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Ballester MP, Elshabrawi A, Jalan R. Extracorporeal liver support and liver transplantation for acute-on-chronic liver failure. Liver Int 2025; 45:e15647. [PMID: 37312660 PMCID: PMC11815617 DOI: 10.1111/liv.15647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/31/2023] [Accepted: 06/04/2023] [Indexed: 06/15/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is defined by acute decompensation, organ failure and a high risk of short-term mortality. This condition is characterized by an overwhelming systemic inflammatory response. Despite treating the precipitating event, intensive monitoring and organ support, clinical deterioration can occur with very poor outcomes. During the last decades, several extracorporeal liver support systems have been developed to try to reduce ongoing liver injury and provide an improved environment for the liver to regenerate or as a bridging therapy until liver transplantation. Several clinical trials have been performed to evaluate the clinical efficacy of extracorporeal liver support systems, but no clear impact on survival has been proven. DIALIVE is a novel extracorporeal liver support device that has been built to specifically address the pathophysiological derangements responsible for the development of ACLF by replacing dysfunctional albumin and removing pathogen and damage-associated molecular patterns (PAMPs and DAMPs). In phase II clinical trial, DIALIVE appears to be safe, and it seems to be associated with a faster time to the resolution of ACLF compared with standard medical treatment. Even in patients with severe ACLF, liver transplantation saves lives and there is clear evidence of transplant benefit. Careful selection of patients is required to attain good results from liver transplantation, but many questions remain unanswered. In this review, we describe the current perspectives on the use of extracorporeal liver support and liver transplantation for ACLF patients.
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Affiliation(s)
- Maria Pilar Ballester
- Digestive Disease DepartmentHospital Clínico Universitario de ValenciaValenciaSpain
- INCLIVA Biomedical Research InstituteHospital Clínico Universitario de ValenciaValenciaSpain
| | - Ahmed Elshabrawi
- Liver Failure Group, Institute for Liver & Digestive HealthUniversity College LondonLondonUK
- Endemic Hepatology and Gastroenterology DepartmentMansoura UniversityMansouraEgypt
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver & Digestive HealthUniversity College LondonLondonUK
- European Foundation for the Study of Chronic Liver Failure (EF Clif)BarcelonaSpain
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Wu SC, Cheng CC, Yeh HC, Cheng HT, Wang YC, Tzeng CW, Hsu CH, Muo CH. High Volume Plasma Exchange Improves Survival Rates in Surgical Critically Ill Patients With Medical Jaundice and Hepatic Failure: A Comparative Study. World J Surg 2025; 49:364-373. [PMID: 39794861 DOI: 10.1002/wjs.12483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 11/21/2024] [Accepted: 12/29/2024] [Indexed: 01/13/2025]
Abstract
OBJECTIVES Acute liver failure poses a significant challenge in surgical critically ill patients. Treatments typically focus on physiological support and alleviation of hepatic insult. This study aims to evaluate the role of high-volume plasma exchange (HVPE) in surgical critically ill patients with medical jaundice and hepatic failure. METHOD A retrospective review was conducted on surgical critically ill patients with hepatic failure unresponsive to conventional therapy, excluding those with obstructive jaundice. HVPE was considered for patients with persistent hyperbilirubinemia (> 10 mg/dL) and coexisting conditions such as coagulopathy, hyperammonemia, more than Grade II hepato-encephalopathy, or exacerbated sepsis/septic shock status or multiple organ failure. Patients were categorized into standard medical treatment (SMT) and SMT + HVPE groups. Demographics and laboratory data were collected for analysis. RESULT A total of 117 patients were enrolled, with 79 in the SMT group and 38 in the SMT + HVPE group. There were no significant differences in laboratory data and MELD score upon admission. Before treatment, patients in the SMT + HVPE group exhibited higher levels of T-bil., D-bil., and sugar than the SMT group. After treatment, the SMT + HVPE group showed lower serum D-bil. and AST levels but higher levels of albumin and platelets compared to the SMT group. The SMT + HVPE group demonstrated significantly lower delta T-bil., delta D-bil., and higher delta platelet levels. The survival rate was 31.6% (12/38) in the SMT + HVPE group and 1.3% (1/79) in the SMT group. The in-hospital mortality rate in the SMT + HVPE group was lower than that in the SMT group, with a hazard ratio of 0.42 in the crude model and 0.34 (95% CI = 0.20-0.60 and p = 0.0002) in the adjusted model. CONCLUSION Our findings suggest that HVPE improves survival rates in surgical critically ill patients with medical jaundice and hepatic failure. However, due to its retrospective nature, further studies were warranted.
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Affiliation(s)
- Shih-Chi Wu
- School of Medicine, China Medical University, Taichung, Taiwan
- Trauma and Emergency Center, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Chung Cheng
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Chieh Yeh
- Kidney Institute and Division of Nephrology, China Medical University Hospital, Taichung, Taiwan
| | - Han-Tsung Cheng
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Yu-Chun Wang
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Wei Tzeng
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Hao Hsu
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsin Muo
- Management Office for Health Data, China Medical University and Hospital, Taichung, Taiwan
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Brown RS, Fisher RA, Subramanian RM, Griesemer A, Fernandes M, Thatcher WH, Stiede K, Curtis M. Artificial Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure: Systematic Review and Meta-Analysis. Crit Care Explor 2025; 7:e1199. [PMID: 39804005 PMCID: PMC11732652 DOI: 10.1097/cce.0000000000001199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2025] Open
Abstract
OBJECTIVES To systematically review the safety and efficacy of nonbiological (NBAL) or biological artificial liver support systems (BAL) and whole-organ extracorporeal liver perfusion (W-ECLP) systems, in adults with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). DATA SOURCES Eligible NBAL/BAL studies from PubMed/Embase searches were randomized controlled trials (RCTs) in adult patients with ALF/ACLF, greater than or equal to ten patients per group, reporting outcomes related to survival, adverse events, transplantation rate, and hepatic encephalopathy, and published in English from January 2000 to July 2023. Separately, we searched for studies evaluating W-ECLP in adult patients with ALF or ACLF published between January1990 and July 2023. STUDY SELECTION AND DATA EXTRACTION Two researchers independently screened citations for eligibility and, of eligible studies, retrieved data related to study characteristics, patients and interventions, outcomes definition, and intervention effects. The Cochrane Risk of Bias 2 tool and Joanna Briggs Institute checklists were used to assess individual study risk of bias. Meta-analysis of mortality at 28-30 days post-support system initiation and frequency of at least one serious adverse event (SAE) generated pooled risk ratios (RRs), based on random (mortality) or fixed (SAE) effects models. DATA SYNTHESIS Of 17 trials evaluating NBAL/BAL systems, 11 reported 28-30 days mortality and five reported frequency of at least one SAE. Overall, NBAL/BAL was not statistically associated with mortality at 28-30 days (RR, 0.85; 95% CI, 0.67-1.07; p = 0.169) or frequency of at least one SAE (RR, 1.15; 95% CI, 0.99-1.33; p = 0.059), compared with standard medical treatment. Subgroup results on ALF patients suggest possible benefit for mortality (RR, 0.67; 95% CI, 0.44-1.03; p = 0.069). From six reports of W-ECLP (12 patients), more than half (58%) of severe patients were bridged to transplantation and survived without transmission of porcine retroviruses. CONCLUSIONS Despite no significant pooled effects of NBAL/BAL devices, the available evidence calls for further research and development of extracorporeal liver support systems, with larger RCTs and optimization of patient selection, perfusion durability, and treatment protocols.
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Affiliation(s)
- Robert S. Brown
- Center for Liver Disease, Weill Cornell Medicine, New York, NY
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Novokhodko A, Hao S, Ahmad S, Gao D. Non-Cell-Based Extracorporeal Artificial Liver Systems: Historic Perspectives, Approaches and Mechanisms, Current Applications, and Challenges. Artif Organs 2024. [PMID: 39737603 DOI: 10.1111/aor.14931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/03/2024] [Accepted: 12/09/2024] [Indexed: 01/01/2025]
Abstract
BACKGROUND Liver disease is a growing burden. Transplant organs are scarce. Extracorporeal liver support systems (ELSS) are a bridge to transplantation for eligible patients. For transplant-ineligible patients the objective becomes liver recovery. METHODS We review seven decades of non-cell-based ELSS research in humans. Where possible, we emphasize randomized controlled trials (RCTs). When RCTs are not available, we describe the available human clinical data. RESULTS There are three broad cell-free approaches to remove protein-bound toxins (PBTs) and treat liver failure. The first is a dialysate binder suspension. A material that binds the PBT (the binder) is added to the dialysate. Binders include albumin, charcoal, and polystyrene sulfonate sodium. The unbound fraction of the PBT crosses the dialyzer membrane along a chemical gradient and binds to the binder. The second approach is using grains of sorbent fixed in a plastic housing to remove PBTs. Toxin-laden blood or plasma flows directly through the column. Toxins are removed by binding to the sorbent. The third approach is exchanging toxin-laden blood, or fractions of blood, for a healthy donor blood product. Most systems lack widespread acceptance, but plasma exchange (PE) is recommended in many guidelines. The large donor plasma requirement of PE creates demand for systems to complement or replace it. CONCLUSIONS Now that PE has become recommended in some, but not all, jurisdictions, we discuss the importance of reporting precise PE protocols and dose. Our work provides an overview of promising new systems and lessons from old technologies to enable ELSS improvement.
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Affiliation(s)
- Alexander Novokhodko
- Department of Mechanical Engineering, University of Washington, Seattle, Washington, USA
| | - Shaohang Hao
- Department of Mechanical Engineering, University of Washington, Seattle, Washington, USA
| | - Suhail Ahmad
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Dayong Gao
- Department of Mechanical Engineering, University of Washington, Seattle, Washington, USA
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Yadav M, Maiwal R, Kumar Br V, Tripathi G, Sharma N, Sharma N, Bindal V, Mathew B, Pandey S, Singh SP, Tevathia HV, Maras JS, Sarin SK. Comparative metabolome analysis reveals higher potential of haemoperfusion adsorption in providing favourable outcome in ACLF patients. Liver Int 2024; 44:1189-1201. [PMID: 38358068 DOI: 10.1111/liv.15858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 01/02/2024] [Accepted: 01/21/2024] [Indexed: 02/16/2024]
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed. METHODS We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post-HA and TPE sessions on days 7 and 14 using high-resolution mass spectrometry. RESULTS The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p < .05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine-proline metabolism (6 metabolites) and microbial metabolism respectively (p < .05). Metabolites linked to taurine-hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post-TPE therapy (p < .05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post-HA therapy compared to TPE and SMT (p < .05). Higher baseline plasma level of 11-deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p < .05) and mortality (log-rank-p < .05). Notably, 51 of the 64 metabolite signatures (ACLF non-survivor) were reversed post-HA treatment compared to TPE and SMT(p < .05). CONCLUSION HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11-deoxycorticosterone level correlates with early mortality in ACLF patients.
