Therapeutic Plasma Exchanges in Acute Liver Failure: where do we stand in 2025?

Abstract

Acute Liver Failure (ALF) is a rare but life-threatening critical illness that occurs most often in patients who do not have preexisting liver disease. In Europe, paracetamol intoxication is the first cause of ALF, and Liver Transplantation (LT) is the gold-standard treatment for cases meeting poor prognosis criteria. Regardless etiology, ALF is characterized by both hepatic and systemic inflammation, which is responsible for extra-hepatic organ failures, which can lead to death. The pathophysiological rationale for the use of Therapeutic Plasma Exchange (TPE) in the management of ALF lies in the removal and reduction of inflammatory plasma mediators to mitigate their systemic consequences. This concept, proposed many years ago, initially demonstrated clinical benefits (hemodynamic, neurological, and biological improvements) in small case series. In 2016, a randomized controlled trial ultimately confirmed the utility of High-Volume Plasma Exchange (HVPE) in ALF, demonstrating improved free-transplant survival. In 2021, a second randomized trial corroborated these findings, albeit using lower exchanged volumes. More recently, real-world data have been published in the literature, with sometimes conflicting results. While TPE have demonstrated an impact on free-transplant survival in ALF, further studies are required to better define their role. These should clarify key factors such as initiation criteria, exchanged volumes, and frequency of treatment.