# Transplant-free survival in acute liver failure patients receiving MARS®, plasma exchange or no liver support.
## A real-life 21-year retrospective cohort study in a referral center

Kieran Pinceaux, Félicie Belicard, Valentin Coirier, Estelle Le Pabic, Pauline

Guillot, Flora Delamaire, Benoit Painvin, Quentin Quelven, Mathieu

Lesouhaitier, Adel Maamar, et al.

► To cite this version:

Kieran Pinceaux, Félicie Belicard, Valentin Coirier, Estelle Le Pabic, Pauline Guillot, et al. Transplant-free survival in acute liver failure patients receiving MARS®, plasma exchange or no liver support. A real-life 21-year retrospective cohort study in a referral center. Annals of Intensive Care, 2025, 15 (1), pp.124. 10.1186/s13613-025-01506-3. hal-05249385

HAL Id: hal-05249385

https://hal.science/hal-05249385v1

Submitted on 15 Nov 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
RESEARCH

Open Access

<figure><img src="image_2.png" /></figure>

Check for
updates

# Transplant-free survival in acute liver failure patients receiving MARS®, plasma exchange or no liver support. A real-life 21-year retrospective cohort study in a referral center

Kieran Pinceaux¹, Félicie Bélicard¹, Valentin Coirier¹, Estelle Le Pabic², Pauline Guillot¹, Flora Delamaire¹, Benoît Painvin¹, Quentin Quelven¹, Mathieu Lesouhaitier¹, Adel Maamar¹, Arnaud Gacouin¹, Pauline Houssel-Debry³, Karim Boudjema⁴, Edouard Bardou-Jacquet³, Jean-Marc Tadié¹, Florian Reizine¹ and Christophe Camus¹*

**Abstract**

**Background** Whether Molecular Adsorbent Recirculating System (MARS) dialysis and high-volume plasma exchange (HVPE) may improve survival in acute liver failure (ALF) remains unclear. A referral center retrospective cohort study was conducted on patients admitted to ICU with ALF and who fulfilled liver transplantation (LTx) criteria from 2000 to 2021.

**Methods** The whole study period was divided into three 7-year consecutive periods (A, B, C) depending on the patients' date of admission. MARS was optionally performed only in periods A and B and HVPE was only performed in period C. Day-21 transplant-free survival (TFS) and day-28 overall survival (OS) were endpoints. The effect of MARS was assessed in periods A and B by comparing the patients treated with MARS with those not treated. Three treatment groups consisting of two different durations of total MARS therapy or no MARS were also compared. HVPE-treated patients (period C, n = 45) were compared to a control group of patients receiving no liver support or a short duration of MARS therapy that was not considered to be effective (over periods A, B, C, n = 126). Survival curves were compared by the Gehan-Breslow-Wilcoxon test and the logrank test.

**Results** 199 patients were enrolled and distributed as follows: A, n = 68; B, n = 70; C, n = 61. TFS did not differ with and without MARS (p = 0.19). Although MARS duration therapy could not be predicted at the time of MARS initiation, the patients treated ≥ 17 h (≥ 3 sessions) had better survival compared to treatment < 17 h or no MARS (78.6%, 30.4%, 43.8%; p = 0.0002). TFS was 55.6% versus 38.1% in the HVPE- and control groups (p = 0.003; adjusted HR 0.54 [0.32–0.93], p = 0.0257) and OS was 75.9% and 52.9%, respectively (p = 0.03).

**Conclusions** MARS therapy improved TFS only in patients who received ≥ 3 sessions. Compared with controls, HVPE-treated patients experienced improved transplant-free and overall survival.

