Global evidence on molecular adsorbent recirculating system uses for trauma-induced acute liver failure: A scoping review

Abstract

The molecular adsorbent recirculating system (MARS) is an extracorporeal liver support therapy used in acute liver failure, including cases related to trauma; however, evidence supporting its use in trauma-induced liver dysfunction remains limited. This scoping review aimed to systematically map the available literature on the use of MARS therapy in trauma patients and to identify knowledge gaps to guide future research. The review was conducted according to Joanna Briggs Institute methodology and reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines, with a protocol prospectively registered in the Open Science Framework. Six electronic databases and two clinical trial registries were searched through December 2025, with additional backward citation tracking. Four observational studies met inclusion criteria, comprising 247 patients treated with MARS therapy, of whom only 11 had confirmed trauma-related acute liver failure. No randomized controlled trials were identified. Trauma-specific outcomes were inconsistently reported, and adverse events were not uniformly documented. Survival and liver function recovery varied across studies, and methodological heterogeneity precluded reliable assessment of clinical effectiveness or safety. Current evidence remains sparse and insufficient to support routine clinical use in trauma populations.

Key Words: Molecular adsorbent recirculating system; Liver failure; Acute liver failure; Acute-on-chronic liver failure; Trauma; Traumatic liver injury; Extracorporeal liver support

Core Tip: Evidence on the use of molecular adsorbent recirculating system in trauma-induced liver failure remains extremely limited, and trauma patients are frequently included within broader liver failure cohorts without separate reporting. This scoping review identified only 11 trauma cases that have been clearly documented worldwide, precluding any reliable assessment of survival benefit or safety in this specific setting. Although biochemical improvements are frequent, the true clinical impact of molecular adsorbent recirculating system in trauma cannot be determined without trauma-focused studies using standardized protocols and clearly defined outcomes.

INTRODUCTION

Molecular adsorbent recirculating system (MARS) is an extracorporeal liver support therapy designed to remove albumin-bound toxins and improve clinical parameters in patients with severe liver dysfunction, such as acute liver failure (ALF), acute-on-chronic liver failure, and other hepatic conditions[1,2]. Studies have demonstrated its potential to reduce bilirubin, ammonia, and other toxic metabolites, thereby stabilizing patients awaiting liver transplantation or spontaneous recovery.

While MARS has been increasingly utilized in various liver failure contexts, its application in traumatic liver injury, a distinct clinical entity caused by blunt or penetrating trauma, remains poorly characterized. The literature includes only a limited number of trauma-specific reports, and findings regarding survival, organ function recovery, and adverse events remain inconclusive[3,4]. The most comprehensive cohort to date[5] consolidated trauma-related MARS cases from a single institution, but broader evidence remains sparse.

Furthermore, a recent meta-analysis on MARS therapy[6], despite its comprehensive evaluation of hepatic indications, excluded trauma-related cases entirely, underscoring a persistent gap in the evidence base and highlighting the need for a structured mapping of available trauma-specific evidence.

This scoping review aims to systematically map the existing literature on MARS therapy in trauma-induced liver failure, with emphasis on survival, liver function recovery, key biochemical parameters such as bilirubin, ammonia, and liver enzymes, and reported adverse events, as described in case reports, case series, and observational cohort studies published through December 2025.

LITERATURE REVIEW

This review was conducted according to the Joanna Briggs Institute methodology[7] and reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines[8], with a protocol prospectively registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/R4ZSH).

Eligibility criteria

Studies were included if they addressed the use of MARS therapy in adults (≥ 18 years) with acute or acute-on-chronic liver failure resulting from trauma or related conditions (e.g., hemorrhagic shock, massive transfusion, blunt or penetrating hepatic injury). Eligible designs encompassed randomized trials, cohort studies, case series, and case reports, regardless of sample size. Outcomes of interest included mortality, liver function recovery, bilirubin clearance, organ dysfunction, intensive care unit length of stay, MARS indications, and adverse events. No restrictions were applied regarding language or publication date.

