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Introduction

Chronic liver disease affects 10% of the world’s population, and acute liver failure compromises approximately 5 million patients per year in Western countries [1]. Liver failure prevents the liver from performing normal functions, such as detoxification, biotransformation, excretion and synthesis, with accumulation of toxins and lethal complications [2]. Its causes include undetermined aetiology, secondary to drugs, viral infection, exotoxic from alcohol abuse and autoimmune diseases [2]. Acute liver failure (ALF) describes a dysfunction with encephalopathy, impaired liver synthesis, and metabolic function. Acute-on-chronic liver failure (ACLF) describes an exacerbation of underlying chronic disease such as alcohol-based exotoxic hepatopathy, HBV and HCV viral infections [2]. ACLF has a high mortality rate of between 50% and 90% with development of jaundice, systemic port encephalopathy and multiple organ failure [3]. Endogenous toxins found in patients with acute liver failure include bilirubin, ammonium, glutamine, lactate, aromatic amino acids, free fatty acids, phenol, mercaptans, and pro-inflammatory cytokines. The loss of hepatocytes promotes a progressive increase in apoptosis and hepatic necrosis. The liver has a great capacity to regenerate itself after partial hepatectomy or iatrogenic intoxication such as paracetamol, maintaining sufficient liver function for adequate homeostasis [4].  Hepatic toxins are hydrophobic with a molecular weight < 1000 Da (Bilirubin = 406 Da, cholic acid = 283 Da, chenodeoxycholic acid = 272 Da) and have a protein bond that prevents free diffusion of bilirubin and bile acids resulting in toxicity in human tissue. These characteristics explain why classical renal dialysis techniques based on convection and diffusion are not effective in removing these toxins [5]. Orthotopic liver transplantation has been the treatment of choice, but there are no available organs. High mortality rate needs new treatment as a “bridge” to liver transplantation or as a replacement treatment until spontaneous recovery of liver function [6]. Extracorporeal liver support devices (ECLSDs) serve as a bridge until a donor liver becomes available or hepatic recovery occurs. There are two main types of ECLSDs: artificial and bioartificial [7]. Biological methods are difficult to implement and very expensive; non-biological ECLSDs are the most commonly used. The main indications for the use of ECLSDs are: ALF from paracetamol intoxication, ALF from hepatitis A and B, ACLF from chronic hepatopathy, type 1 or 2 hepatorenal syndrome, severe acute cholestatic hepatitis, pruritus unresponsive to medical therapy, systemic port encephalopathy and hyperbilirubinemia while waiting for a liver transplant, primary or secondary dysfunction of a liver transplant [6]. Understanding how ECLSDs operate requires acknowledging that liver failure primarily compromises the liver’s detoxification capacity. Therefore, water-soluble (or non-albumin-bound, such as ammonium) and hydrophobic (or albumin-bound, non-removable with dialysis, such as bilirubin and bile acids) substances accumulate in the plasma. ECLSDs aim to remove liver toxins and were developed from the experience and technology of renal function replacement treatments with haemodialysis. Some toxins such as small water-soluble toxins like ammonium can be removed easily with haemodialysis techniques of haemodiafiltration; for larger, protein-bound molecules, other methods combining diffusion, convection techniques together with filtration and adsorption are required [8]. Principles for the extraction of hydrophobic (lipid-soluble) and albumin-bound toxins are: pheresis, direct removal of plasma or albumin from the patient, taking the albumin-bound toxins with it; adsorption, direct extraction of the toxins present in the albumin, through the use of sorbents; facilitated diffusion: indirect method using a dialysate with albumin.  Thus, the albumin circuit enables the facilitated diffusion of albumin-bound toxins, driven by oncotic pressure gradients. The solutes in question are separated from the patient’s albumin and subsequently bind to the albumin in the dialysate to be removed through the passage of a dialysis membrane.

ECLSDs improve symptoms (systemic port encephalopathy, pruritus) and survival by reducing ammonium, bilirubin, and transaminase levels. Bilirubin is used as a biochemical marker of treatment efficacy due to the toxins’ characteristics, high affinity for proteins, and ease of measurement in any laboratory. The binding between bilirubin and albumin is extremely effective (9.5 × 10⁷ M⁻¹) and just one ninety-fifth millionth of a mole of bilirubin is able to saturate 50% of the albumin bonds. The direct adsorption technique is the best option for removing albumin-bound toxins. ECLSDs techniques with filtration and adsorption show better removal of protein-bound toxins and water-soluble toxins [9].

