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Riva I, Marino A, Valetti TM, Marchesi G, Fabretti F. Extracorporeal liver support techniques: a comparison. J Artif Organs 2024; 27:261-268. [PMID: 37335451 PMCID: PMC11345327 DOI: 10.1007/s10047-023-01409-9] [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: 03/16/2023] [Accepted: 06/06/2023] [Indexed: 06/21/2023]
Abstract
ExtraCorporeal Liver Support (ECLS) systems were developed with the aim of supporting the liver in its detoxification function by clearing the blood from hepatic toxic molecules. We conducted a retrospective comparative analysis on patients presenting with liver failure who were treated with different extracorporeal techniques in our intensive care unit to evaluate and compare their detoxification abilities. To verify the effectiveness of the techniques, mass balance (MB) and adsorption per hour were calculated for total bilirubin (TB), direct bilirubin (DB), and bile acids (BA) from the concentrations measured. MB represents the total amount (mg or mcMol) of a molecule removed from a solution and is the only representative parameter to verify the purification effectiveness of one system as it is not affected by the continuous production of the molecules, released in the circulation from the tissues, as it is the case for the reduction rate (RR). The total adsorption per hour is calculated by the ratio between MB and the time duration and shows the adsorption ability in an hour. Our comparative study shows the superior adsorption capability of CytoSorb system regarding TB, DB, and BA, evaluated through the MB and adsorption per hour, in comparison with CPFA, MARS, Prometheus, and PAP. In conclusion, as extracorporeal purification in liver failure could be considered useful for therapeutic purposes, Cytosorb, being more performing than other systems considered, could represent the device of first choice.
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Affiliation(s)
- Ivano Riva
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy.
| | - Antonella Marino
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy.
| | - Tino Martino Valetti
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy
| | - Gianmariano Marchesi
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy
| | - Fabrizio Fabretti
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy
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Li Y, Zhang Y, Zhong K, Liao S, Zhang G. The Development of a 3D PET Fibrous Scaffold Modified with an Umbilical Cord dECM for Liver Tissue Engineering. Polymers (Basel) 2024; 16:1794. [PMID: 39000651 PMCID: PMC11243929 DOI: 10.3390/polym16131794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 06/07/2024] [Accepted: 06/17/2024] [Indexed: 07/17/2024] Open
Abstract
Organ and tissue dysfunction represents a clinically significant condition. By integrating cell biology with materials science, tissue engineering enables the reconstruction and restoration of damaged tissues or organs, offering a noninvasive repair approach. In our study, we replicated the cellular growth environment by utilizing a human umbilical cord-derived decellularized extracellular matrix (dECM) as a modifying agent for the polyethylene terephthalate (PET) polymeric fiber scaffold. This allowed us to create a dECM-coated polyester fiber-based scaffold, PET-dECM, tailored for liver tissue engineering purposes. We effectively produced a decellularized human umbilical cord-derived ECM through a combined decellularization process involving trypsin/EDTA, TritonX-100, and sodium deoxycholate. The application of the dECM coating onto the PET material was accomplished through several steps, such as ester hydrolysis, EDC/NHS-activated crosslinking, and dECM conjugation. The biological performance of the PET-dECM was validated using RG cell culture assays. Notably, the dECM coating significantly improved PET's hydrophilicity and biocompatibility, thereby aiding cell adhesion, proliferation, and functional differentiation (p < 0.05). It was further found that the hepatocyte function of HepaRG was significantly enhanced on the PET-dECM, which may be attributed to the dECM's ability to facilitate the restoration of cell polarity. The PET-dECM holds promise as an effective hepatocyte culture carrier and could potentially find application in liver tissue engineering.
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Affiliation(s)
- Yang Li
- National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
- School of Chemical and Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
- Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Yang Zhang
- National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
| | - Kebo Zhong
- Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Shuguang Liao
- Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Guifeng Zhang
- National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
- School of Chemical and Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
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Duarte T, Fidalgo P, Karvellas CJ, Cardoso FS. What every Intensivist should know about ... Ammonia in liver failure. J Crit Care 2024; 81:154456. [PMID: 37945461 DOI: 10.1016/j.jcrc.2023.154456] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 08/18/2023] [Accepted: 09/12/2023] [Indexed: 11/12/2023]
Abstract
PURPOSE Acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) patients have high short-term mortality and morbidity. In the context of liver failure, increased serum ammonia is associated with worse neurological outcomes, including high-grade hepatic encephalopathy (HE), cerebral edema, and intracranial hypertension. Besides its neurotoxicity, hyperammonemia may contribute to immune dysfunction and the risk of infection, a frequent trigger for multi-organ failure in these patients. MATERIAL AND METHODS We performed a literature-based narrative review. Publications available in PubMed® up to June 2023 were considered. RESULTS In the ICU management of liver failure patients, serum ammonia may play an important role. Accordingly, in this review, we focus on recent insights about ammonia metabolism, serum ammonia measurement strategies, hyperammonemia prognostic value, and ammonia-targeted therapeutic strategies. CONCLUSIONS Serum ammonia may have prognostic value in liver failure. Effective ammonia targeted therapeutic strategies are available, such as laxatives, rifaximin, L-ornithine-l-aspartate, and continuous renal replacement therapy.
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Affiliation(s)
- Tiago Duarte
- Intensive Care Unit, Curry Cabral Hospital, Lisbon, Portugal
| | - Pedro Fidalgo
- Intensive Care Unit, São Francisco Xavier Hospital, Lisbon, Portugal
| | | | - Filipe S Cardoso
- Transplant Unit, Intensive Care Unit, Curry Cabral Hospital, Nova Medical School, Lisbon, Portugal.
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Dong J, Huang L, Li C, Wu B, Yang X, Ge Y. Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute liver failure: A single center experience from China. J Clin Apher 2024; 39:e22100. [PMID: 37986652 DOI: 10.1002/jca.22100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 09/22/2023] [Accepted: 11/05/2023] [Indexed: 11/22/2023]
Abstract
OBJECTIVE To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF). METHODS In this retrospective study, we enrolled patients with ALF (serum total bilirubin >10 mg/dL or Model for End-Stage Liver Disease [MELD] Score >18) hospitalized between August 2017 and August 2022. All patients had at least two sessions of FPSA-CVVH. The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH. RESULTS Seventy-eight patients with ALF were enrolled. The MELD score at baseline was 22.9 ± 7.5. The mean total bilirubin was 22.05 ± 5.94 mg/dL, direct bilirubin was 16.33 ± 4.60 mg/dL and indirect bilirubin was 3.43 ± 1.60 mg/dL. One hundred and eighty seven sessions of FPSA-CVVH treatment lasting 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs were 52.0% ± 7.6% for total bilirubin, 59.4% ± 13.0% for direct bilirubin and 36.9% ± 15.4% for indirect bilirubin. Twenty nine patients (37.2%) survived and were discharged from the hospital, 12 of them recovered their liver function while the remaining 17 patients needed intermittent artificial liver support therapy. CONCLUSION FPSA-CVVH therapy is an effective artificial liver support therapy in patients with ALF. It may be considered as a "bridge technique" to the recovery of liver function in critical ill patients with ALF.