Exclusion criteria comprised studies focused exclusively on other liver support systems (e.g., single-photon avalanche diode, Prometheus, bioartificial devices), publications limited to non-traumatic liver failure, and non-original material (e.g., reviews, editorials, commentaries). Conference abstracts were considered if they contained sufficient methodological or outcome-related information.

To address potential overlap in trauma cohorts from the same institution[5,9,10], only the most comprehensive dataset[5] was retained for analysis, as confirmed by author correspondence. Earlier studies[9,10] were excluded from this analysis. The study by Shiber et al[11] was excluded because it was unclear whether trauma patients received MARS therapy. The optional stakeholder consultation step was not conducted.

Search strategy and data extraction

This scoping review systematically mapped the available evidence on the use of MARS in adults aged 18 years or older with trauma-associated acute or acute-on-chronic liver failure. A comprehensive search strategy was applied across eight databases, including PubMed, EMBASE, Cochrane Central, Scopus, Web of Science, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, covering all records from database inception through December 2025. Grey literature was excluded to focus on indexed, peer-reviewed publications. The search combined controlled vocabulary (e.g., Medical Subject Headings, Excerpta Medica Tree) and free-text terms for MARS and trauma-related liver failure. Reference lists of included studies were manually screened (Supplementary material).

References were managed in Zotero, with duplicates removed prior to screening. Two reviewers independently screened titles and abstracts in Rayyan using predefined criteria. Discrepancies were resolved by consensus or third-party adjudication, per Joanna Briggs Institute methodology. Full texts of potentially relevant studies were reviewed, and backward citation tracking was performed.

Data were extracted using a standardized form capturing study design, trauma characteristics, MARS treatment parameters (timing and number of sessions), and outcomes such as survival, bilirubin clearance, organ dysfunction, and adverse events.

Data synthesis and handling of heterogeneous datasets

Given the anticipated clinical and methodological heterogeneity across studies, no quantitative pooling or meta-analysis was performed. Evidence was synthesized descriptively and narratively, to characterize available data rather than estimate effect sizes. Studies including mixed-etiology cohorts were not combined quantitatively, and trauma-related data were analyzed separately whenever explicitly reported. In the absence of stratified trauma-specific outcomes, findings were interpreted qualitatively and with caution, and suspected duplicate reporting was managed by prioritizing the dataset with the most complete trauma-specific information. This approach is consistent with scoping review methodology and reflects the limited number of trauma-specific cases available in the literature.

Quality assessment

Study quality was assessed using the Newcastle-Ottawa Scale[12,13] for observational studies, evaluating selection, comparability, and outcome domains. Two reviewers independently scored each study, resolving disagreements by consensus or with a third reviewer. Scores range from 0 to 9, with studies classified as high (6-9), moderate (3-5), or low quality (0-2). This descriptive evaluation aimed to contextualize methodological features, not to determine eligibility, consistent with Joanna Briggs Institute’s recommendations for scoping reviews[7].

SUMMARY OF FINDINGS

Study selection and baseline characteristics

As shown in the Preferred Reporting Items for Systematic Reviews and Meta-analyses flow diagram (Figure 1), 3053 records were identified across eight databases and backward citation tracking. After removing 826 duplicates, 2227 titles and abstracts were screened; 2193 were excluded for not meeting inclusion criteria. Of 34 full-text articles reviewed, 29 were excluded: 26 for lacking trauma-related liver failure, 1 for not specifying trauma case numbers, 1 for trauma cases not confirmed to receive MARS, and 2 for overlapping cases, yielding four included studies.

Figure 1 Flowchart of study selection. The flowchart illustrates the process of selecting studies for the scoping review. WHO ICTRP: World Health Organization International Clinical Trials Registry Platform; MARS: Molecular adsorbent recirculating system.

These studies encompassed 247 patients treated with MARS for liver dysfunction, among whom 11 had trauma-related ALF. The studies, published between 2003 and 2024, were conducted across North America, Europe, and the Middle East, and included one case report, three observational cohort studies. Details are summarized in Supplementary Table 1.

