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Roy A, Kumar Y, Verma N. Coagulopathy in acute liver failure. Best Pract Res Clin Gastroenterol 2024; 73:101956. [PMID: 39709211 DOI: 10.1016/j.bpg.2024.101956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 10/22/2024] [Indexed: 12/23/2024]
Abstract
Acute liver failure (ALF) is a rare but rapidly progressing syndrome, marked by severe liver dysfunction and altered mental status. While definitions of ALF vary across different guidelines, with timelines ranging from 4 to 26 weeks between jaundice onset and encephalopathy, the key defining features remain encephalopathy and coagulopathy. Elevated coagulation markers, particularly prothrombin time and international normalized ratio, have traditionally been associated with bleeding risks. However, emerging evidence suggests a rebalanced state of coagulation in ALF, similar to cirrhosis, where bleeding risks-both spontaneous and procedural-are surprisingly low. Viscoelastic hemostatic assays and thrombin generation assays further confirm this rebalanced hemostatic state. Current guidelines for correcting coagulopathy in ALF remain limited, typically reserved for active bleeding or prior to high-risk invasive procedures.
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Affiliation(s)
- Akash Roy
- Institute of Gastrosciences and Liver Transplantation, Apollo Multi-speciality Hospitals, Kolkatta, India
| | - Yogendra Kumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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2
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Mi H, Fang J, Wu S, Mao S, Jiang W, Tong J, Lu C. Comparison of Postoperative Hemorrhage Risk After Partial Liver Transplantation Versus Whole Liver Transplantation: A Single-Center Experience. Transplant Proc 2023; 55:2444-2449. [PMID: 37891019 DOI: 10.1016/j.transproceed.2023.09.014] [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: 12/06/2022] [Revised: 07/18/2023] [Accepted: 09/22/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND We aimed to identify risk factors associated with reoperation for postoperative intraperitoneal hemorrhage (PIH) after orthotopic liver transplantation and investigate if partial liver transplantation (PLT) increases the risk of PIH. METHODS We retrospectively analyzed the medical records of 304 consecutive recipients who underwent orthotopic liver transplantation at the Affiliated Lihuili Hospital, Ningbo University, from January 2016 to July 2022. Data were compared between recipients who experienced PIH requiring reoperation and those who did not. Subgroup propensity score matching analysis was performed to assess the impact of PLT on PIH risk. Neither prisoners nor participants who were coerced or paid were used in the study. RESULTS Among the 304 recipients, 22 (7.2%) underwent reoperation for PIH. Multivariate analysis revealed that the recipient Model for End-Stage Liver Disease (MELD) score (odds ratio = 1.066, 95% CI [1.025-1.109], P = .001) and volume of intraoperative packed red blood cell transfusion (odds ratio = 1.089, 95% CI [1.032-1.481], P = .002) were independent risk factors for PIH. No significant differences were observed in the risk of PIH between PLT and whole liver transplantation. CONCLUSION Preoperative MELD score and intraoperative packed red blood cell transfusion should be carefully considered to manage the risk of PIH in liver transplantation recipients. Partial liver transplantation, a crucial approach for addressing donor shortages, does not increase the risk of reoperation for PIH in recipients.
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Affiliation(s)
- Hongchao Mi
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Jiongze Fang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Shengdong Wu
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Shuqi Mao
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Wei Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Jingshu Tong
- School of Medicine, Ningbo University, Ningbo, China
| | - Caide Lu
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
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Terrault NA, Francoz C, Berenguer M, Charlton M, Heimbach J. Liver Transplantation 2023: Status Report, Current and Future Challenges. Clin Gastroenterol Hepatol 2023; 21:2150-2166. [PMID: 37084928 DOI: 10.1016/j.cgh.2023.04.005] [Citation(s) in RCA: 112] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 03/29/2023] [Accepted: 04/04/2023] [Indexed: 04/23/2023]
Abstract
Liver transplantation offers live-saving therapy for patients with complications of cirrhosis and stage T2 hepatocellular carcinoma. The demand for organs far outstrips the supply, and innovations aimed at increasing the number of usable deceased donors as well as alternative donor sources are a major focus. The etiologies of cirrhosis are shifting over time, with more need for transplantation among patients with alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease and less for viral hepatitis, although hepatitis B remains an important indication for transplant in countries with high endemicity. The rise in transplantation for alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease has brought attention to how patients are selected for transplantation and the strategies needed to prevent recurrent disease. In this review, we present a status report on the most pressing topics in liver transplantation and future challenges.
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Affiliation(s)
- Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California.
| | - Claire Francoz
- Liver Intensive Care and Liver Transplantation Unit, Hepatology, Hospital Beaujon, Clichy, France
| | - Marina Berenguer
- Hepatology and Liver Transplantation Unit, Hospital Universitario la Fe - IIS La Fe Valencia; CiberEHD and University of Valencia, Valencia, Spain
| | - Michael Charlton
- Transplantation Institute, University of Chicago, Chicago, Illinois
| | - Julie Heimbach
- William von Liebig Center for Transplantation, Mayo Clinic Rochester, Minnesota
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4
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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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Curakova Ristovska E, Genadieva-Dimitrova M. Prognostic value of von-Willebrand factor in patients with liver cirrhosis and its relation to other prognostic indicators. World J Hepatol 2022; 14:812-826. [PMID: 35646274 PMCID: PMC9099105 DOI: 10.4254/wjh.v14.i4.812] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/18/2021] [Accepted: 03/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Von-Willebrand factor (vWF) disposes certain prognostic value in patients with liver cirrhosis, but its relation to other prognostic indicators has not been fully investigated.
AIM To analyze the relation between vWF and other prognostic indicators in cirrhotic patients and to evaluate its prognostic value for mortality.