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Affiliation(s)
- Jianhua Dong
- National Clinical Research Center of Kidney Diseases, JinLing Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Li Huang
- National Clinical Research Center of Kidney Diseases, JinLing Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Chuan Li
- National Clinical Research Center of Kidney Diseases, JinLing Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Bian Wu
- National Clinical Research Center of Kidney Diseases, JinLing Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Xi Yang
- National Clinical Research Center of Kidney Diseases, JinLing Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Yongchun Ge
- National Clinical Research Center of Kidney Diseases, JinLing Hospital, Nanjing University School of Medicine, Nanjing, China
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Huang T, Huang J, Liu TCY, Li M, She R, Liu L, Qu H, Liang F, Cao Y, Chen Y, Tang L. Evaluating the Effect of Artificial Liver Support on Acute-on-Chronic Liver Failure Using the Quantitative Difference Algorithm: Retrospective Study. JMIR Form Res 2023; 7:e45395. [PMID: 37874632 PMCID: PMC10630873 DOI: 10.2196/45395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 07/31/2023] [Accepted: 09/13/2023] [Indexed: 10/25/2023] Open
Abstract
BACKGROUND Liver failure, including acute-on-chronic liver failure (ACLF), occurs mainly in young adults and is associated with high mortality and resource costs. The prognosis evaluation is a crucial part of the ACLF treatment process and should run through the entire diagnosis process. As a recently proposed novel algorithm, the quantitative difference (QD) algorithm holds promise for enhancing the prognosis evaluation of ACLF. OBJECTIVE This study aims to examine whether the QD algorithm exhibits comparable or superior performance compared to the Model for End-Stage Liver Disease (MELD) in the context of prognosis evaluation. METHODS A total of 27 patients with ACLF were categorized into 2 groups based on their treatment preferences: the conventional treatment (n=12) and the double plasma molecular absorption system (DPMAS) with conventional treatment (n=15) groups. The prognosis evaluation was performed by the MELD and QD scoring systems. RESULTS A significant reduction was observed in alanine aminotransferase (P=.02), aspartate aminotransferase (P<.001), and conjugated bilirubin (P=.002), both in P values and QD value (Lτ>1.69). A significant decrease in hemoglobin (P=.01), red blood cell count (P=.01), and total bilirubin (P=.02) was observed in the DPMAS group, but this decrease was not observed in QD (Lτ≤1.69). Furthermore, there was a significant association between MELD and QD values (P<.001). Significant differences were observed between groups based on patients' treatment outcomes. Additionally, the QD algorithm can also demonstrate improvements in patient fatigue. DPMAS can reduce alanine aminotransferase, aspartate aminotransferase, and unconjugated bilirubin. CONCLUSIONS As a dynamic algorithm, the QD scoring system can evaluate the therapeutic effects in patients with ACLF, similar to MELD. Nevertheless, the QD scoring system surpasses the MELD by incorporating a broader range of indicators and considering patient variability.
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Affiliation(s)
- Tinghuai Huang
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, China
| | - Jianwei Huang
- Department of Gastroenterology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Timon Cheng-Yi Liu
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, China
| | - Meng Li
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, China
| | - Rui She
- Department of Gastroenterology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Liyu Liu
- Department of Gastroenterology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Hongguang Qu
- Department of Gastroenterology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Fei Liang
- Department of Gastroenterology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yuanjing Cao
- Department of Gastroenterology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yuanzheng Chen
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, China
| | - Lu Tang
- Civil Aviation Flight University of China, Chengdu, China
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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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Abstract
Acute-on-chronic liver failure (ACLF) is characterized by the presence of chronic liver disease and extrahepatic organ failure and is associated with a high rate of short-term mortality. International societies have sought to define the criteria for ACLF and differ on definitions. Encephalopathy is an important organ failure in ACLF cases and is included as a marker of ACLF across society definitions. Both brain failure and ACLF commonly occur in the presence of a triggering event and in the setting of the large amount of inflammation that ensues. The presence of encephalopathy as a part of ACLF not only increases the chances of mortality but also provides unique challenges in that the patient will be limited in conversations around major decisions such as need for advanced level of care, liver transplant, or even end-of-life decisions. Many decisions need to be made quickly and occur in parallel in the care of patients with encephalopathy and ACLF and include stabilizing the patient, identifying precipitants or alternative diagnoses, and medical management. Infections has emerged as a major trigger for both ACLF and encephalopathy, and special attention should be given to identifying and treating infections as they occur.
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Affiliation(s)
- Bryan D Badal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, 1201 Broad Rock Boulevard, Richmond, VA, USA
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, 1201 Broad Rock Boulevard, Richmond, VA, USA.
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Luo J, Li J, Li P, Liang X, Hassan HM, Moreau R, Li J. Acute-on-chronic liver failure: far to go-a review. Crit Care 2023; 27:259. [PMID: 37393351 PMCID: PMC10315037 DOI: 10.1186/s13054-023-04540-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 06/22/2023] [Indexed: 07/03/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) has been recognized as a severe clinical syndrome based on the acute deterioration of chronic liver disease and is characterized by organ failure and high short-term mortality. Heterogeneous definitions and diagnostic criteria for the clinical condition have been proposed in different geographic regions due to the differences in aetiologies and precipitating events. Several predictive and prognostic scores have been developed and validated to guide clinical management. The specific pathophysiology of ACLF remains uncertain and is mainly associated with an intense systemic inflammatory response and immune-metabolism disorder based on current evidence. For ACLF patients, standardization of the treatment paradigm is required for different disease stages that may provide targeted treatment strategies for individual needs.
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Affiliation(s)
- Jinjin Luo
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Jiaqi Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital Affiliated of Hangzhou Medical College, Hangzhou, China
| | - Peng Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Xi Liang
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Hozeifa Mohamed Hassan
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain.
- Centre de Recherche Surl'Inflammation (CRI), Institut National de La Santé Et de La Recherche Médicale (INSERM) & Université Paris-Cité, Paris, France.
- Service d'Hépatologie, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Beaujon, Clichy, France.
| | - Jun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.
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Lamm V, Ekser B, Vagefi PA, Cooper DK. Bridging to Allotransplantation-Is Pig Liver Xenotransplantation the Best Option? Transplantation 2022; 106:26-36. [PMID: 33653996 PMCID: PMC10124768 DOI: 10.1097/tp.0000000000003722] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
In the past 20 y, the number of patients in the United States who died while waiting for a human donor liver totaled >52 000. The median national wait time for patients with acute liver failure and the most urgent liver transplant listing was 7 d in 2018. The need for a clinical "bridge" to allotransplantation is clear. Current options for supporting patients with acute liver failure include artificial liver support devices, extracorporeal liver perfusion, and hepatocyte transplantation, all of which have shown mixed results with regard to survival benefit and are largely experimental. Progress in the transplantation of genetically engineered pig liver grafts in nonhuman primates has grown steadily, with survival of the pig graft extended to almost 1 mo in 2017. Further advances may justify consideration of a pig liver transplant as a clinical bridge to allotransplantation. We provide a brief history of pig liver xenotransplantation, summarize the most recent progress in pig-to-nonhuman primate liver transplantation models, and suggest criteria that may be considered for patient selection for a clinical trial of bridging by genetically engineered pig liver xenotransplantation to liver allotransplantation.
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Affiliation(s)
- Vladimir Lamm
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | - Burcin Ekser
- Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Parsia A. Vagefi
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - David K.C. Cooper
- Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
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Hemoadsorption in 'Liver Indication'-Analysis of 109 Patients' Data from the CytoSorb International Registry. J Clin Med 2021; 10:jcm10215182. [PMID: 34768702 PMCID: PMC8584981 DOI: 10.3390/jcm10215182] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/01/2021] [Accepted: 11/03/2021] [Indexed: 12/26/2022] Open
Abstract
Background: Our aim is to report the results of the ‘liver indication’ subset of patients in the CytoSorb International Registry. Methods: Structured data were recorded. Treatment characteristics and changes from T1 (start of hemoadsorption) to T2 (termination) were evaluated with a special focus on bilirubin, C-reactive protein, procalcitonin, interleukin-6, platelet levels, SOFA scores, mortality, and subjective assessment by the attending physicians. Results: Until January 2021, from the total 1434 patients, 109 (age: 49.2 ± 17.1 years, 57.8% males) received treatment for hyperbilirubinemia. APACHE II-predicted mortality was 49.6 ± 26.8%. In the study, 91% of patients were alive at the termination of hemoadsorption and improvement was observed by the physicians in 75 cases. Overall, 65 (59.6%) patients died in the hospital, and 60 (55.0%) died in the ICU. Patients received a median of two treatments for a median of 43 h (interquartile range: 24–72 h) in total. Serum bilirubin levels reduced significantly to −4.6 (95% CI: −6.329 to −2.8) mg/dL. Thrombocytopenia was reported in four patients as an adverse event. Conclusions: We report the largest case series on hemoadsorption for ‘liver indication’ from the CytoSorb International Registry. The finding of significant bilirubin removal observed in our study could have substantial impact in designing and executing further studies on the effects of hemoadsorption in liver dysfunction, which are certainly warranted.