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Affiliation(s)
- Manisha Yadav
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vinay Kumar Br
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Gaurav Tripathi
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Neha Sharma
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nupur Sharma
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vasundhra Bindal
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Babu Mathew
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sushmita Pandey
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Satender Pal Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Jaswinder Singh Maras
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Butt MF, Jalan R. Review article: Emerging and current management of acute-on-chronic liver failure. Aliment Pharmacol Ther 2023; 58:774-794. [PMID: 37589507 DOI: 10.1111/apt.17659] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/02/2023] [Accepted: 07/24/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a clinically and pathophysiologically distinct condition from acutely decompensated cirrhosis and is characterised by systemic inflammation, extrahepatic organ failure, and high short-term mortality. AIMS To provide a narrative review of the diagnostic criteria, prognosis, epidemiology, and general management principles of ACLF. Four specific interventions that are explored in detail are intravenous albumin, extracorporeal liver assist devices, granulocyte-colony stimulating factor, and liver transplantation. METHODS We searched PubMed and Cochrane databases for articles published up to July 2023. RESULTS Approximately 35% of hospital inpatients with decompensated cirrhosis have ACLF. There is significant heterogeneity in the criteria used to diagnose ACLF; different definitions identify different phenotypes with varying mortality. Criteria established by the European Association for the Study of the Liver were developed in prospective patient cohorts and are, to-date, the most well validated internationally. Systemic haemodynamic instability, renal dysfunction, coagulopathy, neurological dysfunction, and respiratory failure are key considerations when managing ACLF in the intensive care unit. Apart from liver transplantation, there are no accepted evidence-based treatments for ACLF, but several different approaches are under investigation. CONCLUSION The recognition of ACLF as a distinct entity from acutely decompensated cirrhosis has allowed for better patient stratification in clinical settings, facilitating earlier engagement with the intensive care unit and liver transplantation teams. Research priorities over the next decade should focus on exploring novel treatment strategies with a particular focus on which, when, and how patients with ACLF should be treated.
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Affiliation(s)
- Mohsin F Butt
- Centre for Neuroscience, Trauma and Surgery, Wingate Institute of Neurogastroenterology, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Liver Failure Group, University College London Medical School, Royal Free Hospital Campus, London, UK
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottinghamshire, UK
| | - Rajiv Jalan
- Liver Failure Group, University College London Medical School, Royal Free Hospital Campus, London, UK
- European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium, Barcelona, Spain
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7
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Sommerfeld O, Neumann C, Becker J, von Loeffelholz C, Roth J, Kortgen A, Bauer M, Sponholz C. Extracorporeal albumin dialysis in critically ill patients with liver failure: Comparison of four different devices-A retrospective analysis. Int J Artif Organs 2023; 46:481-491. [PMID: 37609875 PMCID: PMC10483887 DOI: 10.1177/03913988231191952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 06/26/2023] [Indexed: 08/24/2023]
Abstract
BACKGROUND Besides standard medical therapy and critical care monitoring, extracorporeal liver support may provide a therapeutic option in patients with liver failure. However, little is known about detoxification capabilities, efficacy, and efficiency among different devices. METHODS Retrospective single-center analysis of patients treated with extracorporeal albumin dialysis. Generalized Estimating Equations with robust variance estimator were used to account for repeated measurements of several cycles and devices per patient. RESULTS Between 2015 and 2021 n = 341 cycles in n = 96 patients were eligible for evaluation, thereof n = 54 (15.8%) treatments with Molecular Adsorbent Recirculating System, n = 64 (18.7%) with OpenAlbumin, n = 167 (48.8%) Advanced Organ Support treatments, and n = 56 (16.4%) using Single Pass Albumin Dialysis. Albumin dialysis resulted in significant bilirubin reduction without differences between the devices. However, ammonia levels only declined significantly in ADVOS and OPAL. First ECAD cycle was associated with highest percentage reduction in serum bilirubin. With the exception of SPAD all devices were able to remove the water-soluble substances creatinine and urea and stabilized metabolic dysfunction by increasing pH and negative base excess values. Platelets and fibrinogen levels frequently declined during treatment. Periprocedural bleeding and transfusion of red blood cells were common findings in these patients. CONCLUSIONS From this clinical perspective ADVOS and OPAL may provide higher reduction capabilities of liver solutes (i.e. bilirubin and ammonia) in comparison to MARS and SPAD. However, further prospective studies comparing the effectiveness of the devices to support liver impairment (i.e. bile acid clearance or albumin binding capacity) as well as markers of renal recovery are warranted.
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Affiliation(s)
- Oliver Sommerfeld
- Department of Anaesthesiology and Critical Care Medicine, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Thuringia, Germany
| | - Caroline Neumann
- Department of Anaesthesiology and Critical Care Medicine, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Thuringia, Germany
| | - Jan Becker
- Department of Anaesthesiology and Critical Care Medicine, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Thuringia, Germany
| | - Christian von Loeffelholz
- Department of Anaesthesiology and Critical Care Medicine, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Thuringia, Germany
| | - Johannes Roth
- Department of Anaesthesiology and Critical Care Medicine, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Thuringia, Germany
| | - Andreas Kortgen
- Department of Anaesthesiology and Critical Care Medicine, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Thuringia, Germany
| | - Michael Bauer
- Department of Anaesthesiology and Critical Care Medicine, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Thuringia, Germany
| | - Christoph Sponholz
- Department of Anaesthesiology and Critical Care Medicine, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Thuringia, Germany
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Saliba F, Bañares R, Larsen FS, Wilmer A, Parés A, Mitzner S, Stange J, Fuhrmann V, Gilg S, Hassanein T, Samuel D, Torner J, Jaber S. Artificial liver support in patients with liver failure: a modified DELPHI consensus of international experts. Intensive Care Med 2022; 48:1352-1367. [PMID: 36066598 DOI: 10.1007/s00134-022-06802-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 06/24/2022] [Indexed: 02/04/2023]
Abstract
The present narrative review on albumin dialysis provides evidence-based and expert opinion guidelines for clinicians caring for adult patients with different types of liver failure. The review was prepared by an expert panel of 13 members with liver and ntensive care expertise in extracorporeal liver support therapies for the management of patients with liver failure. The coordinating committee developed the questions according to their importance in the management of patients with liver failure. For each indication, experts conducted a comprehensive review of the literature aiming to identify the best available evidence and assessed the quality of evidence based on the literature and their experience. Summary statements and expert's recommendations covered all indications of albumin dialysis therapy in patients with liver failure, timing and intensity of treatment, efficacy, technical issues related to the device and safety. The panel supports the data from the literature that albumin dialysis showed a beneficial effect on hepatic encephalopathy, refractory pruritus, renal function, reduction of cholestasis and jaundice. However, the trials lacked to show a clear beneficial effect on overall survival. A short-term survival benefit at 15 and 21 days respectively in acute and acute-on-chronic liver failure has been reported in recent studies. The technique should be limited to patients with a transplant project, to centers experienced in the management of advanced liver disease. The use of extracorporeal albumin dialysis could be beneficial in selected patients with advanced liver diseases listed for transplant or with a transplant project. Waiting future large randomized controlled trials, this panel experts' statements may help careful patient selection and better treatment modalities.
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Affiliation(s)
- Faouzi Saliba
- AP-HP Hôpital Paul Brousse, Hepato-Biliary Center and Liver Transplant ICU, University Paris Saclay, INSERM Unit N°1193, Villejuif, France
| | - Rafael Bañares
- Gastroenterology and Hepatology Department, Hospital General Universitario Gregorio Marañón, IISGM, Madrid, Spain.,Facultad de Medicina, Universidad Complutense, Madrid, Spain.,CIBERehd, Madrid, Spain
| | - Fin Stolze Larsen
- Department of Hepatology and Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Alexander Wilmer
- Medical Intensive Care Unit, Department of General Internal Medicine, KU Leuven University Hospitals Leuven, Leuven, Belgium
| | - Albert Parés
- Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Steffen Mitzner
- Division of Nephrology and Fraunhofer Institute for Cell Therapy and Immunology, Department of Medicine, University Hospital Rostock, Rostock, Germany
| | - Jan Stange
- Center for Extracorporeal Organ Support, Nephrology, Internal Medicine, Rostock University Medical Center, Rostock, Germany.,Albutec GmbH, Rostock, Germany
| | - Valentin Fuhrmann
- Klinik für Innere Medizin, Heilig Geist-Krankenhaus, Cologne, Germany.,Klinik für Intensivmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Gilg
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Solna, Sweden.,Department of HPB Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Tarek Hassanein
- Southern California Liver Centers, 131 Orange Avenue, Suite 101, Coronado, CA, 92118, USA
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Hepato-Biliary Center and Liver Transplant ICU, University Paris Saclay, INSERM Unit N°1193, Villejuif, France
| | | | - Samir Jaber
- Department of Anesthesia and Intensive Care Unit, Regional University Hospital of Montpellier, St-Eloi Hospital, University of Montpellier, PhyMedExp, INSERM U1046, CNRS UMR, 9214, Montpellier Cedex 5, France. .,Département d'Anesthésie Réanimation B (DAR B), 80 Avenue Augustin Fliche, 34295, Montpellier, France.
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9
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Lei Y, Liang Y, Zhang X, Wang X, Zhang Y, Chan YM, Tang C, Zheng Z. Alternating therapeutic plasma exchange (TPE) with double plasma molecular adsorption system (DPMAS) for the treatment of fulminant hepatic failure (FHF). Clin Case Rep 2021; 9:e05220. [PMID: 34938567 PMCID: PMC8667290 DOI: 10.1002/ccr3.5220] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/24/2021] [Accepted: 12/03/2021] [Indexed: 01/14/2023] Open
Abstract
Alternating therapeutic plasma exchange with double plasma molecular adsorption system can rapidly remove bilirubin and ammonia and supplement the essential substance from the blood, which could be used as an effective treatment for fulminant hepatic failure.
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Affiliation(s)
- Yan Lei
- Department of NephrologyCenter of Nephrology and UrologyThe Seventh Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Yuling Liang
- Department of NephrologyCenter of Nephrology and UrologyThe Seventh Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Xuemei Zhang
- Department of NephrologyCenter of Nephrology and UrologyThe Seventh Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Xiaohua Wang
- Department of NephrologyCenter of Nephrology and UrologyThe Seventh Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Yu Zhang
- Department of NephrologyCenter of Nephrology and UrologyThe Seventh Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Yuk Ming Chan
- Department of NephrologyCenter of Nephrology and UrologyThe Seventh Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Chun Tang
- Department of NephrologyCenter of Nephrology and UrologyThe Seventh Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Zhihua Zheng
- Department of NephrologyCenter of Nephrology and UrologyThe Seventh Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
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10
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Matar AJ, Subramanian R. Extracorporeal Liver Support: A Bridge to Somewhere. Clin Liver Dis (Hoboken) 2021; 18:274-279. [PMID: 34976371 PMCID: PMC8688900 DOI: 10.1002/cld.1140] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 05/13/2021] [Accepted: 05/18/2021] [Indexed: 02/04/2023] Open
Abstract
Content available: Audio Recording.
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Affiliation(s)
- Abraham J. Matar
- Department of SurgeryDivision of SurgeryEmory UniversityAtlantaGA
| | - Ram Subramanian
- Department of MedicineDivision of HepatologyEmory UniversityAtlantaGA,Department of MedicineDivision of Critical Care MedicineEmory UniversityAtlantaGA
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11
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Ocskay K, Kanjo A, Gede N, Szakács Z, Pár G, Erőss B, Stange J, Mitzner S, Hegyi P, Molnár Z. Uncertainty in the impact of liver support systems in acute-on-chronic liver failure: a systematic review and network meta-analysis. Ann Intensive Care 2021; 11:10. [PMID: 33462764 PMCID: PMC7813174 DOI: 10.1186/s13613-020-00795-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 12/18/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. METHODS The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). RESULTS In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6-0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. CONCLUSION PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.
