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Hernaez R, Li H, Moreau R, Coenraad MJ. Definition, diagnosis and epidemiology of acute-on-chronic liver failure. Liver Int 2025; 45:e15670. [PMID: 37424175 DOI: 10.1111/liv.15670] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 06/14/2023] [Accepted: 06/27/2023] [Indexed: 07/11/2023]
Abstract
This narrative review addresses the definition of acute-on-chronic liver failure, a condition associated with high short-term mortality in patients with chronic liver disease and/or cirrhosis. We provide two major points of view: the East and the West perspective. Both definitions vary regarding the underlying patient population and organ failure(s) definition. Nevertheless, all the definitions have their clinical utility: from the core concept of having the "liver" as a conditio sine qua non, the syndrome cannot exist (Asian Pacific Association for the Study of the Liver); a data-driven, robust definition (European Association for the Study of the Liver); a bedside tool that can quickly identify patients at high risk of dying (North American Consortium for the Study of End-stage Liver Disease [NACSELD]). In each section, we provide the overall definitions, the criteria of organ failure(s), and some epidemiological data illustrating how these apply in each area of the world.
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Affiliation(s)
- Ruben Hernaez
- Section of Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, TX Center, Houston, Texas, USA
- VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Hai Li
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, France
- INSERM, Université de Paris Cité, Centre de Recherche sur l'Inflammation (CRI), Service d'Hépatologie, Paris, France
- Assistance Publique-Hôpitaux de Paris (AP-HP), and Hôpital Beaujon, Clichy, France
| | - Minneke J Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
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Isha S, Jenkins AS, Hanson AJ, Satashia PH, Narra SA, Mundhra GD, Hasan MM, Donepudi A, Giri A, Johnson PW, Villar D, Santos C, Canabal J, Lowman P, Franco PM, Sanghavi DK. The Effect of Molecular Adsorbent Recirculating System in Patients With Liver Failure: A Case Series of 44 Patients. Transplant Proc 2023; 55:2126-2133. [PMID: 37806867 DOI: 10.1016/j.transproceed.2023.07.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 06/19/2023] [Accepted: 07/04/2023] [Indexed: 10/10/2023]
Abstract
BACKGROUND Liver failure is associated with a high mortality rate, with many patients requiring transplant for definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a nonbiologic system that provides extracorporeal support. Literature on MARS therapy is mixed: outcomes support MARS therapy for patients with isolated acute liver failure, but data on patients with chronic disease is varied. Several case studies report success using MARS as a bridging treatment for patients awaiting transplant. The purpose of this case series is to present the outcomes of 44 patients who underwent MARS therapy for liver failure, 19 of whom used MARS therapy as a bridging therapy to transplant. METHODS This study retrospectively identified 44 patients who underwent MARS therapy for liver failure at Mayo Clinic, Jacksonville, between January 2014 and April 2021. Variables of interest included changes in laboratory markers of hepatic functioning, number and length of MARS therapy sessions, transplantation status, and mortality. RESULTS Following MARS therapy, there were improvements in mean serum bilirubin, ammonia, urea, creatinine, International Normalized Ratio, alanine aminotransferase, and aspartate aminotransferase levels. Twenty-seven patients (61.36%) survived the hospital stay; 17 (38.63%) died in the hospital. The majority of surviving patients (n = 19; 73.07%) received liver transplant. Six did not require transplant (22.22%). All but 1 patient who received MARS as a bridging treatment to transplant survived the follow-up period (n = 18; 94.74%). CONCLUSIONS Outcomes of these 44 cases suggest that MARS improves liver failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant.
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Affiliation(s)
- Shahin Isha
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | - Anna S Jenkins
- Mayo Clinic Alix School of Medicine, Jacksonville, Florida
| | - Abby J Hanson
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | | | - Sai Abhishek Narra
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | - Gunjan D Mundhra
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | | | - Ashrita Donepudi
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | - Abishek Giri
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | - Patrick W Johnson
- Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida
| | - Dolores Villar
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | - Christan Santos
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | - Juan Canabal
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | - Philip Lowman
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida
| | - Pablo Moreno Franco
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida; Department of Transplantation, Mayo Clinic, Jacksonville, Florida
| | - Devang K Sanghavi
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, Florida.
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Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of liver support systems for adults with acute‐on‐chronic liver failure.
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4
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Martí-Carvajal AJ, Gluud C, Gluud LL, Pavlov CS, Mauro E, Monge Martín D, Liu JP, Nicola S, Comunián-Carrasco G, Martí-Amarista CE. Liver support systems for adults with acute liver failure. Hippokratia 2022. [DOI: 10.1002/14651858.cd015059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Arturo J Martí-Carvajal
- Facultad de Ciencias de la Salud Eugenio Espejo; Universidad UTE (Cochrane Ecuador); Quito Ecuador
- Facultad de Medicina, Universidad Francisco de Vitoria (Cochrane Madrid); Madrid Spain
- Cátedra Rectoral de Medicina Basada en la Evidencia; Universidad de Carabobo; Valencia Venezuela
| | - Christian Gluud
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research; The Capital Region, Copenhagen University Hospital - Rigshospitalet; Copenhagen Denmark
- Department of Regional Health Research; The Faculty of Health Sciences, University of Southern Denmark; Odense Denmark
| | - Lise Lotte Gluud
- Gastrounit, Medical Division; Copenhagen University Hospital Hvidovre; Hvidovre Denmark
| | - Chavdar S Pavlov
- Cochrane Hepato-Biliary Group; Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet; Copenhagen Denmark
- Department of Therapy ; IM Sechenov First Moscow State Medical University; Moscow Russian Federation
- Department of Gastroenterology; Botkin Hospital; Moscow Russian Federation
| | - Ezequiel Mauro
- Liver Unit & Liver Transplant Unit; Hospital Italiano de Buenos Aires; Buenos Aires Argentina
| | - Diana Monge Martín
- Facultad de Medicina; Universidad Francisco de Vitoria (Cochrane Madrid); Madrid Spain
| | - Jian Ping Liu
- Centre for Evidence-Based Chinese Medicine; Beijing University of Chinese Medicine; Beijing China
| | - Susana Nicola
- Centro Asociado Cochrane Ecuador, Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC); Universidad UTE; Quito Ecuador
| | - Gabriella Comunián-Carrasco
- Cátedra Rectoral de Medicina Basada en la Evidencia; Universidad de Carabobo; Valencia Venezuela
- Departamento de Obstetricia y Ginecología; Universidad de Carabobo; Valencia Venezuela
| | - Cristina Elena Martí-Amarista
- Division of General, Geriatric and Hospital Medicine; Stony Brook University, Renaissance School of Medicine HSC, Level 2, Rm 155; Stony Brook, 11794-8228 New York USA
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Yoo SW, Ki MJ, Kim D, Kim SK, Park S, Han HJ, Lee HB. Bleeding complications associated with the molecular adsorbent recirculating system: a retrospective study. Acute Crit Care 2022; 36:322-331. [PMID: 35263827 PMCID: PMC8907459 DOI: 10.4266/acc.2021.00276] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 08/25/2021] [Indexed: 01/15/2023] Open
Abstract
Background The molecular adsorbent recirculating system (MARS) is a hepatic replacement system that supports excretory liver function in patients with liver failure. However, since MARS has been employed in our hospital, bleeding complications have occurred in many patients during or after MARS. The objective of this study was to determine how MARS affects coagulopathy and identify specific factors associated with bleeding complications. Methods We retrospectively analyzed data from 17 patients undergoing a total of 41 MARS sessions. Complete blood count, coagulation profiles, and blood chemistry values were compared before and after MARS. To identify pre-MARS factors associated with increased bleeding after MARS, we divided patients into bleeder and non-bleeder groups and compared their pre-MARS laboratory values. Results MARS significantly reduced bilirubin and creatinine levels. MARS also increased prothrombin time and reduced platelet and fibrinogen, thus negatively impacting coagulation. Pre-MARS hemoglobin was significantly lower in the bleeder group than in the non-bleeder group (P=0.015). When comparing the upper and lower 33% of MARS sessions based on the hemoglobin reduction rate, hemoglobin reduction was significantly greater in MARS sessions involving patients with low pre-MARS international normalized ratio of prothrombin time (PT-INR) and factor V (P=0.038 and P=0.023, respectively). Conclusions MARS could appears to alter coagulation-related factors such as factor V and increase the risk of bleeding complications particularly in patient with low hemoglobin. However, individual differences among patients were large, and various factors, such as low hemoglobin, PT-INR, and factor V levels, appear to be involved.