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Abstract
PURPOSE OF REVIEW While liver transplantation is an established treatment for liver failure, the number of patients with liver failure amenable to such intervention far outnumbers the donor supply of livers. Technologies serving to bridge this gap are required. Artificial livers may serve as an alternative. In this review, we discuss the development of artificial liver technologies. RECENT FINDINGS The accrued clinical data suggest that current liver assist devices may serve a role in specific liver diseases, but for the most part no survival benefit has been demonstrated. More clinical trials are expected to elucidate their utilization. Simultaneously, recent advances in materials and tissue engineering are allowing for exciting developments for novel artificial livers. SUMMARY As there continues to be more clinical data regarding the use of current liver devices, new intricate artificial liver technologies, with the use of sophisticated three-dimensional materials, are being developed that may help improve outcomes of liver failure patients.
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Affiliation(s)
- Asish C Misra
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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Chris-Olaiya A, Kapoor A, Ricci KS, Lindenmeyer CC. Therapeutic plasma exchange in liver failure. World J Hepatol 2021; 13:904-915. [PMID: 34552697 PMCID: PMC8422921 DOI: 10.4254/wjh.v13.i8.904] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/12/2021] [Accepted: 07/20/2021] [Indexed: 02/06/2023] Open
Abstract
The multi-organ failure syndrome associated with acute and acute-on-chronic liver failure (ACLF) is thought to be mediated by overwhelming systemic inflammation triggered by both microbial and non-microbial factors. Therapeutic plasma exchange (TPE) has been proven to be an efficacious therapy in autoimmune conditions and altered immunity, with more recent data supporting its use in the management of liver failure. Few therapies have been shown to improve survival in critically ill patients with liver failure who are not expected to survive until liver transplantation (LT), who are ineligible for LT or who have no access to LT. TPE has been shown to reduce the levels of inflammatory cytokines, modulate adaptive immunity with the potential to lessen the susceptibility to infections, and reduce the levels of albumin-bound and water-bound toxins in liver failure. In patients with acute liver failure, high volume TPE has been shown to reduce the vasopressor requirement and improve survival, particularly in patients not eligible for LT. Standard volume TPE has also been shown to reduce mortality in certain sub-populations of patients with ACLF. TPE may be most favorably employed as a bridge to LT in patients with ACLF. In this review, we discuss the efficacy and technical considerations of TPE in both acute and acute-on-chronic liver failure.
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Affiliation(s)
| | - Aanchal Kapoor
- Department of Critical Care, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Kristin S Ricci
- Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Christina C Lindenmeyer
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
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13
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Cheungpasitporn W, Thongprayoon C, Zoghby ZM, Kashani K. MARS: Should I Use It? Adv Chronic Kidney Dis 2021; 28:47-58. [PMID: 34389137 DOI: 10.1053/j.ackd.2021.02.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 01/20/2021] [Accepted: 02/02/2021] [Indexed: 11/11/2022]
Abstract
Severe liver failure, including acute liver failure and acute-on-chronic liver failure, is associated with high mortality, and many patients die despite aggressive medical therapy. While liver transplantation is a viable treatment option for liver failure patients, a large proportion of these patients die given the shortage in the liver donation and the severity of illness, leading to death while waiting for a liver transplant. Extracorporeal liver support devices, including molecular adsorbent recirculating system (MARS), have been developed as bridge to transplantation (bridge for patients who are decompensating while waiting for liver transplantation) and bridge to recovery (for whom recovery is deemed reasonable). In addition to its uses in acute liver failure and acute-on-chronic liver failure, the MARS system has also been applied in various clinical settings, such as drug overdosing and poisoning and intractable cholestatic pruritus refractory to pharmacological treatment. This review aims to discuss the controversies, potential benefits, practicalities, and disadvantages of using MARS in clinical practice.
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Naorungroj T, Yanase F, Eastwood GM, Baldwin I, Bellomo R. Extracorporeal Ammonia Clearance for Hyperammonemia in Critically Ill Patients: A Scoping Review. Blood Purif 2020; 50:453-461. [PMID: 33279903 DOI: 10.1159/000512100] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/02/2020] [Indexed: 01/17/2023]
Abstract
INTRODUCTION Hyperammonemia is a life-threatening condition. However, clearance of ammonia via extracorporeal treatment has not been systematically evaluated. METHODS We searched EMBASE and MEDLINE databases. We included all publications reporting ammonia clearance by extracorporeal treatment in adult and pediatric patients with clearance estimated by direct dialysate ammonia measurement or calculated by formula. Two reviewers screened and extracted data independently. RESULTS We found 1,770 articles with 312 appropriate for assessment and 28 studies meeting eligibility criteria. Most of the studies were case reports. Hyperammonemia was typically secondary to inborn errors of metabolisms in children and to liver failure in adult patients. Ammonia clearance was most commonly reported during continuous renal replacement therapy (CRRT) and appeared to vary markedly from <5 mL/min/m2 to >250 mL/min/m2. When measured during intermittent hemodialysis (IHD), clearance was highest and correlated with blood flow rate (R2 = 0.853; p < 0.001). When measured during CRRT, ammonia clearance could be substantial and correlated with effluent flow rate (EFR; R2 = 0.584; p < 0.001). Neither correlated with ammonia reduction. Peritoneal dialysis (PD) achieved minimal clearance, and other extracorporeal techniques were rarely studied. CONCLUSIONS Extracorporeal ammonia clearance varies widely with sometimes implausible values. Treatment modality, blood flow, and EFR, however, appear to affect such clearance with IHD achieving the highest values, PD achieving minimal values, and CRRT achieving substantial values especially at high EFRs. The role of other techniques remains unclear. These findings can help inform practice and future studies.
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Affiliation(s)
- Thummaporn Naorungroj
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
- Department of Intensive Care, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Fumitaka Yanase
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
- Monash University School and Public Health and Preventive Medicine, ANZICS-RC, Melbourne, Victoria, Australia
| | - Glenn M Eastwood
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Ian Baldwin
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia,
- Centre for Integrated Critical Care, The University of Melbourne, Melbourne, Victoria, Australia,
- Data Analytics Research and Evaluation (DARE) Centre, The University of Melbourne and Austin Health, Melbourne, Victoria, Australia,
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15
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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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16
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Sparrelid E, Gilg S, van Gulik TM. Systematic review of MARS treatment in post-hepatectomy liver failure. HPB (Oxford) 2020; 22:950-960. [PMID: 32249030 DOI: 10.1016/j.hpb.2020.03.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 01/26/2020] [Accepted: 03/11/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Post-hepatectomy liver failure (PHLF) remains a serious complication after major liver resection with severe 90-day mortality. Molecular adsorbent recirculating system (MARS) is a potential treatment option in PHLF. This systematic review sought to analyze the experiences and results of MARS in PHLF. METHODS Following the PRISMA guidelines, a systematic literature review using PubMed and Embase was performed. Non-randomized trials were assessed by the MINORS criteria. RESULTS 2884 records were screened and 22 studies were extracted (no RCT). They contained 809 patients including 82 patients with PHLF. Five studies (n = 34) specifically investigated the role of MARS in patients with PHLF. In these patients, overall 90-day survival was 47%. Patients with primary PHLF had significantly better 90-day survival compared to patients with secondary PHLF (60% vs 14%, p = 0.03) and treatment was started earlier (median POD 6 (range 2-21) vs median POD 30 (range 15-39); p < 0.001). Number of treatments differed non-significantly in these groups. Safety and feasibility of early MARS treatment following hepatectomy was demonstrated in one prospective study. No major adverse events have been reported. CONCLUSION Early MARS treatment is safe and feasible in patients with PHLF. Currently, MARS cannot be recommended as standard of care in these patients. Further prospective studies are warranted.