Quality assessment

One study received 7/9[5]. Two studies were rated moderate quality (5-6/9) due to small trauma cohorts or incomplete stratification[4,14]. One case report was deemed low quality (2/9)[3]. Common limitations across studies included lack of randomization, small trauma-specific samples, and selection bias (Supplementary Table 2).

Study findings

Only one study[3] exclusively reported a trauma-related case treated with MARS. All other studies included trauma patients, but did not provide separate analysis or results specific to that subgroup[4,5,14], making it impossible to isolate outcomes related solely to traumatic liver injury.

High-grade liver injuries (American Association for the Surgery of Trauma grades III-V) and extensive hepatic necrosis were described in earlier publications, although injury severity was not specified in the most recent dataset[5]. MARS therapy was generally initiated as a bridge to recovery or transplantation, with individual sessions lasting approximately eight hours and the total number of sessions ranging from one to over thirteen. Trauma patients frequently received concurrent continuous renal replacement therapy (CRRT) and other supportive interventions.

Survival outcomes varied. A 50% survival rate (4/8) was observed, though transplantation data specific to traumatic liver injury were not disclosed[5]. Full recovery was recorded in a single case[3]. Other study presented only aggregated data, limiting trauma-specific interpretation[14]. One study documented 100% mortality in a mixed cohort that included a trauma patient[4].

Biochemical responses to MARS were favorable. Significant reductions were observed in aspartate aminotransferase (from 3334 U/L to 344 U/L), alanine aminotransferase (from 1410 U/L to 347 U/L), international normalized ratio (INR; from 3.2 to 1.5), and lactate (from 7.7 mmol/L to 2.4 mmol/L), with no meaningful change in ammonia levels (from 58 μmol/L to 39 μmol/L; P = 0.44)[5]. Resolution of hepatic encephalopathy was also noted in prior accounts, although no improvement was reported in the trauma subgroup of the most recent dataset[3,5].

Adverse events were rarely stratified by etiology. Thrombocytopenia was identified, although its association with trauma cases remained unclear[4,14]. No complications directly attributable to traumatic liver injury were described, and no major adverse events were identified in this subgroup[5].

Population and interventions

Study populations and intervention protocols are summarized in Table 1. Trauma cases involved blunt mechanisms, and, in some publications, extensive hepatic necrosis[3,5]. In one cohort, trauma accounted for 13% of ALF cases, although demographic data specific to traumatic liver injury were not separately presented[5].

Table 1 Outcomes of studies included in the scoping review.

Ref.	Population	Type of trauma (if applicable)	Intervention	Duration/number of sessions
Ben-Abraham et al[3]; 2003	Post-traumatic acute liver failure due to blunt trauma (n = 1)	Isolated grade V blunt liver trauma with major hepatic necrosis (1/1)	Molecular adsorbent recirculating system	3 sessions of 8 hours
Rittler et al[4]; 2004	Post-operative acute liver failure and septic multiple organ failure (n = 5); includes 1 trauma patient	1 blunt trauma (1/5); no subgroup outcomes reported	Molecular adsorbent recirculating system	Mean 13.4 cycles, 11.8 hours/cycle
Monet et al[14]; 2022	Heterogeneous cohort: Acute-on-chronic liver failure, acute liver failure, post-operative, pruritus, drug intoxication (n = 180)	Trauma listed as 1 of 32 acute liver failure cases; not separately analyzed	Molecular adsorbent recirculating system	Mean 2.9 sessions, 7 hours 33 minutes/session
Powell et al[5]; 2024	Acute liver failure due to trauma, drug toxicity, acute-on-chronic liver failure, others (n = 61)	Includes 8 patients with severe trauma (8/61); trauma-specific outcomes not separately reported	Molecular adsorbent recirculating system, continuous renal replacement therapy, standard medical therapy	1 to > 3 session (majority 3), 8 hours/session

MARS therapy was most commonly administered in 8-hour sessions over one to three consecutive days[3,5,14], although longer sessions and extended protocols were also reported[4]. The total number of sessions varied across studies, ranging from a single session to 14 sessions per patient, with treatment durations extending up to 17 days in one series[4]. In trauma patients, MARS therapy was frequently used in conjunction with CRRT and standard supportive measures, including angioembolization or hepatic resection when indicated[5]. In this cohort, 56% of patients received CRRT for ammonia clearance, and MARS protocols were individualized according to clinical response and transplant candidacy[5].