Taking into account the physical principles mentioned, ECLSD techniques are based on diffusion, convection, adsorption and pheresis mechanisms, applied singly or in combination. The common goal of these methods is the removal of liver toxins that accumulate in patients with acute or acute-on-chronic liver failure through elimination of both water-soluble toxins (ammonium), hydrophobic toxins bound to albumin (bilirubin and bile acids), an elimination that cannot be achieved with conventional dialysis alone. The various technologies differ in terms of technical configuration, materials used (presence or absence of albumin, need for adsorbent cartridges), blood flows, costs, and system complexity. In the following sections, the main solutions available today will be described in detail, with a focus on the advantages and limitations of each system.

	Plasmapheresis	SPAD (Single Pass Albumin Dialysis)	MARS (Molecular Adsorbent Recirculation System)	PROMETHEUS (Fractionated Plasma Separation and Adsorption)	CPFA (Coupled Plasma Filtration Adsorption)	DPMAS (Dual Plasma Molecular Adsorption System)	Cytosorb
Albumin or plasma	yes	yes	yes	no	no	no	no
Collaboration with TRRC	no	yes	yes	no	yes	yes	yes
plasmapheresis	yes	no	no	yes albuminopheresis	yes	yes	no
adsorption cartridge	no	no	yes (two)	yes (two)	yes	yes (two)	yes
special device	no	no	yes	yes	yes	no	no
blood flow (ml/min)	100-150	100-250	100-150	200-350	100-200	100-200	100-350

Table 1. Summary table of different non-organic extracorporeal liver support devices (ECLSDs).

 

Plasmapheresis

Plasmapheresis and haemoperfusion were the first techniques used as ECLSDs. The former involves the direct extraction of plasma (apheresis), while the latter consists of the direct adsorption of fat-soluble solutes from the blood through an activated charcoal cartridge. Both techniques have demonstrated limited efficacy and are not without complications (infection, thrombocytopenia, hypoglycemia), so they are not currently used as liver support therapies [10].

MARS (Molecular Adsorbent Recirculation System)

The MARS is an extracorporeal detoxification technique that combines conventional haemodialysis with albumin dialysis. It utilizes a standard haemodialysis or haemofiltration device integrated with a specific module that circulates human albumin (10-20%) as a dialysate [11]. The patient’s blood passes through a filter where albumin-bound and water-soluble toxins diffuse across a semipermeable membrane (cutoff ~50 kDa), binding to the exogenous albumin. The albumin-containing dialysate, enriched with toxins, then flows through a conventional dialysis filter (removing hydrophilic solutes) and two adsorber cartridges (resin and activated charcoal), which eliminate albumin-bound substances. The purified albumin is recirculated, allowing continuous detoxification. A typical session lasts 6-8 hours and is usually performed daily [12]. This system removes both water-soluble and albumin-bound toxins, improves liver function parameters and stabilizes patients as a bridge to recovery or transplantation, and improves renal function in hepatorenal syndrome [13]. There are limitations like specialized equipment and trained staff; adverse events include transient haemodynamic instability and thrombocytopenia [15]. Cost and session duration (6-8 hours) may limit widespread applications. Most clinical studies on MARS have been performed in patients with acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). Only three randomized trials have assessed its effect on survival. In a prospective randomized controlled trial, Mitzner et al. (2000) demonstrated improved renal and liver function and increased survival in patients with hepatorenal syndrome treated with MARS compared to standard medical therapy [13]. A subsequent randomized study in ACLF patients confirmed similar results [14]. Moreover, one economic analysis suggested that MARS may be cost-effective compared to conventional therapy [15].

