflammation, Immunantwort und Regeneration.

Abstract

Patients with liver cirrhosis who require treatment in an intensive care unit (ICU) have a high mortality rate. It is important to distinguish decompensated liver cirrhosis with typical disease-associated complications (e.g., esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or ascites) from acute-on-chronic liver failure (ACLF), in which single or multiple organ failure rapidly develops on top of a pre-existing decompensated chronic liver disease. Organ failure is clearly defined by the CLIF‑C organ failure (OF) score. In both decompensated cirrhosis and ACLF, structured ICU management that includes the treatment of precipitating events (e.g., bleeding, infections volume depletion, medication) and concomitant organ failure (e.g., renal failure, encephalopathy) is essential. Of particular importance is rapid and adequate (antibiotic and antifungal) infectious therapy, and clear treatment algorithms exist for cirrhosis-associated complications such as renal failure/hepatorenal syndrome, hepatic encephalopathy, ascites or variceal bleeding. The possibility of liver transplantation should always be part of an interdisciplinary discussion about individual therapeutic strategies. New treatment approaches for ACLF address mechanisms of inflammation, immune response, and regeneration in clinical trials.

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Literatur

  1. 1.

    Pimpin L, Cortez-Pinto H, Negro F, Corbould E, Lazarus JV, Webber L et al (2018) Burden of liver disease in europe: epidemiology and analysis of risk factors to identify prevention policies. J Hepatol 69(3):718–735

  2. 2.

    Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J et al (2013) Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 144(7):1426–1437 (37 e1–9)

  3. 3.

    Sandahl TD, Jepsen P, Thomsen KL, Vilstrup H (2011) Incidence and mortality of alcoholic hepatitis in Denmark 1999–2008: a nationwide population based cohort study. J Hepatol 54(4):760–764

  4. 4.

    Jalan R, Saliba F, Pavesi M, Amoros A, Moreau R, Gines P et al (2014) Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 61(5):1038–1047

  5. 5.

    Jalan R, Pavesi M, Saliba F, Amoros A, Fernandez J, Holland-Fischer P et al (2015) The CLIF consortium acute decompensation score (CLIF‑C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 62(4):831–840

  6. 6.

    Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia-Tsao G et al (2012) Acute-on chronic liver failure. J Hepatol 57(6):1336–1348

  7. 7.

    D’Amico G, Morabito A, D’Amico M, Pasta L, Malizia G, Rebora P et al (2018) Clinical states of cirrhosis and competing risks. J Hepatol 68(3):563–576

  8. 8.

    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

  9. 9.

    Peng Y, Qi X, Guo X (2016) Child-pugh versus MELD score for the assessment of prognosis in liver cirrhosis: a systematic review and meta-analysis of observational studies. Medicine (Baltimore) 95(8):e2877

  10. 10.

    Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC (2000) A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31(4):864–871

  11. 11.

    Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A et al (2015) Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the international club of ascites. J Hepatol 62(4):968–974

  12. 12.

    Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C et al (2015) Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology 62(1):243–252

  13. 13.

    Engelmann C, Thomsen KL, Zakeri N, Sheikh M, Agarwal B, Jalan R et al (2018) Validation of CLIF‑C ACLF score to define a threshold for futility of intensive care support for patients with acute-on-chronic liver failure. Crit Care 22(1):254

  14. 14.

    Arroyo V, Moreau R, Jalan R, Gines P, EASL-CLIF Consortium CANONIC Study (2015) Acute-on-chronic liver failure: a new syndrome that will re-classify cirrhosis. J Hepatol 62(1):S131–43

  15. 15.

    Macdonald S, Andreola F, Bachtiger P, Amoros A, Pavesi M, Mookerjee R et al (2018) Cell death markers in patients with cirrhosis and acute decompensation. Hepatology 67(3):989–1002

  16. 16.

    Michelena J, Altamirano J, Abraldes JG, Affo S, Morales-Ibanez O, Sancho-Bru P et al (2015) Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis. Hepatology 62(3):762–772

  17. 17.