METHODS This analytic prospective study was carried out in a tertiary center and initially enrolled 71 patients with liver cirrhosis and portal hypertension. It analyzed the relation between vWF and the stage of the disease and several inflammatory and prognostic indicators. The prospective analysis, performed on a sample of 63 patients, evaluated the association between the selected variables [vWF, Model for End-stage Liver Disease (MELD) score, C-reactive protein (CRP), ferritin, vitamin D, activated partial thromboplastin time, thrombin time, D-dimer concentration] and the survival time as well as their predictive value in terms of 3-mo, 6-mo and 1-year mortality.
RESULTS vWF was significantly higher in patients with higher Child-Turcotte-Pugh class (P = 0.0045), MELD group (P = 0.0057), ferritin group (P = 0.0278), and D-dimer concentration (P = 0.0232). vWF significantly correlated with D-dimer concentration, ferritin, CRP, International Normalized Ratio, and MELD, Child-Turcotte-Pugh, Sequential Organ Failure Assessment, and CLIF-consortium organ failure (CLIF-C OF) scores. vWF, MELD score, and CRP were significantly associated with death and were significant predictors of 3-mo, 6-mo, and 1-year mortality. Each vWF unit significantly increased the probability for 3-mo mortality by 1.005 times (P = 0.008), for 6-mo mortality by 1.006 times (P = 0.005), and for 1-year mortality by 1.007 times (P = 0.002). There was no significant difference between the diagnostic performance of vWF and MELD score and also between vWF and CRP regarding the 3-mo, 6-mo, and 1-year mortality.
CONCLUSION In patients with liver cirrhosis, vWF is significantly related to other prognostic indicators and is a significant predictor of 3-mo, 6-mo, and 1-year mortality similar to MELD score and CRP.
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Affiliation(s)
- Elena Curakova Ristovska
- Intensive Care Unit, University Clinic for Gastroenterohepatology, Skopje 1000, North Macedonia
- Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Skopje 1000, North Macedonia
| | - Magdalena Genadieva-Dimitrova
- Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Skopje 1000, North Macedonia
- Hepatology Department, University Clinic for Gastroenterohepatology, Skopje 1000, North Macedonia
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Kezer CA, Buryska SM, Ahn JC, Harmsen WS, Dunn W, Singal AK, Arab JP, Díaz LA, Arnold J, Kamath PS, Shah VH, Simonetto DA. The Mortality Index for Alcohol-Associated Hepatitis: A Novel Prognostic Score. Mayo Clin Proc 2022; 97:480-490. [PMID: 35181163 DOI: 10.1016/j.mayocp.2021.10.026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 09/17/2021] [Accepted: 10/26/2021] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To develop a new scoring system that more accurately predicts 30-day mortality in patients with alcohol-associated hepatitis (AH). METHODS A cohort of consecutive adults diagnosed with AH at a single academic center from January 1, 1998, to December 31, 2018, was identified for model derivation. Multivariate logistic regression was used to create a new scoring system to predict 30-day mortality. External validation of this score was performed on a multicenter retrospective cohort. RESULTS In the derivation cohort of 266 patients, the 30-day mortality rate was 19.2%. The following variables were found to be significantly associated with mortality on multivariate analysis: age (P=.002), blood urea nitrogen (P=.003), albumin (P=.01), bilirubin (P=.02), and international normalized ratio (P=.001). A model incorporating these variables, entitled the Mortality Index for Alcohol-Associated Hepatitis (MIAAH), achieved a C statistic of 0.86. Comparison of the accuracy of the MIAAH to existing prognostic models, including the Model for End-Stage Liver Disease and Maddrey Discriminant Function, showed that the highest concordance was achieved by the MIAAH and that this difference was significant. In the validation cohort of 249 patients, the MIAAH C statistic decreased to 0.73 and was found to be significantly superior to the Maddrey Discriminant Function but not to the Model for End-Stage Liver Disease. CONCLUSION The MIAAH competes with the current prognostication models and is at a minimum as accurate as these existing scores in identifying patients with AH at high risk of short-term mortality. Furthermore, the MIAAH demonstrates advantageous performance characteristics in its ability to increasingly accurately dichotomize patients into those at highest risk of death and those likely to survive.
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Affiliation(s)
| | - Seth M Buryska
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Joseph C Ahn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | - Winston Dunn
- Division of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City
| | - Ashwani K Singal
- University of South Dakota Sanford School of Medicine and Transplant Hepatologist, Avera Transplant Institute, Sioux Falls
| | - Juan P Arab
- Department of Gastroenterology and Hepatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis A Díaz
- Department of Gastroenterology and Hepatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jorge Arnold
- Department of Gastroenterology and Hepatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Vijay H Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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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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Blasi A, Cardenas A. Invasive Procedures in Patients with Cirrhosis: A Clinical Approach Based on Current Evidence. Clin Liver Dis 2021; 25:461-470. [PMID: 33838861 DOI: 10.1016/j.cld.2021.02.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The aim on of this article is to provide an update on the coagulation disturbances of patients with cirrhosis. It summarizes basic concepts of coagulation in cirrhosis, available tests used to predict bleeding, procedures and risk of bleeding, and the rationale and expert-based recommendations of prophylactic measures for patients with cirrhosis who undergo invasive procedures.
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Affiliation(s)
- Annabel Blasi
- Anesthesia Department, Hospital Clinic of Barcelona, Villarroel 170, Barcelona 08036, Spain; Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Andres Cardenas
- Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain; GI/Liver Unit, Institut Clínic de Malalties Digestives i Metabòliques, Hospital Clínic, Barcelona, Spain; Department of Medicine, University of Barcelona, Spain.