**Keywords** Acute liver failure, Extracorporeal liver support, Molecular adsorbent recirculating system, Plasma exchange, Liver transplantation

<figure><img src="image_3.png" /></figure>

<footnote>*Correspondence:
Christophe Camus
christophecamus57@orange.fr
Full list of author information is available at the end of the article</footnote>
## Background

Acute liver failure (ALF) is a rare and life-threatening condition characterized by a sudden decline in hepatic functions. It is defined by elevated transaminases, coagulopathy with prothrombin index (PI) and/or factor V<50% of the normal ratio and hepatic encephalopathy (HE) evolving over less than 26 weeks, in the absence of pre-existing liver disease [1]. Paracetamol toxicity, ischaemia, drug-induced liver injury, hepatitis B virus, and autoimmunity account for 80% of etiologies in developed countries [1-4]. Because sudden hepatic injury may rapidly evolve into a critically ill state with multiorgan failure, brain edema and ultimately death [4-6], ALF requires prompt admission to the intensive care unit (ICU) [1, 3, 6]. To date, liver transplantation (LTx) remains the gold standard curative treatment for patients with terminal ALF, with a five-year survival rate of up to 70% in Europe [7, 8]. Liver support therapies have been used as a bridge to LTx, or as a bridge to recovery in order to avoid LTx. The Molecular Adsorbent Recirculating System (MARS) is the most widely used device worldwide. Even though prolonged MARS therapy, typically involving ≥3 sessions, was associated with better transplant-free survival (TFS) [9, 11, 14], conclusive data from clinical trials are lacking [9-12]. High-volume plasma exchange (HVPE) [15] and standard-volume PE [17] were also reported to improve TFS in ALF. Despite occasional inclusion in international guidelines [18, 19], the benefit of such techniques is not clear in the real-life. The aim of this study was to evaluate the impact of MARS and HVPE, each used for different periods, on the survival of patients with ALF admitted to ICU.

## Materials and methods

### Study design

We conducted a single-center, retrospective, study in the Rennes University Hospital. This hospital is a large volume LTx center and our unit is a referral ICU for the management of ALF patients from a large western area in France (Normandy, Brittany and Pays de la Loire, population of 8 millions inhabitants). From January 1st, 2000 to June 1st, 2021, all patients admitted to the ICU with ALF and who met the usual LTx criteria [20-22] or were listed for LTx were eligible. ALF was defined by the coexistence of elevated transaminases, coagulopathy (PI/factor V<50%) and HE in patients without preexisting liver disease [1]. Exclusion criteria were: 1) previously known chronic liver disease; 2) admission after LTx for ALF; or 3) refusal to participate. The main endpoint was day-21 TFS defined as the probability of remaining alive and free from LTx. The secondary endpoint was day-28 overall survival (OS). Our study received approval by the Ethics

Committee of Rennes University Hospital (n°21.83) and every survivor of the study received written information.

### General management of ALF in our ICU

All patients had etiological assessment including serum acetaminophen levels, diagnosis for hepatitis viruses, urinary toxicologic screening, auto-immunity, copper dosage, echocardiography and liver imaging [1, 6]. Patients received specific organ support as needed, N-acetylcysteine infusion and discontinuation of hepatotoxic drugs. Depending on etiology, specific treatments, such as antivirals, steroids or anticoagulants, were given. Indications for LTx and decision for listing were discussed on a case-by-case basis using usual LTx criteria depending on the ALF etiology (Supplementary Table 1).

### Extracorporeal liver supports

From January 2000 to June 2016, patients could receive MARS dialysis as an adjunct to standard medical therapy (SMT) after individual assessment by clinicians on a case-by-case basis. Because there was no guidelines on the use of MARS in ALF, the decision to initiate MARS therapy in emergency was left to the discretion of the ICU physician in charge of the patient. Since July 1st, 2016, following the results of Larsen's trial [15], we implemented a new bundle that strongly encouraged the use of HVPE in ALF and MARS dialysis was abandoned [16]. Because this was a new complex protocol, adherence was poor during the first two years. After training sessions with the medical and nursing team, compliance with the protocol became excellent. Finally, all ALF patients received HVPE except for device breakdown, equipment supply problems, unavailability of dedicated staff or moribund patient requiring limited care. The whole study period was divided into 3 chronological periods depending on admission dates: periods A (2000-2007), B (2008-July 2016) and C (August 2016-June 2021). MARS was used only during periods A and B and HVPE was performed in period C. Throughout the study period, MARS and HVPE were realized by a dedicated team specifically trained in extracorporeal therapies (renal replacement therapies [RRT], PE and MARS).