    Claria J, Stauber RE, Coenraad MJ, Moreau R, Jalan R, Pavesi M et al (2016) Systemic inflammation in decompensated cirrhosis: characterization and role in acute-on-chronic liver failure. Hepatology 64(4):1249–1264

  18. 18.

    Albillos A, Lario M, Alvarez-Mon M (2014) Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol 61(6):1385–1396

  19. 19.

    Meersseman P, Langouche L, du Plessis J, Korf H, Mekeirele M, Laleman W et al (2018) The intensive care unit course and outcome in acute-on-chronic liver failure are comparable to other populations. J Hepatol 69(4):803–809

  20. 20.

    Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M et al (2015) Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 62(1):232–242

  21. 21.

    Krahenbuhl L, Lang C, Ludes S, Seiler C, Schafer M, Zimmermann A et al (2003) Reduced hepatic glycogen stores in patients with liver cirrhosis. Liver Int 23(2):101–109

  22. 22.

    Koch A, Bundgens L, Tacke F (2019) Nutrition support therapy in critically ill patients. Dtsch Med Wochenschr 144(13):897–909

  23. 23.

    Fernandez J, Acevedo J, Wiest R, Gustot T, Amoros A, Deulofeu C et al (2017) Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut 67(10):1870–1880. https://doi.org/10.1136/gutjnl-2017-314240

  24. 24.

    Mucke MM, Rumyantseva T, Mucke VT, Schwarzkopf K, Joshi S, Kempf VAJ et al (2018) Bacterial infection-triggered acute-on-chronic liver failure is associated with increased mortality. Liver Int 38(4):645–653

  25. 25.

    Bajaj JS, O’Leary JG, Reddy KR, Wong F, Biggins SW, Patton H et al (2014) Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology 60(1):250–256

  26. 26.

    Fernandez J, Acevedo J, Castro M, Garcia O, de Lope CR, Roca D et al (2012) Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology 55(5):1551–1561

  27. 27.

    Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P et al (2014) Bacterial infections in cirrhosis: a position statement based on the EASL special conference 2013. J Hepatol 60(6):1310–1324

  28. 28.

    Bassetti M, Peghin M, Carnelutti A, Righi E, Merelli M, Ansaldi F et al (2017) Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study. Intensive Care Med 43(4):509–518

  29. 29.

    Kim JJ, Tsukamoto MM, Mathur AK, Ghomri YM, Hou LA, Sheibani S et al (2014) Delayed paracentesis is associated with increased in-hospital mortality in patients with spontaneous bacterial peritonitis. Am J Gastroenterol 109(9):1436–1442

  30. 30.

    Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M et al (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315(8):801–810

  31. 31.

    Bajaj JS, O’Leary JG, Wong F, Reddy KR, Kamath PS (2012) Bacterial infections in end-stage liver disease: current challenges and future directions. Gut 61(8):1219–1225

  32. 32.

    Papp M, Vitalis Z, Altorjay I, Tornai I, Udvardy M, Harsfalvi J et al (2012) Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infections. Liver Int 32(4):603–611

  33. 33.

    European Association for the Study of the Liver, Clinical Practice Guidelines Panel, Wendon J, Panel Members, Cordoba J, Dhawan A et al (2017) EASL clinical practical guidelines on the management of acute (fulminant) liver failure. J Hepatol 66(5):1047–1081

  34. 34.

    Gerbes AL, Labenz J, Appenrodt B, Dollinger M, Gundling F, Gulberg V et al (2019) Updated S2k-guideline “complications of liver cirrhosis”. German society of gastroenterology (DGVS). Z Gastroenterol 57(5):e168

  35. 35.

    Garcia-Tsao G, Parikh CR, Viola A (2008) Acute kidney injury in cirrhosis. Hepatology 48(6):2064–2077

  36. 36.

    Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD 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(2):715–735

  37. 37.