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Affiliation(s)
- Ernesto Sparrelid
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
| | - Stefan Gilg
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Thomas M van Gulik
- Department of Surgery, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands
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17
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Yang L, Wu T, Li J, Xin J, Shi D, Jiang J, Liang X, Lu Y, Yao H, Zhang H, Sun S, Li T, Mohamed Hassan Mohamed H, Li J, Ren K, Guo B, Zhou X, Chen J, Hao S, Chen J, Xin S, Pan C, Han T, Chen Y, Lin S, Duan Z, Xu X, Huang J, Chen X, Li L, Li J. Artificial liver treatment improves survival in patients with hepatitis B virus-related acute-on-chronic liver failure: A case-control matched analysis. Hepatol Res 2020; 50:656-670. [PMID: 32134538 DOI: 10.1111/hepr.13497] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 02/18/2020] [Accepted: 03/02/2020] [Indexed: 12/19/2022]
Abstract
AIM The artificial liver support system (ALSS) is recognized as a bridge to liver transplantation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. However, patient survival remains unknown. We aim to assess the effects of ALSS on survival in HBV-ACLF patients. METHODS The clinical data of HBV-ACLF patients receiving standard medical treatment (SMT) plus ALSS (ALSS group, n = 507) or only SMT (SMT group, n = 417) were collected for survival assessment. The main end-points were cumulative survival rates at days 21, 28, and 90. Four different rigorous analyses were carried out to reduce bias and confounding. RESULTS In the entire cohort, the cumulative survival rates at days 21, 28, and 90 were significantly higher in patients who underwent ALSS treatment (73.3% vs. 59.6%, 69.2% vs. 56.6%, 56.5% vs. 49.1%, respectively, P < 0.01) than in those who underwent SMT only. In the 276-pair case-control matched cohort, a significantly higher survival rate was also observed in the ALSS group than in the SMT group on days 21, 28, and 90 (72.5% vs. 60.3%, 68.3% vs. 57.4%, 55.9% vs. 48.5%, respectively, P < 0.05), especially in patients with ACLF-1 and -2. By a multivariable-adjusted analysis, ALSS treatment was associated with a significantly lower risk of mortality, especially for ACLF-2 at days 21, 28, and 90. These findings were also confirmed through propensity score matching and inverse probability treatment weighting analysis. CONCLUSIONS ALSS treatment can improve short-term survival and is associated with a significantly lower risk of short-term mortality in patients with HBV-ACLF, especially ACLF-2.
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Affiliation(s)
- Lingling Yang
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Tianzhou Wu
- Precision Medicine Center, Taizhou Central Hospital, Taizhou University Medical School, Taizhou, China
| | - Jiang 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiaojiao Xin
- 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, Zhejiang University School of Medicine, Hangzhou, China.,Precision Medicine Center, Taizhou Central Hospital, Taizhou University Medical School, Taizhou, China
| | - Dongyan Shi
- 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, Zhejiang University School of Medicine, Hangzhou, China.,Precision Medicine Center, Taizhou Central Hospital, Taizhou University Medical School, Taizhou, China
| | - Jing Jiang
- 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, Zhejiang University School of Medicine, Hangzhou, China.,Precision Medicine Center, Taizhou Central Hospital, Taizhou University Medical School, Taizhou, China
| | - Xi Liang
- Precision Medicine Center, Taizhou Central Hospital, Taizhou University Medical School, Taizhou, China
| | - Yingyan Lu
- Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Heng Yao
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Huafen Zhang
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Suwan Sun
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Tan 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Hozeifa Mohamed Hassan Mohamed
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiaqi 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Keke Ren
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Beibei Guo
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Xingping 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiaxian Chen
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Shaorui Hao
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiajia Chen
- 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Shaojie Xin
- Department of liver and Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Chen Pan
- Department of Liver and Infectious Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Tao Han
- Department of Liver and Infectious Diseases, Tianjin Third Central Hospital, Tianjin, China
| | - Yongping Chen
- Department of liver and infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shumei Lin
- Department of Liver and Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhongping Duan
- Department of Liver and Infectious Diseases, Beijing YouAn Hospital, Capital Medical University, Beijing, 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianrong 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Xin Chen
- Precision Medicine Center, Taizhou Central Hospital, Taizhou University Medical School, Taizhou, China.,Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 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, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun 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, Zhejiang University School of Medicine, Hangzhou, China.,Precision Medicine Center, Taizhou Central Hospital, Taizhou University Medical School, Taizhou, China
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18
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Chancharoenthana W, Leelahavanichkul A. Acute kidney injury spectrum in patients with chronic liver disease: Where do we stand? World J Gastroenterol 2019; 25:3684-3703. [PMID: 31391766 PMCID: PMC6676545 DOI: 10.3748/wjg.v25.i28.3684] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 06/13/2019] [Accepted: 07/03/2019] [Indexed: 02/06/2023] Open
Abstract
Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.
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Affiliation(s)
- Wiwat Chancharoenthana
- Immunology Unit, Department of Microbiology, Faculty of Medicine Chulalongkorn University, Bangkok 10330, Thailand
| | - Asada Leelahavanichkul
- Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Faculty of Medicine Chulalongkorn University, Bangkok 10330, Thailand
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20
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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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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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22
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Gong D, Cruz D, Ronco C. Depurative capacity of molecular adsorbent recycling system (MARS): A focus on bilirubin removal. Int J Artif Organs 2018; 31:875-81. [DOI: 10.1177/039139880803101003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The molecular adsorbent recycling system (MARS) is now widely used in the treatment of patients with hepatic failure (HF). A great deal of interest has been directed toward its effect on clinical outcome, whereas its depurative capacity also needs attention. Bilirubin, a tightly albumin-bound toxin accumulating in patients with HF, is regarded as a surrogate to evaluate the depurative capacity of albumin-bound toxins by blood purification modalities. The removal of bilirubin by MARS is difficult to predict, because both the clearance of bilirubin and the reduction ratio of bilirubin after a single session differ between patients and sessions. A reduction of depurative capacity over the course of a treatment is observed. Furthermore, the later sessions are likely less efficient than previous ones. It cannot be taken for granted that the reduction of depurative capacity is due to the saturation and reduced efficiency of the adsorbent columns used in MARS. The answer lies in the property of bilirubin/albumin binding. The removal of bilirubin by MARS is a diffusion process, dependent on the free bilirubin concentration. Bilirubin binds to albumin in 3 ways with different affinity. High-affinity binding bilirubin is difficult to dissociate from albumin and is accompanied by a smaller free fraction, which means it is also difficult for MARS to remove. The factors affecting the free fraction of bilirubin will impact on bilirubin removal by MARS. Among them, the molar ratio of bilirubin to albumin is the most important one. Other factors include the interaction of other agents with bilirubin/albumin binding, the albumin concentration, plasma ion strength, and pH.