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Affiliation(s)
- Seon Woo Yoo
- Department of Anesthesiology and Pain Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Min-Jong Ki
- Department of Anesthesiology and Pain Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Dal Kim
- Department of Anesthesiology and Pain Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Seul Ki Kim
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.,Humidifier Disinfectant Health Center, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - SeungYong Park
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.,Humidifier Disinfectant Health Center, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.,Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Hyo Jin Han
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.,Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Heung Bum Lee
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.,Humidifier Disinfectant Health Center, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.,Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
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Vipani A, Lindenmeyer CC, Sundaram V. Treatment of Severe Acute on Chronic Liver Failure: Management of Organ Failures, Investigational Therapeutics, and the Role of Liver Transplantation. J Clin Gastroenterol 2021; 55:667-676. [PMID: 34028394 DOI: 10.1097/mcg.0000000000001568] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, in the setting of organ system failures. Given this prognosis, there is an urgent need to understand risk factors for this condition, for appropriate medical management of organ failures, and for selection criteria for patients who may benefit from liver transplantation (LT). Although several definitions exist to identify ACLF, all of them are designed to identify patients with uniquely high mortality. Currently, management of severe ACLF relies on best supportive care for specific organ failures. Thromboelastography should guide the evaluation of coagulation pathways and hyperfibrinolysis in ACLF; prophylactic blood product transfusions and thrombopoetin agonists are not recommended. Combination therapy with terlipressin and albumin has been shown to be efficacious in the management of the hepatorenal syndrome but should be administered with caution in patients with ACLF-3. Recent data have characterized the role of beta-blockers and transjugular intrahepatic portosystemic shunt placement in the management of ACLF. Investigational therapies such as extracorporeal liver support and hepatocyte stem cell therapies have shown promise; larger scale studies may better define the subpopulations of patients with ACLF mostly likely to benefit from these evolving therapeutics. Regarding LT in ACLF, data suggest that even patients with 3 or more organ system failures may have a 1-year survival >80%. However, further efforts are needed to understand the predictors of post-LT survival to facilitate LT criteria for this condition.
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Affiliation(s)
| | | | - Vinay Sundaram
- Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
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7
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Kanjo A, Ocskay K, Gede N, Kiss S, Szakács Z, Párniczky A, Mitzner S, Stange J, Hegyi P, Molnár Z. Efficacy and safety of liver support devices in acute and hyperacute liver failure: a systematic review and network meta-analysis. Sci Rep 2021; 11:4189. [PMID: 33602961 PMCID: PMC7893063 DOI: 10.1038/s41598-021-83292-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 01/28/2021] [Indexed: 12/19/2022] Open
Abstract
Acute liver failure (ALF) is a potentially life-threatening condition. Liver support therapies can be applied as a bridging-to-transplantation or bridging-to-recovery; however, results of clinical trials are controversial. Our aim was to compare liver support systems in acute and hyperacute liver failure with network meta-analysis. After systematic search, randomized controlled trials (RCT) comparing liver support therapies in adults with acute or hyperacute liver failure were included. In-hospital mortality was the primary outcome, the secondary outcomes were hepatic encephalopathy and mortality-by-aetiology. A Bayesian-method was used to perform network meta-analysis and calculate surface under the cumulative ranking curve (SUCRA) values to rank interventions. Eleven RCTs were included. BioLogic-DT and molecular adsorbent recirculating system (MARS) resulted in the lowest mortality (SUCRAs: 76% and 73%, respectively). In non-paracetamol-poisoned patients, BioLogic-DT, charcoal hemoperfusion and MARS may be equally efficient regarding mortality (SUCRAs: 53%, 52% and 52%, respectively). Considering hepatic encephalopathy, extracorporeal liver assist device (ELAD) may be the most effective option (SUCRA: 78%). However, in pairwise meta-analysis, there were no statistically significant differences between the interventions in the outcomes. In conclusion, MARS therapy seems to be the best available option in reducing mortality. Further research is needed on currently available and new therapeutic modalities. (CRD42020160133).
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Affiliation(s)
- Anna Kanjo
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.,Heim Pál National Paediatric Institute, Budapest, Hungary.,Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
| | - Klementina Ocskay
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Noémi Gede
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Szabolcs Kiss
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.,Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
| | - Zsolt Szakács
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.,János Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Andrea Párniczky
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.,Heim Pál National Paediatric Institute, Budapest, Hungary.,Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
| | - Steffen Mitzner
- Division of Nephrology, Department of Medicine, University of Rostock, Rostock, Germany
| | - Jan Stange
- Division of Nephrology, Department of Medicine, University of Rostock, Rostock, Germany
| | - Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.,Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary.,János Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Zsolt Molnár
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary. .,Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary. .,Department of Anesthesiology and Intensive Therapy, Poznan University for Medical Sciences, Medical Faculty, Poznan, Poland.
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8
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Ocskay K, Kanjo A, Gede N, Szakács Z, Pár G, Erőss B, Stange J, Mitzner S, Hegyi P, Molnár Z. Uncertainty in the impact of liver support systems in acute-on-chronic liver failure: a systematic review and network meta-analysis. Ann Intensive Care 2021; 11:10. [PMID: 33462764 PMCID: PMC7813174 DOI: 10.1186/s13613-020-00795-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 12/18/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. METHODS The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). RESULTS In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6-0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. CONCLUSION PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.