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9
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Ivanics T, Abreu P, De Martin E, Sapisochin G. Changing Trends in Liver Transplantation: Challenges and Solutions. Transplantation 2021; 105:743-756. [PMID: 32910093 DOI: 10.1097/tp.0000000000003454] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Despite improvements in postliver transplant outcomes through refinements in perioperative management and surgical techniques, several changing trends in liver transplantation have presented challenges. Mortality on the waitlist remains high. In the United States, Europe, and the United Kingdom, there is an increasing need for liver transplantation, primarily as a result of increased incidence of nonalcoholic steatohepatitis-related cirrhosis and cancer indications. Meanwhile, donor suitability has decreased, as donors are often older and have more comorbidities. Despite a mismatch between organ need and availability, many organs are discarded. Notwithstanding this, many solutions have been developed to overcome these challenges. Innovative techniques in allograft preservation, viability assessment, and reconditioning have allowed the use of suboptimal organs with adequate results. Refinements in surgical procedures, including live donor liver transplantations, have increased the organ pool and are decreasing the time and mortality on the waitlist. Despite many challenges, a similar number of solutions and prospects are on the horizon. This review seeks to explore the changing trends and challenges in liver transplantation and highlight possible solutions and future directions.
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Affiliation(s)
- Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Phillipe Abreu
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Eleonora De Martin
- APHP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM 1193, Université Paris-Sud, DHU Hepatinov, Villejuif, France
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
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Kim A, Niu B, Woreta T, Chen PH. Clinical Considerations of Coagulopathy in Acute Liver Failure. J Clin Transl Hepatol 2020; 8:407-413. [PMID: 33447524 PMCID: PMC7782116 DOI: 10.14218/jcth.2020.00058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 08/08/2020] [Accepted: 08/31/2020] [Indexed: 12/12/2022] Open
Abstract
Acute liver failure (ALF) is the rapid onset of severe liver dysfunction, defined by the presence of hepatic encephalopathy and impaired synthetic function (international normalized ratio of ≥1.5) in the absence of underlying liver disease. The elevated international normalized ratio value in ALF is often misinterpreted as an increased hemorrhagic tendency, which can lead to inappropriate, prophylactic transfusions of blood products. However, global assessments of coagulopathy via viscoelastic tests or thrombin generation assay suggest a reestablished hemostatic, or even hypercoagulable, status in patients with ALF. Although the current versions of global assays are not perfect, they can provide more nuanced insights into the hemostatic system in ALF than the conventional measures of coagulopathy.
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Affiliation(s)
- Ahyoung Kim
- Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Bolin Niu
- Division of Gastroenterology & Hepatology, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Tinsay Woreta
- Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Po-Hung Chen
- Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Correspondence to: Po-Hung Chen, Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Suite 429, Baltimore, MD 21287, USA. Tel: +1-410-614-3530, Fax: +1-410-550-7861, E-mail:
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11
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Hsu YC, Yang YY, Tsai IT. Lymphocyte-to-monocyte ratio predicts mortality in cirrhotic patients with septic shock. Am J Emerg Med 2020; 40:70-76. [PMID: 33348227 DOI: 10.1016/j.ajem.2020.11.071] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/28/2020] [Accepted: 11/29/2020] [Indexed: 11/29/2022] Open
Abstract
INTRODUCTION Patients with liver cirrhosis and septic shock have a significantly higher risk of mortality and morbidity compared with non-cirrhotic patients. The peripheral blood lymphocyte-to-monocyte ratio (LMR) can determine the prognosis of cirrhotic patients. Our study aimed to investigate the usefulness of LMR as a predictive marker of mortality risk in cirrhotic patients with septic shock. METHODS This single-center, retrospective case-control study included adult patients who visited the emergency department between January 1, 2018 and June 30, 2020 and diagnosed with liver cirrhosis and septic shock. They were divided into survivor and non-survivor groups according to their survival status at the 60-day follow-up. We used a Cox proportional hazards regression model to identify independent factors associated with mortality risk and tested the mortality discriminative ability of those factors using the area under a receiver operating characteristic curve. RESULTS A total of 93 patients were eligible for this study. Compared with the patients in the survivor group, those in the non-survivor group had significantly higher Child-Pugh (11 ± 2 vs. 9 ± 2, p < 0.001) and MELD scores (29 ± 6 vs. 22 ± 8, p < 0.001), higher serum international normalized ratio (1.7 vs.1.4, p = 0.03), bilirubin (6.0 vs. 3.3 mg/dL, p = 0.02), lactate (5.4 vs. 2.7 mmol/L, p < 0.01), creatinine (2.2 vs. 1.6 mg/dL, p = 0.04), higher neutrophil-to-lymphocyte ratio (13.0 vs. 10.3, p = 0.02), and lower LMR (1.1 vs. 2.3, p < 0.01). The LMR (adjusted hazard ratio [aHR] = 1.54, p = 0.01) and lactate (aHR = 1.03, p < 0.01) were identified as independent predictive factors for mortality in the multivariate regression model. Furthermore, LMR (area under curve [AUC]: 0.87) revealed a superior discrimination ability in mortality prediction compared with the Child-Pugh (AUC: 0.72) and MELD (AUC: 0.76) scores. CONCLUSIONS The LMR can be used to predict mortality risk in cirrhotic patients with septic shock.
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Affiliation(s)
- Yin-Chou Hsu
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan
| | - Yong-Ye Yang
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - I-Ting Tsai
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine for International Student, I-Shou University, Kaohsiung, Taiwan.
