Christian M Lange1, Richard Moreau2. 1. Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany. 2. Centre de Recherche sur l'Inflammation (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Diderot, Paris, France.
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.
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.
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