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.