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12
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Abdel-Wahab R, Hassan MM, George B, Carmagnani Pestana R, Xiao L, Lacin S, Yalcin S, Shalaby AS, Al-Shamsi HO, Raghav K, Wolff RA, Yao JC, Girard L, Haque A, Duda DG, Dima S, Popescu I, Elghazaly HA, Vauthey JN, Aloia TA, Tzeng CW, Chun YS, Rashid A, Morris JS, Amin HM, Kaseb AO. Impact of Integrating Insulin-Like Growth Factor 1 Levels into Model for End-Stage Liver Disease Score for Survival Prediction in Hepatocellular Carcinoma Patients. Oncology 2020; 98:836-846. [PMID: 33027788 PMCID: PMC7704605 DOI: 10.1159/000502482] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 03/27/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Liver reserve affects survival in hepatocellular carcinoma (HCC). Model for End-Stage Liver Disease (MELD) score is used to predict overall survival (OS) and to prioritize HCC patients on the transplantation waiting list, but more accurate models are needed. We hypothesized that integrating insulin-like growth factor 1 (IGF-1) levels into MELD score (MELD-IGF-1) improves OS prediction as compared to MELD. METHODS We measured plasma IGF-1 levels in training (n = 310) and validation (n = 155) HCC cohorts and created MELD-IGF-1 score. Cox models were used to determine the association of MELD and MELD-IGF-1 with OS. Harrell's c-index was used to compare the predictive capacity. RESULTS IGF-1 was significantly associated with OS in both cohorts. Patients with an IGF-1 level of ≤26 ng/mL in the training cohort and in the validation cohorts had significantly higher hazard ratios than patients with the same MELD but IGF-1 >26 ng/mL. In both cohorts, MELD-IGF-1 scores had higher c-indices (0.60 and 0.66) than MELD scores (0.58 and 0.60) (p < 0.001 in both cohorts). Overall, 26% of training and 52.9% of validation cohort patients were reclassified into different risk groups by MELD-IGF-1 (p < 0.001). CONCLUSIONS After independent validation, the MELD-IGF-1 could be used to risk-stratify patients in clinical trials and for priority assignment for patients on liver transplantation waiting list.
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Affiliation(s)
- Reham Abdel-Wahab
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Department of Clinical Oncology, Assiut University, Assiut, Egypt
| | - Manal M Hassan
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Bhawana George
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Roberto Carmagnani Pestana
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Lianchun Xiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Sahin Lacin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Hacettepe University Institute of Cancer, Ankara, Turkey
| | - Suayib Yalcin
- Hacettepe University Institute of Cancer, Ankara, Turkey
| | - Ahmed S Shalaby
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Humaid O Al-Shamsi
- Medical Oncology Department, Alzahra Hospital Dubai, Dubai, United Arab Emirates
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Emirates Oncology Society, Dubai, United Arab Emirates
| | - Kanwal Raghav
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Robert A Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - James C Yao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Lauren Girard
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Abedul Haque
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Dan G Duda
- Steele Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Simona Dima
- Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Irinel Popescu
- Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | | | - Jean-Nicolas Vauthey
- Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Thomas A Aloia
- Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ching-Wei Tzeng
- Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Yun Shin Chun
- Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Asif Rashid
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jeffrey S Morris
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Hesham M Amin
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas, USA
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA,
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13
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Association between intraoperative rotational thromboelastometry or conventional coagulation tests and bleeding in liver transplantation: an observational exploratory study. Anaesth Crit Care Pain Med 2020; 39:765-770. [PMID: 33011332 DOI: 10.1016/j.accpm.2020.07.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 07/16/2020] [Accepted: 07/16/2020] [Indexed: 01/23/2023]
Abstract
INTRODUCTION Liver transplantation is associated with major blood loss and transfusions. Our objective was to evaluate the association between coagulation results (rotational thromboelastometry (ROTEM) and conventional coagulation tests) and intraoperative bleeding or perioperative red blood cell (RBC) transfusions in liver transplantation. METHODS We measured ROTEM values and conventional coagulation tests at the beginning of surgery, after graft reperfusion and at the end of surgery. We did bivariate correlation and multivariable regression analyses to explore the association between test results and either intraoperative bleeding or perioperative RBC transfusions. RESULTS We enrolled 75 consecutive patients. Median [Q1-Q3] intraoperative blood loss was 1400 mL [675-2300] and 59% of patients did not receive any RBC transfusion either intraoperatively or postoperatively. In multivariable analyses, FIBTEM maximal clot firmness (MCF) measured at the beginning of surgery was associated with lower intraoperative blood loss (ß = -106 mL for each mm; 95% CI, -203 to -9 mL). Both a higher haemoglobin concentration (multiplicative factor = 0.89 for each g/L; 95% CI, 0.84 to 0.95) and FIBTEM MCF measured at the end of surgery (multiplicative factor = 0.68 for each mm; 95% CI, 0.48 to 0.95) were associated with fewer postoperative RBC transfusions. CONCLUSION FIBTEM MCF was strongly associated with intraoperative blood loss and postoperative transfusions while other coagulation results were not. This study might inform future clinical trials on ROTEM-based interventions in liver transplantation. STUDY REGISTRATION Clinical Trials.gov: NCT02356068.