Outcomes

Primary and secondary outcomes are summarized in Table 2. Primary endpoints included survival and recovery of liver function, while secondary outcomes encompassed biochemical indicators (e.g., bilirubin, INR, ammonia), clinical manifestations (e.g., hepatic encephalopathy), and adverse events.

Table 2 Clinical and laboratory outcomes of molecular adsorbent recirculating system therapy in trauma-associated acute liver dysfunction.

Ref.	Primary outcomes	Secondary outcomes	Adverse events
Ben-Abraham et al[3]; 2003	Survival 100% (1/1), liver recovery (1/1)	Normalized intracranial pressure, improved bilirubin, ammonia, international normalized ratio, factor V	Not reported
Rittler et al[4]; 2004	Mortality 100% (5/5)	Reduced bilirubin; no improvement in ammonia, coagulopathy	Bleeding, thrombocytopenia
Monet et al[14]; 2022	Survival 40%, transplantation-free (acute liver failure, 13/32); variable by group	Improved bilirubin, prothrombin time, hepatic encephalopathy, pruritus	Thrombocytopenia (30.6%), hypotension, hypothermia
Powell et al[5]; 2024	Survival 50% (4/8 trauma cases)	Improved aspartate aminotransferase, alanine aminotransferase, international normalized ratio, lactic acid; no change in ammonia; no improvement in hepatic encephalopathy	Not reported

In trauma-specific studies, survival rates ranged from 50% to 100%. One investigation documented full patient recovery without the need for transplantation[3]. A retrospective analysis identified survival in 4 of 8 trauma patients within a broader ALF cohort (n = 61), with 30% of the total population undergoing transplantation, though specific data on transplant rates for trauma patients were not provided[5]. Another study noted a 40% transplantation-free survival rate in a cohort with ALF (n = 32, including 1 trauma patient), though trauma-related outcomes were not disaggregated[14]. A separate publication described 100% mortality (n = 5, including 1 trauma case), attributed to progressive septic organ failure[4].

DISCUSSION

MARS is an extracorporeal liver support system that has been explored in ALF, including trauma-induced hepatic necrosis; however, evidence specific to trauma remains extremely limited. This scoping review identified four observational studies addressing its clinical use, limitations, and potential future applications in trauma-related liver dysfunction[3-5,14]. While outcomes, mechanisms, and research gaps are discussed, the present review is inherently exploratory. No meta-analysis was performed, and the risk of bias was assessed descriptively. Despite a comprehensive search, publication bias cannot be excluded. The absence of control groups and the heterogeneity of study designs reflect an early stage of evidence development.

Available data suggest that MARS may be associated with hemodynamic stabilization and biochemical improvement, particularly when initiated early in patients without systemic complications; however, these observations do not constitute evidence of clinical effectiveness or safety in trauma populations. Improvements in detoxification and synthetic functions, including reductions in bilirubin, INR, and ammonia levels, as well as reports of transplant avoidance, have been described[3,5,14]. These findings must be interpreted cautiously and do not support the routine use of MARS as a bridge to recovery in trauma patients, given the absence of trauma-specific comparative data. Variability in outcomes, likely due to patient selection, comorbidities, and treatment timing, underscores the need for prospective, trauma-focused investigations. Differences in treatment protocols, including session number, duration, and the use of adjunctive therapies such as CRRT, further limit comparability across studies.