### Data collection

A standardized case report form was used to collect patients' data including demographic characteristics, and clinical and laboratory parameters at ICU admission and during hospitalization. The severity scores were Glasgow Coma Scale (GCS) score, Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA) score and Model for End stage Liver Disease (MELD) score. HE severity was graded according to the West Haven criteria [23]. Biological
tests included PI, International Normalized Ratio (INR), factor V, fibrinogen, phosphorus, ammonia, creatinine, lactate, pH, bicarbonate, aspartate aminotransferase, alanine aminotransferase, bilirubin, lactate dehydrogenase (LDH). Treatments, organ supports (mechanical ventilation, vasopressors, RRT use, MARS or HVPE) and outcomes (ICU and hospital length of stay, LTx, TFS and OS) were recorded. According to the interval between jaundice and the onset of hepatic encephalopathy, ALF was classified into hyperacute, acute and subacute [2]. ALF etiology was classified into five categories (acetaminophen-related, non-acetaminophen drug-induced or toxic-related, viral, other, indeterminate) and reclassified in two main etiologies: acetaminophen/drug/toxic and non-acetaminophen/drug/toxic.

## Statistical analysis

The statistical analysis was made using Statview® (version 5.0) and SAS® (version 9.4) softwares. Continuous variables were expressed as median (interquartile range [IQR]: 25th percentile-75th percentile) and compared using the Kruskal–Wallis or Mann–Whitney U tests. Categorical variables were reported as numbers and percentages and compared using the Chi-square test or the Fisher's exact test when appropriate. All tests were two-sided and the statistical significance level was a p-value < 0.05.

Variables associated with day-21 TFS were identified by univariate and multivariate analysis using a Cox model with a stepwise backward selection. The results were reported with Hazard Ratio (HR) of events and 95 percent confidence intervals (95% CI), a HR value < 1 indicating a lower risk of event (improved survival). Survival rates were estimated using the Kaplan–Meier curves and compared by the Gehan-Breslow-Wilcoxon test (day-21 TFS) or the logrank test (day-28 OS). To assess the effect of HVPE, the treated group was compared to a control group comprising all the patients who received either no liver support or an insufficient duration of MARS, considered ineffective [13, 14]. Survival analysis was adjusted for prognostic variables, including ALF etiology, N-acetyl-cysteine treatment, HE severity, INR, lactate levels, SOFA score and organ failure support.

## Results

### Patient characteristics at baseline and clinical course in ICU

Among the 296 patients admitted to ICU with ALF, 70 did not meet transplant criteria and 27 had exclusion criteria. Finally, 199 patients were included in the study (flowchart, Fig. 1). They were distributed in 68, 70 and 61 patients for periods A, B and C respectively. Baseline characteristics at admission to the ICU are shown in Supplementary Table 2. Patients were predominantly female (52.3%) with a median age of 47 years (35–57).

<figure><img src="image_4.png" /><figcaption>**Fig. 1** Patient selection flowchart. ALF Acute Liver Failure, ICU Intensive Care Unit, LTx Liver transplantation</figcaption></figure>

Clinical characteristics were mostly similar between periods, except for neurological history, prior immunosuppressive therapy and use of RRT during the first 24 h in ICU. Biological features at admission were mostly identical, except for INR, creatinine, LDH and MELD score. All five etiologies were equally distributed during the periods although acetaminophen-related ALF tended to increase over time ($\chi^2$-test for trend, p=0.0129). Patients course in ICU and hospital stay is described in Supplementary Table 3. ALF was classified into hyperacute (n=167, [83.9%]), acute (n=20, [10.1%]) and subacute (n=12, [6.0%]), without difference between periods. One hundred percent of paracetamol-related ALF, 93% of toxic-non-paracetamol ALF (41/44) and 78% of viral ALF (14/18) were hyperacute. There were some differences regarding the worst values of INR, phosphorus, pH, LDH and the highest MELD score. Treatment and outcomes did not differ over time except for the use of N-acetylcysteine and specific etiological treatment and the registration on the transplant list.

