Acute liver failure (ALF) is a life-threatening syndrome characterized by abrupt hepatic dysfunction accompanied by systemic inflammatory response and immune dysregulation, resulting in a high susceptibility to infectious complications. In the intensive care unit (ICU) setting, bacterial sepsis and invasive fungal infections represent critical determinants of multiorgan failure, liver transplant eligibility, and patient survival.
Main body
This narrative review synthesizes current evidence on infectious risk, diagnostic challenges, and antimicrobial management in ALF. The immune response to massive hepatocellular necrosis is initially driven by damage-associated and pathogen-associated molecular patterns, resulting in a sepsis-like hyperinflammatory state. This phase is followed by profound immunoparesis, characterized by impaired innate and adaptive immune responses, which facilitates fbacterial translocation, increases susceptibility to nosocomial infections, and promotes colonization and infection with multidrug-resistant (MDR) pathogens. Infections occur in most ALF patients, yet differentiation between sterile systemic inflammatory response and sepsis remains challenging as fever, leukocytosis, and hemodynamic instability are nonspecific and microbiological cultures frequently yield negative results. Conventional biomarkers primarily reflect hepatocellular injury rather than bacterial infection. Antimicrobial therapy should be individualized based on clinical severity, local epidemiology, and MDR colonization, while accounting for profound pharmacokinetic alterations associated with hepatic failure. In liver transplant candidates and recipients, short-course perioperative prophylaxis and judicious interpretation of MDR screening are pivotal to prevent early postoperative infections without promoting antimicrobial resistance.
Conclusions
Optimizing infection diagnosis, biomarker-guided decision-making, and individualized antimicrobial dosing in ALF, particularly in the peri-transplant ICU setting, is critical for improving patient outcomes and limiting the emergence of MDR pathogens.
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