 

SPAD – Single Pass Albumin Dialysis

SPAD is based on conventional dialysis equipment and does not require special modules. It relies on the principle of diffusion using an albumin-enriched dialysate bath. Unlike MARS, the albumin dialysate is single-pass and discarded, without the need for an interposed circuit with adsorbent cartridges. SPAD can be performed with any standard haemodialysis or haemofiltration device. A variant, Single-Pass Albumin Extended Dialysis (SPAED), includes an additional high-flow haemodialysis filter to enhance toxin removal. Advantages are simplicity of use with conventional haemodialysis equipment, does not require additional cartridges or modules, lower cost of disposable material compared to MARS and other non-biological liver support systems [16]. The limitations are large amounts of albumin, which increases overall cost, limited efficiency in a single-pass configuration, since the dialysate is discarded after one use. Clinical experience remains limited, mostly to case reports [18]. Two in-vitro studies compared SPAD with MARS, showing that SPAD may be more effective in removing bilirubin and bile acids, though findings on cost-effectiveness were controversial [17]. A retrospective clinical study in patients with acute liver failure reported comparable efficacy between SPAD and MARS. To overcome the limitation of single-pass use, a modified approach – Multiple Pass Albumin Extended Dialysis (MAED or RAED) – was tested in a small patient cohort. This method, based on recirculation of albumin without regeneration and combined with prolonged haemodialysis, showed a significant reduction in bilirubin levels [18]. However, published clinical evidence on SPAD, SPAED, and MAED is still confined to case reports.

 

PROMETHEUS (Fractionated Plasma Separation and Adsorption)

Prometheus is an extracorporeal liver support technique based on fractionated plasma separation and adsorption (FPSA). The system consists of two circuits in series. In the first circuit, the patient’s albumin is selectively fractionated through the Albuflow filter. The separated albumin is then directly purified by adsorption using two specific resin cartridges (Prometh 01 with neutral resin and Prometh 02 with anion-exchange resin). The detoxified albumin is subsequently reinfused into the bloodstream, closing the first circuit. In the second circuit, the patient’s blood passes through a high-flux dialyser (FX dialyser), which allows conventional haemodialysis and the removal of water-soluble substances. It does not require an exogenous albumin circuit, unlike MARS and SPAD/MAED; it has lower consumption of replacement albumin, since patient’s endogenous albumin is purified and recirculated. It provides combined clearance of both albumin-bound and hydrophilic toxins but requires specialized filters and cartridges [19].  A limitation is a slight reduction in plasma albumin concentration, that may occur at the end of treatment. Clinical efficacy on overall survival remains controversial. The HELIOS (Prometheus European Liver Disease Outcome) study evaluated the impact of Prometheus on survival in patients with cirrhosis and liver failure. This prospective, randomized, international multicentre trial included 145 patients with chronic liver failure (bilirubin > 5 mg/dL; Child-Pugh ≥ 10). Patients were randomized to conventional medical therapy (n = 68) or conventional therapy plus Prometheus (n = 77) for 21 days, with 90-day follow-up. Results showed a trend toward improved overall survival in the Prometheus group, with significantly longer survival observed in the subgroup of patients with type I hepatorenal syndrome (HRS) or a MELD score above 30 [20].

 

CPFA (Coupled Plasma Filtration Adsorption)

CPFA is an extracorporeal liver support technique based on plasma separation followed by adsorption of albumin-bound toxins on a hydrophobic resin. The method requires specialized equipment (e.g., Lynda or Amplya machines) and is performed with anticoagulation using heparin or citrate. Plasma is first separated from whole blood and then passed through a resin cartridge with high affinity for bilirubin and bile acids, the main albumin-binding toxins. The purified plasma is subsequently reinfused, completing the circuit. The advantages are effective removal of bilirubin, bile acids, and other albumin-bound toxins, haemodynamic stability, even in septic patients.  This system is well tolerated, with no significant hypotension or major bleeding events, and it offers potentially lower cost and greater technical flexibility compared to other systems such as MARS or Prometheus [21]. However, there are high procedural costs and the need for dedicated equipment, limited clinical evidence, mostly based on small single-centre observational studies and no significant impact on MELD score demonstrated. The HERCOLE (Hepatic Replacement by Coupled Plasma Filtration and Adsorption in Liver Failure) study evaluated the efficacy and safety of CPFA in 12 patients with acute liver failure (ALF) or acute-on-chronic liver failure (AoCLF) treated at S. Orsola Hospital, Bologna (2013-2017). Inclusion criteria were bilirubin >20 mg/dL or MELD score >20. A total of 31 CPFA sessions (6 hours each) were performed. Results showed a mean bilirubin reduction of 28.8% per session (range 2.2-40.5%), with a low rebound effect at 24 hours (median 8.9% after the first session, 6.8% after the second). Resin cartridges demonstrated strong adsorptive capacity, particularly for bilirubin and bile acids. Clinically, one patient underwent liver transplantation, and eight recovered their baseline liver function, with a one-year survival rate of 75%. CPFA was safe, effective in improving biochemical detoxification parameters, and may serve as a bridge to transplantation or recovery. However, due to the small sample size and heterogeneity, further randomized trials are required to confirm its clinical efficacy [21].