### Effect of MARS

Among the 138 patients in periods A and B, 74 (53.6%) received at least one session of MARS dialysis. The elapsed time between ICU admission and the first session was 12 h [7–19], with a median of 2 sessions per patient [1–3]. The session duration was 8 h [6.8–8] and the total duration of MARS therapy was 15.5 h [8–24]. Baseline characteristics and ICU course are detailed in Supplementary Table 4 and were compared depending
on MARS therapy. There was no significant difference between groups except for the SOFA score at admission (p=0.0286), as well as the respiration and coagulation SOFA subscores (p=0.0239 and p=0.0159 respectively). Day-21 TFS did not differ between groups (48.6% in

the MARS group and 43.8% in the no-MARS group, p=0.1876) (Fig. 2). Analysis of day-21 TFS is shown in Table 1. By univariate analysis, MARS was not associated with improved TFS (p=0.37) or OS (p=0.32). In multivariate analysis, acetaminophen or toxic etiology,

<figure><img src="image_5.png" /><figcaption>**Fig. 2** Day-21 transplant-free survival among patients in periods A and B depending on MARS therapy. MARS Molecular Adsorbent Recirculating System</figcaption></figure>

<table><caption>**Table 1** Univariate and multivariate analysis of Day-21 transplant-free survival among the 138 patients in periods A and B</caption><thead><tr><th rowspan="2">Variables</th><th colspan="2">Univariate analysis</th><th colspan="2">Multivariate analysis</th></tr><tr><th>HR [CI 95%]</th><th>p-value</th><th>HR [CI 95%]</th><th>p-value</th></tr></thead><tbody><tr><td>Obesity</td><td>3.28 [1.70-6.32]</td><td>0.0004</td><td></td><td></td></tr><tr><td>Acetaminophen or toxic etiology</td><td>0.38 [0.24-0.61]</td><td>&lt;0.0001</td><td>0.54 [0.30-0.97]</td><td>0.0397</td></tr><tr><td>SOFA score &gt; 8 at admission</td><td>1.70 [1.07-2.70]</td><td>0.0247</td><td></td><td></td></tr><tr><td>SAPS II &gt; 50 at admission</td><td>2.53 [1.56-4.12]</td><td>0.0002</td><td></td><td></td></tr><tr><td>MELD &gt; 38 at admission</td><td>2.31 [1.43-3.73]</td><td>0.0006</td><td></td><td></td></tr><tr><td>Grade 3-4 (or intubation) HE at admission</td><td>1.85 [0.96-3.59]</td><td>0.028</td><td>2.14 [1.06-4.34]</td><td>0.0274</td></tr><tr><td>Need for vasopressors during the first 24 h</td><td>2.36 [1.49-3.74]</td><td>0.0002</td><td></td><td></td></tr><tr><td>Need for mechanical ventilation during the first 24 h</td><td>2.10 [1.31-3.38]</td><td>0.0022</td><td></td><td></td></tr><tr><td>Need for renal replacement therapy during the first 24 h</td><td>1.89 [1.20-2.99]</td><td>0.0064</td><td></td><td></td></tr><tr><td>Improvement of HE within 24 h after admission</td><td>0.16 [0.06-0.40]</td><td>&lt;0.0001</td><td>0.16 [0.06-0.42]</td><td>0.0001</td></tr><tr><td>INR &gt; 6.5 at admission</td><td>1.90 [1.20-3.01]</td><td>0.0059</td><td>1.82 [1.10-3.00]</td><td>0.0190</td></tr><tr><td>Lactate &gt; 5 mmol/L at admission</td><td>2.56 [1.58-4.16]</td><td>0.0001</td><td>1.78 [1.06-3.00]</td><td>0.0296</td></tr><tr><td>Use of MARS therapy</td><td>0.81 [0.51-1.28]</td><td>0.3721</td><td></td><td></td></tr><tr><td>Immunosuppressive therapy during the past year</td><td>1.88 [1.03-3.43]</td><td>0.0385</td><td></td><td></td></tr><tr><td>Use of N-acetyl-cysteine</td><td>0.37 [0.23-0.60]</td><td>&lt;0.0001</td><td>0.51 [0.28-0.92]</td><td>0.0247</td></tr></tbody></table>

SOFA Sequential Organ Failure Assessment, SAPS II Simplified Acute Physiology Score II, MELD Model for End stage Liver Disease, HE Hepatic Encephalopathy, INR International Normalized Ratio, MARS Molecular Adsorbent Recirculating System
improvement of HE within the first 24 h in ICU and therapy by N-acetyl-cysteine were associated with a higher day-21 TFS, and HE of grade 3–4 (or intubation), INR > 6.5 and lactate > 5 mmol/L at admission with a lower day-21 TFS.