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Affiliation(s)
- Klementina Ocskay
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624 Hungary
| | - Anna Kanjo
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624 Hungary
- Heim Pál National Paediatric Institute, Budapest, Hungary
| | - Noémi Gede
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624 Hungary
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Zsolt Szakács
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624 Hungary
| | - Gabriella Pár
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Bálint Erőss
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624 Hungary
| | - Jan Stange
- Division of Nephrology, Department of Medicine, University of Rostock, Rostock, Germany
| | - Steffen Mitzner
- Division of Nephrology, Department of Medicine, University of Rostock, Rostock, Germany
| | - Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624 Hungary
- First Department of Medicine, University of Szeged, Szeged, Hungary
- Translational Medicine Foundation, Szeged, Hungary
| | - Zsolt Molnár
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624 Hungary
- Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland
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12
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A prognostic score for patients with acute-on-chronic liver failure treated with plasma exchange-centered artificial liver support system. Sci Rep 2021; 11:1469. [PMID: 33446902 PMCID: PMC7809456 DOI: 10.1038/s41598-021-81019-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/30/2020] [Indexed: 02/05/2023] Open
Abstract
Artificial liver support system (ALSS) therapy is widely used in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop a predictive score to identify the subgroups who may benefit from plasma exchange (PE)-centered ALSS therapy. A total of 601 patients were retrospectively enrolled and randomly divided into a derivation cohort of 303 patients and a validation cohort of 298 patients for logistic regression analysis, respectively. Five baseline variables, including liver cirrhosis, total bilirubin, international normalized ratio of prothrombin time, infection and hepatic encephalopathy, were found independently associated with 3-month mortality. A predictive PALS model and the simplified PALS score were developed. The predicative value of PALS score (AUROC = 0.818) to 3-month prognosis was as capable as PALS model (AUROC = 0.839), R score (AUROC = 0.824) and Yue-Meng’ score (AUROC = 0.810) (all p > 0.05), and superior to CART model (AUROC = 0.760) and MELD score (AUROC = 0.765) (all p < 0.05). The PALS score had significant linear correlation with 3-month mortality (R2 = 0.970, p = 0.000). PALS score of 0–2 had both sensitivity and negative predictive value of > 90% for 3-month mortality, while PALS score of 6–9 had both specificity and positive predictive value of > 90%. Patients with PALS score of 3–5 who received 3–5 sessions of ALSS therapy had much lower 3-month mortality than those who received 1–2 sessions (32.8% vs. 59.2%, p < 0.05). The more severe patients with PALS score of 6–9 could still benefit from ≥ 6 sessions of ALSS therapy compared to ≤ 2 sessions (63.6% vs. 97.0%, p < 0.05). The PALS score could predict prognosis reliably and conveniently. It could identify the subgroups who could benefit from PE-centered ALSS therapy, and suggest the reasonable sessions. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032055. Registered 19th April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52471.
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13
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Camus C, Locher C, Saliba F, Goubaux B, Bonadona A, Lavayssiere L, Paugam C, Quinart A, Barbot O, Dharancy S, Delafosse B, Pichon N, Barraud H, Galbois A, Veber B, Cayot S, Souche B. Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: A national multicenter study. JGH Open 2020; 4:757-763. [PMID: 32782967 PMCID: PMC7411551 DOI: 10.1002/jgh3.12359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 03/11/2020] [Accepted: 05/02/2020] [Indexed: 12/22/2022]
Abstract
Background and Aim The molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real‐life use are lacking. Methods This was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives. Results A total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 μmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury–hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44–54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1‐year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant‐free survival. Conclusion Our study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF.
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Affiliation(s)
- Christophe Camus
- Service de Reanimation medicale, Hôpital Pontchaillou Rennes France
| | - Clara Locher
- Laboratoire de Pharmacologie, Centre d'Investigation Clinique INSERM 1414 Rennes France
| | - Faouzi Saliba
- AP-HP Hôpital Paul Brousse Centre Hépato-biliaire Villejuif France
| | - Bernard Goubaux
- Service d'Anesthesie Reanimation, Hôpital de l'Archet II Nice France
| | - Agnès Bonadona
- Service de Reanimation medicale, Hôpital La Tronche Grenoble France
| | | | - Catherine Paugam
- Service d'Anesthesie Reanimation chirurgicale, Hôpital Beaujon Clichy France
| | - Alice Quinart
- Service d'Anesthesie Reanimation, Hôpital Pellegrin Bordeaux France
| | - Olivier Barbot
- Service de Reanimation medicale, Hôpital Jean Minjoz Besançon France
| | | | - Bertrand Delafosse
- Service d' Anesthesie Reanimation chirurgicale, Hôpital Edouard Herriot Lyon France
| | - Nicolas Pichon
- Service de Reanimation medicale, Hôpital Dupuytren Limoges France
| | - Hélène Barraud
- Service d'Hepato-gastroenterologie, Hôpital de Brabois Vandoeuvre-les-Nancy France
| | - Arnaud Galbois
- Service de Reanimation medicale, Hôpital Saint-Antoine Paris France
| | - Benoit Veber
- Service de Reanimation chirurgicale, Hôpital Charles Nicolle Rouen France
| | - Sophie Cayot
- Service de Reanimation, CHU Estaing Clermont-Ferrand France
| | - Bruno Souche
- Service d'Anesthesie reanimation, Hôpital Saint-Eloi Montpellier France
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14
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Trebicka J, Sundaram V, Moreau R, Jalan R, Arroyo V. Liver Transplantation for Acute-on-Chronic Liver Failure: Science or Fiction? Liver Transpl 2020; 26:906-915. [PMID: 32365422 DOI: 10.1002/lt.25788] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 04/02/2020] [Accepted: 04/05/2020] [Indexed: 12/17/2022]
Abstract
Acute clinical deterioration of a patient with chronic liver disease remains a decisive time point both in terms of medical management and prognosis. This condition, also known as acute decompensation (AD), is an important event determining a crossroad in the trajectory of patients. A significant number of patients with AD may develop hepatic or extrahepatic organ failure, or both, which defines the syndrome acute-on-chronic liver failure (ACLF), and ACLF is associated with a high morbidity and short-term mortality. ACLF may occur at any phase during chronic liver disease and is pathogenetically defined by systemic inflammation and immune metabolic dysfunction. When organ failures develop in the presence of cirrhosis, especially extrahepatic organ failures, liver transplantation (LT) may be the only curative treatment. This review outlines the evidence supporting LT in ACLF patients, highlighting the role of timing, bridging to LT, and possible indicators of futility. Importantly, prospective studies on ACLF and transplantation are urgently needed.
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Affiliation(s)
- Jonel Trebicka
- Translational Hepatology, Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.,Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.,Institute for Bioengineering of Catalonia, Barcelona, Spain
| | - Vinay Sundaram
- Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.,U1149, Centre de Recherche sur l'Inflammation, UMRS1149 Université de Paris, INSERM, Paris, France.,Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Rajiv Jalan
- Translational Hepatology, Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany.,Royal Free Hospital, London, United Kingdom
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
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15
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Kade G, Lubas A, Spaleniak S, Wojtecka A, Leśniak K, Literacki S, Niemczyk S, Dyrla P. Application of the Molecular Adsorbent Recirculating System in Type 1 Hepatorenal Syndrome in the Course of Alcohol-Related Acute on Chronic Liver Failure. Med Sci Monit 2020; 26:e923805. [PMID: 32602472 PMCID: PMC7346750 DOI: 10.12659/msm.923805] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND This study aimed to evaluate the Molecular Adsorbent Recirculating System (MARS) effectiveness in patients with alcohol-related acute-on-chronic liver failure (AoCLF) complicated with type 1 hepatorenal syndrome (HRS). So far, MARS efficacy and safety has been demonstrated in various acute liver failure scenarios. MATERIAL AND METHODS Data from 41 MARS procedures (10 patients with type 1 HRS, in the course of alcohol-related AoCLF were considered for this study. Biochemical tests of blood serum were performed before and after each procedure. The condition of patients was determined before and after the treatment with the use of the model for end-stage liver disease - sodium (MELD-Na) and the stage of encephalopathy severity based on the West Haven criteria. RESULTS During the observation period (20.5±13.9 days), 5 patients died, and the remaining 5 surviving patients were discharged from the hospital. In the group of 10, the 14-day survival, starting from the first MARS treatment, was 90%. The MARS procedure was associated with a 19% reduction in bilirubin (27.5±6.1 versus 22.3±4.0 mg/dL, P<0.001), 37% reduction in ammonia (44.1±22.5 versus 27.6±20.9 P<0.001), 27% reduction in creatinine (1.5±1.0 versus 1.1±0.6 mg/dL, P<0.001) and 14% reduction urea (83.8±36.1 versus 72.1±33.3, P<0.001) in blood serum samples, with stable hemodynamic parameters. In the group of patients discharged from the clinic (n=5), the MARS treatments resulted in an improvement in hepatic encephalopathy (West Haven; P=0.043), as well as a reduction in the MELD-Na score (P=0.015). CONCLUSIONS MARS is a hemodynamically safe method for supporting the function of the liver and the kidneys. Application of the MARS reduces the symptoms of encephalopathy in patients with alcohol-related type 1 HRS.
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Affiliation(s)
- Grzegorz Kade
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland
| | - Arkadiusz Lubas
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland
| | - Sebastian Spaleniak
- Department of Internal Medicine and Nephrodiabetology, Chair of Internal Diseases and Cardiology, Medical University of Łódź, Łódź, Poland
| | - Anna Wojtecka
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland
| | - Ksymena Leśniak
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland
| | - Sławomir Literacki
- Department of Laboratory Diagnostics, Military Institute of Medicine, Warsaw, Poland
| | - Stanisław Niemczyk
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland
| | - Przemysław Dyrla
- Department of Gastroenterology, Endocrinology and Internal Diseases, Military Institute of Medicine, Warsaw, Poland
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16
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17
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Critical care management in patients with acute liver failure. Best Pract Res Clin Anaesthesiol 2020; 34:89-99. [PMID: 32334790 DOI: 10.1016/j.bpa.2020.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 12/19/2019] [Accepted: 01/08/2020] [Indexed: 12/19/2022]
Abstract
Acute liver failure (ALF) is defined as severe hepatic dysfunction (marked transaminases elevation, detoxification disorder (jaundice and coagulopathy with international normal ratio (INR) > 1.5), the presence of hepatic encephalopathy, and exclusion of underlying chronic liver disease, and a secondary cause like sepsis or cardiogenic shock. Reasons for ALF include paracetamol and warfarin toxicity, autoimmune and viral (mainly hepatitis B and E) hepatitis, and herbal and dietary supplements. Even in terms of meticulous and careful review of the patient, around 20-30% of the reasons remains unknown. In order of its rarity, a randomized controlled trial could hardly be done. However, because of improved ICU treatment, the mortality, even in the advanced stage of ALF decreased. However, in 5-10% of the cases an emergency transplantation is required. This justifies the treatment of this patient cohort in institutions that can provide this kind of treatment.
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18
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Ehrmann J, Urban O, Dvoran P. Alcohol-related liver diseases. Cent Eur J Public Health 2020; 27 Suppl:S10-S14. [PMID: 31901188 DOI: 10.21101/cejph.a5999] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 12/04/2019] [Indexed: 11/15/2022]
Abstract
This educational article/narrative review reflects the European Association for the Study of the Liver (EASL) clinical practice guidelines: management of alcohol-related liver disease. An important change contrasting with the 2012 guidelines is the new terminology of alcohol-related liver diseases. Another important outcome is the strong emphasis on prevention of alcohol use disorder which may be performed at all stages of public health care.
