Interpreting liver function markers in children on continuous renal replacement therapy for acute liver failure

Children with acute liver failure (ALF) often experience hyperammonaemia, fluid overload, metabolic derangements, and multi-organ failure. Continuous renal replacement therapy (CRRT) is commonly used for renal and non-renal indications, particularly in those with hyperammonaemia and hepatic encephalopathy. However, the non-selective nature of CRRT can result in the clearance of beneficial metabolites and liver-related biomarkers, which are important for monitoring disease progression or improvement. Therefore, understanding the kinetic principles governing molecular clearance during CRRT is crucial for accurate interpretation of liver biochemistry to inform clinical decision-making. By considering the kinetic properties of hepatic markers, including bilirubin, bile acids, liver enzymes, metabolites, waste products, inflammatory markers, albumin, and coagulation proteins, we describe the impact of CRRT on the plasma levels of these markers. In addition, we discuss various CRRT attributes, and the removal of these markers is also discussed. Metabolites and waste products, including ammonia, lactate, and urea, are the most useful markers to inform CRRT responsiveness, owing to their small molecular size, low degree of protein binding, and small volume of distribution; whereas bilirubin, bile acids, coagulation factors, and albumin remain true indicators of hepatic function and clinical condition. It should be noted that the overall plasma levels of any molecules reflect the balance between production and clearance, even for molecules with a high degree of CRRT removal. Awareness of these properties helps clinicians differentiate dialytic response versus genuine hepatic recovery or deterioration, guiding a more rational interpretation of clinical progression in ALF with liver transplant/spontaneous native recovery or mortality as the outcomes.Conclusion: Understanding the kinetic behaviour of liver-related markers during CRRT is essential to distinguish between dialytic clearance and true changes in hepatic function. This knowledge enables more accurate clinical interpretation, guiding decision-making in children with acute liver failure and optimizing management strategies toward recovery or timely transplantation.