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Affiliation(s)
- Klementina Ocskay
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary
| | - Anna Kanjo
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary.,Heim Pál National Paediatric Institute, Budapest, Hungary
| | - Noémi Gede
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary.,Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Zsolt Szakács
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary
| | - Gabriella Pár
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Bálint Erőss
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary
| | - Jan Stange
- Division of Nephrology, Department of Medicine, University of Rostock, Rostock, Germany
| | - Steffen Mitzner
- Division of Nephrology, Department of Medicine, University of Rostock, Rostock, Germany
| | - Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary.,First Department of Medicine, University of Szeged, Szeged, Hungary.,Translational Medicine Foundation, Szeged, Hungary
| | - Zsolt Molnár
- Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary. .,Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland.
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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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Alshamsi F, Alshammari K, Belley-Cote E, Dionne J, Albrahim T, Albudoor B, Ismail M, Al-Judaibi B, Baw B, Subramanian RM, Steadman R, Galusca D, Huang DT, Nanchal R, Al Quraini M, Yuan Y, Alhazzani W. Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials. Intensive Care Med 2019; 46:1-16. [PMID: 31588983 DOI: 10.1007/s00134-019-05783-y] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure. METHODS We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. RESULTS We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain. CONCLUSIONS ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.
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Affiliation(s)
- Fayez Alshamsi
- Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates
| | - Khalil Alshammari
- Department of Internal Medicine, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Emilie Belley-Cote
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Joanna Dionne
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Talal Albrahim
- Department of Anesthesiology and Critical Care Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Budoor Albudoor
- Department of Critical Care Medicine, Shaikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Mona Ismail
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Al-Khobar, Saudi Arabia
| | - Bandar Al-Judaibi
- Transplant Hepatology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, USA, 14642
| | - Bandar Baw
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Ram M Subramanian
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Randolph Steadman
- Department of Anesthesiology and Perioperative Medicine, Ronald Reagan Medical Center, University of California Los Angeles, Los Angeles, USA
| | - Dragos Galusca
- Department of Anesthesiology, Henry Ford Hospital, Detroit, MI, USA
| | - David T Huang
- Department of Critical Care Medicine, Director Multidisciplinary Acute Care Research Organization (MACRO), University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Rahul Nanchal
- Department of Pulmonary, Critical Care and Sleep Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mustafa Al Quraini
- Department of Pulmonary and Critical Care Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Yuhong Yuan
- Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Waleed Alhazzani
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada.
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada.
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11
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Bañares R, Ibáñez-Samaniego L, Torner JM, Pavesi M, Olmedo C, Catalina MV, Albillos A, Larsen FS, Nevens F, Hassanein T, Schmidt H, Heeman U, Jalan R, Moreau R, Arroyo V. Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity. Therap Adv Gastroenterol 2019; 12:1756284819879565. [PMID: 31632458 PMCID: PMC6767713 DOI: 10.1177/1756284819879565] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues. METHODS We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus ⩽ 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality. RESULTS Three RCTs suitable for the meta-analysis (n = 285, ACLF patients = 165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p = 0.001; 30-day survival: 73.9% versus 64.3%, p = 0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p = 0.001; 30-day survival: 73.3% versus 58.5%, p = 0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy. CONCLUSION HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials.
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Affiliation(s)
| | - Luis Ibáñez-Samaniego
- Servicio de Medicina de Aparato Digestivo,
Hospital General Universitario Gregorio Marañón, CIBERehd, Madrid,
Spain
- Instituto de Investigación Sanitaria Gregorio
Marañón, Madrid, Spain
| | - Josep María Torner
- EASL CLIF Consortium, European Foundation for
the Study of Chronic Liver Failure (EfClif), Barcelona, Spain
| | - Marco Pavesi
- EASL CLIF Consortium, European Foundation for
the Study of Chronic Liver Failure (EfClif), Barcelona, Spain
| | - Carmen Olmedo
- Instituto de Investigación Sanitaria Gregorio
Marañón, Madrid, Spain
| | - María Vega Catalina
- Servicio de Medicina de Aparato Digestivo,
Hospital General Universitario Gregorio Marañón, CIBERehd, Madrid,
Spain
- Instituto de Investigación Sanitaria Gregorio
Marañón, Madrid, Spain
| | - Agustín Albillos
- Department of Gastroenterology and Hepatology,
Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid,
Spain
| | - Fin Stolze Larsen
- Department of Hepatology, Copenhagen University
Rigshospitalet, Copenhagen, Denmark
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology,
University Hospitals Leuven, KU Leuven, Belgium
| | - Tarek Hassanein
- The University of California, San Diego School
of Medicine, Southern California Liver Centers, Southern California Research
Center, San Diego, USA
| | - Harmuth Schmidt
- Klinik für Transplantationsmedizin,
Universitätsklinikum Münster, Münster, Germany
| | - Uwe Heeman
- Department of Nephrology, Klinikum Rechts der
Isar, Technische Universität München, Munich, Germany
| | - Rajiv Jalan
- Division of Medicine, UCL Medical School, Royal
Free Hospital, UCL Institute for Liver and Digestive Health, London,
UK
| | - Richard Moreau
- INSERM, Center de Recherche sur l’Inflammation
(CRI); Université Paris Diderot, Sorbonne Paris; Service d’Hépatologie,
Hôpital Beaujon, Clichy, France
| | - Vicente Arroyo
- EASL CLIF Consortium, European Foundation for
the Study of Chronic Liver Failure (EfClif), Barcelona, Spain
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12
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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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13
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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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14
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Mastropietro CW, Valentine KM. Medical Management of Acute Liver Failure. PEDIATRIC CRITICAL CARE 2018. [PMCID: PMC7121299 DOI: 10.1007/978-3-319-96499-7_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Pediatric acute liver failure is a rapidly progressive, life-threatening, and devastating illness in children without preexisting liver disease. Due to the rarity and heterogeneity of this syndrome, there is a significant lack of data to guide evaluation and management of this disease. Most of our practice is extrapolated from adult literature and guidelines. This leads to significant controversies in medical management of acute liver failure in children. With advances in critical care, there has been a tremendous improvement in outcomes with decreased morbidity and mortality; however, there is a dire need for more research in this field. This chapter discusses challenges as well as controversies in diagnostic evaluation and management of this rare but potentially fatal disease. Latest developments in supportive care of liver failure, including advances in the area of liver support systems, are also discussed.