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Affiliation(s)
- Jiří Ehrmann
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine, Palacky University Olomouc and University Hospital, Olomouc, Czech Republic
| | - Ondřej Urban
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine, Palacky University Olomouc and University Hospital, Olomouc, Czech Republic
| | - Pavol Dvoran
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine, Palacky University Olomouc and University Hospital, Olomouc, Czech Republic
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19
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Huang K, Ji F, Xie Z, Wu D, Xu X, Gao H, Ouyang X, Xiao L, Zhou M, Zhu D, Li L. Artificial liver support system therapy in acute-on-chronic hepatitis B liver failure: Classification and regression tree analysis. Sci Rep 2019; 9:16462. [PMID: 31712684 PMCID: PMC6848208 DOI: 10.1038/s41598-019-53029-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 10/28/2019] [Indexed: 02/08/2023] Open
Abstract
Artificial liver support systems (ALSS) are widely used to treat patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). The aims of the present study were to investigate the subgroups of patients with HBV-ACLF who may benefit from ALSS therapy, and the relevant patient-specific factors. 489 ALSS-treated HBV-ACLF patients were enrolled, and served as derivation and validation cohorts for classification and regression tree (CART) analysis. CART analysis identified three factors prognostic of survival: hepatic encephalopathy (HE), prothrombin time (PT), and total bilirubin (TBil) level; and two distinct risk groups: low (28-day mortality 10.2-39.5%) and high risk (63.8-91.1%). The CART model showed that patients lacking HE and with a PT ≤ 27.8 s and a TBil level ≤455 μmol/L experienced less 28-day mortality after ALSS therapy. For HBV-ACLF patients with HE and a PT > 27.8 s, mortality remained high after such therapy. Patients lacking HE with a PT ≤ 27.8 s and TBil level ≤ 455 μmol/L may benefit markedly from ALSS therapy. For HBV-ACLF patients at high risk, unnecessary ALSS therapy should be avoided. The CART model is a novel user-friendly tool for screening HBV-ACLF patient eligibility for ALSS therapy, and will aid clinicians via ACLF risk stratification and therapeutic guidance.
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Affiliation(s)
- Kaizhou Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Feiyang Ji
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Zhongyang Xie
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Daxian Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Xiaowei Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Hainv Gao
- Shulan Hangzhou Hospital, Shulan Health, Hangzhou, Zhejiang Province, China
| | - Xiaoxi Ouyang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Lanlan Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Menghao Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Danhua Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
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20
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Alshamsi F, Alshammari K, Belley-Cote E, Dionne J, Albrahim T, Albudoor B, Ismail M, Al-Judaibi B, Baw B, Subramanian RM, Steadman R, Galusca D, Huang DT, Nanchal R, Al Quraini M, Yuan Y, Alhazzani W. Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials. Intensive Care Med 2019; 46:1-16. [PMID: 31588983 DOI: 10.1007/s00134-019-05783-y] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure. METHODS We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. RESULTS We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain. CONCLUSIONS ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.
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Affiliation(s)
- Fayez Alshamsi
- Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates
| | - Khalil Alshammari
- Department of Internal Medicine, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Emilie Belley-Cote
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Joanna Dionne
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Talal Albrahim
- Department of Anesthesiology and Critical Care Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Budoor Albudoor
- Department of Critical Care Medicine, Shaikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Mona Ismail
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Al-Khobar, Saudi Arabia
| | - Bandar Al-Judaibi
- Transplant Hepatology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, USA, 14642
| | - Bandar Baw
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Ram M Subramanian
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Randolph Steadman
- Department of Anesthesiology and Perioperative Medicine, Ronald Reagan Medical Center, University of California Los Angeles, Los Angeles, USA
| | - Dragos Galusca
- Department of Anesthesiology, Henry Ford Hospital, Detroit, MI, USA
| | - David T Huang
- Department of Critical Care Medicine, Director Multidisciplinary Acute Care Research Organization (MACRO), University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Rahul Nanchal
- Department of Pulmonary, Critical Care and Sleep Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mustafa Al Quraini
- Department of Pulmonary and Critical Care Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Yuhong Yuan
- Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Waleed Alhazzani
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada.
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada.
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21
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Bañares R, Ibáñez-Samaniego L, Torner JM, Pavesi M, Olmedo C, Catalina MV, Albillos A, Larsen FS, Nevens F, Hassanein T, Schmidt H, Heeman U, Jalan R, Moreau R, Arroyo V. Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity. Therap Adv Gastroenterol 2019; 12:1756284819879565. [PMID: 31632458 PMCID: PMC6767713 DOI: 10.1177/1756284819879565] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues. METHODS We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus ⩽ 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality. RESULTS Three RCTs suitable for the meta-analysis (n = 285, ACLF patients = 165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p = 0.001; 30-day survival: 73.9% versus 64.3%, p = 0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p = 0.001; 30-day survival: 73.3% versus 58.5%, p = 0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy. CONCLUSION HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials.
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Affiliation(s)
| | - Luis Ibáñez-Samaniego
- Servicio de Medicina de Aparato Digestivo,
Hospital General Universitario Gregorio Marañón, CIBERehd, Madrid,
Spain
- Instituto de Investigación Sanitaria Gregorio
Marañón, Madrid, Spain
| | - Josep María Torner
- EASL CLIF Consortium, European Foundation for
the Study of Chronic Liver Failure (EfClif), Barcelona, Spain
| | - Marco Pavesi
- EASL CLIF Consortium, European Foundation for
the Study of Chronic Liver Failure (EfClif), Barcelona, Spain
| | - Carmen Olmedo
- Instituto de Investigación Sanitaria Gregorio
Marañón, Madrid, Spain
| | - María Vega Catalina
- Servicio de Medicina de Aparato Digestivo,
Hospital General Universitario Gregorio Marañón, CIBERehd, Madrid,
Spain
- Instituto de Investigación Sanitaria Gregorio
Marañón, Madrid, Spain
| | - Agustín Albillos
- Department of Gastroenterology and Hepatology,
Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid,
Spain
| | - Fin Stolze Larsen
- Department of Hepatology, Copenhagen University
Rigshospitalet, Copenhagen, Denmark
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology,
University Hospitals Leuven, KU Leuven, Belgium
| | - Tarek Hassanein
- The University of California, San Diego School
of Medicine, Southern California Liver Centers, Southern California Research
Center, San Diego, USA
| | - Harmuth Schmidt
- Klinik für Transplantationsmedizin,
Universitätsklinikum Münster, Münster, Germany
| | - Uwe Heeman
- Department of Nephrology, Klinikum Rechts der
Isar, Technische Universität München, Munich, Germany
| | - Rajiv Jalan
- Division of Medicine, UCL Medical School, Royal
Free Hospital, UCL Institute for Liver and Digestive Health, London,
UK
| | - Richard Moreau
- INSERM, Center de Recherche sur l’Inflammation
(CRI); Université Paris Diderot, Sorbonne Paris; Service d’Hépatologie,
Hôpital Beaujon, Clichy, France
| | - Vicente Arroyo
- EASL CLIF Consortium, European Foundation for
the Study of Chronic Liver Failure (EfClif), Barcelona, Spain
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22
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Artru F, Samuel D. Approaches for patients with very high MELD scores. JHEP Rep 2019; 1:53-65. [PMID: 32039352 PMCID: PMC7001538 DOI: 10.1016/j.jhepr.2019.02.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 01/31/2019] [Accepted: 02/04/2019] [Indexed: 02/08/2023] Open
Abstract
In the era of the "sickest first" policy, patients with very high model for end-stage liver disease (MELD) scores have been increasingly admitted to the intensive care unit with the expectation that they will receive a liver transplant (LT) in the absence of improvement on supportive therapies. Such patients are often admitted in a context of acute-on-chronic liver failure with extrahepatic failures. Sequential assessment of scores or classification based on organ failures within the first days after admission help to stratify the risk of mortality in this population. Although the prognosis of severely ill cirrhotic patients has recently improved, transplant-free mortality remains high. LT is still the only curative treatment in this population. Yet, the increased relative scarcity of graft resource must be considered alongside the increased risk of losing a graft in the initial postoperative period when performing LT in "too sick to transplant" patients. Variables associated with poor immediate post-LT outcomes have been identified in large studies. Despite this, the performance of scores based on these variables is still insufficient. Consideration of a patient's comorbidities and frailty is an appealing predictive approach in this population that has proven of great value in many other diseases. So far, local expertise remains the last safeguard to LT. Using this expertise, data are accumulating on favourable post-LT outcomes in very high MELD populations, particularly when LT is performed in a situation of stabilization/improvement of organ failures in selected candidates. The absence of "definitive" contraindications and the control of "dynamic" contraindications allow a "transplantation window" to be defined. This window must be identified swiftly after admission given the poor short-term survival of patients with very high MELD scores. In the absence of any prospect of LT, withdrawal of care could be discussed to ensure respect of patient life, dignity and wishes.
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Affiliation(s)
- Florent Artru
- Liver Unit, CHRU Lille, France, University of Lille, LIRIC team, Inserm unit 995
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, F-94800, France; Inserm, Unité 1193, Université Paris-Saclay, Villejuif, F-94800, France; Hepatinov, Villejuif, F-94800, France
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24
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Abstract
Extracorporeal liver support (ECLS) emerged from the need stabilize high-acuity liver failure patients with the highest risk of death. The goal is to optimize the hemodynamic, neurologic, and biochemical parameters in preparation for transplantation or to facilitate spontaneous recovery. Patients with acute liver failure and acute-on-chronic liver failure stand to benefit from these devices, especially because they have lost many of the primary functions of the liver, including detoxifying the blood of various endogenous and exogenous substances, manufacturing circulating proteins, secreting bile, and storing energy. Existing ECLS devices are designed to mimic some of these functions.
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Affiliation(s)
- Prem A Kandiah
- Division of Neuro Critical Care & co appt. in 5E Surgical/Transplant Critical Care, Department of Neurosurgery, Emory University Hospital, 1364 Clifton Road Northeast, 2nd Floor, 2D ICU- D264, Atlanta, GA 30322, USA; Department of Neurology, Emory University Hospital, 1364 Clifton Road Northeast, 2nd Floor, 2D ICU- D264, Atlanta, GA 30322, USA
| | - Ram M Subramanian
- Critical Care and Hepatology, Emory University, 1364 Clifton Road Northeast, 2nd Floor, 2D ICU- D264, Atlanta, GA 30322, USA.
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25
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Fujiwara K, Abe R, Yasui S, Yokosuka O, Kato N, Oda S. High recovery rate of consciousness by high-volume filtrate hemodiafiltration for fulminant hepatitis. Hepatol Res 2019; 49:224-231. [PMID: 30277289 DOI: 10.1111/hepr.13255] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 09/23/2018] [Accepted: 09/26/2018] [Indexed: 12/12/2022]
Abstract
AIM An artificial liver support (ALS) system sustaining patients with acute liver failure (ALF) in good condition until recovery of the native liver or performance of liver transplantation (LT), is essential for the improvement of the poor prognosis of ALF despite the lack of survival benefit. We aimed to investigate the efficacy of various ALS systems for fulminant hepatitis (FH) carried out in our liver unit so far, focusing on the restoration of consciousness from hepatic encephalopathy. METHODS One hundred and ten consecutive adult Japanese patients with FH admitted to Chiba University Hospital (Chiba, Japan) between 1988 and 2016 who received ALS were analyzed. RESULTS Recovery rate of consciousness improved with the increased dialysate flow rate and filtrate rate: 37.5% by plasma exchange (PE), 51.9% by PE + continuous hemodiafiltration (CHDF), 57.7% by slow PE (sPE) + high-flow CHDF (HFCHDF) (QD = 300 mL/min), 88.6% by HFCHDF (QD = 500 mL/min) (+ sPE), and 92.9% by on-line HDF (OLHDF) (+ sPE). All patients except one, who could not be fully treated because of circulatory failure, recovered consciousness by OLHDF, including those whose liver function were completely abolished. Superiority of HFCHDF (QD = 500 mL/min) and OLHDF was also shown in patients who died without LT or received LT. CONCLUSIONS More effective ALS should be recognized considering the extremely high recovery rate of consciousness. In particular, OLHDF with predilution reduces the cost of substitution fluid by supplying an unlimited amount of dialysate as substitution fluid prepared using an on-line system, and simplifies the procedure for the management.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ryuzo Abe
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shin Yasui
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
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26
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Piechota M, Piechota A, Misztal M, Bernas S, Pietraszek-Grzywaczewska I. An evaluation of the usefulness of extracorporeal liver support techniques in patients with severe liver dysfunction. Arch Med Sci 2019; 15:99-112. [PMID: 30697259 PMCID: PMC6348365 DOI: 10.5114/aoms.2017.67998] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Accepted: 01/02/2017] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The mortality rate in patients with severe liver dysfunction with no option of transplantation is unacceptably high. The main aim of this study was to evaluate the usefulness of applying extracorporeal liver support (ECLS) techniques in this group of patients. MATERIAL AND METHODS Data from hospital admissions of 101 patients with severe liver dysfunction who were admitted to the department of Anaesthesiology and intensive therapy between 2006 and 2015 were retrospectively analysed. The study group was divided into two subgroups. Standard Medical therapy (SMT) was a subgroup of patients receiving standard Medical therapy, and SMT + ECLS was a subgroup containing patients receiving standard medical therapy complemented by at least one extracorporeal liver support procedure. RESULTS Significantly lower intensive care unit (ICU) mortality and 30-day mortality rates were found in the SMT + ECLS subgroup (p = 0.0138 and p = 0.0238 respectively). No difference in 3-month mortality was identified between the two groups. In a multivariate model, independent risk factors for ICU mortality proved to be the SOFA score and prothrombin time. The highest discriminatory power for ICU mortality was demonstrated for the SOFA score, followed by APACHE II, SAPS II, MELD UNOS and GCS scores. For 30-day mortality, however, the best discriminatory power was shown for the SAPS II score, followed by SOFA, APACHE II, MELD UNOS and GCS scores. CONCLUSIONS Further studies are needed to assess the contribution of non-biological extracorporeal liver support procedures to a decrease in mortality rates in the population of patients with severe liver dysfunction.