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Affiliation(s)
- D. Gong
- Research Institute of Nephrology, Jingling Hospital, Nanjing University School of Medicine, Nanjing - PR China
| | - D. Cruz
- Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, International Renal Research Institute Vicenza (IRRIV), Vicenza - Italy
| | - C. Ronco
- Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, International Renal Research Institute Vicenza (IRRIV), Vicenza - Italy
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Viggiano D, de Pascale E, Marinelli G, Pluvio C. A comparison among three different apheretic techniques for treatment of hyperbilirubinemia. J Artif Organs 2017; 21:110-116. [PMID: 28887736 DOI: 10.1007/s10047-017-0986-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 08/28/2017] [Indexed: 12/26/2022]
Abstract
Liver failure is associated to high mortality due to the accumulation of protein-bound metabolites, such as bilirubin, not removed by conventional hemodialysis. Different methods can efficiently remove them, such as the molecular adsorbent recirculating system (MARS), plasma exchange (PEX), and bilirubin or plasma adsorption perfusion (PAP). No direct comparison exists between MARS, PEX and PAP, and current guidelines do not specify which method (and when) to use. We have retrospectively evaluated MARS, PEX and PAP in their effectiveness in lowering plasma bilirubin concentration, and their effects on liver and kidney function. A total of 98 patients have been recruited, which comprised 68 patients treated with PAP (177 sessions), 16 patients with PEX (41 sessions) and 11 patients with MARS (21 sessions). Bilirubin, creatinine, liver enzymes were analyzed before and after the first treatment with each technique. The three methods did not differ for bilirubin lowering efficiency, with MARS showing only slightly less effective reductions. Finally, the three techniques did not differ in the amount of change of cholinesterase, but a lower reduction in AST was found using PAP. Our retrospective observation is one of the largest case series of hepatic failure treated with bilirubin absorption. The choice of the technique cannot be based on the desired reduction in bilirubin concentration. Based on costs and duration of treatment, we suggest that PAP could be considered as a first-line approach. In case of kidney involvement, MARS remains a valuable option.
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Affiliation(s)
- Davide Viggiano
- Department of Medicine and Health Sciences, University of Molise, 86100, Campobasso, Italy.
| | - Emanuela de Pascale
- AORN dei Colli, D. Cotugno Hospital, Department of Dialysis with Hepatic-Infective Complications, via L. Bianchi, 80131, Naples, Italy
| | - Gaia Marinelli
- AORN dei Colli, D. Cotugno Hospital, Department of Dialysis with Hepatic-Infective Complications, via L. Bianchi, 80131, Naples, Italy
| | - Corrado Pluvio
- AORN dei Colli, D. Cotugno Hospital, Department of Dialysis with Hepatic-Infective Complications, via L. Bianchi, 80131, Naples, Italy.
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Hamdi T, Palmer BF. Review of Extracorporeal Membrane Oxygenation and Dialysis-Based Liver Support Devices for the Use of Nephrologists. Am J Nephrol 2017; 46:139-149. [PMID: 28738354 DOI: 10.1159/000479342] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Acute kidney injury in the intensive care unit (ICU) is a manifestation of an underlying severe illness that commonly involves other organ systems. Pulmonary, cardiac, and hepatic failures are the most prevalent. This article provides a simplified review of the technical aspects of extracorporeal cardiopulmonary and liver support devices used in the adult ICU patient, as well as a summary of the most relevant and up-to-date clinical evidence that supports their use.
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Affiliation(s)
- Tamim Hamdi
- Department of Internal Medicine, Division of Nephrology, UT Southwestern, Dallas, TX, USA
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Abstract
Extracorporeal liver support systems (ELSS), encompassing artificial and bioartificial devices, have been used for decades, with the aim of supporting patients with acute liver failure and acute-on chronic liver failure, as a bridge to recovery (acute liver failure only) or liver transplantation, in an era of organ donation shortage. Although biochemical efficacy has been consistently demonstrated by these devices, translation into clinical and survival benefits has been unclear, due to study limitations and lack of reliable prognostic scoring in liver failure. Consequently, extracorporeal devices are not widely accepted as routine therapy in adult liver failure. Recent large multicentre trials using artificial liver systems have not revealed beneficial outcomes associated with albumin dialysis but plasma exchange practices have shown some potential. In paediatric liver failure, data on extracorporeal systems is scarce, comprising few reports on albumin dialysis (namely, Molecular Adsorbent Recirculating System; MARS) and plasma exchange. When extrapolating data from adult studies differences in disease presentation, aetiology, prognosis and the suitability, and safety of such devices in children must be considered. The aim of this review is to critically appraise current practices of extracorporeal liver support systems to help determine efficacy in paediatric liver failure.
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Postoperative Liver Failure. GI SURGERY ANNUAL 2017. [PMCID: PMC7123164 DOI: 10.1007/978-981-10-2678-2_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Technical innovations in surgical techniques, anaesthesia, critical care and a spatial understanding of the intra-hepatic anatomy of the liver, have led to an increasing number of liver resections being performed all over the world. However, the number of complications directly attributed to the procedure and leading to inadequate or poor hepatic functional status in the postoperative period remains a matter of concern. There has always been a problem of arriving at a consensus in the definition of the term: postoperative liver failure (PLF). The burgeoning rate of living donor liver transplants, with lives of perfectly healthy donors involved, has mandated a consensual definition, uniform diagnosis and protocol for management of PLF. The absence of a uniform definition has led to poor comparison among various trials. PLF remains a dreaded complication in resection of the liver, with a reported incidence of up to 8 % [1], and mortality rates of up to 30–70 % have been quoted [2]. Several studies have quoted a lower incidence of PLF in eastern countries, but when it occurs the mortality is as high as in the West [3].
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Lee JS, Yoon H, Yoon D, Kim GH, Yang HT, Chun W. Development of hepatic blocks using human adipose tissue-derived stem cells through three-dimensional cell printing techniques. J Mater Chem B 2017; 5:1098-1107. [DOI: 10.1039/c6tb03055f] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Currently, most acute liver diseases are treated through liver transplantation.
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Affiliation(s)
- Ji-Seon Lee
- Burn Institute
- Hangang Sacred Heart Hospital
- College of Medicine
- Hallym University
- Seoul
| | - Hyeon Yoon
- Burn Institute
- Hangang Sacred Heart Hospital
- College of Medicine
- Hallym University
- Seoul
| | - Dajeong Yoon
- Burn Institute
- Hangang Sacred Heart Hospital
- College of Medicine
- Hallym University
- Seoul
| | - Geun Hyung Kim
- Department of Biomechatronic Engineering
- Sungkyunkwan University
- Suwon
- South Korea
| | - Hyeong Tae Yang
- Department of Surgery
- Hangang Sacred Heart Hospital
- College of Medicine
- Hallym University
- Youngdeungpo-dong
| | - Wook Chun
- Burn Institute
- Hangang Sacred Heart Hospital
- College of Medicine
- Hallym University
- Seoul
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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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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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Abstract
Acute-on-chronic liver failure combines an acute deterioration in liver function in an individual with pre-existing chronic liver disease and hepatic and extrahepatic organ failures, and is associated with substantial short-term mortality. Common precipitants include bacterial and viral infections, alcoholic hepatitis, and surgery, but in more than 40% of patients, no precipitating event is identified. Systemic inflammation and susceptibility to infection are characteristic pathophysiological features. A new diagnostic score, the Chronic Liver Failure Consortium (CLIF-C) organ failure score, has been developed for classification and prognostic assessment of patients with acute-on-chronic liver failure. Disease can be reversed in many patients, and thus clinical management focuses upon the identification and treatment of the precipitant while providing multiorgan-supportive care that addresses the complex pattern of physiological disturbance in critically ill patients with liver disease. Liver transplantation is a highly effective intervention in some specific cases, but recipient identification, organ availability, timing of transplantation, and high resource use are barriers to more widespread application. Recognition of acute-on-chronic liver failure as a clinically and pathophysiologically distinct syndrome with defined diagnostic and prognostic criteria will help to encourage the development of new management pathways and interventions to address the unacceptably high mortality.