 

Dual Plasma Molecular Adsorption System (DPMAS)

Dual Plasma Molecular Adsorption System (DPMAS) is a system that combines plasma filtration and two adsorbent resins: a broad-spectrum resin (HA330-II) for inflammatory mediators and a specific resin (BS330) for bilirubin. This device is easy to use even on standard CRRT machines without the need for dedicated equipment. The advantages of DPMAS are good removal of protein-bound toxins (bilirubin), cytokines and inflammatory mediators, improvements in liver biochemistry, coagulation function and inflammatory and immune indices, good tolerability and safety with citrate anticoagulation. DPMAS in combination with plasmapheresis not only improves bilirubin levels but also 28-day survival in patients with HBV-related ACLF and reduces the need for transplantation in patients with cholestatic hepatitis. The isolated use of DPMAS improves prothrombin activity. Despite promising data, the routine use of DPMAS requires further confirmation through randomised multicentre studies. However, thanks to its ease of use, it appears to be a promising option [22].

Cytosorb

Cytosorb is a whole blood adsorption device designed to eliminate middle-molecular-weight substances, particularly cytokines and inflammatory mediators, and can be easily integrated into any extracorporeal blood circuit, including CRRT, without the need for plasmapheresis, albumin, or plasma replacement. Its main indication is the reduction of inflammatory mediators in sepsis and septic shock, but it is also employed in other critical care settings such as ARDS and ECMO therapy [23], in acute liver failure and rhabdomyolysis for the removal of bilirubin and myoglobin [24], and in cardiac surgery for the elimination of antiplatelet and anticoagulant agents such as ticagrelor and rivaroxaban [25]. In a retrospective comparative study, individual sessions of Cytosorb and MARS were both associated with significant reductions in bilirubin (p = 0.04 and p = 0.04, respectively) and ammonia (p = 0.04 and p = 0.04, respectively), but only Cytosorb achieved additional significant decreases in lactate dehydrogenase (p = 0.04) and platelet count (p = 0.04). After a complete treatment cycle, Cytosorb maintained superiority, showing significant reductions in lactate (p = 0.01), bilirubin (p = 0.01), ammonia (p = 0.02), and lactate dehydrogenase (p = 0.01), while MARS-treated patients did not display significant improvements in liver function parameters. Moreover, only Cytosorb was associated with a significant improvement in the MELD score (p = 0.04), highlighting its superior efficacy over MARS in enhancing liver compensation [26]. Another comparative study assessed detoxification efficiency across several extracorporeal liver support systems and demonstrated that Cytosorb had the highest adsorption capacity for total bilirubin, direct bilirubin, and bile acids when compared with CPFA, MARS, Prometheus, and plasmaperfusion, supporting its potential role as the device of choice in advanced liver failure [27]. Additional real-world evidence will derive from the COSMOS registry, launched in July 2022 and currently enrolling patients in Germany, Spain, Portugal, and Italy, which aims to provide large-scale observational data on the safety and efficacy of Cytosorb in critically ill patients [28].

Experience of our group

ECLSD methods are based on the principles of diffusion, convection, adsorption and phoresis, with the aim of removing water-soluble and hydrophobic toxins bound to albumin that accumulate in acute or acute-on-chronic liver failure. The techniques currently available vary in complexity, effectiveness and accessibility, but none has yet established itself as the absolute standard of treatment. Our group’s experience has included the use of a technique involving the recirculation of albumin without regeneration, RAED (Recirculated Albumin Extended Dialysis), a variant of SPAD that involves the recirculation of albumin without regeneration. In this mode, albumin is used as dialysate in a multi-pass circuit, with the aim of optimising its use and improving the efficiency of removing albumin-bound toxins, while maintaining a simple technical configuration without adsorbent columns. Albumin is circulated through a secondary circuit connected to a high-cut-off dialyzer, facilitating the diffusion of toxic substances from the blood to the albumin dialysate. Although this strategy does not involve the regeneration of the albumin solution using adsorbent cartridges, as is the case with the RHENOB system, it has shown reasonable effectiveness in reducing bilirubin and other toxic markers in patients with acute or acute-on-chronic liver failure. RAED therefore represents an intermediate option between SPAD and more complex systems such as MARS or Prometheus, offering a good compromise between simplicity, effectiveness and low cost, and formed the technological basis for the subsequent development of the RHENOB (Reemplazo Hepático No Biológico) system (Table 2). The system consists (Figure 1) of an albumin recirculation circuit placed in series with a renal circuit (haemodialysis, haemofiltration or haemodiafiltration) and includes albumin regeneration through the use of DPMAS (Double Plasma Molecular Adsorption System; Jafron).

