Systemic Inflammation and Acute-on-Chronic Liver Failure: Too Much, Not Enough

Abstract

ACLF is a specific, but complex and multifactorial form of acute decompensation of cirrhosis and is characterized by an extraordinary dynamic natural course, rapidly evolving organ failure, and high short-term mortality. Dysbalanced immune function is central to its pathogenesis and outcome with an initial excessive systemic inflammatory response that drives organ failure and mortality. Later in its course, immuno-exhaustion/immunoparalysis prevails predisposing the patient to secondary infectious events and reescalation in end-organ dysfunction and mortality. The management of patients with ACLF is still poorly defined. However, as its pathophysiology is gradually being unravelled, potential therapeutic targets emerge that warrant further study such as restoring or substituting albumin via plasma exchange or via albumin dialysis and evaluating usefulness of TLR4 antagonists, modulators of gut dysbiosis (pre- or probiotics), and FXR-agonists.

The Role of Macrophage-Inducible C-Type Lectin in Different Stages of Chronic Liver Disease

“…Although advanced chronic liver disease features systemic inflammation, "sepsis-like" immune paralysis develops in more severe stages facilitating secondary infections and organ failure (37,38). Mincle possibly plays an important role in these apparently opposing observations, since the dysregulation of mincle signaling in spleen and PBMC, as important compartments of the immune system, could be responsible for the failure to clear invading gut bacteria and consequent systemic inflammation.…”

N‐myc and STAT interactor correlates with severity and prognosis in acute‐on‐chronic liver failure of hepatitis B virus

“…In addition to the established prognostic scores that based on conventional clinical parameters, biomarkers related to inflammation and immune for early prediction of HBV‐ACLF are also being explored . Zhang et al .…”

“…In addition to the established prognostic scores that based on conventional clinical parameters, biomarkers related to inflammation and immune for early prediction of HBV-ACLF are also being explored. 28 Zhang et al report that frequency of Th17 cells predicts 3-month prognosis equivalent to MELD and CLIF-C ACLF scores in HBV-ACLF. 29 Similarly, our current study showed that serum NMI may have prognostic value equivalent to MELD and CLIF-C ACLFs in predicting 3-month mortality in HBV-ACLF patients.…”

Compartmentalization of immune response and microbial translocation in decompensated cirrhosis

“…Acquired dysfunctional immunity in cirrhosis predisposes patients to frequent bacterial infections contributing to disease progression and may lead to the development of acute-onchronic liver failure (ACLF) (1). Especially, spontaneous bacterial peritonitis (SBP) is one of the most frequent infections in cirrhosis and therefore a trigger for ACLF (2).…”