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

Abstract

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.

Beyond Varices: Complications of Cirrhotic Portal Hypertension in Pediatrics

“…Patients with cirrhosis have higher levels of proinflammatory cytokines, alterations in innate immunity leading to impaired pathogen surveillance, increased bacterial translocation leading to systemic endotoxemia, and a state of chronic inflammation with decreased effectiveness to respond to and clear pathogenic insults. [41][42][43][44] All of these factors increase the risk of infection including SBP. 36,45,46…”

Faecal microbiota transplant restores intestinal barrier function and augments ammonia metabolism in patients with cirrhosis: a randomised single-blind placebo-controlled trial

“…(7) BT is a signi cant driver of cirrhosis-associated immune dysfunction (CAID) which increases susceptibility to infection. (8,9) Gut microbiota manipulation with the non-absorbable antibiotic rifaximin-α in cirrhotic patients led to a reduction in hospitalisation and 30-day readmission. (10,11) Furthermore, we have recently shown that rifaximin-treated cirrhotic patients were less likely to develop infection.…”

Assessment of neutrophil subsets and immune checkpoint inhibitor expressions on T lymphocytes in liver transplantation: A preliminary study beyond the neutrophil-lymphocyte ratio

“…In addition to CAID, LT amplifies the profound immunosuppressive state of patients due to major surgery, immunosuppressive drugs, and intensive care unit stay). Therefore, infections constitute a major clinical issue in pre- and post-LT patients ( Tranah et al, 2022 ). Before LT, infections in cirrhotic patients are both more frequent and more severe in association with cirrhosis severity and they can delay the access to a graft and increase mortality risk ( Finkenstedt et al, 2013 ).…”

“…Before LT, infections in cirrhotic patients are both more frequent and more severe in association with cirrhosis severity and they can delay the access to a graft and increase mortality risk ( Finkenstedt et al, 2013 ). After LT, infections increase morbidity and graft dysfunction ( Tranah et al, 2022 ). Noteworthy, infections represent the major cause of death in the first year following LT in ACLF patients ( Sundaram et al, 2020 ).…”