Neuroprotection in ALF: Journal of Hepatology | March 2026

Introduction

Neuroprotection remains a central challenge in the management of acute liver failure, where cerebral oedema and intracranial hypertension are major drivers of mortality. Traditionally, invasive intracranial pressure monitoring has been used to guide management, but recent shifts in clinical practice suggest a move away from this approach. This evolving paradigm reflects a deeper understanding of the pathophysiology of brain injury in acute liver failure, where ammonia toxicity, systemic inflammation, and blood–brain barrier dysfunction act synergistically rather than independently.

Summary

This article highlights a significant transition in neuroprotective strategies in acute liver failure following evidence that declining use of invasive intracranial pressure monitoring has not adversely affected survival outcomes. The focus is shifting from reactive management of intracranial hypertension to proactive prevention of cerebral oedema. Blood ammonia is emphasised as a key early biomarker for identifying high-risk patients, although it is recognised as a downstream marker rather than the primary driver of injury. Increasing attention is being directed toward upstream mechanisms, particularly systemic inflammation and cytokine-mediated neurotoxicity, which may offer future therapeutic targets.

The second major shift is toward non-invasive, multimodal neurological monitoring. Emerging tools such as transcranial Doppler, near-infrared spectroscopy, and continuous electroencephalography offer dynamic insights into cerebral perfusion, oxygenation, and neuronal activity, enabling a more comprehensive and individualised assessment of brain function without procedural risk.

Finally, the reduction in invasive monitoring introduces a critical clinical challenge: determining irreversible brain injury and transplant eligibility. The author proposes a multimodal framework combining imaging, functional neurophysiology, and biomarkers to guide decision-making. This approach is essential to ensure appropriate use of liver transplantation while avoiding both futile interventions and missed opportunities for timely transplantation.