The total number of MARS sessions and the total duration of MARS were associated with improved day-21 TFS (HR per MARS session 0.58 [0.41–0.81], p=0.0016; HR per hour of MARS 0.94 [0.90–0.97], p=0.009). Sensitivity analysis found that the best threshold for predicting day-21 TFS was a total duration of MARS therapy ≥ 17 h. Among the 74 patients treated with MARS, 46 (62.2%) received ≥ 17 h and 28 (37.8%) received < 17 h. Baseline characteristics and outcomes of both subgroups were compared in Supplementary Table 5. There was no significant difference at baseline. The proportion of patients with contraindications to LTx was 19.6% and 46.4% in the groups receiving < 17 h and ≥ 17 h of MARS, respectively (p=0.0142). The number of sessions per patient and the total duration of MARS therapy was 1 [1, 2], 8 h [7.5–13.5] and 3 [3, 4], 24 h [22.25–32] in the < 17 h and ≥ 17 h of MARS groups, respectively (p < 0.0001). The variables associated with day-21 TFS among the 74 patients treated with MARS are shown in Supplementary Table 6. HE improvement within the first 24 h, N-acetyl-cysteine therapy and receiving ≥ 17 h of MARS were associated with a higher day-21 TFS, and admission MELD

score > 38 and vasopressors during the first 24 h with a lower day-21 TFS.

Survival was assessed in three groups of patients in periods A and B. TFS was 78.6% in the group receiving ≥ 17 h of MARS, 30.4% in the group receiving < 17 h of MARS and 43.8% in the group without MARS (p=0.0002, Fig. 3). There was no significant difference between the group receiving < 17 h of MARS and the group without MARS (p=0.5401).

The day-28 OS was 82.1% in the group receiving ≥ 17 h of MARS, 60.9% in the group receiving < 17 h of MARS and 62.5% in the group without MARS (p=0.13, Fig. 4). The day-28 OS was higher in the group receiving ≥ 17 h of MARS compared to the group receiving < 17 h of MARS (after stratification for LTx, HR 0.29 [0.10–0.79], p=0.0163).

## Effect of HVPE

Forty-five patients received HVPE treatment. They were compared to the 126 patients of the control group, who received either no liver support or MARS therapy < 17 h (2 or 1 session). Those who received ≥ 17 h (≥ 3 sessions) of MARS were excluded from the control group. Among the HVPE group, the time from ICU admission to the first session was 9 h [4.65–21], with a median number of sessions per patient of 3 [2, 3]. Seven (15.6%), 10 (22.2%) and 28 (62.2%) patients

<figure><img src="image_6.png" /><figcaption>**Fig. 3** Day-21 transplant-free survival among patients in periods A and B according to MARS therapy duration. MARS Molecular Adsorbent Recirculating System</figcaption></figure>
<figure><img src="image_7.png" /><figcaption>**Fig. 4** Day-28 overall survival among patients in periods A and B according to MARS therapy duration. MARS Molecular Adsorbent Recirculating System</figcaption></figure>

received one, two and three sessions, respectively. Baseline characteristics, course and outcomes of the 45 HVPE patients and 126 controls are detailed in Supplementary Table 7. Both groups were comparable, except for more frequent prior immunosuppression, higher baseline SOFA score, more frequent RRT within the first 24 h and less frequent use of N-acetylcysteine in the control group. In the crude analysis, the day-21 TFS was 55.6% in the HVPE group and 38.1% in the control group (p=0.003, Fig. 5). After adjustment for confounding factors (HE grade, SOFA score, need for RRT within the first 24 h, immunosuppressive therapy, N-acetylcysteine treatment, ALF etiology, SAPS II, INR, worsening of HE after admission), day-21 TFS remained higher in the HVPE group (HR 0.54 [0.32–0.93], p=0.0257). The day-28 OS was 75.6% in the HVPE group and 59.5% in the control group (logrank, stratification for LTx, p=0.03, Supplementary Fig. 1). Among the 121 patients without LTx contraindications (31 in the HVPE group and 90 in the control group), day-21 TFS was higher in the HVPE-treated compared to controls (61.3% vs 46.7%, p=0.0150, Supplementary Fig. 2). Among patients not listed for LTx, the day-28 OS was higher in the HVPE group (75.9% vs 52.9%, p=0.0364, Supplementary Fig. 3). Among those not listed due to contraindications, the day-28 OS was 42.9% in the HVPE group and 16.7% in the control group (p=0.0583, Supplementary Fig. 4).