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Affiliation(s)
- Christopher W. Mastropietro
- grid.257413.60000 0001 2287 3919Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN USA
| | - Kevin M. Valentine
- grid.257413.60000 0001 2287 3919Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN USA
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15
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Jitraruch S, Dhawan A, Hughes RD, Filippi C, Lehec SC, Glover L, Mitry RR. Cryopreservation of Hepatocyte Microbeads for Clinical Transplantation. Cell Transplant 2018; 26:1341-1354. [PMID: 28901189 PMCID: PMC5680969 DOI: 10.1177/0963689717720050] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Intraperitoneal transplantation of hepatocyte microbeads is an attractive option for the management of acute liver failure. Encapsulation of hepatocytes in alginate microbeads supports their function and prevents immune attack of the cells. Establishment of banked cryopreserved hepatocyte microbeads is important for emergency use. The aim of this study was to develop an optimized protocol for cryopreservation of hepatocyte microbeads for clinical transplantation using modified freezing solutions. Four freezing solutions with potential for clinical application were investigated. Human and rat hepatocytes cryopreserved with University of Wisconsin (UW)/10% dimethyl sulfoxide (DMSO)/5% (300 mM) glucose and CryoStor CS10 showed better postthawing cell viability, attachment, and hepatocyte functions than with histidine-tryptophan-ketoglutarate/10% DMSO/5% glucose and Bambanker. The 2 freezing solutions that gave better results were studied with human and rat hepatocytes microbeads. Similar effects on cryopreserved microbead morphology (external and ultrastructural), viability, and hepatocyte-functions post thawing were observed over 7 d in culture. UW/DMSO/glucose, as a basal freezing medium, was used to investigate the additional effects of cytoprotectants: a pan-caspase inhibitor (benzyloxycarbonyl-Val-Ala-dl-Asp-fluoromethylketone [ZVAD]), an antioxidant (desferoxamine [DFO]), and a buffering and mechanical protectant (human serum albumin [HSA]) on RMBs. ZVAD (60 µM) had a beneficial effect on cell viability that was greater than with DFO (1 mM), HSA (2%), and basal freezing medium alone. Improvements in the ultrastructure of encapsulated hepatocytes and a lower degree of cell apoptosis were observed with all 3 cytoprotectants, with ZVAD tending to provide the greatest effect. Cytochrome P450 activity was significantly higher in the 3 cytoprotectant groups than with fresh microbeads. In conclusion, developing an optimized cryopreservation protocol by adding cytoprotectants such as ZVAD could improve the outcome of cryopreserved hepatocyte microbeads for future clinical use.
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Affiliation(s)
- Suttiruk Jitraruch
- 1 Dhawan Lab at Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom.,2 Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Anil Dhawan
- 1 Dhawan Lab at Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom
| | - Robin D Hughes
- 1 Dhawan Lab at Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom
| | - Celine Filippi
- 1 Dhawan Lab at Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom
| | - Sharon C Lehec
- 1 Dhawan Lab at Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom
| | - Leanne Glover
- 3 Centre for Ultrastructural Imaging, King's College London, London, United Kingdom
| | - Ragai R Mitry
- 1 Dhawan Lab at Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom
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16
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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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17
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Affiliation(s)
- Stephen Warrillow
- Department of Intensive Care, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
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18
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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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19
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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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20
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Abstract
Pediatric acute liver failure is rare but life-threatening illness that occurs in children without preexisting liver disease. The rarity of the disease, along with its severity and heterogeneity, presents unique clinical challenges to the physicians providing care for pediatric patients with acute liver failure. In this review, practical clinical approaches to the care of critically ill children with acute liver failure are discussed with an organ system-specific approach. The underlying pathophysiological processes, major areas of uncertainty, and approaches to the critical care management of pediatric acute liver failure are also reviewed.
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21
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Abstract
Drug-induced acute liver failure (ALF) disproportionately affects women and nonwhites. It is most frequently caused by antimicrobials and to a lesser extent by complementary and alternative medications, antiepileptics, antimetabolites, nonsteroidals, and statins. Most drug-induced liver injury ALF patients have hepatocellular injury pattern. Cerebral edema and intracranial hypertension are the most serious complications of ALF. Other complications include coagulopathy, sepsis, metabolic derangements, and renal, circulatory, and respiratory dysfunction. Although advances in intensive care have improved outcome, ALF has significant mortality without liver transplantation. Liver-assist devices may provide a bridge to transplant or to spontaneous recovery.
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Affiliation(s)
- Shahid Habib
- Department of Medicine, Southern Arizona Veterans Affairs Healthcare System 3601 S 6th Avenue, Tucson, AZ 85723 USA
| | - Obaid S Shaikh
- Section of Gastroenterology, Department of Medicine, Veterans Affairs Pittsburgh Healthcare System, University Drive C, FU #112, Pittsburgh, PA 15240, USA; Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
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22
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Acute-on-chronic hepatitis. A case report of autoimmune hepatitis/primary sclerosing cholangitis/ulcerative colitis overlap syndrome in a 15-year-old patient. Clin Exp Hepatol 2017; 3:28-32. [PMID: 28856287 PMCID: PMC5497451 DOI: 10.5114/ceh.2017.65501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2016] [Accepted: 12/06/2016] [Indexed: 12/30/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a disease in which a rapid deterioration of liver function occurs in patients with chronic liver disease, and is usually associated with a precipitating event. We present the case of a boy with autoimmune hepatitis/primary sclerosing cholangitis/ulcerative colitis (AIH/PSC/UC) overlap syndrome, in whom liver function was stable for 4.5 years of treatment. At 15 years of age the patient was hospitalized due to a deterioration of his general condition, severe abdominal pain, diarrhoea, vomiting and weight loss. There was also a rapid deterioration of liver function and a deterioration of renal function. Despite a wide spectrum of diagnostic examinations, no precipitating agent was found. After two episodes of massive bleeding from the gastrointestinal tract, the patient was transferred to the intensive care unit. The patient underwent a successful liver transplantation. ACLF can cause irreversible liver failure with a high mortality rate, which calls for liver transplantation.
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23
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Cardoso FS, Marcelino P, Bagulho L, Karvellas CJ. Acute liver failure: An up-to-date approach. J Crit Care 2017; 39:25-30. [PMID: 28131021 DOI: 10.1016/j.jcrc.2017.01.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2016] [Revised: 01/05/2017] [Accepted: 01/09/2017] [Indexed: 12/14/2022]
Abstract
Acute liver failure is a rare but potentially devastating disease. Throughout the last few decades, acute liver failure outcomes have been improving in the context of the optimized overall management. This positive trend has been associated with the earlier recognition of this condition, the improvement of the intensive care unit management, and the developments in emergent liver transplantation. Accordingly, we aimed to review the current diagnostic and therapeutic approach to this syndrome, especially in the intensive care unit setting.
