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Are MELD and MELDNa Still Reliable Tools to Predict Mortality on the Liver Transplant Waiting List? Transplantation 2022; 106:2122-2136. [PMID: 35594480 DOI: 10.1097/tp.0000000000004163] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Liver transplantation is the only curative treatment for end-stage liver disease. Unfortunately, the scarcity of donor organs and the increasing pool of potential recipients limit access to this life-saving procedure. Allocation should account for medical and ethical factors, ensuring equal access to transplantation regardless of recipient's gender, race, religion, or income. Based on their short-term prognosis prediction, model for end-stage liver disease (MELD) and MELD sodium (MELDNa) have been widely used to prioritize patients on the waiting list for liver transplantation resulting in a significant decrease in waiting list mortality/removal. Recent concern has been raised regarding the prognostic accuracy of MELD and MELDNa due, in part, to changes in recipients' profile such as body mass index, comorbidities, and general condition, including nutritional status and cause of liver disease, among others. This review aims to provide a comprehensive view of the current state of MELD and MELDNa advantages and limitations and promising alternatives. Finally, it will explore future options to increase the donor pool and improve donor-recipient matching.
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Nguyen G, Lejeune M, Crichi B, Frere C. Hemostasis testing in patients with liver dysfunction: Advantages and caveats. World J Gastroenterol 2021; 27:7285-7298. [PMID: 34876789 PMCID: PMC8611202 DOI: 10.3748/wjg.v27.i42.7285] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/08/2021] [Accepted: 10/20/2021] [Indexed: 02/06/2023] Open
Abstract
Due to concomitant changes in pro- and anti-coagulant mechanisms, patients with liver dysfunction have a “rebalanced hemostasis”, which can easily be tipped toward either a hypo- or a hypercoagulable phenotype. Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities. Conventional coagulation screening tests, such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures. The introduction of global coagulation assays, such as viscoelastic testing (VET), has been an important step forward in the assessment of the overall hemostasis profile. A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings. The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.
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Affiliation(s)
- Guillaume Nguyen
- Department of Hematology, Trousseau Hospital, Assistance Publique Hôpitaux de Paris, Paris 75012, France
| | - Manon Lejeune
- Department of Hematology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris 75013, France
| | - Benjamin Crichi
- Department of Internal Medicine, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris 75010, France
| | - Corinne Frere
- Department of Hematology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris 75013, France
- Inserm UMRS_1166, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris 75013, France
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Coagulation, Vascular Morphology, and Vasculogenesis in Spinal Ligament Ossification Model Mice. Spine (Phila Pa 1976) 2021; 46:E802-E809. [PMID: 33337674 DOI: 10.1097/brs.0000000000003891] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN In vivo studies of the vascular system in ossification of the posterior longitudinal ligament (OPLL) model mice. OBJECTIVE The aim of this study was to investigate blood coagulability, vascular morphology, and vasculogenesis capability, known as venous thromboembolism (VTE) risk factors in the ossification model, tiptoe walking (ttw) mice. SUMMARY OF BACKGROUND DATA Patients with OPLL are more likely to develop VTE after spinal cord injury. Capillary mesh invasion of spinal ligaments precedes spinal ligament ossification in ttw mice. Investigation on vascular systems of ttw mice may contribute to clarifying its pathology. METHODS Coagulability of blood samples from ttw and C57BL/6 (WT) mice were evaluated at 8, 16, and 24 weeks of age. Vascular morphology was assessed from a Hematoxylin-Eosin stained section by measuring vessel area. A tube formation assay was performed with endothelial cells isolated from the aorta to assess vasculogenesis. RESULTS Prothrombin time was significantly shorter in ttw mice than in WT at 8 and 16 weeks. Fibrinogen had a greater increase in ttw mice than in WT at 16 weeks. The vascular area and vascular wall area were significantly smaller in ttw mice than in WT at all timepoints. The ratio of vascular wall area to vascular area was significantly smaller in ttw mice than in WT at 24 weeks. The endothelial cells from ttw mice formed significantly higher numbers of total branching points than WT cells. CONCLUSION Ossification model mice had impaired blood coagulation and vascular morphology and high capacity for vasculogenesis. With regard to the pathogenesis of VTE, ttw mice harbor an environment that promotes the development of VTE.Level of Evidence: N/A.