## Discussion

Our study aimed to assess the effect of MARS dialysis and HVPE on survival outcomes in patients with severe ALF meeting transplant criteria. The baseline characteristics of our cohort align with existing literature data and the prognosis factors identified by multivariate analysis were consistent with previous studies [2–4, 20].

Our findings indicated that the use of MARS did not improve survival outcomes, in agreement with the results of one randomized clinical trial conducted by Saliba et al. (FULMAR study) [9]. Importantly, our study evaluated nearly twice more patients treated with MARS, with a lower proportion of patients undergoing LTx in our study (23.9% vs 64.7%). However, we found a relationship between the duration of MARS and TFS. Patients receiving ≥17 h of MARS therapy (in practice, 3 sessions or more) had a better day-21 TFS, suggesting that a minimum of 3 sessions are required to achieve survival improvement, in accordance with prior studies [9, 11, 14]. We were not able to predict the duration of MARS therapy at the time of initiation, since we found no difference in baseline characteristics between the patients treated <17 h and those treated ≥17 h (Supplementary Table 5). Due to the retrospective design of our study, it was not possible to fully explain the decision to MARS dialysis. Many factors could have interfered with the initiation and the duration of MARS: logistical problems related to dedicated staff or MARS device, contraindication to MARS (hemodynamic instability, very low
<figure><img src="image_8.png" /><figcaption>**Fig. 5** Day-21 transplant-free survival in 45 patients treated with HVPE and in 126 controls. HVPE High Volume Plasma Exchange</figcaption></figure>

fibrinogen or platelet count), premature coagulation of the circuit or filter clogging, intra-dialytic disseminated intravascular coagulation, hypotension and hypothermia [9, 10, 24]. In patients listed for "superurgence" LTx, the time between the initiation of MARS dialysis and the availability of a liver graft was an important competing factor for the total duration of MARS therapy. The time between listing and graft proposal could be very short (<24 h) in the French allocating system and precipitate the interruption of MARS sessions generally performed on a daily schedule. Because nearly half of the patients receiving MARS for ≥ 17 h had contraindications to LTx, MARS therapy could better target ALF patients who are not suitable for LTx.

Regarding the effect of HVPE, our results showed that day-21 TFS was improved in patients treated with HVPE as compared with controls (HR 0.54 [0.32–0.93], p=0.0257). This finding was consistent with the results of Larsen et al. (HR=0.56 [0.36–0.86], p=0.0083) [15]. In our study, the beneficial effect of HVPE was also observed in day-28 OS (p=0.03) and in patients without LTx contraindications (p=0.0150). Additionally, although statistical significance was not reached, our results also showed a benefit of HVPE on survival in patients not listed due to contraindication to LTx (42.9% vs 16.7%, p=0.0583), similar to the results of Larsen et al. in the same subgroup of patients (36% vs 20%, p=0.03).

Altogether, these data indicate that HVPE could be used not only for patients who are contraindicated to LTx or in settings with limited access to grafts, but also for those on the waiting list. Whether the efficacy of PE is related to the high volume substituted is unclear. A randomized controlled study using standard-volume plasma exchange (SVPE) vs SMT in ALF patients with no absolute contraindication to LTx also found a benefit on TFS [17]. More recently, Kulkarni et al. suggested that HVPE and SVPE had similar efficacy [25].

Our study has several limitations. First, due to its single-center and retrospective design, the conclusions are not necessarily generalizable to other centers. Second, the potential benefit of prolonged MARS therapy is limited by the impossibility to predict the total treatment duration at the time of MARS initiation. Third, the extended inclusion period of the control group over 21 years implies potential changes in practices and recruitment in the ICU. This limits the comparability between the HVPE group and the control group, emphasizing the need for cautious interpretation of our findings. However, our study reflected the real-world use of two invasive extracorporeal liver support modalities, administered by a specialized team in a tertiary-referral ICU. Because ALF is a rare disease, the size of our cohort is significant and may provide useful insights into clinical practice. Given the complexity of conducting randomized controlled
trials assessing extracorporeal liver support devices in ALF, retrospective series like ours may offer valuable evidence on the effect of MARS therapy and HVPE.