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Locke JE, Shelton BA, Olthoff KM, Pomfret EA, Forde KA, Sawinski D, Gray M, Ascher NL. Quantifying Sex-Based Disparities in Liver Allocation. JAMA Surg 2020; 155:e201129. [PMID: 32432699 DOI: 10.1001/jamasurg.2020.1129] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Importance Differences in local organ supply and demand have introduced geographic inequities in the Model for End-stage Liver Disease (MELD) score-based liver allocation system, prompting national debate and patient-initiated lawsuits. No study to our knowledge has quantified the sex disparities in allocation associated with clinical vs geographic characteristics. Objective To estimate the proportion of sex disparity in wait list mortality and deceased donor liver transplant (DDLT) associated with clinical and geographic characteristics. Design, Setting, and Participants This retrospective cohort study used adult (age ≥18 years) liver-only transplant listings reported to the Organ Procurement and Transplantation Network from June 18, 2013, through March 1, 2018. Exposure Liver transplant waiting list. Main Outcomes and Measures Primary outcomes included wait list mortality and DDLT. Multivariate Cox proportional hazards regression models were constructed, and inverse odds ratio weighting was used to estimate the proportion of disparity across geographic location, MELD score, and candidate anthropometric and liver measurements. Results Among 81 357 adults wait-listed for liver transplant only, 36.1% were women (mean [SD] age, 54.7 [11.3] years; interquartile range, 49.0-63.0 years) and 63.9% were men (mean [SD] age, 55.7 [10.1] years; interquartile range, 51.0-63.0 years). Compared with men, women were 8.6% more likely to die while on the waiting list (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.04-1.18) and were 14.4% less likely to receive a DDLT (aHR, 0.86; 95% CI, 0.84-0.88). In the geographic domain, organ procurement organization was the only variable that was significantly associated with increased disparity between female sex and wait list mortality (22.1% increase; aHR, 1.22; 95% CI, 1.09-1.30); no measure of the geographic domain was associated with DDLT. Laboratory and allocation MELD scores were associated with increases in disparities in wait list mortality: 1.14 (95% CI, 1.09-1.19; 50.1% increase among women) and DDLT: 0.87 (95% CI, 0.86-0.88; 10.3% increase among women). Candidate anthropometric and liver measurements had the strongest association with disparities between men and women in wait list mortality (125.8% increase among women) and DDLT (49.0% increase among women). Conclusions and Relevance Our findings suggest that addressing geographic disparities alone may not mitigate sex-based disparities, which were associated with the inability of the MELD score to accurately estimate disease severity in women and to account for candidate anthropometric and liver measurements in this study.
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Affiliation(s)
- Jayme E Locke
- Division of Transplantation, Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham
| | - Brittany A Shelton
- Division of Transplantation, Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham
| | - Kim M Olthoff
- Division of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Elizabeth A Pomfret
- Division of Transplantation, Department of Surgery, University of Colorado School of Medicine, Aurora
| | - Kimberly A Forde
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Deirdre Sawinski
- Division of Renal and Electrolytes, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Meagan Gray
- Division of Transplantation, Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham
| | - Nancy L Ascher
- Division of Transplantation, Department of Surgery, University of California School of Medicine, San Francisco, San Francisco
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15
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Verna EC, Connelly C, Dove LM, Adem P, Babic N, Corsetti J, Faix J, Hayden JA, Lifshitz M, Stotler B, Jin Z, Mohan S, Emond JC, Hod EA, Kratz A. Center-related Bias in MELD Scores Within a Liver Transplant UNOS Region: A Call for Standardization. Transplantation 2020; 104:1396-1402. [DOI: 10.1097/tp.0000000000003031] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
Disorders of the mesenteric, portal, and hepatic veins and mesenteric and hepatic arteries have important clinical consequences and may lead to acute liver failure, chronic liver disease, noncirrhotic portal hypertension, cirrhosis, and hepatocellular carcinoma. Although literature in the field of vascular liver disorders is scant, these disorders are common in clinical practice, and general practitioners, gastroenterologists, and hepatologists may benefit from expert guidance and recommendations for management of these conditions. These guidelines represent the official practice recommendations of the American College of Gastroenterology. Key concept statements based on author expert opinion and review of literature and specific recommendations based on PICO/GRADE analysis have been developed to aid in the management of vascular liver disorders. These recommendations and guidelines should be tailored to individual patients and circumstances in routine clinical practice.
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17
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Bulut Y, Sapru A, Roach GD. Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies. Front Pediatr 2020; 8:618119. [PMID: 33425821 PMCID: PMC7786276 DOI: 10.3389/fped.2020.618119] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/08/2020] [Indexed: 12/12/2022] Open
Abstract
Pediatric Acute Liver Failure (PALF) is a rapidly progressive clinical syndrome encountered in the pediatric ICU which may rapidly progress to multi-organ dysfunction, and on occasion to life threatening cerebral edema and hemorrhage. Pediatric Acute Liver Failure is defined as severe acute hepatic dysfunction accompanied by encephalopathy and liver-based coagulopathy defined as prolongation of International Normalized Ratio (INR) >1.5. However, coagulopathy in PALF is complex and warrants a deeper understanding of the hemostatic balance in acute liver failure. Although an INR value of >1.5 is accepted as the evidence of coagulopathy and has historically been viewed as a prognostic factor of PALF, it may not accurately reflect the bleeding risk in PALF since it only measures procoagulant factors. Paradoxically, despite the prolongation of INR, bleeding risk is lower than expected (around 5%). This is due to "rebalanced hemostasis" due to concurrent changes in procoagulant, anticoagulant and fibrinolytic systems. Since the liver is involved in both procoagulant (Factors II, V, IX, XI, and fibrinogen) and anticoagulant (Protein C, Protein S, and antithrombin) protein synthesis, PALF results in "rebalanced hemostasis" or even may shift toward a hypercoagulable state. In addition to rebalanced coagulation there is altered platelet production due to decreased thrombopoietin production by liver, increased von Willebrand factor from low grade endothelial cell activation, and hyperfibrinolysis and dysfibrinogenemia from altered synthetic liver dysfunction. All these alterations contribute to the multifactorial nature of coagulopathy in PALF. Over exuberant use of prophylactic blood products in patients with PALF may contribute to morbidities such as fluid overload, transfusion-associated lung injury, and increased thrombosis risk. It is essential to use caution when using INR values for plasma and factor administration. In this review we will summarize the complexity of coagulation in PALF, explore "rebalanced hemostasis," and discuss the limitations of current coagulation tests. We will also review strategies to accurately diagnose the coagulopathy of PALF and targeted therapies.