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Affiliation(s)
- William Bernal
- Liver Intensive Therapy Unit, King's College Hospital, London, UK.
| | - Rajiv Jalan
- Liver Failure Group, Division of Medicine, University College London, London, UK; Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK; Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK
| | - Alberto Quaglia
- Histopathology Section, Institute of Liver Studies, King's College Hospital, London, UK
| | - Kenneth Simpson
- Department of Hepatology, University of Edinburgh, Edinburgh, UK
| | - Julia Wendon
- Liver Intensive Therapy Unit, King's College Hospital, London, UK
| | - Andrew Burroughs
- Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK; Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK
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Matoori S, Leroux JC. Recent advances in the treatment of hyperammonemia. Adv Drug Deliv Rev 2015; 90:55-68. [PMID: 25895618 DOI: 10.1016/j.addr.2015.04.009] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Revised: 03/30/2015] [Accepted: 04/13/2015] [Indexed: 02/07/2023]
Abstract
Ammonia is a neurotoxic agent that is primarily generated in the intestine and detoxified in the liver. Toxic increases in systemic ammonia levels predominantly result from an inherited or acquired impairment in hepatic detoxification and lead to potentially life-threatening neuropsychiatric symptoms. Inborn deficiencies in ammonia detoxification mainly affect the urea cycle, an endogenous metabolic removal system in the liver. Hepatic encephalopathy, on the other hand, is a hyperammonemia-related complication secondary to acquired liver function impairment. A range of therapeutic options is available to target either ammonia generation and absorption or ammonia removal. Therapies for hepatic encephalopathy decrease intestinal ammonia production and uptake. Treatments for urea cycle disorders eliminate ammoniagenic amino acids through metabolic transformation, preventing ammonia generation. Therapeutic approaches removing ammonia activate the urea cycle or the second essential endogenous ammonia detoxification system, glutamine synthesis. Recent advances in treating hyperammonemia include using synergistic combination treatments, broadening the indication of orphan drugs, and developing novel approaches to regenerate functional liver tissue. This manuscript reviews the various pharmacological treatments of hyperammonemia and focuses on biopharmaceutical and drug delivery issues.
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Ołdakowska-Jedynak U, Jankowska I, Hartleb M, Jirsa M, Pawłowska J, Czubkowski P, Krawczyk M. Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis. Hepatol Res 2014; 44:E304-E308. [PMID: 24164717 DOI: 10.1111/hepr.12262] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2013] [Revised: 10/10/2013] [Accepted: 10/21/2013] [Indexed: 02/08/2023]
Abstract
Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5-year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.
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Extrakorporale Therapien bei Patienten mit Lebererkrankungen auf der Intensivstation. Med Klin Intensivmed Notfmed 2014; 109:246-51. [DOI: 10.1007/s00063-013-0321-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Accepted: 03/21/2014] [Indexed: 12/14/2022]
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Maiwall R, Maras JS, Nayak SL, Sarin SK. Liver dialysis in acute-on-chronic liver failure: current and future perspectives. Hepatol Int 2014. [PMID: 26201332 DOI: 10.1007/s12072-014-9534-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Patients with acute-on-chronic liver failure (ACLF) are known to have a very high mortality rate as the majority of these patients succumb to multiorgan failure. Liver transplant remains the only option for these patients; however, there are problems with its availability, cost and also the complications and side effects associated with immunosuppression. Unlike advanced decompensated liver disease, there is a potential for hepatic regeneration and recovery in patients with ACLF. A liver support system, cell or non-cell based, logically is likely to provide temporary functional support until the donor liver becomes available or the failing liver survives the onslaught of the acute insult and spontaneously regenerates. Understanding the pathogenesis of liver failure and regeneration is essential to define the needs for a support system. Removal of hepatotoxic metabolites and inhibitors of hepatic regeneration by liver dialysis, a non-cell-based hepatic support, could help to provide a suitable microenvironment and support the failing liver. The current systems, i.e., MARS and Prometheus, have failed to show survival benefits in patients with ACLF based on which newer devices with improved functionality are currently under development. However, larger randomized trials are needed to prove whether these devices can enable restoration of the complex dysregulated immune system and impact organ failure and mortality in these patients.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), D1, Vasantkunj, New Delhi, 110070, India
| | - Jaswinder Singh Maras
- Department of Research, Institute of Liver and Biliary Sciences (ILBS), D1, Vasantkunj, New Delhi, 110070, India
| | - Suman Lata Nayak
- Department of Nephrology, Institute of Liver and Biliary Sciences (ILBS), D1, Vasantkunj, New Delhi, 110070, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), D1, Vasantkunj, New Delhi, 110070, India.
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Ouellet G, Bouchard J, Ghannoum M, Decker BS. Available extracorporeal treatments for poisoning: overview and limitations. Semin Dial 2014; 27:342-9. [PMID: 24697909 DOI: 10.1111/sdi.12238] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Poisoning is a significant public health problem. In severe cases, extracorporeal treatments (ECTRs) may be required to prevent or reverse major toxicity. Available ECTRs include intermittent hemodialysis, sustained low-efficiency dialysis, intermittent hemofiltration and hemodiafiltration, continuous renal replacement therapy, hemoperfusion, therapeutic plasma exchange, exchange transfusion, peritoneal dialysis, albumin dialysis, cerebrospinal fluid exchange, and extracorporeal life support. The aim of this article was to provide an overview of the technical aspects, as well as the potential indications and limitations of the different ECTRs used for poisoned patients.
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Affiliation(s)
- Georges Ouellet
- Division of Nephrology, Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal, Quebec, Canada
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Marangoni R, Bellati G, Castelli A, Romagnoli E. Development of high-efficiency molecular adsorbent recirculating system: preliminary report. Artif Organs 2014; 38:879-83. [PMID: 24392970 DOI: 10.1111/aor.12250] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Molecular Adsorbent Recirculating System (MARS) is a liver support system widely employed in the treatment of liver failure. The method is normally well tolerated. To develop a liver support system combining high efficiency and tolerability, we modified the MARS albumin circuit with the insertion of double adsorption units in parallel. Four patients have been treated with this modified method (high-efficiency MARS, HE MARS): two had very high serum bilirubin and two had very high total bile acids. After a single MARS session bilirubin was reduced more with HE MARS than standard MARS (from 27.6 to 52.3% in patient A and from 27.9 to 49.1% in patient B), and bile acid reduction increased from 40 to 59.8% in patient C and from 39.9 to 60% in patient D. The results of this preliminary investigation in only a very small number of patients do support the possibility of developing a liver support system that combines good tolerability and high efficacy.
