Artificial Liver Support Effectively Removes Immunosuppressive Bile Acids From Circulation in Patients With Severe Liver Failure: A Proof of Concept Study

Clinical Snapshot

Key Findings

• P Value: 0.051 for between-group comparison

• Effect Size: 60% reduction with OPAL vs 39% reduction with MARS

• Primary Outcome: Reduction in TGR5 activation by circulating bile acids

• Nnt Or Sensitivity: Not calculable from available data

• Confidence Interval: Not reported

Clinical Application

Both MARS and OPAL are available in major Australian tertiary centres, though OPAL may require additional expertise Relevant to Australian liver transplant centres and ICUs. Neither technology specifically PBS-listed but available through hospital funding. Aligns with ANZICS guidelines for liver failure management ICU patients with severe liver failure and bilirubin >12 mg/dL requiring artificial liver support

Abstract

OBJECTIVE: Bile acids that induce immunosuppression through activation of the Takeda G protein-coupled receptor 5 (TGR5) have recently been identified in the circulation of patients with liver failure and sepsis. These bile acids are associated with increased susceptibility to infection and a high short-term mortality. Furthermore, TGR5 activation by bile acids has been implicated in the development of pruritus. However, therapies targeting TGR5-activating bile acids in patients have not yet been reported. This study investigates the effects of two artificial liver support systems, the Molecular Adsorbent Recirculating System (MARS) and the open albumin dialysis (OPAL). DESIGN: Proof of concept study, multicenter study. SETTING: University Hospital Jena, University Hospital Ulm, and University Hospital Münster, Germany. PATIENTS: Patients with severe liver failure, as defined by the Sequential Organ Failure Assessment hepatic sub-score (i.e., bilirubin > 12 mg/dL). INTERVENTIONS: Patients with severe liver failure were randomized to receive one session of MARS or OPAL for 8 hours, followed by crossover to the other treatment on the next day. MEASUREMENTS AND MAIN RESULTS: Bilirubin, circulating total and individual bile acids, albumin function, and TGR5 activation induced by circulating bile acids were assessed before and after each treatment session. Both OPAL and MARS significantly removed bilirubin, as well as individual and total bile acids from circulation. OPAL was superior to MARS in removing protein-bound lipophilic bile acids and restoring patients' albumin function (i.e., albumin-binding capacity, detoxification efficiency, and binding efficiency). TGR5 activation induced by circulating bile acids was reduced by 60% with OPAL compared with 39% with MARS (median values, p = 0.051). CONCLUSIONS: Artificial liver support systems effectively remove immunosuppressive bile acids from circulation. The clinical implications of bile acid reduction, however, require further study.

References

1. 1.Leonhardt, J., Schmidt, H. H., Koball, S., Dollinger, M., Wilms, C., Neugebauer, S., Kunze, J., Kiehntopf, M., Hinz, M., Backhus, J., Henschel, J., Klammt, S., Sponholz, C., Dominik, A., Mitzner, S., Stange, J., Bauer, M., & Kortgen, A. (2026). Artificial liver support effectively removes immunosuppressive bile acids from circulation in patients with severe liver failure: A proof of concept study. Critical Care Explorations. https://doi.org/10.1097/CCE.0000000000001419