Therapeutic plasma exchange in amatoxin associated acute liver failure-results from the multi-center Amanita-PEX study.

Klaus Stahl, Bahar Nalbant, Thorben Pape, Isaure Breteau, Valentin Coirier, Filipe S Cardoso, Jubi de Haan, Maciej K Janik, Jan-Christian Wasmuth, João Madaleno, Uta Merle, Josephine Frohme, Phil-Robin Tepasse, Martina Müller, Karsten Große, Alexandra Linke, Nikola Mareljic, Fin Stolze Larsen, Gérladine Dahlqvist, Mirjam Kolev, Marie Schulze, Katharina Willuweit, Petra Janke-Maier, Felix Dondorf, Óscar M Fierro-Angulo, Anja Geerts, David Toapanta, Camille Dejean, Mohamed Alharthi, Enric Reverter, Heiko Schenk, Sarah Raevens, Ricardo Ulises Macías-Rodríguez, Falk Rauchfuß, Christoph P Berg, Hartmut Schmidt, Andreas Geier, Nasser Semmo, Nicolas Lanthier, Peter N Bjerring, Christian M Lange, Martina Sterneck, Tony Bruns, Stephan Schmid, Dominik van de Loo, Münevver Demir, Tobias Boettler, Catarina Borges, Jacob Nattermann, Karolina Wronka, Caroline M den Hoed, Hugo P Marques, Florent Artru, Eric Levesque, Heiner Wedemeyer, Alejandro Campos-Murguia, Richard Taubert

Journal: Critical care (London, England) 2025;29(1):458

PMID: 41163058

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Abstract

BACKGROUND

Amatoxin-related acute liver failure (AT-ALF) carries high mortality without liver transplantation (LTX). While therapeutic plasma exchange (PEX) might improve LTX-free survival in other ALF cases, its role in AT-ALF is unclear. Clinical practice varies, and, given the rarity of this ALF entity, the feasibility of conducting a randomized controlled trial to investigate PEX in AT-ALF is more or less impossible.

METHODS

The Amanita-PEX study is a multi-center, international, retrospective study analyzing patients with AT-ALF from 2013 to 2024. The primary outcome was 28-day LTX-free survival (composite endpoint: death or LTX) after ALF diagnosis.

RESULTS

The study included 111 patients from 25 centers: 82 received standard-of-care (SOC), and 29 received at least one PEX-session. PEX and SOC-groups were comparable at baseline, but 76% of PEX- vs. 58% of SOC-patients developed hepatic-encephalopathy (HE) grade ≥ 2 (p = 0.021). While the primary outcome of 28-day LTX-free survival in all patients was not different between the SOC and PEX-groups, in the subgroup of patients with maximal HE grade ≥ 2, LTX-free survival was 19.1% (n = 8/42) in the SOC group, while it was 36.4% (n = 8/22) in patients receiving adjunctive PEX (Gehan-Breslow-Wilcoxon-p = 0.041, Log-Rank-p = 0.060). PEX was independently associated with reduced risk of the combined endpoint death or liver transplantation within 28 days from inclusion in patients with HE grade ≥ 2 (HR 0.37, 95%-CI 0.19-0.73, p = 0.004). After propensity-score-matching, LTX-free survival was 28% in the SOC- and 52% in the PEX group (Gehan-Breslow-p = 0.036; Log-Rank-p = 0.035).

CONCLUSIONS

In this real-world study, adjunctive use of PEX was associated with increased LTX-free-survival in patients with AT-ALF and HE grade ≥ 2.

Address: Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover, 30625, Germany. [email protected].; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany. [email protected].; Department of Respiratory Medicine and Infectious Diseases, and German Centre of Lung Research (DZL), Hannover Medical School, Hannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Anesthesia and Intensive Care, University Hospitals of Tours, Tours, France.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Liver Department, Médecine Intensive Réanimation, Rennes University Hospital, Rennes, France.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Curry Cabral Hospital, Nova Medical School, Lisbon, Portugal.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Intensive Care, Erasmus University Medical Center, Rotterdam, The Netherlands.; Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Internal Medicine I, German Center for Infection Research (DZIF), University of Bonn, Bonn, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Liver Disease Unit - Internal Medicine Department and Adult Liver Transplant Unit, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Medical Faculty, Department of Internal Medicine IV, Heidelberg University, University Hospital, Heidelberg, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Muenster, Muenster, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Medicine II, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Hepatology and Gastroenterology, Rigshospitalet, Copenhagen University Hospitalet, Copenhagen, Denmark.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Service d'Hépato-gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Visceral Surgery and Medicine, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.; Department of Internal Medicine II, Hepatology, University Hospital of Würzburg, Würzburg, Germany.; Department of Gastroenterology, Hepatology and Transplantational Medicine University Hospital Essen, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.; Department of Gastroenterology, Gastrointestinal Onkology, Hepatology, Infektious Diseases,and Geriatrics, University of Tuebingen, Tuebingen, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany.; Division of Hepatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.; Department of Gastroenterology & Hepatology, Ghent University Hospital, Ghent, Belgium.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Liver Unit, IDIBAPS, and CIBEREHD, Liver ICU, Hospital Clinic, University of Barcelona, Barcelona, Spain.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.; Department of Medicine II, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany.; Apheresis Unit - Blood and Transfusion Medicine Department, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover, 30625, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover, 30625, Germany. [email protected].; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany. [email protected].

DOI: 10.1186/s13054-025-05560-y

MeSH Terms: Humans, Male, Female, Plasma Exchange, Liver Failure, Acute, Middle Aged, Retrospective Studies, Amanitins, Adult, Amanita, Mushroom Poisoning, Aged