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Increased risk of acute liver failure by pain killer drugs in NAFLD: Focus on nuclear receptors and their coactivators. Dig Liver Dis 2021; 53:26-34. [PMID: 32546444 DOI: 10.1016/j.dld.2020.05.034] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 05/05/2020] [Accepted: 05/18/2020] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a global condition characterized by an accumulation of lipids in the hepatocytes. NAFLD ranges from simple steatosis, a reversible and relatively benign condition, to fibrosis with non-alcoholic steatohepatitis (NASH), potentially leading to cirrhosis and hepatocarcinoma. NAFLD can increase the susceptibility to severe liver injury with eventual acute liver failure induced by specific hepatotoxic drugs, including acetaminophen (APAP), which is commonly used as analgesic and antipyretic. Although several animal models have been used to clarify the predisposing role of hepatic steatosis to APAP intoxication, the exact mechanism is still not clear. Here, we shed a light into the association between NAFLD and APAP toxicity by examining the peculiar role of nuclear receptor peroxisome proliferator-activated receptor α (PPARα) and coactivator peroxisome proliferator-activated receptor gamma coactivator 1-β (PGC-1β) in driving fatty acid metabolism, inflammation and mitochondria redox balance. The knowledge of the mechanism that exposes patients with NAFLD to higher risk of acute liver failure by pain killer drug is the first step to eventually claim for a reduction of the maximal diurnal dose of APAP for subjects with liver steatosis.
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Mullier F, Paridaens M, Evrard J, Baudar J, Guldenpfennig M, Devroye C, Miller L, Chatelain B, Lessire S, Jacqmin H. Evaluation of a new thromboplastin reagent STA‐NeoPTimal on a STA R Max analyzer for the measurement of prothrombin time, international normalized ratio and extrinsic factor levels. Int J Lab Hematol 2020; 42:650-660. [DOI: 10.1111/ijlh.13236] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 04/17/2020] [Accepted: 04/21/2020] [Indexed: 11/28/2022]
Affiliation(s)
- François Mullier
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | | | | | - Justine Baudar
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Maité Guldenpfennig
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Celia Devroye
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Laurence Miller
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Bernard Chatelain
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Sarah Lessire
- Department of Anesthesiology Université catholique de LouvainCHU UCL NamurNamur Thrombosis and Hemostasis Center (NTHC)Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Hugues Jacqmin
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
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Wendon, J, Cordoba J, Dhawan A, Larsen FS, Manns M, Samuel D, Simpson KJ, Yaron I, Bernardi M. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol 2017; 66:1047-1081. [PMID: 28417882 DOI: 10.1016/j.jhep.2016.12.003] [Citation(s) in RCA: 602] [Impact Index Per Article: 75.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 12/07/2016] [Indexed: 02/06/2023]
Abstract
The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction. In the context of hepatological practice, however, ALF refers to a highly specific and rare syndrome, characterised by an acute abnormality of liver blood tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately necessary when the patient presents for medical attention. These, as well as additional clinical procedures will be the subject of these clinical practice guidelines.