    Kaplan PW, Rossetti AO (2011) EEG patterns and imaging correlations in encephalopathy: encephalopathy part II. J Clin Neurophysiol 28(3):233–251

  38. 38.

    Kerbert AJ, Engelmann C, Jalan R (2018) Neurocritical care management of hepatic encephalopathy and coma in liver failure. Semin Respir Crit Care Med 39(5):523–537

  39. 39.

    Garcia-Pagan JC, Caca K, Bureau C, Laleman W, Appenrodt B, Luca A et al (2010) Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 362(25):2370–2379

  40. 40.

    Artru F, Louvet A, Ruiz I, Levesque E, Labreuche J, Ursic-Bedoya J et al (2017) Liver transplantation in the most severely ill cirrhotic patients: a multicenter study in acute-on-chronic liver failure grade 3. J Hepatol 67(4):708–715

  41. 41.

    Sundaram V, Shah P, Wong RJ, Karvellas CJ, Fortune BE, Mahmud N et al (2019) Patients with acute on chronic liver failure grade 3 have greater 14-day waitlist mortality than status-1a patients. Hepatology 70(1):334–345

  42. 42.

    Linecker M, Krones T, Berg T, Niemann CU, Steadman RH, Dutkowski P et al (2018) Potentially inappropriate liver transplantation in the era of the “sickest first” policy—a search for the upper limits. J Hepatol 68(4):798–813

  43. 43.

    Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC et al (2012) Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology 142(3):505–512 e1

  44. 44.

    Engelmann C (2019) Granulocyte-colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure (graft trial): interim analysis of the first randomised European multicentre trial. Hepatology 70:1 (Abstract#17)

  45. 45.

    Oya S, Yokoyama Y, Kokuryo T, Uno M, Yamauchi K, Nagino M (2014) Inhibition of toll-like receptor 4 suppresses liver injury induced by biliary obstruction and subsequent intraportal lipopolysaccharide injection. Am J Physiol Gastrointest Liver Physiol 306(3):G244–52

  46. 46.

    Banares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M et al (2013) Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology 57(3):1153–1162

  47. 47.

    Kribben A, Gerken G, Haag S, Herget-Rosenthal S, Treichel U, Betz C et al (2012) Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology 142(4):782–789 e3

  48. 48.

    Gerth HU, Pohlen M, Tholking G, Pavenstadt H, Brand M, Husing-Kabar A et al (2017) Molecular adsorbent recirculating system can reduce short-term mortality among patients with acute-on-chronic liver failure—a retrospective analysis. Crit Care Med 45(10):1616–1624

  49. 49.

    Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC et al (2016) High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol 64(1):69–78

  50. 50.

    Chen JJ, Huang JR, Yang Q, Xu XW, Liu XL, Hao SR et al (2016) Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-on-chronic liver failure: a nationwide prospective multicenter study in China. Hepatobiliary Pancreat Dis Int 15(3):275–281

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Author information

Correspondence to Prof. Dr. F. Tacke.

Ethics declarations

Interessenkonflikt

C. Engelmann erhielt Forschungsgelder sowie Reisekostenunterstützung von Novartis, Sequana Medical und Merz Pharmaceuticals und wurde durch Gelder der Deutschen Forschungsgemeinschaft (DFG) finanziert. F. Tacke hat Forschungsgelder von Galapagos, Allergan, Bristol-Myers Squibb und Inventiva erhalten.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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A. Koch, Aachen,

A. Canbay, Bochum

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Engelmann, C., Tacke, F. Dekompensierte Leberzirrhose und akut-auf-chronisches Leberversagen. Gastroenterologe (2020) doi:10.1007/s11377-019-00407-9

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Schlüsselwörter

  • Multiples Organversagen
  • Intensivmedizin
  • Regeneration
  • Infektionen
  • Angeborene und erworbene Immunität

Keywords

  • Multiple organ failure
  • Intensive care
  • Regeneration
  • Infections
  • Innate and adaptive immunity