Sepsis in liver failure patients: Diagnostic challenges and recent advancements

Acute liver failure (ALF) and acute-on-chronic LF (ACLF) are prevalent hepatic emergencies characterized by an increased susceptibility to bacterial infections (BI), despite significant systemic inflammation. Literature indicates that 30%-80% of ALF patients and 55%-81% of ACLF patients develop BI, attributed to immunological dysregulation. Bacterial sepsis in these patients is associated with adverse clinical outcomes, including prolonged hospitalization and increased mortality. Early detection of bacterial sepsis is critical; however, distinguishing between sterile systemic inflammation and sepsis poses a significant challenge due to the overlapping clinical presentations of LF and sepsis. Conventional sepsis biomarkers, such as procalcitonin and C-reactive protein, have shown limited utility in LF patients due to inconsistent results. In contrast, novel biomarkers like presepsin and sTREM-1 have demonstrated promising discriminatory performance in this population, pending further validation. Moreover, emerging research highlights the potential of machine learning-based approaches to enhance sepsis detection and characterization. Although preliminary findings are encouraging, further studies are necessary to validate these results across diverse patient cohorts, including those with LF. This article provides a comprehensive review of the magnitude, impact, and diagnostic challenges associated with BI in LF patients, focusing on novel advancements in early sepsis detection and characterization.