Feature	RAED (Recirculated Albumin Extended Dialysis)	RHENOB (Reemplazo Hepático No Biológico)
System type	Variant of SPAD with recirculated albumin (multi-pass)	RAED circuit combined with albumin regeneration (via DPMAS)
Albumin circuit	Uses human albumin (20%) recirculated without regeneration	Human albumin (20%) recirculated with regeneration through dual resin cartridges (HA330-II, BS330)
Membrane type	High cut-off dialyzer for albumin circuit	High cut-off dialyzer for albumin circuit + standard dialysis/hemofiltration membrane for renal circuit
Dialysis configuration	Series circuit: blood + albumin dialysate, no adsorbent columns	Two circuits in series: renal replacement therapy + albumin recirculation/regeneration
Albumin volume	~300 ml of 20% albumin solution	~300 ml of 20% albumin solution (regenerated by DPMAS)
Flow rates	Blood flow: 150–300 ml/min; albumin flow: 15–20 ml/min	Blood flow: according to RRT mode (HD/HDF); albumin dialysate flow: ~200 ml/min
Anticoagulation	Heparin (standard dialysis dose)	Heparin via renal circuit
Technical complexity	Moderate – no special equipment needed beyond dialysis machine	Higher – requires integration with DPMAS cartridges for albumin regeneration
Main advantage	Simple, low-cost, reduces bilirubin; feasible in centres with standard dialysis equipment	More efficient toxin clearance (bilirubin, bile acids, cytokines) with lower albumin consumption
Limitation	No regeneration → less efficient, higher albumin use over multiple sessions	Greater complexity, need for DPMAS system, limited published data

Table 2. Technical comparison of RAED and RHENOB systems.

For the renal circuit, a dialysis membrane is used depending on the method chosen (low-flow haemodialysis, high-flow haemodialysis, haemofiltration or haemodiafiltration); for the albumin circuit, a high-cut-off dialysis membrane is used; 300 ml of 20% human albumin in the albumin circuit acts as dialysate and is passed through the dialysate compartment of the blood-cut dialyzer. The blood and dialysate flow rates depend on the haemodialysis technique used; the albumin dialysate flow rate is 200 ml/min. Heparin is administered through the renal circuit.

Age	Gender	Etiology	Liver Tx	MELD	Bilirubin Levels (mg/dl)	Percentage change in bilirubin after treatment	Number of RHENOB sessions performed	Outcome
53	F	Hepatic failure of unknown cause – AKIN 3	Yes	28	23	56 %	5	Alive
45	M	Alcoholic – Acute on Chronic Liver Failure – AKIN 3	Yes	31	18	44 %	4	Alive
42	M	Covid Pneumonia – Liver Failure – AKIN 3	No	30	25	52 %	3	Alive
63	F	Amiloidosis AL – AKIN 3	No	32	19	47 %	4	Alive
47	F	Primary Biliary Cirrhosis	No	36	17	43 %	3	Dead
66	F	Liver Transplant – Rejection – Cholestasis	Yes	40	21	42 %	2	Dead
61	M	Hepatitis B – Fulminat Subacute Hepatitis	Yes	31	22	50 %	5	Alive

Table 3. Patient characteristics.

Table 3 presents the clinical and biochemical characteristics of each patient, including age, gender, underlying diagnosis, MELD score, baseline total bilirubin levels, number of RHENOB sessions performed, and percentage change in bilirubin after treatment. The mean age of patients was approximately 52 years, ranging from 42 to 66 years; the male prevalence reflects the known distribution of advanced liver disease. Diagnoses included severe alcoholic hepatitis, viral hepatitis, and acute post-transplant graft dysfunction, highlighting the heterogeneity of treatment indications. The MELD score at the start of therapy was high in all cases (median MELD >30), confirming the severity of liver impairment.

