The Problem These Systems Address

The failing liver accumulates protein-bound toxins — unconjugated bilirubin, bile acids, short-chain fatty acids, aromatic amino acids — that standard renal dialysis cannot remove, because they are bound to albumin in blood rather than dissolved freely. These toxins cause hepatic encephalopathy, systemic vasodilation, renal injury, and systemic inflammation. They also bind to the albumin used in treatment, progressively “poisoning” the albumin’s carrying capacity. Extracorporeal liver support systems are specifically designed to remove these protein-bound toxins by exploiting competitive binding to exogenous albumin or fresh plasma.

High-Volume Plasma Exchange (HVP)

In high-volume plasma exchange, the patient’s own plasma is separated from blood cells by plasmapheresis and discarded — replaced by fresh frozen plasma (FFP) or a combination of FFP and human albumin. Each session replaces approximately 8–12 litres of plasma (roughly 1.5× the patient’s calculated plasma volume). This simultaneously removes protein-bound toxins, replaces depleted coagulation factors, and replenishes functional albumin.

The evidence in ALF is the strongest: a randomised controlled trial by Larsen et al. (2016, N Engl J Med) showed that high-volume plasma exchange significantly improved 28-day transplant-free survival in ALF patients compared to standard care alone. The benefit in ACLF is less clearly established in randomised data, but plasma exchange is widely used as a bridging strategy in ACLF patients awaiting transplant or showing early signs of recovery. Typically 3 consecutive sessions are performed, with liver function and encephalopathy assessed after each.

MARS — Molecular Adsorbent Recirculating System

MARS (Gambro, now Baxter) is an albumin dialysis system. The patient’s blood circulates against a membrane. On the other side of the membrane is albumin dialysate — a 20% human albumin solution. Protein-bound toxins cross from the patient’s blood into the albumin dialysate by competitive displacement. The albumin dialysate then circulates through two further cleaning modules: an activated charcoal column and an anion exchange resin, which strip the adsorbed toxins from the albumin and regenerate it for re-use in the same session.

Because MARS incorporates a standard hemodialysis circuit, it simultaneously provides renal support — critical in ACLF, where acute kidney injury accompanies liver failure in the majority of grade 3 ACLF patients. Sessions typically run 6–8 hours. MARS does not supply the liver’s synthetic functions (it does not produce albumin, coagulation factors, or glucose) — it only removes toxins. Its role is therefore as a bridge, not as a replacement liver.

SPAD — Single-Pass Albumin Dialysis

SPAD is a simpler albumin dialysis technique where fresh albumin is continuously infused and discarded in a single pass, rather than recirculated. It is less expensive than MARS but also less efficient per session. SPAD is used where MARS equipment is unavailable or when shorter sessions are planned. Evidence is less extensive than for MARS or plasma exchange.

Who Are These Therapies For?

• ACLF Grade 2–3: Patients with two or more organ failures with evidence of toxin accumulation (high bilirubin, encephalopathy), listed or being considered for urgent liver transplant
• Acute Liver Failure (ALF): Drug-induced, viral, Wilson’s disease — plasma exchange is particularly well-supported in this context
• Not suitable: Patients with irreversible brain herniation, non-liver causes of multi-organ failure, or who have clearly decided against transplant — liver support in these situations does not change outcomes

The decision to start liver support is made jointly by Dr Kalal and the ICU team. It is always coupled with a parallel transplant assessment — because liver support systems can stabilise a patient but rarely regenerate a failed liver on their own. They create a window. How that window is used determines the outcome.