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Affiliation(s)
- Mariusz Piechota
- Department of Anaesthesiology and Intensive Therapy – Centre for Artificial Extracorporeal Kidney and Liver Support, Dr Wł. Biegański Regional Specialist Hospital, Lodz, Poland
| | - Anna Piechota
- Department of Insurance, Faculty of Economics and Sociology, University of Lodz, Lodz, Poland
| | - Małgorzata Misztal
- Faculty of Economics and Sociology, Chair of Statistical Methods, University of Lodz, Lodz, Poland
| | - Szymon Bernas
- Department of Anaesthesiology and Intensive Therapy – Centre for Artificial Extracorporeal Kidney and Liver Support, Dr Wł. Biegański Regional Specialist Hospital, Lodz, Poland
| | - Iwona Pietraszek-Grzywaczewska
- Department of Anaesthesiology and Intensive Therapy – Centre for Artificial Extracorporeal Kidney and Liver Support, Dr Wł. Biegański Regional Specialist Hospital, Lodz, Poland
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27
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García Martínez JJ, Bendjelid K. Artificial liver support systems: what is new over the last decade? Ann Intensive Care 2018; 8:109. [PMID: 30443736 PMCID: PMC6238018 DOI: 10.1186/s13613-018-0453-z] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 11/07/2018] [Indexed: 12/16/2022] Open
Abstract
The liver is a complex organ that performs vital functions of synthesis, heat production, detoxification and regulation; its failure carries a highly critical risk. At the end of the last century, some artificial liver devices began to develop with the aim of being used as supportive therapy until liver transplantation (bridge-to-transplant) or liver regeneration (bridge-to-recovery). The well-recognized devices are the Molecular Adsorbent Recirculating System™ (MARS™), the Single-Pass Albumin Dialysis system and the Fractionated Plasma Separation and Adsorption system (Prometheus™). In the following years, experimental works and early clinical applications were reported, and to date, many thousands of patients have already been treated with these devices. The ability of artificial liver support systems to replace the liver detoxification function, at least partially, has been proven, and the correction of various biochemical parameters has been demonstrated. However, the complex tasks of regulation and synthesis must be addressed through the use of bioartificial systems, which still face several developmental problems and very high production costs. Moreover, clinical data on improved survival are conflicting. This paper reviews the progress achieved and new data published on artificial liver support systems over the past decade and the prospects for these devices.
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Affiliation(s)
- Juan José García Martínez
- Intensive Care Unit, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1205, Geneva, Switzerland. .,Faculty of Medicine, University of Geneva, Geneva, Switzerland.
| | - Karim Bendjelid
- Intensive Care Unit, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1205, Geneva, Switzerland.,Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Geneva Hemodynamic Research Group, Geneva, Switzerland
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28
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Gilg S, Sparrelid E, Saraste L, Nowak G, Wahlin S, Strömberg C, Lundell L, Isaksson B. The molecular adsorbent recirculating system in posthepatectomy liver failure: Results from a prospective phase I study. Hepatol Commun 2018; 2:445-454. [PMID: 29619422 PMCID: PMC5880195 DOI: 10.1002/hep4.1167] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 02/06/2018] [Accepted: 02/10/2018] [Indexed: 12/11/2022] Open
Abstract
Posthepatectomy liver failure (PHLF) represents the single most important cause of postoperative mortality after major liver resection, yet no effective treatment option is available. Extracorporeal liver support devices might be helpful, but systematic studies are lacking. Accordingly, we aimed to assess the safety and feasibility of the Molecular Adsorbent Recirculating System (MARS) in patients with PHLF. Between December 2012 and May 2015, a total of 206 patients underwent major or extended hepatectomy, and 10 consecutive patients with PHLF (according to the Balzan 50:50 criteria) were enrolled into the study. MARS treatment was initiated on postoperative day 5-7, and five to seven consecutive treatment sessions were completed for each patient. In total, 59 MARS cycles were implemented, and MARS was initiated and completed without major complications in any patient. However, 1 patient developed an immense asymptomatic hyperbilirubinemia (without encephalopathy), 1 had repeated clotting problems in the MARS filter, and 2 patients experienced access problems with the central venous line. Otherwise, no adverse events were observed. In 9 patients, the bilirubin level and international normalized ratio decreased significantly (P < 0.05) during MARS treatment. The 60- and 90-day mortality was 0% and 10%, respectively. Among the 9 survivors, 4 still had liver dysfunction at 90 days postoperatively. Five patients were alive 1 year postoperatively without any signs of liver dysfunction or disease recurrence. Conclusion: The use of MARS in PHLF is feasible and safe and improves liver function in patients with PHLF. In the present study, 60- and 90-day mortality rates were unexpectedly low compared to a historical control group. The impact of MARS treatment on mortality in PHLF should be further evaluated in a randomized controlled clinical trial. (Hepatology Communications 2018;2:445-454).
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Affiliation(s)
- Stefan Gilg
- Department for Clinical Science, Intervention and Technology Karolinska InstituteStockholmSweden.,Department of Surgery at the Center for Digestive Diseases Karolinska University Hospital Stockholm Sweden
| | - Ernesto Sparrelid
- Department for Clinical Science, Intervention and Technology Karolinska InstituteStockholmSweden.,Department of Surgery at the Center for Digestive Diseases Karolinska University Hospital Stockholm Sweden
| | - Lars Saraste
- Department of Anesthesiology and Intensive Care Karolinska University Hospital Stockholm Sweden
| | - Greg Nowak
- Department for Clinical Science, Intervention and Technology Karolinska InstituteStockholmSweden.,Department of Transplantation Surgery Karolinska University Hospital Stockholm Sweden
| | - Staffan Wahlin
- Department for Clinical Science, Intervention and Technology Karolinska InstituteStockholmSweden.,Department of Hepatology Karolinska University Hospital Stockholm Sweden
| | - Cecilia Strömberg
- Department for Clinical Science, Intervention and Technology Karolinska InstituteStockholmSweden.,Department of Surgery at the Center for Digestive Diseases Karolinska University Hospital Stockholm Sweden
| | - Lars Lundell
- Department for Clinical Science, Intervention and Technology Karolinska InstituteStockholmSweden.,Department of Surgery at the Center for Digestive Diseases Karolinska University Hospital Stockholm Sweden
| | - Bengt Isaksson
- Department for Clinical Science, Intervention and Technology Karolinska InstituteStockholmSweden.,Department of Surgical Sciences Uppsala University Hospital Uppsala Sweden
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29
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Gong D, Ji D, Ren B, Tao J, Xu B, Ronco C, Li L. Significant Decrease in Dialysate Albumin Concentration during Molecular Adsorbent Recirculating System (M.A.R.S.) Therapy. Int J Artif Organs 2018; 31:333-9. [PMID: 18432590 DOI: 10.1177/039139880803100410] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Aim The molecular adsorbent recirculating system (M.A.R.S.) is widely used as liver support therapy in patients with hepatic dysfunction. The goal of this study was to measure changes in dialysate albumin and bilirubin concentrations during clinical MARS treatments. Methods Eight patients with acute liver dysfunction and hyperbilirubinemia were enrolled in this study. Five of them received a total of 10 treatments with MARS, in which 600 mL of 20% human albumin was used as dialysate, continuously regenerated by two adsorbent columns in the circuit. Three patients received 4 treatments of a modified MARS, in which the two adsorbent columns were bypassed in the first course for 4 h, and then connected to the circuit in the second course for another 4 h. The total, conjugated and unconjugated bilirubin (TB, CB, UCB) and albumin concentrations in serum and albumin dialysate were dynamically measured, and the adsorbent column inlet pressures were recorded during each session. In one session, dialysate albumin levels were measured during the priming process, at the time points prior to the priming process, immediately after priming, and at the end of the treatment. Results During MARS therapies, the reduction ratio of serum TB, CB and UCB was 26.6±9.0%, 29.5±9.6% and 14.8±12.3%, respectively. The molar ratio of TB/albumin in serum was approximately 20-fold higher than dialysate at all time points. A significant albumin concentration decrease from baseline in the dialysate was found (mean±SD, 34.6±16.6%). For the first four hours of modified treatments, in which only albumin dialysis without albumin regeneration by adsorbent columns was performed, the dialysate albumin decrease was substantially smaller (mean, 8.3±1.5%). After switching to standard MARS, there was a further decrease in the dialysate albumin concentration of 35.1±14.5%. In one session, dialysate albumin concentrations were measured during the priming process, and levels decreased from 196.9 g/L to 144.4 g/L. Adsorber inlet pressure increased from 40±10mmHg at the start of priming to 150±50mmHg at the end of priming, and further increased to 340±100mmHg at the end of treatment. Conclusion There is a significant reduction in dialysate albumin concentration during MARS therapy. Binding of albumin to the adsorbent columns used for albumin regeneration is largely responsible for this decrease.
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Affiliation(s)
- D. Gong
- Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing - P.R. China
| | - D. Ji
- Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing - P.R. China
| | - B. Ren
- Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing - P.R. China
| | - J. Tao
- Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing - P.R. China
| | - B. Xu
- Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing - P.R. China
| | - C. Ronco
- Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital - International Renal Research Institute Vicenza (IRRIV), Vicenza - Italy
| | - L. Li
- Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing - P.R. China
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Olson JC, Karvellas CJ. Critical care management of the patient with cirrhosis awaiting liver transplant in the intensive care unit. Liver Transpl 2017; 23:1465-1476. [PMID: 28688155 DOI: 10.1002/lt.24815] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 06/28/2017] [Accepted: 06/29/2017] [Indexed: 02/07/2023]
Abstract
Patients with cirrhosis who are awaiting liver transplantation (LT) are at high risk for developing critical illnesses. Current liver allocation policies that dictate a "sickest first" approach coupled with a mismatch between need and availability of organs result in longer wait times, and thus, patients are becoming increasingly ill while awaiting organ transplantation. Even patients with well-compensated cirrhosis may suffer acute deterioration; the syndrome of acute-on-chronic liver failure (ACLF) results in multisystem organ dysfunction and a marked increase in associated short-term morbidity and mortality. For patients on transplant waiting lists, the development of multisystem organ failure may eliminate candidacy for transplant by virtue of being "too sick" to safely undergo transplantation surgery. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (eg, infection and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo LT. Management of the critically ill ACLF patient awaiting transplantation is best accomplished by multidisciplinary teams with expertise in critical care and transplant medicine. Such teams are well suited to address the needs of this unique patient population and to identify patients who may be too ill to proceed to transplantation surgery. The focus of this review is to identify the common complications of ACLF and to describe our approach management in critically ill patients awaiting LT in our centers. Liver Transplantation 23 1465-1476 2017 AASLD.
