Pathophysiologie der Dekompensation bei Leberzirrhose – Prognose-Scores

Was ist neu?

Die periphere arterielle Vasodilatations-Hypothese In der Vergangenheit war das führende Modell für die Erklärung der Entstehung von Dekompensationsereignissen bei der Zirrhose die periphere arterielle Vasodilatations-Hypothese. Diese hat man zuletzt zunehmend verlassen, stattdessen rückt eine chronische Inflammation in den Fokus.

Systemische Inflammation als Trigger für die Dekompensation der Leberzirrhose Aktuelle Studien konnten zeigen, dass bei der akuten Dekompensation (AD) wie dem ACLF ein inflammatorischer Status vorherrscht. Darüber hinaus ist die Inflammation auch eng mit dem weiteren klinischen Verlauf und der Prognose nach einem Dekompensationsereignis verknüpft.

Die Leberzirrhose als inflammatorisch getriggerte Multisystem-Erkrankung Der inflammatorische Zustand bei der Leberzirrhose führt über verschiedenste Mechanismen auch zu einer Beeinträchtigung der Funktion extrahepatischer Organsysteme, wie bspw. der Niere oder dem Herz. Die Leberzirrhose kann daher als inflammatorisch getriggerte Multisystem-Erkrankung betrachtet werden.

Neue klinische Scores bei Patienten mit einer Leberzirrhose Der zunehmende Fokus auf die Inflammation findet auch Berücksichtigung in aktuellen prognostischen Scores. So ist die Leukozytenzahl, als inflammatorischer Parameter, Bestandteil des CLIF-C-AD-Scores sowie des CLIF-C-ACLF-Scores, die der Prognoseabschätzung bei einer AD beziehungsweise einem ACLF dienen.

Abstract

Acute decompensation and acute-on chronic liver failure (ACLF) are associated with a significant reduced prognosis. Previously, the pathophysiological concept of acute decompensation was mainly based on the peripheral vasodilatation hypothesis. However, during the last years, systemic inflammation was recognized as a major driver for decompensation of liver cirrhosis and ACLF. Further, it has been shown that systemic inflammation is associated with the clinical course and the prognosis of the patients. Inflammation also affects the function of extrahepatic organs and therefore leads to the development of an inflammatory cirrhotic multi-organ syndrome. The importance of systemic inflammation in the context of decompensated liver cirrhosis is also transferred to new clinical scores such as the CLIF-C AD and CLIF-C ACLF score. In this article, we provide an overview of the new systemic inflammation hypothesis of decompensated cirrhosis and also discuss current clinical scores for prognostication in different stages of liver cirrhosis.

Schlüsselwörter

Leberzirrhose - Entzündung - Dekompensation - ACLF - Scores

Key words

liver cirrhosis - inflammation - decompensation - ACLF - scores

^* geteilte Erstautorenschaft.

Publication History

Article published online:
30 May 2022

• Literatur

• 1 D’Amico G, Pasta L, Morabito A. et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther 2014; 39 (10) 1180-1193
• 2 Moreau R, Jalan R, Gines P. et al. Acute-on-Chronic Liver Failure Is a Distinct Syndrome That Develops in Patients With Acute Decompensation of Cirrhosis. Gastroenterology 2013; 144 (07) 1426-1437
• 3 Bernardi M, Moreau R, Angeli P. et al. Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol 2015; 63 (05) 1272-1284
• 4 D’Amico G, Bernardi M, Angeli P. Towards a new definition of decompensated cirrhosis. J Hepatol 2022; 76 (01) 202-207
• 5 Trebicka J, Fernandez J, Papp M. et al. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology. J Hepatol 2020; 73 (04) 842-854
• 6 Arroyo V, Angeli P, Moreau R. et al. The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis. J Hepatol 2021; 74 (03) 670-685
• 7 Merli M, Lucidi C, Pentassuglio I. et al. Increased risk of cognitive impairment in cirrhotic patients with bacterial infections. J Hepatol 2013; 59 (02) 243-250
• 8 Aldridge DR, Tranah EJ, Shawcross DL. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol 2015; 5 (Suppl. 01) S7-S20
• 9 Bellot P, García-Pagán JC, Francés R. et al. Bacterial DNA translocation is associated with systemic circulatory abnormalities and intrahepatic endothelial dysfunction in patients with cirrhosis. Hepatology 2010; 52 (06) 2044-2052
• 10 Yoon KT, Liu H, Lee SS. Cirrhotic Cardiomyopathy. Curr Gastroenterol Rep 2020; 22 (09) 45
• 11 Stadlbauer V, Stadlbauer VP, Wright GAK. et al. Relationship between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis. Gastroenterology 2008; 134 (01) 111-119
• 12 Shah N, Mohamed FE, Jover-Cobos M. et al. Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis. Liver Int 2013; 33 (03) 398-409
• 13 Kubes P, Mehal WZ. Sterile Inflammation in the Liver. Gastroenterology 2012; 143 (05) 1158-1172
• 14 Salerno F, Merli M, Cazzaniga M. et al. MELD score is better than Child-Pugh score in predicting 3-month survival of patients undergoing transjugular intrahepatic portosystemic shunt. J Hepatol 2002; 36 (04) 494-500
• 15 Jalan R, Pavesi M, Saliba F. et al. Amorós A, Fernandez J, Holland-Fischer P, u. a. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 2015; 62 (04) 831-840
• 16 Jalan R, Saliba F, Pavesi M. et al. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014; 61 (05) 1038-1047
• 17 Sturm L, Bettinger D, Giesler M. et al. Treatment with proton pump inhibitors increases the risk for development of hepatic encephalopathy after implantation of transjugular intrahepatic portosystemic shunt (TIPS). United European Gastroenterol J 2018; 6 (09) 1380-1390
• 18 Bettinger D, Sturm L, Pfaff L. et al. Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival. J Hepatol 2021; 74 (06) 1362-1372