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Stiffel M, Dammeier N, Schmidt S, Szyszkowitz T, Sikole M, Sieveking C, Stange J. 24-Hour Performance of Albumin Dialysis Assessed by a New Two-Compartment In Vitro Model. Ther Apher Dial 2013; 18:79-86. [DOI: 10.1111/1744-9987.12025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Melanie Stiffel
- Department of Medicine; Division of Nephrology; Medical Faculty of the University of Rostock; Rostock Germany
| | - Nele Dammeier
- Department of Medicine; Division of Nephrology; Medical Faculty of the University of Rostock; Rostock Germany
| | - Stephanie Schmidt
- Department of Medicine; Division of Nephrology; Medical Faculty of the University of Rostock; Rostock Germany
| | - Tina Szyszkowitz
- Department of Medicine; Division of Nephrology; Medical Faculty of the University of Rostock; Rostock Germany
| | - Magdalena Sikole
- Department of Medicine; Division of Nephrology; Medical Faculty of the University of Rostock; Rostock Germany
| | - Catharina Sieveking
- Department of Medicine; Division of Nephrology; Medical Faculty of the University of Rostock; Rostock Germany
| | - Jan Stange
- Department of Medicine; Division of Nephrology; Medical Faculty of the University of Rostock; Rostock Germany
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Abstract
Liver failure is associated with a high morbidity and mortality rate and is the seventh leading cause of death worldwide. Orthotopic liver transplantation remains the definitive treatment; however, because of the limited number of available organs many patients expire while on the transplant list. Currently, there are no established means for providing liver support as a means of bridging patients to transplantation or allowing for recovery from liver injury. Analogous to the clinical situation of renal failure, there is great interest in developing liver support systems that replace the metabolic and waste removal functions of the liver. These support systems are of two general types: artificial and bioartificial livers. In this review, based on a presentation from the 57th American Society of Artificial Internal Organs Annual Meeting (Washington, D.C., June 2011), we review the current status of liver support systems.
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Lee K, Mun CH, Min BG. Development of a multifunctional detoxifying unit for liver failure patients. Blood Purif 2012; 34:225-30. [PMID: 23171622 DOI: 10.1159/000341552] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2012] [Accepted: 07/03/2012] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Extracorporeal blood detoxification strategies aimed at supporting impaired liver function have been explored because of the imbalance between donor organs and waiting patients. A limited number of artificial devices are now available clinically, and these are characterized by the use of multistage adsorption procedures in conjunction with hemodialysis, but these features simultaneously increase system complexity and treatment costs. METHODS The authors developed a simpler strategy for liver dialysis based on the use of a multifunctional filter, which enables plasma separation and perfusion in a single unit. RESULTS Liver dialysis treatments were successfully performed using the devised unit when bovine blood containing uremic and hepatic toxins was circulated. Removal of the solutes under investigation was significant, and reduction ratios of 78% for urea, 98% for creatinine and 91% for bilirubin were achieved. Plasma free hemoglobin levels were reasonably maintained despite prolonged blood recirculation for 5 h, and platelet, hematocrit and hemoglobin levels remained uniform throughout liver dialysis sessions. CONCLUSION The devised liver support unit may offer a straightforward and efficient means of cleansing blood for patients with hepatic failure.
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Abstract
1. The goals of liver support therapy include the following: To provide detoxification and synthetic function during liver failure. To remove or reduce the production of proinflammatory cytokines to correct the systemic inflammatory response of liver failure. To stimulate the regeneration of the injured liver and increase the likelihood of spontaneous recovery. 2. There is a large unmet need for a liver support device because of the shortage of organs for liver transplantation and the risks of major surgery. 3. Liver support devices can be divided into 2 groups: purely mechanical artificial devices and cell-based bioartificial devices. Both provide detoxification, but bioartificial liver devices provide the option of synthetic function and biotransformation activities that are not possible with a purely mechanical device. 4. An abundant high-quality supply of human hepatocytes is not currently available for liver cell therapy. However, such a supply is essential for successful bioartificial liver therapy. Novel options are under development for the unlimited production of high-quality human hepatocytes.
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Affiliation(s)
- Scott L Nyberg
- Division of Transplantation Surgery, 200 First Street SW, Mayo Clinic, Rochester, MN 55905, USA.
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Kribben A, Gerken G, Haag S, Herget-Rosenthal S, Treichel U, Betz C, Sarrazin C, Hoste E, Van Vlierberghe H, Escorsell A, Hafer C, Schreiner O, Galle PR, Mancini E, Caraceni P, Karvellas CJ, Salmhofer H, Knotek M, Ginès P, Kozik-Jaromin J, Rifai K. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology 2012; 142:782-789.e3. [PMID: 22248661 DOI: 10.1053/j.gastro.2011.12.056] [Citation(s) in RCA: 263] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2010] [Revised: 12/15/2011] [Accepted: 12/29/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Fractionated plasma separation and adsorption (FPSA) is an extracorporeal procedure that supports liver function by removing endogenous toxins that cause complications from acute-on-chronic liver failure (AOCLF). We performed a randomized trial to investigate survival of patients with AOCLF treated with FPSA. METHODS Patients with AOCLF were randomly assigned to groups given a combination of FPSA and standard medical therapy (SMT) (FPSA group, n = 77) or only SMT (SMT group, n = 68). The Prometheus liver support system was used to provide 8 to 11 rounds of FPSA (minimum of 4 hours each) for 3 weeks. Primary end points were survival probabilities at days 28 and 90, irrespective of liver transplantation. RESULTS Baseline clinical parameters and number of transplant patients were similar between study arms. Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Baseline factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects. CONCLUSIONS Among all patients with AOCLF, extracorporeal liver support with FPSA does not increase the probability of survival. Further studies are needed to assess whether therapy might be beneficial in specific subsets of patients.
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Affiliation(s)
- Andreas Kribben
- Department of Nephrology, University Duisburg-Essen, Essen, Germany.
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Benyoub K, Muller M, Bonnet A, Simon R, Gazon M, Duperret S, Aubrun F, Viale JP. Amounts of bile acids and bilirubin removed during single-pass albumin dialysis in patients with liver failure. Ther Apher Dial 2012; 15:504-6. [PMID: 21974706 DOI: 10.1111/j.1744-9987.2011.00980.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Rademacher S, Oppert M, Jörres A. Artificial extracorporeal liver support therapy in patients with severe liver failure. Expert Rev Gastroenterol Hepatol 2011; 5:591-9. [PMID: 21910577 DOI: 10.1586/egh.11.59] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Severe liver failure is common and carries a high mortality risk in patients with both acute and acute-on-chronic liver failure. The failing liver constitutes a medical emergency, and in many cases liver transplantation is the only definite treatment. Extracorporeal liver support can be employed as a strategy for bridging to transplantation or recovery. This article focuses on options for artificial (nonbiological) extracorporeal treatment: single-pass albumin dialysis, fractionated plasma separation and adsorption (Prometheus(®)) and the molecular adsorbent recirculatory system. Their different principles, potential advantages and indications are discussed. Despite proven biochemical efficacy, there are little data regarding clinical end points. Thus far, molecular adsorbent recirculatory system therapy in acute and acute-on-chronic liver failure showed no survival benefit compared with standard medical therapy. Prometheus therapy showed reduced mortality in subgroups of higher severity of disease compared with standard medical therapy. Nevertheless, the value of extracorporeal liver support remains to be corroborated by further clinical studies that include the optimal timing, mode, intensity and duration of this treatment.
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Affiliation(s)
- Sibylle Rademacher
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin, 13353 Germany
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Abstract
PURPOSE OF REVIEW Acute-on-chronic liver failure (ACLF), a syndrome precipitated by acute liver injury in patients with advanced cirrhosis, is associated with multiorgan dysfunction and high rates of mortality. Liver support systems have been developed in an attempt to improve survival of patients with ACLF by providing a bridge until recovery of the native liver function. RECENT FINDINGS Nonbiological devices such as molecular adsorbent recirculating system (MARS) and fractionated plasma separation and adsorption (Prometheus) are effective in improving severe hepatic encephalopathy and cholestasis, have good safety and tolerability profiles and are frequently employed in patients with ACLD; however, randomized controlled trials (RCTs) failed to show improvement in survival. Biologic devices that incorporate hepatic cells in bioreactors are also under development. Recent data from pilot studies suggested improvement in survival rates in some groups of patients with ACLF; however, their effect on patient survival in RCT is still unknown. SUMMARY Liver support systems are safe and well tolerated when used in management of patients with ACLF. Their use should continue in controlled clinical trials to explore their role in bridging patients to liver transplantation or recovery in well defined patient groups.