## Conclusions

In ALF patients, MARS dialysis improved TFS only in those who could receive three complete sessions or more. Because LTx could compete with MARS dialysis, this therapy could best target patients with contraindications to LTx. Compared with a historical control group, HVPE-treated patients had both improved TFS and OS. As there is growing evidence for survival benefit with PE to treat ALF, HVPE could be used not only in patients contraindicated for LTx but also in those without contraindications, as a bridge to recovery or second-step LTx. The interest of MARS combined with PE deserves further investigation.

## Abbreviations

MARS Molecular adsorbent recirculating system

HVPE High-volume plasma exchange

ALF Acute liver failure

LTx Liver transplantation

TFS Transplant-free survival

OS Overall survival

PI Prothrombin index

HE Hepatic encephalopathy

ICU Intensive care unit

SMT Standard medical therapy

RRT Renal replacement therapies

GCS Glasgow Coma Scale

SAPS II Simplified acute physiology score II

SOFA Sequential organ failure assessment

MELD Model for end stage liver disease

INR International normalized ratio

LDH Lactate dehydrogenase

IQR Interquartile range

HR Hazard ratio

SVPE Standard-volume plasma exchange

## Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13613-025-01506-3.

Additional file 1.

## Acknowledgements

We thank the teams from the participating ICU and especially the specialized nurse team.

## Author contributions

C.C. and K.P. conceived, designed, coordinated the data collection and supervised the study. K.P., F.B., V.C., F.D., P.G., F.D., B.P. Q.Q., M.L., A.M., A.G., P.HD., K.B., E.B.J., J.M.T., F.R. and C.C. collected, analysed and interpreted the data. C.C. and E.L.P performed the statistical analysis. K.P. and C.C. wrote the first draft of the article. All authors revised the manuscript, approved the final version of the manuscript and agreed to submit the manuscript for publication.

## Funding

This study did not receive any financial support.

## Data availability

All data generated or analysed during this study are included in this published article and its supplementary information files.

## Declarations

### Ethics approval and consent to participate

Our study received approval by the Ethics Committee of Rennes University Hospital (n°21.83) and complied with French Research Methodology MR003 regarding health-data privacy, and the French National Commission on Informatics and Liberty.

### Consent for publication

Every survivor of the study received written information and consented to be included in the study.

### Competing interests

The authors declare that they have no competing interests.

### Author details

¹Service de Médecine Intensive - Réanimation, CHU de Rennes, 35000 Rennes, France. ²Centre d'Investigation Clinique, CHU de Rennes, 35000 Rennes, France. ³Service des Maladies du Foie, CHU de Rennes, 35000 Rennes, France. ⁴Service de Chirurgie Hépatobiliaire et Digestive, CHU de Rennes, 35000 Rennes, France.

Received: 3 July 2024 Accepted: 19 June 2025

Published online: 26 August 2025

## References

1. Paugam-Burtz C, Levesque E, Louvet A, Thabut D, Amathieu R, Bureau C, et al. Management of liver failure in general intensive care unit. Anaesth Crit Care Pain Med. 2020;39(1):143–61.

2. Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet. 2010;376(9736):190–201.

3. Bernal W, Hyryylainen A, Gera A, Audimoolam VK, McPhail MJ, Auzinger G, Rela M, Heaton N, O'Grady JG, Wendon J, Williams R. Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. J Hepatol. 2013;59(1):74–80.

4. Stravitz RT, Lee WM. Acute liver failure. Lancet. 2019;394(10201):869–81.

5. Reuben A, Tillman H, Fontana RJ, Davern T, McGuire B, Stravitz RT, et al. Outcomes in adults with acute liver failure between 1998 and 2013: an observational cohort study. Ann Intern Med. 2016;164(11):724–32.