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Affiliation(s)
- Jody C Olson
- Divisions of Critical Care Medicine and Hepatology, University of Kansas Medical Center, Kansas City, KS
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.,Division of Division of Gastroenterology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
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31
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Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis. Crit Care Med 2017. [PMID: 28640024 PMCID: PMC5598913 DOI: 10.1097/ccm.0000000000002562] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Supplemental Digital Content is available in the text. Objectives: Acute-on-chronic liver failure is associated with numerous consecutive organ failures and a high short-term mortality rate. Molecular adsorbent recirculating system therapy has demonstrated beneficial effects on the distinct symptoms, but the associated mortality data remain controversial. Design: Retrospective analysis of acute-on-chronic liver failure patients receiving either standard medical treatment or standard medical treatment and molecular adsorbent recirculating system. Secondary analysis of data from the prospective randomized Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial by applying the recently introduced Chronic Liver Failure-criteria. Setting: Medical Departments of University Hospital Muenster (Germany). Patients: This analysis was conducted in two parts. First, 101 patients with acute-on-chronic liver failure grades 1–3 and Chronic Liver Failure-C-Organ Failure liver subscore equals to 3 but stable pulmonary function were identified and received either standard medical treatment (standard medical treatment, n = 54) or standard medical treatment and molecular adsorbent recirculating system (n = 47) at the University Hospital Muenster. Second, the results of this retrospective analysis were tested against the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial. Interventions: Standard medical treatment and molecular adsorbent recirculating system. Measurements and Main Results: Additionally to improved laboratory variables (bilirubin and creatinine), the short-term mortality (up to day 14) of the molecular adsorbent recirculating system group was significantly reduced compared with standard medical treatment. A reduced 14-day mortality rate was observed in the molecular adsorbent recirculating system group (9.5% vs 50.0% with standard medical treatment; p = 0.004), especially in patients with multiple organ failure (acute-on-chronic liver failure grade 2–3). Concerning the affected organ system, this effect of molecular adsorbent recirculating system on mortality was particularly evident among patients with increased kidney, brain, or coagulation Chronic Liver Failure-C-Organ Failure subscores. Subsequent reanalysis of the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure dataset with adoption of the Chronic Liver Failure-classification resulted in similar findings. Conclusions: Molecular adsorbent recirculating system treatment was associated with an improved short-term survival of patients with acute-on-chronic liver failure and multiple organ failure. Among these high-risk patients, molecular adsorbent recirculating system treatment might bridge to liver recovery or liver transplantation.
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32
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Karvellas CJ, Subramanian RM. Current Evidence for Extracorporeal Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure. Crit Care Clin 2017; 32:439-51. [PMID: 27339682 DOI: 10.1016/j.ccc.2016.03.003] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Artificial (nonbiological) extracorporeal liver support devices aim to remove albumin-bound and water-soluble toxins to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. The following beneficial effects have been documented: improvement of jaundice, amelioration of hemodynamic instability, reduction of portal hypertension, and improvement of hepatic encephalopathy. The only randomized prospective multicenter controlled trial to show an improvement in transplant-free survival was for high-volume plasmapheresis. Biological (cell-based) extracorporeal liver support systems aim to support the failing liver through detoxification and synthetic function and warrant further study for safety and benefit.
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Affiliation(s)
- Constantine J Karvellas
- Division of Hepatology, University of Alberta, Edmonton, Alberta, Canada; Division of Critical Care Medicine, University of Alberta, 1-40 Zeidler Ledcor Building, Edmonton, Alberta T6G-2X8, Canada.
| | - Ram M Subramanian
- Division of Hepatology, Emory University, Atlanta, GA, USA; Division of Critical Care Medicine, Emory University, Atlanta, GA, USA
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Extrakorporale Therapien bei Lebererkrankungen. Med Klin Intensivmed Notfmed 2017; 112:444-453. [DOI: 10.1007/s00063-017-0289-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Accepted: 03/24/2017] [Indexed: 10/19/2022]
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Hernaez R, Solà E, Moreau R, Ginès P. Acute-on-chronic liver failure: an update. Gut 2017; 66:541-553. [PMID: 28053053 PMCID: PMC5534763 DOI: 10.1136/gutjnl-2016-312670] [Citation(s) in RCA: 433] [Impact Index Per Article: 54.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 10/10/2016] [Accepted: 10/13/2016] [Indexed: 02/06/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%-50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care.
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Affiliation(s)
- Ruben Hernaez
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Elsa Solà
- Liver Unit, Hospital Clinic de Barcelona, Universitat de Barcelona, Barcelona, Spain,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain,Centro d'Investigaciones Biomedicas en Red, enfermedades Hepaticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Richard Moreau
- Inserm, U1149, Centre de Recerche sur l'inflammation (CRI), Paris, France,Faculté de Médicine, Université Paris Diderot, Paris, France,Départment Hospitalo-Universitaire (DHU) UNITY, Service d'Hépatologie, Hôpital Beaujon, AP-HP, Clichy, France,Laboratoire d'Excellence (Labex) Inflamex, CUE Sorbonne Paris Cité, Paris, France,European Foundation for the Study of Chronic Liver Failure (EF-CLIF), Barcelona, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clinic de Barcelona, Universitat de Barcelona, Barcelona, Spain,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain,Centro d'Investigaciones Biomedicas en Red, enfermedades Hepaticas y Digestivas (CIBEReHD), Barcelona, Spain
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Huber W, Henschel B, Schmid R, Al-Chalabi A. First clinical experience in 14 patients treated with ADVOS: a study on feasibility, safety and efficacy of a new type of albumin dialysis. BMC Gastroenterol 2017; 17:32. [PMID: 28209134 PMCID: PMC5312588 DOI: 10.1186/s12876-017-0569-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 01/06/2017] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Liver failure (LF) is associated with prolonged hospital stay, increased cost and substantial mortality. Due to the limited number of donor organs, extracorporeal liver support is suggested as an appealing concept to "bridge to transplant" or to avoid transplant in case of recovery. ADVanced Organ Support (ADVOS) is a new type of albumin dialysis, that provides rapid regeneration of toxin-binding albumin by two purification circuits altering the binding capacities of albumin by biochemical (changing of pH) and physical (changing of temperature) modulation of the dialysate. It was the aim of this study to evaluate feasibility, efficacy and safety of ADVOS in the first 14 patients ever treated with this procedure. METHODS Patients included suffered from acute on chronic LF (n = 9) or "secondary" LF (n = 5) which resulted from non-hepatic diseases such as sepsis. The primary endpoint was the change of serum bilirubin, creatinine and serum BUN levels before and after the first treatment with ADVOS. The Wilcoxon Signed Rank test for paired samples was used to analyze the data. RESULTS A total of 239 treatments (1 up to 101 per patient) were performed in 14 patients (6 female, 8 male). Mean age 54 ± 13; MELD-score 34 ± 7; CLIF-SOFA 15 ± 3. Serum bilirubin levels were significantly decreased by 32% during the first session (26.0 ± 15.4 vs. 17.7 ± 10.5 mg/dl; p = 0.001). Similarly, serum creatinine (2.2 ± 0.8 vs. 1.6 ± 0.7 mg/dl; p = 0.005) and serum BUN (49.4 ± 23.3 vs. 31.1 ± 19.7 mg/dl; p = 0.003), were significantly lowered by 27% and 37%, respectively. None of the treatment sessions had to be interrupted due to side effects related to the procedure. CONCLUSION ADVOS efficiently eliminates water- and protein-bound toxins in humans with LF. ADVOS is feasible in patients with advanced LF which is emphasized by a total number of more than 100 treatment sessions in one single patient.
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Affiliation(s)
- Wolfgang Huber
- II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, D-81675, Munich, Germany.
| | - Benedikt Henschel
- Klinik für Anaesthesiologie der Universität München, Campus Großhadern, Marchioninistraße, 15 81377, Munich, Germany
| | - Roland Schmid
- II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, D-81675, Munich, Germany
| | - Ahmed Al-Chalabi
- Jamaica Hospital Medical Center, 8900 Van Wyck Expy, Jamaica, NY, 11418, USA
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[Acute-on-chronic liver failure: a diagnostic and therapeutic challenge for intensive care]. Med Klin Intensivmed Notfmed 2017; 113:649-657. [PMID: 28210759 PMCID: PMC7095908 DOI: 10.1007/s00063-017-0263-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Revised: 10/06/2016] [Accepted: 12/16/2016] [Indexed: 12/15/2022]
Abstract
Das akut-auf-chronische Leberversagen („acute-on-chronic liver failure“, ACLF) ist ein emergentes Krankheitssyndrom, das durch einen oder mehrere akute Trigger bei vorgeschädigter Leber ausgelöst wird und vom progressiven hepatalen und nichthepatalen Organversagen, einem gravierenden Risiko infektiöser Komplikationen sowie hoher kurzfristiger Letalität gekennzeichnet ist. Wenngleich pathophysiologisch noch weitgehend unverstanden erfordert das ACLF frühzeitige diagnostische und therapeutische Maßnahmen, die sich auf zugrunde liegende Ursachen sowie das Verhindern von Komplikationen richten, um die Prognose betroffener Patienten zu verbessern.
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Londoño LA, Buckley GJ, Bolfer L, Bandt C. Clearance of plasma ivermectin with single pass lipid dialysis in 2 dogs. J Vet Emerg Crit Care (San Antonio) 2017; 27:232-237. [PMID: 28117946 DOI: 10.1111/vec.12581] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Revised: 06/01/2015] [Accepted: 08/11/2015] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To describe the use of single pass lipid dialysis (SPLD) for treatment of ivermectin toxicosis in 2 Australian Shepherd dogs with the ABCB1-1Δ gene mutation. CASE SERIES SUMMARY Two Australian Shepherd dogs were presented for treatment of ivermectin toxicosis. Dogs were initially treated with intravenous lipid emulsion and supportive care, without improvement of clinical signs. They both developed respiratory paralysis and required mechanical ventilation. In order to increase the clearance of circulating ivermectin, SPLD was performed using dialysate containing 5% lipid. Blood samples were obtained immediately before and after dialysis and analyzed for serum ivermectin concentration. Ivermectin reduction ratio was calculated at 29% and 39% for each dog, respectively. When compared to intrinsic total body ivermectin clearance, only the second dog had a relative improvement of plasma clearance following SPLD. Both dogs were confirmed to be homozygous for ABCB1-1Δ gene mutations. Both dogs remained ventilator dependent for several days and ultimately made a full recovery. NEW OR UNIQUE INFORMATION PROVIDED SPLD may be an adjunctive detoxification strategy for highly lipophilic toxins such as ivermectin.