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Affiliation(s)
- Yonca Bulut
- Department of Pediatrics, Division of Critical Care, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Anil Sapru
- Department of Pediatrics, Division of Critical Care, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Gavin D Roach
- Division of Pediatric Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
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18
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To Thine Own Self Be True. Transplantation 2019; 104:1326-1327. [PMID: 31688806 DOI: 10.1097/tp.0000000000003037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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19
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Abstract
Identifying the optimal allocation policy with regard to hepatocellular carcinoma has been a persistent and evolving challenge. The current criteria for LT for HCC endorsed by the United Network of Organ Sharing (UNOS) are based on the Milan Criteria: a solitary tumor < 5 cm, or maximum of three tumors ≤ 3 cm each, without vascular invasion or evidence of extrahepatic spread. Contraindications to HCC exception points include: stage 1 HCC, ruptured HCC, extrahepatic HCC, and main portal or hepatic vein HCC invasion. Based upon projected waitlist dropout rates due to tumor growth, patients with HCC are assigned MELD standardized exception points. In addition to tumor size and number, AFP levels are an important predictor of recurrence of HCC following liver transplantation. Standardized exception points for HCC patients are not awarded to patients with AFP levels > 1000 ng/mL that do not decrease to < 500 ng/mL with treatment. Appeals for MELD exception points for patients with HCC vary widely between UNOS regions, with success of nonstandardized exception point appeals varying from 3.1 to 21% between regions. In an effort to make prioritization for HCC more consistent, a national liver review board (NLRB)is being convened that will focus on developing a national guidance for assessing common requests and addressing exception points, including for HCC.
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20
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Yoon J, Cheon J, Choi YJ, Byeon G, Ahn J, Choi E, Park JY. The correlation between conventional coagulation tests and thromboelastography in each phase of liver transplantation. Clin Transplant 2019; 33:e13478. [DOI: 10.1111/ctr.13478] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 12/18/2018] [Accepted: 12/23/2018] [Indexed: 11/27/2022]
Affiliation(s)
- Ji‐Uk Yoon
- Department of Anesthesia and Pain Medicine Pusan National University Yangsan Hospital Yangsan Korea
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| | - Ji‐Hyun Cheon
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| | - Yoon Ji Choi
- Department of Anesthesiology and Pain Medicine Korea University Ansan Hospital Ansan Korea
| | - Gyeong‐Jo Byeon
- Department of Anesthesia and Pain Medicine Pusan National University Yangsan Hospital Yangsan Korea
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| | - Ji‐Hye Ahn
- Department of Dental Anesthesia and Pain Medicine, School of Dentistry Pusan National University, Dental Research Institute Yangsan Korea
| | - Eun‐Ji Choi
- Department of Anesthesia and Pain Medicine Pusan National University Yangsan Hospital Yangsan Korea
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| | - Ju Yeon Park
- Department of Anesthesia and Pain Medicine Pusan National University Yangsan Hospital Yangsan Korea
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
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21
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Hawkins RB, Raymond SL, Hartjes T, Efron PA, Larson SD, Andreoni KA, Thomas EM. Review: The Perioperative Use of Thromboelastography for Liver Transplant Patients. Transplant Proc 2018; 50:3552-3558. [PMID: 30577236 DOI: 10.1016/j.transproceed.2018.07.032] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 07/09/2018] [Accepted: 07/18/2018] [Indexed: 12/12/2022]
Abstract
Thromboelastography (TEG) is a viscoelastic test that allows rapid evaluation of clot formation and fibrinolysis from a sample of whole blood. TEG is increasingly utilized to guide blood product resuscitation in surgical patients and transfusions for liver transplant patients. Patients with severe liver failure have significant derangement of their clotting function due to impaired production of procoagulant and anticoagulant factors. Traditional coagulation studies are limited by the short time needed for the result and provide little information about the dynamics and strength of clot formation. In addition, traditional coagulation studies do not correlate well with bleeding episodes and may lead to over-transfusion of various blood products. Evidence is less robust regarding the use of TEG for transfusion management decisions in severe liver failure patients awaiting, undergoing, or immediately after liver transplant surgery. However, the available evidence suggests that systematic implementation of TEG rather than traditional coagulation studies results in the administration of fewer blood products without increased mortality or complications. The purpose of this study is to review the literature regarding the use of TEG in liver failure patients prior to liver transplant, intraoperatively, and postoperatively. Additional high-quality randomized controlled studies should be performed to evaluate the use of TEG to guide transfusion decisions, particularly in the postoperative period following liver transplantation.