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Affiliation(s)
- Filipe S Cardoso
- Intensive Care Unit, Curry Cabral Hospital, Central Lisbon Hospital Center, Lisbon, Portugal.
| | - Paulo Marcelino
- Intensive Care Unit, Curry Cabral Hospital, Central Lisbon Hospital Center, Lisbon, Portugal
| | - Luís Bagulho
- Intensive Care Unit, Curry Cabral Hospital, Central Lisbon Hospital Center, Lisbon, Portugal
| | - Constantine J Karvellas
- Divisions of Gastroenterology (Liver Unit) and Critical Care, University of Alberta Hospital, Edmonton, Canada
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24
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Sparks BE, Cavarocchi NC, Hirose H. Extracorporeal membrane oxygenation with multiple-organ failure: Can molecular adsorbent recirculating system therapy improve survival? J Heart Lung Transplant 2017; 36:71-76. [DOI: 10.1016/j.healun.2016.09.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 08/31/2016] [Accepted: 09/28/2016] [Indexed: 01/27/2023] Open
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Jindal A, Rastogi A, Sarin SK. Reviewing the diagnostic criteria for acute-on-chronic liver failure. Expert Rev Gastroenterol Hepatol 2016; 10:1385-1395. [PMID: 27771965 DOI: 10.1080/17474124.2016.1250622] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
For over 20 years, acute-on-chronic liver failure (ACLF) has taken multiple definitions and/or classifications. The definition outlines the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific time frame. Early and accurate diagnosis is essential as this inflammation of the liver may tilt the balance of liver destruction and regeneration adversely. Various factors such as superadded systemic sepsis, liver reserve, cause of primary chronic liver disease, state of immune system or the state of gut microbial flora might determine the ultimate prognosis. Areas covered: To date, there has been no universally accepted definition of ACLF. In this review, we discuss the strengths and weaknesses, controversies and basis for early identification and accurate diagnosis of ACLF. PubMed and Google scholar database searches were conducted, search terms included 'acute on chronic liver failure,' 'ACLF,' and 'diagnostic criteria.' Expert commentary: With recent advances in the management of advanced cirrhosis, research will gradually shift towards ACLF in the near future, focusing on the pathogenesis, new treatment options and improving survival. Once we improve understanding of this syndrome, newer definitions will evolve, thereby enabling earlier diagnosis and novel therapeutic avenues.
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Affiliation(s)
- Ankur Jindal
- a Departments of Hepatology , Institute of Liver and Biliary Sciences , New Delhi , India
| | - Archana Rastogi
- b Departments of Pathology , Institute of Liver and Biliary Sciences , New Delhi , India
| | - Shiv Kumar Sarin
- a Departments of Hepatology , Institute of Liver and Biliary Sciences , New Delhi , India
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26
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Kim SM, Song IH. [Acute Kidney Injury in Cirrhotic Patients with Portal Hypertension]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2016; 68:237-244. [PMID: 27871159 DOI: 10.4166/kjg.2016.68.5.237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Acute kidney injury (AKI) is one of the most common manifestations encountered in clinical practice. It is associated with high morbidity and mortality in cirrhotic pre- and post-transplantation patients. Hepatorenal syndrome (HRS), a special form of AKI in cirrhotic patients, was recognized as a consequence of renal vasoconstriction from systemic/renal hemodynamic alterations developed in advanced cirrhosis with portal hypertension. Recently, multiple factors-such as infection/inflammation, underlying glomerulonephritis, bile cast, or increased abdominal pressure-have been considered to contribute to renal dysfunction in cirrhotic patients, which were presumed to induce HRS. Moreover, in addition to changing the definition of AKI in the nephrologic guidelines, the new AKI definition for early diagnosis and intervention based on characteristics of liver cirrhosis has been proposed in an international meeting. This article provides a comprehensive and recent review of AKI definition, laying out the topics in accordance with the pathophysiologic mechanisms and therapeutic interventions of AKI in cirrhotic patients with portal hypertension.
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Affiliation(s)
- So Mi Kim
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Il Han Song
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
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27
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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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Role of albumin in diseases associated with severe systemic inflammation: Pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. J Crit Care 2015; 33:62-70. [PMID: 26831575 DOI: 10.1016/j.jcrc.2015.12.019] [Citation(s) in RCA: 127] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 10/21/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023]
Abstract
The metabolism of albumin in inflammatory states such as sepsis or major surgery is complex and still not well characterized. Nevertheless, in inflammatory states, albumin synthesis has been observed to increase. By contrast, in decompensated cirrhosis, a disease characterized by systemic inflammation, albumin synthesis by the liver may decrease to 30% to 50% of normal values. Furthermore, in these conditions, there are high capillary leakage and altered albumin kinetics. The discussion regarding the effect of exogenous albumin administration on intravascular volume in inflammatory states should therefore address albumin turnover. To add complexity to our understanding of the effects of albumin, there are many data indicating that the therapeutic action of albumin is mediated not only through the impact on plasma volume expansion but also through a modulatory effect on inflammation and oxidative stress. All these characteristics are relevant to diseases associated with systemic inflammation including sepsis and decompensated cirrhosis.
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Blasco-Algora S, Masegosa-Ataz J, Gutiérrez-García ML, Alonso-López S, Fernández-Rodríguez CM. Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management. World J Gastroenterol 2015; 21:12125-40. [PMID: 26576097 PMCID: PMC4641130 DOI: 10.3748/wjg.v21.i42.12125] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 08/17/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.
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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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Amarapurkar D, Dharod MV, Chandnani M, Baijal R, Kumar P, Jain M, Patel N, Kamani P, Issar S, Shah N, Kulkarni S, Gautam S, Shah A, Doshi S. Acute-on-chronic liver failure: a prospective study to determine the clinical profile, outcome, and factors predicting mortality. Indian J Gastroenterol 2015; 34:216-24. [PMID: 26080655 DOI: 10.1007/s12664-015-0574-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Accepted: 05/13/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF), defined differently by different associations, lacks consensus on clinical profile, precipitating events and factors predicting mortality. This prospective multicentric study was conducted to determine the relevance of European Association for Study of Liver (EASL) and Asia Pacific Association for Study of Liver (APASL) definitions and to determine prognostic factors predicting the survival. METHODS Consecutive patients over a 3-month period with any form of acute deterioration were evaluated for presence of ACLF, as defined by APASL or EASL-Chronic Liver Failure (CLIF) criteria. Those enrolled underwent complete evaluation for identifying the acute insults, underlying chronic etiologies, presence of organ failures, and short-term survival. RESULTS Sixty-two patients (median age 53 years, 51 males) who presented with either raised bilirubin (n = 52), international normalized ratio (INR) >1.5 (n = 46), new onset ascites (n = 53), or hepatic encephalopathy (n = 39) were included in study. Forty-four patients (36 males, 25 alcoholics) satisfied APASL definition of ACLF, with a mortality rate of 43.1 %. Hepatic encephalopathy (p-value 0.022) was significantly associated with mortality. By CLIF-Sequential Organ Failure Assessment (SOFA) score criteria for organ failure, 50 patients (80.6 %) had at least 1 organ failure whereas 15 had ≥3 organ failures (mortality rate >75 %). Twenty-nine patients classified as ACLF (1, 2, or 3) as per EASL-CLIF criteria. Bacterial infection, >1 precipitating event, additional organ failure, total leukocyte count, INR, and serum creatinine were significantly higher in patients with ACLF across all grades. Mortality rates were 6.6 and >60 % in patients with ACLF only by APASL criteria vs. by both criteria, respectively. CONCLUSIONS ACLF, as defined by APASL in terms of liver failure, identified some patients with better survival rates as compared to EASL-CLIF definition which identifies presence of additional organ failures and high mortality.