All patients showed a significant reduction in bilirubin levels after RHENOB sessions, with an average decrease of between 25% and over 50% in the most severe cases (Figure 2). The therapeutic response was observed after just 1-2 sessions, suggesting that the method is rapidly effective.

In our centre, seven patients with acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) were treated with the RHENOB system. The cohort included heterogeneous etiologies such as severe alcoholic hepatitis, viral hepatitis, acute post-transplant dysfunction, and autoimmune cholestatic disease, with a median MELD score above 30, reflecting advanced liver impairment. All patients experienced a significant reduction in serum bilirubin after treatment, with decreases ranging from 25% to over 50% after only 2-5 sessions. The improvement was evident early, often within the first two sessions, suggesting rapid detoxification efficacy. Treatments were well tolerated in all cases, with no episodes of severe haemodynamic instability, major bleeding, or significant adverse events. Anticoagulation with heparin was sufficient, and no patients required interruption of therapy due to complications. The technique demonstrated good haemodynamic stability, even in patients with concomitant renal failure and critical illness. Among the seven treated patients, three underwent successful liver transplantation after biochemical stabilization, three recovered native liver function, and one patient died due to progression of underlying disease, resulting in an overall survival at hospital discharge of 71%. Importantly, RHENOB allowed stabilization of critical patients awaiting transplantation and facilitated recovery in selected cases, confirming its potential role as an effective “bridge” therapy. Compared to established ECLSD systems, RHENOB provided effective detoxification with lower albumin consumption and without the need for highly specialized infrastructure. These encouraging results support its feasibility in centres without access to advanced extracorporeal liver support devices, although larger prospective studies are needed to confirm its clinical impact on long-term survival and transplant-free recovery. When comparing available non-biological extracorporeal liver support devices (MARS, SPAD, Prometheus, CPFA, DPMAS, Cytosorb, RAED and RHENOB), no single system has yet established itself as the gold standard. MARS and Prometheus remain the most widely studied but are costly and technically demanding, while SPAD and CPFA are simpler yet limited in efficacy or availability. Cytosorb has shown promising detoxification capacity, particularly for bilirubin and bile acids, but requires further validation. Within this landscape, RAED and RHENOB represent pragmatic and innovative approaches: RAED, as a low-cost recirculated albumin method, and RHENOB, as an evolution integrating albumin regeneration with DPMAS, both showing significant bilirubin clearance, good tolerability, and the potential to bridge patients to transplantation or recovery. These techniques, although still supported by limited evidence, offer feasible solutions for centres lacking access to high-cost systems. A call for action is therefore warranted: prospective, multicentre randomized controlled trials should be conducted to consolidate their role, establish standardised protocols, and evaluate their impact on survival and transplant-free outcomes.

 

Conclusions

Several non-biological extracorporeal liver support techniques have been developed with different rationales and performance profiles. MARS and Prometheus remain the most validated, offering effective detoxification but at the cost of complex infrastructure and high resource consumption. SPAD provides a simpler alternative but with limited efficacy and high albumin requirements, while CPFA and DPMAS have shown selective detoxification potential with promising but still preliminary evidence. Cytosorb represents a versatile adsorptive option with encouraging results in bilirubin and cytokine clearance, though standardisation and wider validation are lacking. Within this evolving landscape, our experience with RAED and RHENOB highlights the possibility of achieving clinically meaningful detoxification, particularly bilirubin reduction, with simpler technology and good tolerability. RHENOB, by integrating albumin regeneration, optimises efficiency and reduces costs, while RAED offers an extremely accessible model adaptable to standard dialysis equipment. These approaches may represent valuable opportunities for centres with limited access to high-cost platforms, expanding the applicability of extracorporeal liver support beyond highly specialised units. RAED and RHENOB combine feasibility, tolerability and clinical benefit, potentially filling an important gap in resource-limited settings. Future multicentre randomized controlled trials are warranted to confirm their efficacy, define standardised treatment protocols and establish their role within the broader therapeutic arsenal of extracorporeal liver support.

 

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