Therapeutic plasma exchange in children with acute liver failure (ALF): is it time for incorporation into the ALF armamentarium?

Abstract

Paediatric acute liver failure (PALF) is a rare but devastating condition with high mortality. An exaggerated inflammatory response is now recognised as pivotal in the pathogenesis and prognosis of ALF, with cytokine spill from the liver to systemic circulation implicated in development of multi-organ failure associated with ALF. With advances in medical management, especially critical care, there is an increasing trend towards spontaneous liver regeneration, averting the need for emergency liver transplantation or providing stability to the patient awaiting a graft. Hence, research is ongoing for therapies, including extracorporeal liver support devices, that can bridge patients to transplant or spontaneous liver recovery. Considering the immune-related pathogenesis and inflammatory phenotype of ALF, plasma exchange serves as an ideal liver assist device as it performs both the excretory and synthetic functions of the liver and, in addition, works as an immunomodulatory therapy by suppressing the early innate immune response in ALF. After a recent randomised controlled trial in adults demonstrated a beneficial effect of high-volume plasma exchange on clinical outcomes, this therapy was incorporated in European Association for the Study of Liver (EASL) recommendations for managing adult patients with ALF, but no guidelines exist for PALF. In this review, we discuss rationale, timing, practicalities, and existing evidence regarding the use of plasma exchange as an immunomodulatory treatment in PALF. We discuss controversies in delivery of this therapy as an extracorporeal device, and practicalities of use of plasma exchange as a 'hybrid' therapy alongside other extracorporeal liver assist devices, before finally reviewing outstanding research questions for the future.

Keywords: Acute liver failure; Children; Extracorporeal liver support; Paediatric intensive care unit; Plasma exchange.

Fig. 1

Propagation of early inflammatory response in ALF and spread of inflammatory mediators to the systemic circulation

Fig. 2

Three domains for consideration regarding TPE in ALF: what disease, what dose, and what device

Fig. 3

Relative phase of inflammatory response in the liver according to timing of liver injury and the consequent action of plasma exchange

Fig. 4

Illustration of using one vascular access for TPE and KRT in series (left, using the access lumen) and in parallel (right, on separate catheter lumens)