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Affiliation(s)
- R B Hawkins
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA
| | - S L Raymond
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA
| | - T Hartjes
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA; University of Florida College of Nursing, Gainesville, FL, USA
| | - P A Efron
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA
| | - S D Larson
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA
| | - K A Andreoni
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA
| | - E M Thomas
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
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22
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Pilarczyk K, Carstens H, Heckmann J, Canbay A, Koch A, Pizanis N, Jakob H, Kamler M. The aspartate transaminase/alanine transaminase (DeRitis) ratio predicts mid-term mortality and renal and respiratory dysfunction after left ventricular assist device implantation. Eur J Cardiothorac Surg 2018; 52:781-788. [PMID: 29156019 DOI: 10.1093/ejcts/ezx247] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 04/30/2017] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES Preoperative liver dysfunction is a well-known risk factor for adverse events after major surgery. However, there is only little data regarding the precise role of the Model of End-Stage Liver Disease (MELD) score and the De Ritis ratio (DRR, alanine transaminase/aspartate aminotransferase) as a predictor for outcome after left ventricular assist device (LVAD) implantation. METHODS A retrospective analysis of all patients undergoing LVAD implantation at our institution between January 2012 and August 2014 was performed. The primary outcome was survival at 180 days after surgery. RESULTS During the observation period, 63 patients underwent LVAD implantation (mean age 59.9 ± 8.3 years, 50% male). Mean preoperative ejection fraction was 16.3 ± 7.7, 13 patients required preoperative renal replacement therapy and 9 patients were on extracorporeal life support. Mean Interagency Registry for Mechanically Assisted Circulatory Support level was 2.8 ± 1.3, mean preoperative MELD was 12.7 ± 7.2, mean preoperative DRR was 2.01 ± 4.4. Aspartate aminotransferase (102 ± 220.8 vs 57.8 ± 123.4 U/l, P = 0.041), MELD score (16.1 ± 8.8 vs 11.4 ± 6.1, P = 0.017) and DRR (4.2 ± 7.8 vs 1.1 ± 1.1, P = 0.001) were significantly higher in non-survivors than in survivors after 180 days. Using logistic regression analyses, a DRR >1.37 was an independent predictor for 30-day mortality [odds ratio (OR) 4.5] and 180-day mortality (OR 4.1). In addition, the DRR was associated with postoperative acute kidney injury with need for renal replacement therapy (OR 4.2) and prolonged postoperative ventilation time >72 h (OR 3.8). Using receiver operator characteristics analyses, DRR showed a sensitivity of 0.80 and a specificity of 0.81 (area under the curve 0.834, cut-off 1.37) for 180-day mortality. CONCLUSIONS The DRR is predictive of early and mid-term mortality as well as relevant morbidities in patients undergoing LVAD implantation. Therefore, the DRR should be considered within the preoperative risk stratification and patient selection for LVAD implantation.
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Affiliation(s)
- Kevin Pilarczyk
- Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Essen, Germany.,Department of Critical Care Medicine, imland Klinik Rendsburg, Rendsburg, Germany
| | - Henning Carstens
- Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Essen, Germany
| | - Jens Heckmann
- Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Essen, Germany
| | - Ali Canbay
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Achim Koch
- Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Essen, Germany
| | - Nikolaus Pizanis
- Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Essen, Germany
| | - Heinz Jakob
- Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Essen, Germany
| | - Markus Kamler
- Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Essen, Germany
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Laubham M, Kallwitz E. Coagulation in chronic liver disease and the use of prothrombin complex concentrate for an emergent procedure: a case report and review of literature. J Community Hosp Intern Med Perspect 2018; 8:138-141. [PMID: 29915653 PMCID: PMC5998277 DOI: 10.1080/20009666.2018.1466600] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 04/12/2018] [Indexed: 12/25/2022] Open
Abstract
Synthetic dysfunction observed in cirrhosis results in altered production of procoagulants and anticoagulants that can lead to both bleeding and thrombotic events, respectively. In patients with decompensated cirrhosis, frequent hospital visits often require bedside procedures such as diagnostic paracenteses, thoracenteses and endoscopy. It can be difficult to determine at what coagulation threshold procedures can safely be performed. Currently, the most common therapies given pre-procedurally include fresh frozen plasma (FFP) and vitamin K. The effectiveness of these treatments is estimated by international normalized ratio (INR), an imprecise measure of coagulation in the setting of cirrhosis. Transfusion with FFP may lead to detrimental side effects, including worsening volume overload and increased portal hypertension. We present a case of a 60-year-old patient intubated for acute hypoxic respiratory failure secondary to volume overload who subsequently developed bilateral pneumothoraces, requiring immediate chest tube placement. In this case, the patient had ongoing hepatic decompensation with volume overload and acute worsening of coagulopathy with an INR of 4.2. In this setting, 4-Factor Prothrombin Complex Concentrate (4F-PCC) was chosen to correct coagulation parameters with a low infusion volume. One hour following administration, INR was 1.5. Chest tubes were placed bilaterally and oxygenation improved without bleeding complications. While the data is still lacking, 4F-PCC may be considered for urgent and emergency situations in cirrhotic patients.
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Affiliation(s)
- Matthew Laubham
- Department of Hepatology & Department of Internal Medicine, Loyola University Medical Center, Maywood, IL, USA
| | - Eric Kallwitz
- Department of Hepatology & Department of Internal Medicine, Loyola University Medical Center, Maywood, IL, USA
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Abbas M, Abbas Z. Serum cholinesterase: A predictive biomarker of hepatic reserves in chronic hepatitis D. World J Hepatol 2017; 9:967-972. [PMID: 28839517 PMCID: PMC5550762 DOI: 10.4254/wjh.v9.i22.967] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 03/19/2017] [Accepted: 06/12/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODS In an observational, cross-sectional and retrospective study, consecutive patients with hepatitis D cirrhosis were evaluated. Demographic, clinical and laboratory parameters were recorded. Serum cholinesterase levels were correlated with existing scoring models for chronic liver disease and Liver function tests. Receiver operating characteristic (ROC) curves were constructed to find an optimal cholinesterase level predicting ascites, Child Turcotte Pugh (CTP) score ≥ 10, model for end stage liver disease (MELD) score ≥ 15, baseline-event-anticipation (BEA) score for hepatitis D ≥ 5 and the aspartate transaminase to Platelet Ratio Index (APRI) ≥ 1.5. RESULTS This study investigated 233 patients with chronic liver disease due to hepatitis D; 192 were male, median age 42 (16-69 years). Fifty patients had ascites and 15 had encephalopathy. One hundred and sixty-seven (71.7%) were in Child class A, 52 (22.3%) in Child class B and 14 (5.0%) in class C. A MELD score of 15 or more was seen in 24 patients. Cholinesterase levels correlated well with the INR, albumin, CTP score, MELD, MELD sodium, BEA and APRI scores (P < 0.001 each). Area under the ROC curve for ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5, APRI ≥ 1.5 was 0.836, 0.966, 0.913, 0.871 and 0.825 respectively (P < 0.001 each). Cut off values of cholinesterase (IU/L) for predicting ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5 and APRI ≥ 1.5 were < 3812, < 2853, < 2829, < 4719 and < 3954 with a sensitivity of 80%, 100%, 91.67%, 82.50%, 58.0% and specificity of 81.97%, 84.79%, 87.56%, 77.06% and 55.64% respectively. CONCLUSION Serum cholinesterase demonstrates promising correlations with serum albumin, INR and CTP, MELD, BEA and APRI scores and is predictive of liver reserves in hepatitis D cirrhosis.