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Affiliation(s)
- Leonel A Londoño
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611
| | - Gareth J Buckley
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611
| | - Luiz Bolfer
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611
| | - Carsten Bandt
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611
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Sen S, Jalan R. The role of the Molecular Adsorbents Recirculating System (MARS) in the management of liver failure. Perfusion 2016; 19 Suppl 1:S43-8. [PMID: 15161063 DOI: 10.1191/0267659104pf716oa] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Albumin-bound toxins accumulate in liver failure, and are believed to contribute to the development of the associated end-organ dysfunctions (kidney, circulation, brain). The scavenging functions of albumin are utilized in albumin dialysis for toxin removal. The Molecular Adsorbents Recirculating System (MARS) is an extracorporeal liver support device based on dialysis across an albumin-impregnated membrane, using 20% albumin as dialysate. Charcoal and anion exchange resin columns in the circuit help cleanse and regenerate the dialysate. Clinical studies over the last decade have demonstrated proven reduction in hyperbilirubinaemia, along with an improvement in hepatic encephalopathy, systemic haemodynamics and renal function in liver failure patients, as well as apparent improvement in survival. However, the specific mechanisms underlying these observed clinical changes are as yet unclear. The results of larger controlled clinical trials, as well as studies investigating the pathophysiological basis of its effect, are awaited.
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Affiliation(s)
- Sambit Sen
- Institute of Hepatology, University College London, London, UK
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Kim SM, Song IH. [Acute Kidney Injury in Cirrhotic Patients with Portal Hypertension]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2016; 68:237-244. [PMID: 27871159 DOI: 10.4166/kjg.2016.68.5.237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Acute kidney injury (AKI) is one of the most common manifestations encountered in clinical practice. It is associated with high morbidity and mortality in cirrhotic pre- and post-transplantation patients. Hepatorenal syndrome (HRS), a special form of AKI in cirrhotic patients, was recognized as a consequence of renal vasoconstriction from systemic/renal hemodynamic alterations developed in advanced cirrhosis with portal hypertension. Recently, multiple factors-such as infection/inflammation, underlying glomerulonephritis, bile cast, or increased abdominal pressure-have been considered to contribute to renal dysfunction in cirrhotic patients, which were presumed to induce HRS. Moreover, in addition to changing the definition of AKI in the nephrologic guidelines, the new AKI definition for early diagnosis and intervention based on characteristics of liver cirrhosis has been proposed in an international meeting. This article provides a comprehensive and recent review of AKI definition, laying out the topics in accordance with the pathophysiologic mechanisms and therapeutic interventions of AKI in cirrhotic patients with portal hypertension.
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Affiliation(s)
- So Mi Kim
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Il Han Song
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
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Soo E, Sanders A, Heckert K, Vinke T, Schaefer F, Schmitt CP. Comparison of two different modes of molecular adsorbent recycling systems for liver dialysis. Pediatr Nephrol 2016; 31:2171-4. [PMID: 27394132 DOI: 10.1007/s00467-016-3451-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Revised: 06/22/2016] [Accepted: 06/23/2016] [Indexed: 01/29/2023]
Abstract
BACKGROUND In children acute liver failure is a rare but life-threatening condition from which two-thirds do not recover with supportive therapy. Treatment is limited by the availability of liver transplants. Molecular adsorbent recirculating system (MARS) dialysis is a bridge to transplantation that enhances the chances of survival during the waiting period for a transplant, although it cannot improve survival. Open albumin dialysis (OPAL) is a new mode of albumin dialysis developed to further improve dialysis efficiency. CASE DIAGNOSIS/TREATMENT We report a paediatric case of acute-on-chronic liver failure and compare the two modes of albumin dialysis, namely, the MARS and OPAL, used to treat this patient's cholestatic pruritus. Removal of total and direct bilirubin, ammonia and bile acids were measured by serial blood tests. There was an increased removal of bile acids with the OPAL mode, whereas the removal of total and direct bilirubin and ammonia was similar in both modes. The patient reported better improvement in pruritus following OPAL compared to dialysis with the MARS. CONCLUSION OPAL may offer a better solution than the MARS in the treatment of refractory pruritus in liver failure.
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Affiliation(s)
- Euan Soo
- Division of Paediatric Nephrology, Centre for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
- Paediatric Nephrology Centre, Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, 2-10 Princess Margaret Hospital Road, Kowloon, Hong Kong
| | - Anja Sanders
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Karlheinz Heckert
- Division of Paediatric Nephrology, Centre for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
| | - Tobias Vinke
- Division of Paediatric Nephrology, Centre for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
| | - Franz Schaefer
- Division of Paediatric Nephrology, Centre for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany
| | - Claus Peter Schmitt
- Division of Paediatric Nephrology, Centre for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
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Bolkhir A, Loiselle MM, Evon DM, Hayashi PH. Depression in Primary Caregivers of Patients Listed for Liver or Kidney Transplantation. Prog Transplant 2016; 17:193-8. [DOI: 10.1177/152692480701700306] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Background No studies have examined depression in primary caregivers of adult patients listed for liver or kidney transplantation. Objective To determine the prevalence of depression among primary caregivers of patients listed for liver or kidney transplantation and to compare these 2 groups. Design A cross-sectional survey was conducted. The Center for Epidemiologic Studies Depression Scale and a demographic questionnaire were sent out and returned by mail. Results Of 72 eligible primary caregivers, 42 (58%) participated; the participation rate was similar for caregivers of kidney and liver failure patients (21/32 [66%)] vs 21/40 [53%], P = .3). Mean caregiver age was 54.7 ± 13.6 years. Twenty-three caregivers (54.8%) were spouses, 15 (35.7%) were first-degree relatives, and 26 (62%) were women. Median depression scale score was 5.5 (0–36). Three (7%), 2 (5%), and 3 (7%) participants reported mild, moderate, and severe depression, respectively. Median Center for Epidemiologic Studies Depression Scale score was higher among caregivers of liver versus kidney patients, but the difference was not statistically significant (9 vs 4, P = .2). Depression scale scores did not correlate with age, sex, time listed, or nature or length of relationship with the patient. The prevalence of depression in primary caregivers was 19%; of these caregivers, one third may have had severe depression. Conclusions The prevalence of moderate to severe depression in primary caregivers of liver and kidney transplant candidates is significant. The impact of depression on caregivers as well as patients, both before and after transplantation, deserves study. Screening for depression in caregivers could lead to clinical interventions that benefit caregivers and indirectly improve patient outcomes.
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Affiliation(s)
- Ahmed Bolkhir
- Saint Louis University School of Medicine, Saint Louis, MO (AB, PHH), University of North Carolina, Chapel Hill, NC (MML, DME, PHH)
| | - Marci M. Loiselle
- Saint Louis University School of Medicine, Saint Louis, MO (AB, PHH), University of North Carolina, Chapel Hill, NC (MML, DME, PHH)
| | - Donna M. Evon
- Saint Louis University School of Medicine, Saint Louis, MO (AB, PHH), University of North Carolina, Chapel Hill, NC (MML, DME, PHH)
| | - Paul H. Hayashi
- Saint Louis University School of Medicine, Saint Louis, MO (AB, PHH), University of North Carolina, Chapel Hill, NC (MML, DME, PHH)
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Qin G, Bian ZL, Shen Y, Zhang L, Zhu XH, Liu YM, Shao JG. Logistic regression model can reduce unnecessary artificial liver support in hepatitis B virus-associated acute-on-chronic liver failure: decision curve analysis. BMC Med Inform Decis Mak 2016; 16:59. [PMID: 27260306 PMCID: PMC4893223 DOI: 10.1186/s12911-016-0302-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Accepted: 05/29/2016] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Several models have been proposed to predict the short-term outcome of acute-on-chronic liver failure (ACLF) after treatment. We aimed to determine whether better decisions for artificial liver support system (ALSS) treatment could be made with a model than without, through decision curve analysis (DCA). METHODS The medical profiles of a cohort of 232 patients with hepatitis B virus (HBV)-associated ACLF were retrospectively analyzed to explore the role of plasma prothrombin activity (PTA), model for end-stage liver disease (MELD) and logistic regression model (LRM) in identifying patients who could benefit from ALSS. The accuracy and reliability of PTA, MELD and LRM were evaluated with previously reported cutoffs. DCA was performed to evaluate the clinical role of these models in predicting the treatment outcome. RESULTS With the cut-off value of 0.2, LRM had sensitivity of 92.6 %, specificity of 42.3 % and an area under the receiving operating characteristic curve (AUC) of 0.68, which showed superior discrimination over PTA and MELD. DCA revealed that the LRM-guided ALSS treatment was superior over other strategies including "treating all" and MELD-guided therapy, for the midrange threshold probabilities of 16 to 64 %. CONCLUSIONS The use of LRM-guided ALSS treatment could increase both the accuracy and efficiency of this procedure, allowing the avoidance of unnecessary ALSS.
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Affiliation(s)
- Gang Qin
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Jiangsu, China.
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Jiangsu, China.
| | - Zhao-Lian Bian
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Jiangsu, China
| | - Yi Shen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Jiangsu, China
| | - Lei Zhang
- Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, VIC, Australia
| | - Xiao-Hong Zhu
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Jiangsu, China
| | - Yan-Mei Liu
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Jiangsu, China
| | - Jian-Guo Shao
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Jiangsu, China.
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Lee KCL, Stadlbauer V, Jalan R. Extracorporeal liver support devices for listed patients. Liver Transpl 2016; 22:839-48. [PMID: 26785141 DOI: 10.1002/lt.24396] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 12/22/2015] [Accepted: 01/05/2016] [Indexed: 02/07/2023]
Abstract
An alternative to liver transplantation for patients with liver failure remains an unmet need. In acute liver failure, the ideal extracorporeal liver support device (ELSD) would replace the functions of the failing liver in order to permit spontaneous recovery, given the incredible regenerative potential of the liver, negating the need for transplantation. In acute-on-chronic liver failure, an ELSD would ideally support hepatic function until a recovery to liver function before acute decompensation or until liver transplantation. In decompensated cirrhosis, an ELSD could again be used to support hepatic function until transplant. In addition, ELSDs may have the potential to treat the multiorgan failure that accompanies liver failure including hepatic encephalopathy, renal failure, and immune dysfunction or indeed potential to promote liver regeneration. Creation of an extracorporeal bioartificial liver able to completely replace liver function remains an unmet need. This review will describe a number of technologies suitable for clinical trials in humans, which have resulted from decades of engineering and biological research to develop a bioreactor able to adequately sustain functional hepatocytes. In addition, this review will describe artificial liver support devices that are primarily designed to replace the detoxifying functions of the liver and will consider the current data available or studies required to support their use in liver failure patients on the transplant waiting list. Liver Transplantation 22 839-848 2016 AASLD.