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Affiliation(s)
- Deepak Amarapurkar
- Bombay Hospital and Medical Research Center, 12, Marine Lines, Mumbai, 400 020, India
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Arroyo V, Moreau R, Jalan R, Ginès P. Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis. J Hepatol 2015; 62:S131-43. [PMID: 25920082 DOI: 10.1016/j.jhep.2014.11.045] [Citation(s) in RCA: 287] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 11/19/2014] [Accepted: 11/26/2014] [Indexed: 02/07/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a recently recognized syndrome characterized by acute decompensation (AD) of cirrhosis and organ/system failure(s) (organ failure: liver, kidney, brain, coagulation, circulation and/or respiration) and extremely poor survival (28-day mortality rate 30-40%). ACLF occurs in relatively young patients. It is especially frequent in alcoholic- and untreated hepatitis B associated-cirrhosis, in addition it is related to bacterial infections and active alcoholism, although in 40% of cases no precipitating event can be identified. It may develop at any time during the course of the disease in the patient (from compensated to long-standing cirrhosis). The development of ACLF occurs in the setting of a systemic inflammation, the severity of which correlates with the number of organ failures and mortality. Systemic inflammation may cause ACLF through complex mechanisms including an exaggerated inflammatory response and systemic oxidative stress to pathogen- or danger/damage-associated molecular patterns (immunopathology) and/or alteration of tissue homeostasis to inflammation caused either by the pathogen itself or through a dysfunction of tissue tolerance. A scoring system composed of three scores (CLIF-C OFs, CLIF-C AD, and CLIF-C ACLFs) specifically designed for patients with AD, with and without ACLF, allows a step-wise algorithm for a rational indication of therapy. The management of ACLF should be carried out in enhanced or intensive care units. Current therapeutic measures comprise the treatment for associated complications, organ failures support and liver transplantation.
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Affiliation(s)
- Vicente Arroyo
- Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Richard Moreau
- Inserm Unité 1149, Centre de Recherche sur l'inflammation (CRI) Paris, UMR S_1149, Université Paris Diderot, París, DHU UNITY, Service d'Hepatologie, Hôpital Beaujon, APHP, Clichy, France
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, Royal Free Hospital, UCL, London, United Kingdom
| | - Pere Ginès
- Liver Unit, Hospital Clinic, University of Barcelona, Insitut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBEReHD), Instituto Reina Sofia de Investigacion en Nefrologia (IRSIN), Spain.
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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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Zamora Nava LE, Aguirre Valadez J, Chávez-Tapia NC, Torre A. Acute-on-chronic liver failure: a review. Ther Clin Risk Manag 2014; 10:295-303. [PMID: 24790454 PMCID: PMC4003263 DOI: 10.2147/tcrm.s59723] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
There is no universally accepted definition of acute-on-chronic liver failure; however, it is recognized as an entity characterized by decompensation from an underlying chronic liver disease associated with organ failure that conveys high short-term mortality, with alcoholism and infection being the most frequent precipitating events. The pathophysiology involves inflammatory processes associated with a trigger factor in susceptible individuals (related to altered immunity in the cirrhotic population). This review addresses the different definitions developed by leading research groups, epidemiological and pathophysiological aspects, and the latest treatments for this entity.
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Affiliation(s)
- Luis Eduardo Zamora Nava
- Department of Endoscopy, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Jonathan Aguirre Valadez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | | | - Aldo Torre
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
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Gonwa TA. Should MARS and PROMETHEUS be Used in Patients with Liver Disease? Semin Dial 2014; 27:228-31. [DOI: 10.1111/sdi.12213] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Thomas A. Gonwa
- Mayo Clinic Florida; Department of Transplantation; Jacksonville Florida
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Warrillow SJ, Bellomo R. Preventing cerebral oedema in acute liver failure: the case for quadruple-H therapy. Anaesth Intensive Care 2014; 42:78-88. [PMID: 24471667 DOI: 10.1177/0310057x1404200114] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Severe cerebral oedema is a life-threatening complication of acute liver failure. Hyperammonaemia and cerebral hyperaemia are major contributing factors. A multimodal approach, which incorporates hyperventilation, haemodiafiltration, hypernatraemia and hypothermia (quadruple-H therapy), may prevent or attenuate severe cerebral oedema. This approach is readily administered by critical care clinicians and is likely to be more effective than the use of single therapies. Targeting of PaCO2 in the mild hyperventilation range, as seen in acute liver failure patients before intubation, aims to minimise hyperaemic cerebral oedema. Haemodiafiltration aims to achieve the rapid control of elevated blood ammonia concentrations by its removal and to reduce production via the lowering of core temperature. The administration of concentrated saline increases serum tonicity and further reduces cerebral swelling. In addition, the pathologically increased cerebral blood-flow is further attenuated by therapeutic hypothermia. The combination of all four treatments in a multimodal approach may be a safe and effective means of attenuating or treating the cerebral oedema of acute liver failure and preventing death from neurological complications.
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Affiliation(s)
- S J Warrillow
- Department of Intensive Care, Austin Health, Victoria, Australia
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Abstract
Fulminant hepatic failure presents with a hepatic encephalopathy and may progress to coma and often brain death from cerebral edema. This natural progression in severe cases contributes to early mortality, but outcome can be good if liver transplantation is appropriately timed and increased intracranial pressure (ICP) is managed. Neurologists and neurosurgeons have become more involved in these very challenging patients and are often asked to rapidly identify patients who are at risk of cerebral edema, to carefully select the patient population who will benefit from invasive ICP monitoring, to judge the correct time to start monitoring, to participate in treatment of cerebral edema, and to manage complications such as intracranial hemorrhage or seizures. This chapter summarizes the current multidisciplinary approach to fulminant hepatic failure and how to best bridge patients to emergency liver transplantation.