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Jung A, Korohoda P, Krisper P, Schneditz D. Relationship between kinetics of albumin-bound bilirubin and water-soluble urea in extracorporeal blood purification. Nephrol Dial Transplant 2011; 27:1200-6. [DOI: 10.1093/ndt/gfr413] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Kwon CHD, Lee SK, Park JK, Lee DH, Lee JH. Artificial Liver Devices and Bioartificial Liver Systems: Current Status. KOREAN JOURNAL OF TRANSPLANTATION 2011. [DOI: 10.4285/jkstn.2011.25.1.15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Suk-Koo Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung-Keug Park
- Department of Medical Biotechnology, Dongguk University, Seoul, Korea
| | - Doo-Hoon Lee
- Biomedical Research Institute, Lifeliver Co. Ltd., Seoul, Korea
| | - Ji-Hyun Lee
- Samsung Biomedical Research Institute, Seoul, Korea
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Schaefer B, Schaefer F, Engelmann G, Meyburg J, Heckert KH, Zorn M, Schmitt CP. Comparison of Molecular Adsorbents Recirculating System (MARS) dialysis with combined plasma exchange and haemodialysis in children with acute liver failure. Nephrol Dial Transplant 2011; 26:3633-9. [PMID: 21421589 DOI: 10.1093/ndt/gfr115] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Molecular Adsorbents Recirculating System (MARS) is an extracorporeal liver support system eliminating albumin-bound and water-soluble substances. While it is increasingly applied in patients with acute liver failure (ALF), no comparison with standard dialysis methods has yet been performed. METHODS This is an analysis of ten children (0.1-18 years) with ALF, who underwent a total of 22 MARS sessions. Standard adult MARS sets were used in seven (23.5-72 kg) and MARS Mini in three children (2.8-13 kg). In eight children, MARS was alternated with combined plasma exchange (PE) and haemodialysis (HD) treatments. Mean treatment duration was 7.2 (6-10) h for MARS and 5.7 (4.5-6.6) h for PE/HD. RESULTS Standard MARS treatment only slightly decreased serum bilirubin (16.3 ± 6.5-13.8 ± 5.9 mg/dL) and ammonia (113 ± 62-99 ± 68 μmol/L) and international normalized ratio (INR) tended to increase (1.5 ± 0.3 and 2 ± 1.1). Mini-MARS did not reduce serum bilirubin (19.7 ± 3-20.5 ± 3.2 mg/dL), ammonia slightly decreased (70 ± 24-56 ± 9 μmol/L) and INR increased (2.5 ± 0.7-2.9 ± 1.1, all P = n.s.). In contrast, PE/HD reduced serum bilirubin (23 ± 8.4-14.7 ± 7 mg/dL), ammonia (120 ± 60-70 ± 40 μmol/L) and INR (2.4 ± 0.8-1.4 ± 0.1, all P < 0.05). Intraindividual comparison showed a slight increase in bilirubin by 2 ± 22% with MARS and a reduction by 37 ± 11% with PE/HD (P < 0.001 versus MARS) and a decrease in ammonia of 18 ± 27 and 39 ± 23% (P < 0.05). INR increased during MARS by 26 ± 41% and decreased with PE/HD by 37 ± 20% (P < 0.01). All treatment sessions were well tolerated. Five children died, including the three children treated with Mini-MARS. CONCLUSION Our experience suggests superior efficacy of combined PE/HD as compared to intermittent MARS therapy for treating ALF.
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Affiliation(s)
- Betti Schaefer
- Department of General Pediatrics, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Germany
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Bachli EB, Bösiger J, Béchir M, Stover JF, Stocker R, Maggiorini M, Renner EL, Müllhaupt B, Schuepbach RA. Thromboelastography to monitor clotting/bleeding complications in patients treated with the molecular adsorbent recirculating system. Crit Care Res Pract 2011; 2011:313854. [PMID: 21527982 PMCID: PMC3064997 DOI: 10.1155/2011/313854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Accepted: 01/13/2011] [Indexed: 11/17/2022] Open
Abstract
Background. The Molecular Adsorbent Recirculating System (MARS) has been shown to clear albumin-bound toxins from patients with liver failure but might cause bleeding complications potentially obscuring survival benefits. We hypothesized that monitoring clotting parameters and bed-side thromboelastography allows to reduce bleeding complications. Methods. Retrospective analysis of 25 MARS sessions during which clotting parameters were monitored by a standardized protocol. Results. During MARS therapy median INR increased significantly from 1.7 to 1.9 platelet count and fibrinogen content decreased significantly from 57 fL(-1) to 42 fL(-1) and 2.1 g/L to 1.5 g/L. Nine relevant complications occurred: the MARS system clotted 6 times 3 times we observed hemorrhages. Absent thrombocytopenia and elevated plasma fibrinogen predicted clotting of the MARS system (ROC 0.94 and 0.82). Fibrinolysis, detected by thromboelastography, uniquely predicted bleeding events. Conclusion. Bed-side thromboelastography and close monitoring of coagulation parameters can predict and, therefore, help prevent bleeding complications during MARS therapy.
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Affiliation(s)
- Esther B. Bachli
- Medical Intensive Care Unit, University Hospital Zurich, 8091 Zurich, Switzerland
- Clinic of Internal Medicine, Hospital Uster, 8610 Uster, Switzerland
| | - Jörg Bösiger
- Division of Haematology, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Markus Béchir
- Surgical Intensive Care Unit, University Hospital Zurich, HOF-B-110, Raemistraße 100, 8091 Zurich, Switzerland
| | - John F. Stover
- Surgical Intensive Care Unit, University Hospital Zurich, HOF-B-110, Raemistraße 100, 8091 Zurich, Switzerland
| | - Reto Stocker
- Surgical Intensive Care Unit, University Hospital Zurich, HOF-B-110, Raemistraße 100, 8091 Zurich, Switzerland
| | - Marco Maggiorini
- Medical Intensive Care Unit, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Eberhard L. Renner
- Division of Gastroenterology and Hepatology, University Hospital Zurich, 8091 Zurich, Switzerland
- Multiorgan Transplant Program, University Health Network, University of Toronto, Toronto, Canada ON M5G 2N2
| | - Beat Müllhaupt
- Division of Gastroenterology and Hepatology, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Reto A. Schuepbach
- Medical Intensive Care Unit, University Hospital Zurich, 8091 Zurich, Switzerland
- Surgical Intensive Care Unit, University Hospital Zurich, HOF-B-110, Raemistraße 100, 8091 Zurich, Switzerland
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Sentürk E, Esen F, Ozcan PE, Rifai K, Pinarbaşi B, Cakar N, Telci L. The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications. J Clin Apher 2011; 25:195-201. [PMID: 20818714 DOI: 10.1002/jca.20238] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. PATIENTS AND METHODS FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute-on-chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post-treatment data were performed using paired t-test. RESULTS The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 +/- 9.46 mg/dL vs. 9.76 +/- 7.05 mg/dL; P < 0.0001), ammonia (167.6 +/- 75 mg/dL vs. 120 +/- 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 +/- 13.03 mg/dL vs. 8.18 +/- 8.15 mg/dL; P < 0.0001), creatinine (0.54 +/- 0.47 mg/dL vs. 0.46 +/- 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 +/- 0.05 vs. 7.44 +/- 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. CONCLUSIONS FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment.
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Affiliation(s)
- Evren Sentürk
- Department of Anesthesiology, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey.
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