6. Nanchal R, Subramanian R, Karvellas CJ, Hollenberg SM, Peppard WJ, Singbartl K, et al. Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU: cardiovascular, endocrine, hematologic, pulmonary, and renal considerations. Crit Care Med. 2020;48(3):e173–91.

7. Germani G, Theocharidou E, Adam R, Karam V, Wendon J, O'Grady J, et al. Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database. J Hepatol. 2012;57(2):288–96.

8. Agence de la biomédecine - Le rapport annuel médical et scientifique 2022. https://rams.agence-biomedecine.fr/greffe-hepatique-0. Accessed 30 Jun 2024.

9. Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B, et al. Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med. 2013;159(8):522–31.

10. Monet C, De Jong A, Aarab Y, Piron L, Prades A, Carr J, et al. Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center. Crit Care. 2022;26(1):282.

11. MacDonald AJ, Subramanian RM, Olson JC, Speiser JL, Durkalski-Mauldin VL, Abraldes JG, et al. Use of the molecular adsorbent recirculating system in acute liver failure: results of a multicenter propensity score-matched study. Crit Care Med. 2022;50(2):286–95.

12. Camus C, Lavoué S, Gacouin A, Le Tulzo Y, Lorho R, Boudjéma K, et al. Molecular adsorbent recirculating system dialysis in patients with acute
liver failure who are assessed for liver transplantation. Intensive Care Med.
2006;32(11):1817-25.

13. Camus C, Lavoué S, Gacouin A, Compagnon P, Boudjéma K, Jacquelinet C, et al. Liver transplantation avoided in patients with fulminant hepatic failure who received albumin dialysis with the molecular adsorbent recirculating system while on the waiting list: impact of the duration of therapy. Ther Apher Dial. 2009;13(6):549-55.

14. Camus C, Locher C, Saliba F, Goubaux B, Bonadona A, Lavayssiere L, et al. Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: a national multicenter study. JGH Open. 2020;4(4):757-63.

15. Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, et al. High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol. 2016;64(1):69-78.

16. Coirier V, Quelven Q, Guillot P, Delamaire F, Houssel-Debry P, Maamar A, et al. Adverse events and outcomes of high-volume plasma exchange in 50 acute liver failure patients: a monocentric retrospective real-world study. J Clin Exp Hepatol. 2025;15(1):101934.

17. Maiwall R, Bajpai M, Singh A, Agarwal T, Kumar G, Bharadwaj A, et al. Standard-volume plasma exchange improves outcomes in patients with acute liver failure: a randomized controlled trial. Clin Gastroenterol Hepatol. 2022;20(4):e831-54.

18. Wendon J, Cordoba J, Dhawan A, Larsen FS, Manns M, Samuel D, et al. EASL clinical practical guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017;66(5):1047-81.

19. Anand AC, Nandi B, Acharya SK, Arora A, Babu S, Batra Y, et al. Indian national association for the study of the liver consensus statement on acute liver failure (part 1): epidemiology, pathogenesis, presentation and prognosis. J Clin Exp Hepatol. 2020;10(4):339-76.

20. O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97(2):439-45.

21. Bernuau J, Goudeau A, Poynard T, Dubois F, Lesage G, Yvonnet B, et al. Multivariate analysis of prognostic factors in fulminant hepatitis B. Hepatology. 1986;6(4):648-51.

22. Escudié L, Francoz C, Vinel JP, Moucari R, Cournot M, Paradis V, et al. Amanita phalloides poisoning: reassessment of prognostic factors and indications for emergency liver transplantation. J Hepatol. 2007;46(3):466-73.

23. Conn HO, Leevy CM, Vlahcevic ZR, Rodgers JB, Maddrey WC, Seeff L, et al. Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology. 1977;72(4 Pt 1):573-83.

24. Camus C, Gacouin A, Lavoué S, Marque S, Gros A, et al. Extracorporeal albumin dialysis in acute liver failure: clinical tolerance and effect on coagulation in 69 patients. Liver Transplant. 2011;17(6):S190-1.

25. Kulkarni AV, Venishetty S, Vora M, Naik P, Chouhan D, Iyengar S, et al. Standard-volume is as effective as high-volume plasma exchange for patients with acute liver failure. J Clin Exp Hepatol. 2024;14(3):101354.

**Publisher's Note**

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.