Non-Biological Liver Support Systems for Hepatic Encephalopathy: A Framework for Phenotype-Matched Precision Management

Hepatic encephalopathy (HE) is a severe neurological syndrome arising from the interaction between hyperammonemia and systemic inflammation.In ALF and ACLF, severe HE occurs within a broader context of systemic derangements, including inflammation and hepatic synthetic dysfunction.Despite advances in non-biological liver support systems (NBLSS), improved biochemical clearance has not consistently translated into a survival benefit.This review organizes their therapeutic effects into three principal and overlapping functional domains: metabolic detoxification, inflammatory-mediator clearance, and plasma removal/replacement.Individual modalities may contribute to more than one domain, although their dominant therapeutic functions differ.We observe a clinical transition from monotherapy toward hybrid protocols.Specifically, sequential adsorption and reduced-volume plasma exchange exemplify how complementary clearance and replacement functions can be combined while conserving donor plasma resources.Given the heterogeneity of clinical outcomes, a precision-management approach may better align extracorporeal support with individual physiological requirements.We propose using clinical and biomarker-based indicators to identify metabolic-dominant, inflammationdominant, and synthetic-failure-dominant physiological phenotypes.These phenotypes are conceptualized as overlapping and dynamically evolving physiological patterns rather than mutually exclusive biological subtypes.Cross-cutting homeostatic requirements should be assessed in parallel when selecting and adapting extracorporeal support.Dynamic phenotype-matched multimodal support may better translate biochemical and neurological improvement into clinically meaningful stabilization while providing a bridge to native liver recovery or transplantation.