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Affiliation(s)
- Karla C L Lee
- Department of Clinical Science and Services, The Royal Veterinary College, Hertfordshire, UK
| | - Vanessa Stadlbauer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK
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Schmuck RB, Nawrot GH, Fikatas P, Reutzel-Selke A, Pratschke J, Sauer IM. Single Pass Albumin Dialysis-A Dose-Finding Study to Define Optimal Albumin Concentration and Dialysate Flow. Artif Organs 2016; 41:153-161. [DOI: 10.1111/aor.12736] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 12/29/2015] [Accepted: 02/04/2016] [Indexed: 12/21/2022]
Affiliation(s)
- Rosa Bianca Schmuck
- General, Visceral and Transplantation Surgery, & Experimental Surgery and Regenerative Medicine, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum; Germany
| | - Gesa-Henrike Nawrot
- General, Visceral and Transplantation Surgery, & Experimental Surgery and Regenerative Medicine, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum; Germany
| | - Panagiotis Fikatas
- General, Visceral and Transplantation Surgery, & Experimental Surgery and Regenerative Medicine, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum; Germany
| | - Anja Reutzel-Selke
- General, Visceral and Transplantation Surgery, & Experimental Surgery and Regenerative Medicine, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum; Germany
| | - Johann Pratschke
- General, Visceral and Transplantation Surgery, & Experimental Surgery and Regenerative Medicine, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum; Germany
| | - Igor Maximilian Sauer
- General, Visceral and Transplantation Surgery, & Experimental Surgery and Regenerative Medicine, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum; Germany
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Defterevos G, Nastos C, Papalois A, Kalimeris K, Margelos V, Fragulidis G, Pafiti A, Mikrovas A, Nomikos T, Smyrniotis V, Arkadopoulos N. Peritoneal Albumin Dialysis as a Novel Approach for Liver Support: Study in a Porcine Model of Acute Hepatic Failure. Artif Organs 2016; 40:755-64. [PMID: 27094211 DOI: 10.1111/aor.12687] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 10/23/2015] [Accepted: 11/30/2015] [Indexed: 12/12/2022]
Abstract
Artificial liver support gained considerable interest in recent years due to the development of various albumin dialysis systems, which prolong survival of some patients with acute liver failure (ALF). Τhis study aims to examine the role of peritoneal albumin dialysis in a postoperative ALF model. ALF was induced in 14 female Landrace pigs by a combination of major liver resection (70-75% of total parenchyma) and ischemic-reperfusion injury on the liver remnant. Animals were randomly divided in two groups (n = 7 each). Both were monitored for 12 h of reperfusion and received peritoneal dialysis for 6 h, beginning 6 h after reperfusion. The albumin group received an albumin-rich solution and the control group received albumin-free solution. The control group gradually developed intracranial hypertension, whereas, in the albumin group, rise in the intracranial pressure was substantially attenuated (P < 0.01, t = 12 h). Albumin-treated animals had significantly lower levels of ammonia (P < 0.01), total bile acids (P < 0.01), free fatty acids (P < 0.05), lactate (P < 0.01), and total bilirubin (P < 0.05). Liver malondialdehyde and protein carbonyl were significantly reduced (P = 0.007 and P = 0.001 at t = 12 h) after albumin dialysis. Results suggest that this method may become a useful adjunct in the management of ALF, thus, justifying further study.
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Affiliation(s)
- Georgios Defterevos
- Experimental Surgical Unit, Fourth Department of Surgery, Medical School, National and Kapodistrian University of Athens, Attikon Hospital
| | - Constantinos Nastos
- Department of Pathology, Medical School, National and Kapodistrian University of Athens
| | - Apostolos Papalois
- Experimental Surgical Unit, Second Department of Surgery, Medical School, National and Kapodistrian University of Athens, Aretaieion University Hospital
| | - Konstantinos Kalimeris
- Experimental Surgical Unit, Fourth Department of Surgery, Medical School, National and Kapodistrian University of Athens, Attikon Hospital
| | | | - George Fragulidis
- Department of Pathology, Medical School, National and Kapodistrian University of Athens
| | | | - Aggeliki Mikrovas
- Experimental Surgical Unit, Fourth Department of Surgery, Medical School, National and Kapodistrian University of Athens, Attikon Hospital
| | - Tzortzis Nomikos
- Department of Nutrition, Harokopeion University of Athens, Athens, Greece
| | - Vassilios Smyrniotis
- Experimental Surgical Unit, Fourth Department of Surgery, Medical School, National and Kapodistrian University of Athens, Attikon Hospital
| | - Nikolaos Arkadopoulos
- Experimental Surgical Unit, Fourth Department of Surgery, Medical School, National and Kapodistrian University of Athens, Attikon Hospital
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46
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Aron J, Agarwal B, Davenport A. Extracorporeal support for patients with acute and acute on chronic liver failure. Expert Rev Med Devices 2016; 13:367-80. [PMID: 26894968 DOI: 10.1586/17434440.2016.1154455] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The number of patients developing liver failure; acute on chronic liver failure and acute liver failure continues to increase, along with the demand for donor livers for transplantation. As such there is a clinical need to develop effective extracorporeal devices to support patients with acute liver failure or acute-on-chronic liver failure to allow time for hepatocyte regeneration, and so avoiding the need for liver transplantation, or to bridge the patient to liver transplantation, and also potentially to provide symptomatic relief for patients with cirrhosis not suitable for transplantation. Currently devices can be divided into those designed to remove toxins, including plasma exchange, high permeability dialyzers and adsorption columns or membranes, coupled with replacement of plasma proteins; albumin dialysis systems; and bioartificial devices which may provide some of the biological functions of the liver. In the future we expect combinations of these devices in clinical practice, due to the developments in bioartificial scaffolds.
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Affiliation(s)
- Jonathan Aron
- a King's College Hospital , London , United Kingdom of Great Britain and Northern Ireland
| | - Banwari Agarwal
- b Intensive Care Unit , Royal Free Hospital , London , United Kingdom of Great Britain and Northern Ireland
| | - Andrew Davenport
- c UCL Centre for Nephrology , Royal free Hospital , London , United Kingdom of Great Britain and Northern Ireland
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47
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Nadim MK, Durand F, Kellum JA, Levitsky J, O'Leary JG, Karvellas CJ, Bajaj JS, Davenport A, Jalan R, Angeli P, Caldwell SH, Fernández J, Francoz C, Garcia-Tsao G, Ginès P, Ison MG, Kramer DJ, Mehta RL, Moreau R, Mulligan D, Olson JC, Pomfret EA, Senzolo M, Steadman RH, Subramanian RM, Vincent JL, Genyk YS. Management of the critically ill patient with cirrhosis: A multidisciplinary perspective. J Hepatol 2016; 64:717-35. [PMID: 26519602 DOI: 10.1016/j.jhep.2015.10.019] [Citation(s) in RCA: 208] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 09/30/2015] [Accepted: 10/19/2015] [Indexed: 02/07/2023]
Affiliation(s)
- Mitra K Nadim
- Division of Nephrology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
| | - Francois Durand
- Hepatology and Liver Intensive Care, Hospital Beaujon, Clichy, University Paris VII Diderot, Paris, INSERM U1149, Paris and Département Hospitalo-Universitaire UNITY, Clichy, France
| | - John A Kellum
- Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | - Constantine J Karvellas
- Division of Critical Care Medicine and Gastroenterology/Hepatology, University of Alberta, Edmonton, AB, Canada
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, McGuire VA Medical Center, Richmond, VA, USA
| | - Andrew Davenport
- University College London Center for Nephrology, Royal Free Hospital, University College London Medical School, London, UK
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK
| | - Paolo Angeli
- Unit of Hepatic Emergencies and Liver Transplantation, Department of Medicine, DIMED, University of Padova, Padova, Italy
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, University of Virginia Medical Center, Charlottesville, VA, USA
| | - Javier Fernández
- Liver Unit, Hospital Clinic de Barcelona, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro d'investigación biomedical en red de enfermedades hepáticas y digestivas, Barcelona, Spain
| | - Claire Francoz
- Hepatology and Liver Intensive Care, Hospital Beaujon, Clichy, University Paris VII Diderot, Paris, INSERM U1149, Paris and Département Hospitalo-Universitaire UNITY, Clichy, France
| | - Guadalupe Garcia-Tsao
- Division of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Pere Ginès
- Liver Unit, Hospital Clinic de Barcelona, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro d'investigación biomedical en red de enfermedades hepáticas y digestivas, Barcelona, Spain
| | - Michael G Ison
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - David J Kramer
- Aurora Critical Care Service, Aurora Health Care, Milwaukee, WI, USA
| | - Ravindra L Mehta
- Division of Nephrology, University of California San Diego, San Diego, CA, USA
| | - Richard Moreau
- Hepatology and Liver Intensive Care, Hospital Beaujon, Clichy, University Paris VII Diderot, Paris, INSERM U1149, Paris and Département Hospitalo-Universitaire UNITY, Clichy, France
| | - David Mulligan
- Section of Transplantation and Immunology, Department of Surgery, Yale-New Haven Hospital Transplantation Center, Yale School of Medicine, New Haven, CT, USA
| | - Jody C Olson
- Division of Hepatology, University of Kansas Hospital, Kansas City, KS, USA
| | - Elizabeth A Pomfret
- Department of Transplantation and Hepatobiliary Diseases, Lahey Hospital and Medical Center, Burlington, MA, USA
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgical and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy
| | - Randolph H Steadman
- Department of Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA
| | - Ram M Subramanian
- Divisions of Gastroenterology and Pulmonary & Critical Care Medicine, Emory University Hospital, Atlanta, GA, USA
| | - Jean-Louis Vincent
- Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Yuri S Genyk
- Division of Hepatobiliary Surgery and Abdominal Organ Transplantation, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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48
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Zhang J, Gao S, Duan Z, Hu KQ. Overview on acute-on-chronic liver failure. Front Med 2016; 10:1-17. [PMID: 26976617 DOI: 10.1007/s11684-016-0439-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2015] [Accepted: 01/28/2016] [Indexed: 12/11/2022]
Abstract
Liver failure (LF) is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. Clinical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF (ACLF), and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.
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Affiliation(s)
- Jing Zhang
- Department of Hepatitis C and Drug Induced Liver Injury, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China
| | - Shan Gao
- Beijing Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China
| | - Zhongping Duan
- Beijing Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China.
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China.
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California, Irvine, Medical Center, Orange, CA, 92868, USA.
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49
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Molecular Adsorbent Recirculating System (MARS™ en réanimation pédiatrique. MEDECINE INTENSIVE REANIMATION 2016. [DOI: 10.1007/s13546-015-1162-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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50
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Ibáñez-Samaniego L, Catalina MV, Rincón D, Lo Iacono O, Fernández A, Clemente G, Bañares R, Vaquero J, Salcedo M. Liver Support With Albumin Dialysis Reduces Hepatitis C Virus Viremia and Facilitates Antiviral Treatment of Severe Hepatitis C Virus Recurrence After Liver Transplantation. Ther Apher Dial 2016; 20:189-96. [PMID: 26929255 DOI: 10.1111/1744-9987.12381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 09/11/2015] [Accepted: 10/09/2015] [Indexed: 11/29/2022]
Abstract
Patients with severe hepatitis C virus (HCV) recurrence after liver transplantation (LT) present an ominous prognosis, rarely achieving sustained virological response (SVR). Dialysis procedures may transiently decrease the HCV viral load, but the effect of albumin dialysis is currently unknown. Here, we evaluated the impact of albumin dialysis using the Molecular Adsorbent Recirculating System (MARS) used as a co-adjuvant antiviral treatment for severe HCV recurrence after LT. Thirteen patients (11 males, median age 48 years) with fibrosing cholestatic hepatitis or METAVIR fibrosis score ≥ F3 with severe portal hypertension underwent three consecutive MARS sessions. Antiviral therapy was initiated in 11 patients within 24 h after the MARS sessions. A contemporary cohort of seven patients who did not follow the MARS protocol is shown for comparison. MARS treatment resulted in consistent decreases of viral load from 7.59 log10 IU/mL [6.15-8.90] to 6.79 log10 IU/mL [5.18-7.84] (P = 0.003) as well as in decreases of serum bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The overall rate of SVR was 0% in the Control group and 54.6% in patients initiating antiviral therapy within 24 h after MARS. Survival at 1 and 3 years was, respectively, 93% and 70% in patients undergoing MARS, compared with 29% and 14% in the Control group (P = 0.001). No major adverse events related to MARS treatment were observed. In conclusion, the use of MARS may facilitate the achievement of SVR and improve the prognosis of patients with severe HCV-recurrence after LT by reducing viral load and improving liver function prior to antiviral therapy.
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Affiliation(s)
- Luis Ibáñez-Samaniego
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - María-Vega Catalina
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Diego Rincón
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Oreste Lo Iacono
- Servicio de Gastroenterología, Hospital del Tajo, Aranjuez, Madrid, Spain
| | - Ainhoa Fernández
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Gerardo Clemente
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Bañares
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Facultad de Medicina, Universidad Complutense, Madrid, Spain
| | - Javier Vaquero
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Magdalena Salcedo
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
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