Immunodysfunction in Acute-on-Chronic Liver Failure

Abstract

Background: Increasing evidence reveals a close and reciprocal link between acute-on-chronic liver failure (ACLF) and immunodysfunction. Methods: A literature search in PubMed and abstract databases of relevant congresses was performed. Results: Important characteristics of liver cirrhosis like tissue hypoxia, cell death, or bacterial translocation maintain a state of chronic inflammation. Precipitating events of ACLF such as infections or alcoholic hepatitis are capable of strongly augmenting cirrhosis-associated systemic inflammation to grades sufficient to induce ACLF-defining organ failures. Chronic systemic inflammation, however, is causally linked to profound immunosuppression. As a consequence, patients with liver cirrhosis and in particular with ACLF are at high risk for severe infections. Promising strategies to ameliorate immunodysfunction, like albumin substitution, administration of recombinant interleukin-22 or granulocyte colony-stimulating factor, antibiotic prophylaxis, or anticoagulation, are under development and offer the chance to specifically prevent and treat ACLF. Conclusion: A better understanding of the immunopathology of ACLF will likely translate into the implementation of specific therapeutic modalities to prevent and overcome ACLF.

Intensive Care Therapy for Patients with Advanced Liver Diseases

“…Last but not least, clinical investigations, which clearly identified white blood cell count and C-reactive protein (CRP) as independent predictors of in-hospital survival, add great evidence to the prognosis-relevant role of SI [64,65]. More information on 'immune dysregulation' is given by Lange and Moreau [66] in this focus issue of Visceral Medicine.…”

Metabolic defects in splenic B cell compartments from patients with liver cirrhosis

“…For example, in patients with advanced liver cirrhosis, immune deficiency generally contributes to increased susceptibility to microbial infections, frequently leading to patient death 4 . Alternatively, patients with compensated liver cirrhosis can suffer from acute-on-chronic liver failure (ACLF), which is initiated by various triggering events 5 . The onset of ACLF is related to CAID, during which imbalanced immunity perplexingly causes both hyperinflammation and immune paralysis, leading to dysregulated inflammatory injury during the triggering phase and failed immune defenses during the regenerative phase 5 , 6 .…”

“…Alternatively, patients with compensated liver cirrhosis can suffer from acute-on-chronic liver failure (ACLF), which is initiated by various triggering events 5 . The onset of ACLF is related to CAID, during which imbalanced immunity perplexingly causes both hyperinflammation and immune paralysis, leading to dysregulated inflammatory injury during the triggering phase and failed immune defenses during the regenerative phase 5 , 6 . In addition, cirrhotic patients respond poorly to vaccination, rendering them the most vulnerable population to preventable infectious diseases, such as influenza 7 and viral hepatitis 8 , 9 .…”

Akut-auf-chronisches Leberversagen (ACLF)

“…Die Kombination aus beatmungspflichtigem ARDS, katecholaminpflichtigem Kreislaufversagen und Nierenversagen wurde auch als letale Trias der Transplantation bezeichnet [16]. Die meisten Patienten, die in der genannten Arbeit [15] mit Komplikationen einer Zirrhose auf die Intensivstation aufgenommen wurden, waren aus verschiedensten Gründen keine geeigneten Transplantationskandidaten und letztlich wurden nur 3 % der Patienten während des Intensivaufenthaltes evaluiert und transplantiert.…”