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Lloyd-Donald P, Vasudevan A, Angus P, Gow P, Mårtensson J, Glassford N, Eastwood GM, Hart GK, Bellomo R. Coagulation in acutely ill patients with severe chronic liver disease: Insights from thromboelastography. J Crit Care 2017; 38:215-224. [PMID: 27978499 DOI: 10.1016/j.jcrc.2016.10.030] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 10/23/2016] [Accepted: 10/25/2016] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIMS There is controversy about the true coagulation state of acutely ill patients with chronic liver disease (CLD) due to simultaneous pro- and anticoagulant factor deficits and limitations of conventional coagulation tests (CCTs). Thromboelastography (TEG) may provide more physiologically relevant insights. METHODS In acutely ill patients with severe (Child-Pugh C) CLD, we conducted a prospective observational study of daily coagulation assessment with both CCTs and TEG. RESULTS We studied 34 patients with CLD on a total of 109 occasions (median of 3 samples per patient), comparing findings with 157 healthy controls. Conventional coagulation tests and TEG both demonstrated clear hypocoagulability. Thromboelastography-confirmed delayed clot formation was demonstrated by longer reaction time (1.1 minutes vs 0.6 minutes on rapid TEG; P<.01), longer kinetic time (2.9 minutes vs 1.3; P<.01), more acute α angle (65° vs 72.2°; P<.01), and longer activated clotting time (157 seconds vs 105 seconds; P<.01). Patients with CLD demonstrated weaker thrombus strength (maximum amplitude, 43.3 mm vs 61.8 mm; P<.01) and reduced clot lysis (0% vs 1% on rapid TEG; P<.01). CONCLUSIONS In acutely ill patients with CLD, TEG demonstrates delayed clot formation and weaker thrombus strength despite decreased clot lysis. This challenges the notion that such patients experience a balanced coagulation state, highlighting the complexity of their coagulopathies.
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Affiliation(s)
| | - Abhinav Vasudevan
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Peter Angus
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Paul Gow
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Johan Mårtensson
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia; Department of Anesthesia and Intensive Care Medicine, Karolinska University Hospital, Solna SE-171 77, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-171 77, Sweden
| | - Neil Glassford
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Glenn M Eastwood
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Graeme K Hart
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia; The University of Melbourne, Department of Intensive Care, Austin Hospital, Melbourne, Australia..
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Langness S, Costantini TW, Smith A, Bansal V, Coimbra R. Isolated traumatic brain injury in patients with cirrhosis: do different treatment paradigms result in increased mortality? Am J Surg 2016; 213:80-86. [PMID: 27421188 DOI: 10.1016/j.amjsurg.2016.06.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Revised: 06/03/2016] [Accepted: 06/05/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Cirrhosis is associated with increased mortality in trauma, yet its effects on outcomes after traumatic brain injury (TBI) are unclear. We hypothesized that cirrhosis adversely effects mortality and increases complications after TBI. METHODS Cirrhotic patients with isolated TBI were matched with noncirrhotic TBI patients in a 3:1 ratio based on age, sex, injury mechanism, and injury severity score at our academic, level 1 trauma center. RESULTS Of the 8,748 patients with isolated TBI, 65 patients had concurrent cirrhosis. Cirrhotic patients had increased mortality compared with matched controls (31% vs 17%, P = .03) and were less likely to undergo emergent neurosurgical operation (12% vs 25%, P = .03). There was no difference in admission Glasgow Coma Score, type of intracranial hemorrhage, length of stay, or complications between the groups. CONCLUSIONS Cirrhotic patients have increased mortality after TBI and were less likely to undergo operative intervention. New treatment paradigms may be needed to improve outcomes for cirrhotic patients suffering TBI.
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Affiliation(s)
- Simone Langness
- Department of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, University of California, San Diego, 200 W. Arbor Dr, #8220, San Diego, CA 92103, USA
| | - Todd W Costantini
- Department of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, University of California, San Diego, 200 W. Arbor Dr, #8220, San Diego, CA 92103, USA
| | - Alan Smith
- Department of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, University of California, San Diego, 200 W. Arbor Dr, #8220, San Diego, CA 92103, USA
| | - Vishal Bansal
- Department of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, University of California, San Diego, 200 W. Arbor Dr, #8220, San Diego, CA 92103, USA
| | - Raul Coimbra
- Department of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, University of California, San Diego, 200 W. Arbor Dr, #8220, San Diego, CA 92103, USA.
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