Mechanisms of action and physiological benefits

MARS utilizes albumin dialysis to remove both water-soluble and albumin-bound toxins, including ammonia, bilirubin, and bile acids. Through these mechanisms, it may contribute to hemodynamic stabilization, reduction of neurotoxicity, and partial correction of metabolic acidosis and coagulopathy. Such effects are theoretically relevant in trauma-associated liver failure. Several studies reported post-treatment improvements in ammonia, bilirubin, transaminases, INR, and lactate levels, findings that likely reflect detoxification processes and modulation of systemic inflammation rather than direct evidence of hepatic recovery[3,5,14].

The liver’s intrinsic regenerative capacity, demonstrated by its ability to recover after resection of up to 70% of hepatic parenchyma, provides a physiological basis for functional restoration following severe injury[3]. Within this context, MARS has been temporally associated with recovery of liver function in trauma-induced necrosis, supporting its theoretical role as a supportive measure during hepatic regeneration. Improvements observed in laboratory parameters among broader ALF populations may also suggest regenerative activity, although trauma-specific regenerative markers have not been evaluated[5,14]. Future studies incorporating liver progenitor cell biomarkers or histological assessment are required to clarify whether MARS influences regenerative pathways in trauma-related hepatic injury.

Challenges and limitations

Despite its potential physiological effects, MARS therapy faces significant limitations, particularly in trauma patients with systemic complications such as sepsis or multiple organ failure. In these settings, toxin clearance may be reduced and treatment may exacerbate coagulopathy[4,5], suggesting limited utility once systemic inflammation and organ dysfunction are established.

Bleeding is a recurrent concern, especially in patients with trauma-related coagulopathy. Increased transfusion requirements and laboratory evidence of hemostatic deterioration were noted in some cohorts[4,14]. While several studies reported no hemorrhagic complications[5]. Trauma-specific safety data remain sparse, and causality cannot be reliably attributed to MARS given the baseline bleeding risk inherent to this population. Nonetheless, clinical experience suggests that MARS may contribute to or exacerbate bleeding in selected cases, complicating the distinction between treatment-associated hemorrhage and trauma-related coagulopathy.

A major limitation across three of the four included studies is the use of mixed populations combining trauma-related and non-trauma etiologies without stratifying outcomes[4,5,14], precluding isolation of MARS effects in trauma-induced liver failure. Only one report focused exclusively on a trauma patient, and this consisted of a single case description[3]. Consequently, the existing literature does not permit any reliable assessment of clinical effectiveness or safety of MARS in trauma-specific contexts.

Overlapping cohorts from the same institution further complicate interpretation and may inflate estimates of survival or therapeutic effect[5]. Earlier reports from the same center were therefore excluded from the analysis[9,10]. Additionally, all included studies were observational, introducing risks of bias related to non-standardized inclusion criteria, heterogeneity in MARS protocols, and variability in adjunctive therapies such as CRRT. These limitations highlight the need for well-designed, trauma-specific prospective studies.

Indications and patient selection

Reports suggest that MARS may be more applicable in cases of isolated acute hepatic failure without sepsis or multiple organ dysfunction, including selected trauma patients. A single case report described full recovery following MARS therapy in a trauma patient[3]. Earlier classifications of MARS indications included severe liver trauma, although these cases were later incorporated into broader trauma cohorts without stratified reporting[5].

Institutional selection criteria based on transplant eligibility and reversibility of organ dysfunction have been described, but trauma-specific parameters were not clearly defined[5]. A larger, heterogeneous cohort included only one trauma patient and did not stratify outcomes by etiology, further limiting trauma-specific interpretation[14]. Collectively, these findings emphasize the need for tailored inclusion criteria focusing on trauma patients with isolated hepatic dysfunction.

From a clinical perspective, current evidence does not support routine use of MARS in trauma patients. At most, it suggests that, in highly selected cases with isolated and potentially reversible hepatic dysfunction, MARS may be considered on an individualized basis within experienced centers and following careful multidisciplinary evaluation.

Future directions

Further research is needed to better define the role of MARS in trauma-induced hepatic necrosis, particularly through larger, controlled studies. Key priorities are outlined below, and a summary of knowledge gaps and corresponding research recommendations is provided in Supplementary Table 3.

