Dysfunctional Immune Response in Acute-on-Chronic Liver Failure: It Takes Two to Tango

Conclusion Massive SI and immune cell paralysis associated with ACLF represent the extreme severity of CAID in response to an infectious or sterile challenge. The severe immune disturbance plays a pivotal role in the pathogenesis of the distinctive features of ACLF: organ failure and bacterial infection susceptibility. Excessive SI in ACLF results from the massive activation and dysfunction of an innate immune system challenged by increased PAMPs and DAMPs. SI leads to cell and tissue immunopathology contributing to hepatic and extrahepatic organ failure. Concomitantly, the course of ACLF is associated with a disproportionate compensatory anti-inflammatory response along with exhaustion and dysregulation of the innate and adaptive arms of the immune system, with the subsequent functional immune paralysis that confers a higher risk of infections and further ACLF progression. Therapies aimed at preventing the development of these immune disturbances in ACLF are novel promising strategies to improve survival in these patients. Author Contributions The manuscript was drafted by RM-M and AA. MA-M and AA critically reviewed the manuscript. All the authors approved the final draft for submission. The guarantor of the manuscript is AA. Funding This work was financed by grants from the Ministerio de Sanidad, Consumo y Bienestar Social, Instituto de Salud Carlos III (PI051871, CIBERehd) and Ministerio de Ciencia e Innovación (SAF 2017-86343-R) awarded to AA. Ciberhed is fun...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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