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Regimbeau JM, Fuks D, Chapuis-Roux E, Yzet T, Cosse C, Bartoli E, N'guyen-Khac E, Robert B, Lobjoie E. Addition of Molecular Adsorbent Recirculating System (MARS(®)) Albumin Dialysis for the Preoperative Management of Jaundiced Patients with Hilar Cholangiocarcinoma. Case Rep Gastroenterol 2013; 7:396-403. [PMID: 24163652 PMCID: PMC3806690 DOI: 10.1159/000355343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
The preoperative management of hilar cholangiocarcinoma (HC) with jaundice focuses on decreasing the total serum bilirubin level (SBL) by performing preoperative biliary drainage (PBD). However, it takes about 6–8 weeks for the SBL to fall at a sufficient extent. The objective of this preliminary study was to evaluate the impact of Molecular Adsorbent Recirculating System (MARS®) dialysis (in association with PBD) on SBL decrease. From January 2010 to January 2011, we prospectively selected all jaundiced patients admitted to our university hospital for resectable HC and requiring PBD prior to major hepatectomy. The PBD was followed by 3 sessions of MARS dialysis over a period of 72 h. A total of 10 patients with HC were screened and two of them were included (Bismuth-Corlette stage IIIa, gender ratio 1, median age 68 years). The initial SBL in the two patients was 328 and 242 μmol/l, respectively. After three MARS dialysis sessions, the SBL had fallen by 30 and 52%, respectively. After the end of each session, there was a SBL rebound of about 10 μmol/l. The MARS decreased the serum creatinine level, the platelet count and the prothrombin index, but did not modify the serum albumin level. Pruritus disappeared after one and two sessions, respectively. MARS-related morbidity included hypotension (n = 1), tachycardia (n = 1), thrombocytopenia (n = 2) and anaemia (n = 1). When combined with PBD, MARS dialysis appears to accelerate the decrease in SBL and thus may enable earlier surgery. This hypothesis must be validated in a larger study.
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Affiliation(s)
- Jean-Marc Regimbeau
- Department of Digestive Surgery, Jules Verne University of Picardy, Amiens, France ; Department of EA4294, Jules Verne University of Picardy, Amiens, France
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Duseja A, Choudhary NS, Gupta S, Dhiman RK, Chawla Y. APACHE II score is superior to SOFA, CTP and MELD in predicting the short-term mortality in patients with acute-on-chronic liver failure (ACLF). J Dig Dis 2013; 14:484-90. [PMID: 23692973 DOI: 10.1111/1751-2980.12074] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of the study was to assess the performance of various prognostic scores including the acute physiology and chronic health evaluation (APACHE II), sequential organ failure assessment (SOFA), Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores in predicting short-term mortality in patients with acute-on-chronic liver failure (ACLF). METHODS Altogether 100 consecutive patients with ACLF were evaluated prospectively. The diagnosis of ACLF was based on the Asian-Pacific Association for the Study of the Liver criteria except for the inclusion of non-hepatic insults as acute events. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for predicting short-term mortality was calculated for APACHE II, SOFA, CTP and MELD in all patients and Maddrey's discriminant function (DF) and Glasgow alcoholic hepatitis scores (GAHS) for patients with alcoholic hepatitis only. RESULTS Most patients had alcohol-related cirrhosis and alcoholic hepatitis as acute insults for ACLF. A total of 53 patients either died or left hospital in very sick status and were confirmed to have died the same day after leaving hospital. Overall, the area under the receiver operating characteristic curve of APACHE II was higher than those of MELD, SOFA and CTP scores for predicting short-term mortality. Even for patients with alcoholic hepatitis, APACHE II performed better than DF and GAHS. CONCLUSIONS Short-term mortality is high in patients with ACLF. APACHE II scoring system is superior to other prognostic scores in predicting its short-term mortality.
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Affiliation(s)
- Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Jha AK, Nijhawan S, Rai RR, Nepalia S, Jain P, Suchismita A. Etiology, clinical profile, and inhospital mortality of acute-on-chronic liver failure: a prospective study. Indian J Gastroenterol 2013; 32:108-114. [PMID: 23526372 DOI: 10.1007/s12664-012-0295-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2012] [Accepted: 12/24/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND The causes of acute injury in acute-on-chronic liver failure (ACLF) are variable. There may be simultaneous presence of more than one acute insult. We describe the clinical profile of ACLF and the effect of dual acute insult on the natural history. METHODS Patients with jaundice diagnosed to have ACLF were prospectively enrolled. Patients were evaluated for the clinical presentation, etiology of acute decompensation and underlying chronic liver disease, and inhospital mortality. We compared the clinical profile of patients who had dual acute insult with those of single/unknown insult. RESULTS Fifty-two patients with ACLF (mean age 38.6 ± 16.7 years; M/F 41:11) were included. Hepatitis virus infection (46.1 %) and bacterial infection (36.5 %) were the most common acute insults. Hepatitis virus infections were the sole acute insult in 34.6 % and associated with another injury in 11.5 %. Bacterial infections were identified as acute insult in 19 patients (sole acute insult in 13). Drugs, autoimmune disease, surgery, malaria, and dengue were other acute injuries identified. The cause of acute decompensation was unknown in 11.5 %. Mortality (66.6 % vs. 51.1 %) was higher in patients with dual insult (n=9) as compared with single/unknown insult (n=43). CONCLUSIONS Hepatitis virus and bacterial infection/sepsis were the common acute insults in ACLF. Dual acute insult is not uncommon, poses diagnostic dilemma, and may increase mortality in these patients. Plasmodium falciparum infection and dengue fever may be associated with ACLF.
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Affiliation(s)
- Ashish Kumar Jha
- Department of Gastroenterology, Sawai Man Singh Medical College, Jaipur 302 004, India
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Sharma AD, Iacob R, Cantz T, Manns MP, Ott M. Liver. Regen Med 2013. [DOI: 10.1007/978-94-007-5690-8_37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
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Rodeck B, Zimmer KP. Stoffwechselerkrankungen. PÄDIATRISCHE GASTROENTEROLOGIE, HEPATOLOGIE UND ERNÄHRUNG 2013. [PMCID: PMC7498805 DOI: 10.1007/978-3-642-24710-1_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Entsprechend ihrer Wanderung bei isoelektrischer Fokussierung werden die allelen Varianten des α1-AT als Proteinaseinhibitorphänotypen (Pi) klassifiziert. Die dominierende Isoform ist der normale Phänotyp M, daneben gibt es die Mangelvarianten S und Z sowie eine 0-Variante.
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Affiliation(s)
- Burkhard Rodeck
- Zentrum für Kinder- und Jugendmedizin, Christliches Kinderhospital Osnabrück, Johannisfreiheit 1, 49074 Osnabrück, Deutschland
| | - Klaus-Peter Zimmer
- grid.411067.50000000085849230Abteilung Allgemeine Pädiatrie und Neonatalogie, Universitätsklinikum Gießen und Marburg GmbH, Zentrum für Kinderheilkunde und Jugendmedizin, Feulgenstr. 12, 35392 Gießen, Deutschland
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Abstract
The fact that liver failure constitutes a life-threatening condition and can, in most cases, only be overcome by orthotopic liver transplantation, lead to the development of various artificial and bioartificial liver support devices. While artificial systems are based on the principles of adsorption and filtration, the more complex concept of bioartificial devices includes the provision of liver cells. Instead of solely focussing on detoxification, these concepts also support the failing organ concerning synthetic and regulative functions.The systems were evaluated in a variety of clinical studies, demonstrating their safety and investigating the impact on the patient's clinical condition. This review gives an overview over the most common artificial and bioartificial liver support devices and summarizes the results of the clinical studies.
