Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by acute deterioration of liver function in patients with pre-existing chronic liver disease. It is often accompanied by multiorgan failure and systemic inflammation, with high short-term mortality rates. The triggers for ACLF include bacterial infections, acute alcoholic hepatitis, and ischemic hepatitis, leading to the release of pro-inflammatory mediators.
These systemic inflammatory responses result in immune dysfunction, contributing to the progression of the disease. Recent research has emphasized the metabolic changes in immune cells and the body's catabolic response to meet the energy demands during ACLF. These metabolic alterations, particularly in immune cells, disrupt mitochondrial functions and lead to the accumulation of harmful metabolites, further impairing immune responses.
Understanding these metabolic pathways and their effects on immune function offers new therapeutic targets for managing ACLF. Immune cell alterations in ACLF ACLF patients exhibit significant alterations in their immune cell populations. These include an increase in white blood cells, predominantly neutrophils and monocytes, and a decrease in lymphocytes and natural killer (NK) cells.
Neutrophils, although elevated in number, show functional impairments such as reduced phagocytic activity and decreased pathogen clearance. Furthermore, neutrophils in ACLF patients tend to overproduce neutrophil extracel.