Based on the available evidence, the most urgent research priorities include: (1) Prospective multicenter registries with mandatory trauma-specific outcome stratification; (2) Standardized reporting of injury severity, timing of MARS initiation, and treatment protocols; (3) Clearly defined clinical endpoints such as transplant-free survival and bleeding complications; and (4) Systematic safety monitoring using trauma-adapted coagulation assessments.

Standardized protocols

Substantial variation in session number, duration, and timing, even within the same institution, reflects the absence of consensus on optimal MARS delivery in trauma settings. Trauma-specific protocols are required to enable consistent practice and valid comparisons across studies. Future trials should address initiation thresholds, response-based adjustments, and integration with adjunctive therapies such as CRRT.

Patient selection criteria

Variable outcomes likely result from inconsistent selection criteria. Existing evidence suggests that patients with isolated, reversible hepatic dysfunction may respond more favorably, whereas those with sepsis or multiple organ failure appear less likely to benefit. Prospective studies should define inclusion parameters that consider systemic complications to improve candidate identification.

Biomarkers of recovery

Validated markers to guide MARS therapy are lacking. Although parameters such as aspartate aminotransferase, alanine aminotransferase, INR, and lactate have shown trends in some publications, their predictive accuracy remains uncertain. Further research should evaluate the utility of trauma-specific biomarkers to refine patient selection and monitor response.

Cost-effectiveness

The financial burden associated with MARS, due to equipment, consumables, and critical care requirements raises questions about its clinical value in trauma settings. Although its feasibility has been demonstrated in high-resource centers, dedicated cost-effectiveness analyses comparing MARS with standard therapy or transplantation are needed to inform resource allocation.

Mechanistic studies

The biological mechanisms underlying hepatic recovery during MARS remain poorly defined. Concepts such as the hepatic penumbra and liver progenitor cells activation warrant investigation through trauma-focused preclinical and clinical studies to clarify how MARS contributes to liver regeneration.

Safety and adverse events

Given the bleeding risk inherent to trauma populations, data on MARS-associated complications remain limited. Future studies should employ trauma-relevant coagulation monitoring (e.g., thromboelastography) and report adverse events in a standardized manner to guide safer anticoagulation strategies during treatment.

Potential clinical applications of MARS

Although formal guidelines for the use of MARS in trauma-induced liver failure are lacking because of limited evidence, a small number of clinical scenarios have been discussed in the literature as potentially suitable for consideration. Patients with isolated high-grade liver injuries (American Association for the Surgery of Trauma grades III to V) and evidence of potentially reversible hepatic dysfunction have been described as candidates in whom early MARS initiation could be explored as a temporary supportive strategy rather than as a therapeutic intervention. In cases with associated renal impairment, the combined use of MARS and CRRT has been proposed as a means of providing additional metabolic support. These considerations remain speculative and require confirmation in prospective studies employing standardized inclusion criteria, including clearly defined thresholds of hepatic dysfunction and exclusion of systemic sepsis, as well as robust clinical endpoints such as transplant-free survival, to ensure scientific rigor.

CONCLUSION

Current evidence is insufficient to support definitive conclusions regarding the clinical effectiveness or safety of MARS in trauma-induced hepatic necrosis, even in patients with isolated liver injury. While trauma cases have reported improvements in biochemical parameters and physiological variables, these findings should be considered hypothesis-generating and should not guide routine clinical decision-making. Nonetheless, complications such as coagulopathy and reduced efficacy in the context of sepsis or multiple organ failure underscore the importance of appropriate patient selection and close clinical monitoring. Moving forward, efforts should prioritize the development of standardized protocols, trauma-specific inclusion criteria, and mechanistic research to clarify and expand the role of MARS in trauma-related liver failure.

ACKNOWLEDGEMENTS

Artificial intelligence tools were used to assist with deduplication and citation management (Zotero), study screening (Rayyan), plagiarism checking (Ref-n-write), and language editing (ChatGPT), during manuscript preparation. The authors reviewed and approved all artificial intelligence generated content and are fully responsible for its accuracy and integrity.