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Shi XL, Zhang Y, Chu XH, Han B, Gu JY, Xiao JQ, Tan JJ, Gu ZZ, Ren HZ, Yuan XW, Ding YT. Evaluation of a novel hybrid bioartificial liver based on a multi-layer flat-plate bioreactor. World J Gastroenterol 2012; 18:3752-60. [PMID: 22851870 PMCID: PMC3406430 DOI: 10.3748/wjg.v18.i28.3752] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2011] [Revised: 04/26/2012] [Accepted: 05/12/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy and safety of a hybrid bioartificial liver (HBAL) system in the treatment of acute liver failure.
METHODS: Canine models with acute liver failure were introduced with intravenous administration of D-galactosamine. The animals were divided into: the HBAL treatment group (n = 8), in which the canines received a 3-h treatment of HBAL; the bioartificial liver (BAL) treatment group (n = 8), in which the canines received a 3-h treatment of BAL; the non-bioartificial liver (NBAL) treatment group (n = 8), in which the canines received a 3-h treatment of NBAL; the control group (n = 8), in which the canines received no additional treatment. Biochemical parameters and survival time were determined. Levels of xenoantibodies, RNA of porcine endogenous retrovirus (PERV) and reverse transcriptase (RT) activity in the plasma were detected.
RESULTS: Biochemical parameters were significantly decreased in all treatment groups. The TBIL level in the HBAL group was lower than that in other groups (2.19 ± 0.55 μmol/L vs 24.2 ± 6.45 μmol/L, 12.47 ± 3.62 μmol/L, 3.77 ± 1.83 μmol/L, P < 0.05). The prothrombin time (PT) in the BAL and HBAL groups was significantly shorter than the NBAL and control groups (18.47 ± 4.41 s, 15.5 ± 1.56 s vs 28.67 ± 5.71 s, 21.71 ± 3.4 s, P < 0.05), and the PT in the HBAL group was shortest of all the groups. The albumin in the BAL and HBAL groups significantly increased and a significantly higher level was observed in the HBAL group compared with the BAL group (27.7 ± 1.7 g/L vs 25.24 ± 1.93 g/L). In the HBAL group, the ammonia levels significantly decreased from 54.37 ± 6.86 to 37.75 ± 6.09 after treatment (P < 0.05); there were significant difference in ammonia levels between other the groups (P < 0.05). The levels of antibodies were similar before and after treatment. The PERV RNA and the RT activity in the canine plasma were all negative.
CONCLUSION: The HBAL showed great efficiency and safety in the treatment of acute liver failure.
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Lim CC, Tan HK. An Introduction to Extracorporeal Blood Purification in Critical Illness. PROCEEDINGS OF SINGAPORE HEALTHCARE 2012. [DOI: 10.1177/201010581202100204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Critical care nephrology is an emerging sub-specialty with rapid technological advancement and a growing body of dedicated literature in blood purification techniques. Their applications have been extended to improve morbidity and survival in multiple organ dysfunctions. Novel techniques have also allowed us to push the frontiers in transplant medicine, giving high-immunological risk patients a chance at a kidney transplant where this was previously precluded by hyperacute antibody-mediated rejection. We aim to review the myriad extracorporeal blood purification techniques now available for treating various critical illnesses in our clinical practice. Some of these techniques will still require further clinical research to determine the optimal timing and dose in order to achieve significant improvement in clinical outcomes.
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Affiliation(s)
| | - Han Khim Tan
- Department of Renal Medicine, Singapore General Hospital
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Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, Sakhuja P, Sarin SK. Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology 2012; 142:505-512.e1. [PMID: 22119930 DOI: 10.1053/j.gastro.2011.11.027] [Citation(s) in RCA: 290] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Revised: 11/03/2011] [Accepted: 11/04/2011] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Acute-on-chronic liver failure (ACLF) develops in patients with chronic liver disease and has high mortality. Mobilization of bone marrow-derived stem cells with granulocyte colony-stimulating factor (G-CSF) could promote hepatic regeneration. METHODS Consecutive patients with ACLF were randomly assigned to groups given 5 μg/kg G-CSF subcutaneously (12 doses; group A, n = 23) or placebo (group B, n = 24) plus standard medical therapy. We assessed survival until day 60; Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), and Sequential Organ Failure Assessment (SOFA) scores; and the development of other related complications. RESULTS After 1 week of treatment, group A had higher median leukocyte and neutrophil counts than group B (P < .001). Sixteen patients in group A (69.6%) and 7 in group B (29%) survived; the actuarial probability of survival at day 60 was 66% versus 26%, respectively (P = .001). Treatment with G-CSF also reduced CTP scores in group A by a median of 33.3% compared with an increase of 7.1% in group B (P = .001), along with MELD (median reduction of 15.3% compared with an increase of 11.7% in group B; P = .008) and SOFA scores (median reduction of 50% compared with an increase of 50% in group B; P = .001). The percentages of patients who developed hepatorenal syndrome, hepatic encephalopathy, or sepsis were lower in group A than in group B (19% vs 71% [P = .0002], 19% vs 66% [P = .001], and 14% vs 41% [P = .04], respectively). After 1 month of treatment, G-CSF increased the number of CD34(+) cells in the liver (by 45% compared with 27.5% in group B; P = .01). CONCLUSIONS G-CSF therapy more than doubles the percentage of patients with ACLF who survive for 2 months; it also significantly reduces CTP, MELD, and SOFA scores and prevents the development of sepsis, hepatorenal syndrome, and hepatic encephalopathy.
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Affiliation(s)
- Vishal Garg
- Department of Gastroenterology, GB Pant Hospital, New Delhi, India
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Hepatorenal syndrome: the 8th International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2012; 16:R23. [PMID: 22322077 PMCID: PMC3396267 DOI: 10.1186/cc11188] [Citation(s) in RCA: 116] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2011] [Revised: 12/30/2011] [Accepted: 02/09/2012] [Indexed: 02/08/2023]
Abstract
Introduction Renal dysfunction is a common complication in patients with end-stage cirrhosis. Since the original publication of the definition and diagnostic criteria for the hepatorenal syndrome (HRS), there have been major advances in our understanding of its pathogenesis. The prognosis of patients with cirrhosis who develop HRS remains poor, with a median survival without liver transplantation of less than six months. However, a number of pharmacological and other therapeutic strategies have now become available which offer the ability to prevent or treat renal dysfunction more effectively in this setting. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. Methods We undertook a systematic review of the literature using Medline, PubMed and Web of Science, data provided by the Scientific Registry of Transplant Recipients and the bibliographies of key reviews. We determined a list of key questions and convened a two-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. Results Of the 30 questions considered, we found inadequate evidence for the majority of questions and our recommendations were mainly based on expert opinion. There was insufficient evidence to grade three questions, but we were able to develop a consensus definition for acute kidney injury in patients with cirrhosis and provide consensus recommendations for future investigations to address key areas of uncertainty. Conclusions Despite a paucity of sufficiently powered prospectively randomized trials, we were able to establish an evidence-based appraisal of this field and develop a set of consensus recommendations to standardize care and direct further research for patients with cirrhosis and renal dysfunction.
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