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Implications and Management of Cirrhosis-Associated Immune Dysfunction Before and After Liver Transplantation

Research output: Contribution to journalArticlepeer-review

T H Tranah, V T Kronsten, D L Shawcross

Original languageEnglish
JournalLiver Transplantation
Early online date5 Nov 2021
Accepted/In press2021
E-pub ahead of print5 Nov 2021

Bibliographical note

Funding Information: Thomas H. Tranah has received a grant from Norgine. Debbie L. Shawcross consults, advises, is on the speakers' bureau for, and received grants from Norgine. She advises EnteroBiotix, Kaleido Biosciences, Mallinckrodt, and Shiongi. She is on the speakers' bureau for Falk and Alfa Sigma. Publisher Copyright: © 2021 by the American Association for the Study of Liver Diseases.

King's Authors


Cirrhosis-associated immune dysfunction (CAID) describes a panacea of innate and adaptive deficits that result from the sequelae of cirrhotic portal hypertension that is similar in its manifestations regardless of etiology of chronic liver injury. CAID is associated with synchronous observations of dysregulated priming of innate immune effector cells that demonstrate a proinflammatory phenotype but are functionally impaired and unable to adequately prevent invading pathogens. CAID is mainly driven by gut-barrier dysfunction and is associated with deficits of microbial compartmentalization and homeostasis that lead to tonic activation, systemic inflammation, and exhaustion of innate-immune cells. CAID leads to a high frequency of bacterial and fungal infections in patients with cirrhosis that are often associated with acute decompensation of chronic liver disease and acute-on-chronic liver failure and carry a high mortality rate. Understanding the deficits of mucosal and systemic immunity in the context of chronic liver disease is essential to improving care for patients with cirrhosis, preventing precipitants of acute decompensation of cirrhosis, and improving morbidity and survival. In this review, we summarize the detailed dynamic immunological perturbations associated with advanced chronic liver disease and highlight the importance of recognizing immune dysregulation as a sequela of cirrhosis. Furthermore, we address the role of screening, prevention, and early treatment of infections in cirrhosis in improving patient outcomes in transplant and nontransplant settings.

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