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Affiliation(s)
- Minaam Abbas
- School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, United Kingdorm
| | - Zaigham Abbas
- Department of Medicine, Orthopedic and Medical Institute, Karachi 74400, Pakistan.
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Kaiser T, Kinny-Köster B, Gnewuch C, Karailieva D, Kiehntopf M, Kessler A, Ritter-Sket C, Schmidt M, Brand K, Thiery J, Lichtinghagen R. Limited comparability of creatinine assays in patients with liver cirrhosis and their impact on the MELD score. Pract Lab Med 2017; 8:41-48. [PMID: 28856226 PMCID: PMC5575426 DOI: 10.1016/j.plabm.2017.04.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 04/10/2017] [Accepted: 04/11/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND & AIM Patients with end-stage liver disease require valid estimations of mortality for organ allocation and risk stratification. The model of end-stage liver disease (MELD) score is used for this purpose in most countries and incorporates bilirubin, International Normalized ratio, and creatinine. The aim of this study was to evaluate the comparability of creatinine results from different routine assays in the serum samples of patients with liver cirrhosis. METHODS Residual material from 60 serum samples was available from patients in different stages of liver cirrhosis. Four centers participated; each center analyzed the samples with Jaffé-based and enzymatic routine assays in parallel. In addition, an accredited calibration laboratory certified the panel of samples by an internationally accepted reference measurement procedure (RMP) based on isotope dilution mass spectrometry (ID-MS). This method served as the independent reference. RESULTS All routine methods displayed a high correlation to the RMP (r ≥0.937, p<0.001). Two enzymatic and two Jaffé-based methods provided results that were all within a ±20% range of the RMP. The other methods showed deviations >20% in up to 27% of the samples. The enzymatic methods were systematically lower, whereas the Jaffé-based methods were systematically higher (p<0.001). The resulting MELD scores differed from 0 to 4 points. CONCLUSIONS There are systematic deviations from the RMP. Jaffé-based assays gave higher results, whereas the enzymatic-based assays gave lower results compared to the results of the RMP. The comparability of results is limited and could be disadvantageous to patients listed for liver transplantation.
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Affiliation(s)
- Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany
| | - Benedict Kinny-Köster
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany
| | - Carsten Gnewuch
- Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, Regensburg, Germany
| | - Diana Karailieva
- Institute for Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany
| | - Michael Kiehntopf
- Institute for Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany
| | - Anja Kessler
- Reference Institute for Bioanalytics, Bonn, Germany
| | | | | | - Korbinian Brand
- Hannover Medical University, Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
| | - Joachim Thiery
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany
| | - Ralf Lichtinghagen
- Hannover Medical University, Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
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Roth JA, Chrobak C, Schädelin S, Hug BL. MELD score as a predictor of mortality, length of hospital stay, and disease burden: A single-center retrospective study in 39,323 inpatients. Medicine (Baltimore) 2017; 96:e7155. [PMID: 28614247 PMCID: PMC5478332 DOI: 10.1097/md.0000000000007155] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The laboratory-based model for end-stage liver disease (MELD) score reflects the function of the kidney, liver, and extrinsic coagulation pathway and might be used as a general prognostic tool for the assessment of patients. We therefore aimed to investigate a potential association of the MELD score with mortality, length of hospital stay (LOS), and disease burden in a general patient population.We performed a retrospective observational study at a tertiary referral center. From January 2012 through December 2013, all consecutive inpatients aged 18 years were eligible for the study; patients with missing MELD parameters on hospital admission and/or treatments influencing the international normalized ratio, that is, novel oral anticoagulants and vitamin K antagonists, were excluded. The MELD score on hospital admission was calculated retrospectively. The primary outcome measure was in-hospital all-cause mortality; secondary outcome measures were LOS and the number of comorbidities.A total of 39,323 inpatients were included in the final analysis. On admission, MELD scores of 15 to 19, 20 to 29, and ≥30 points (reference <15 points) showed increased hazard ratios (HRs) for in-hospital mortality in uni- and multivariable analysis with an adjusted HR of 2.52 (95% confidence interval [CI], 1.81-3.49; P < .001), 2.70 (95% CI, 1.89-3.84; P < .001), and 8.00 (95% CI, 3.91-16.39; P < .001), respectively. Increased MELD scores of 15 to 19, 20 to 29, and ≥30 points were positively associated with LOS and the number of comorbidities in uni- and multivariable analysis.In our study population consisting of adult inpatients, the MELD score on hospital admission was significantly associated with mortality, LOS, and the number of comorbidities. We suggest to prospectively validate the MELD score in inpatients as part of clinical decision support systems.
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Affiliation(s)
- Jan A. Roth
- Division of Infectious Diseases & Hospital Epidemiology
- University of Basel
| | - Carl Chrobak
- University of Basel
- Department of Internal Medicine
| | | | - Balthasar L. Hug
- University of Basel
- Department of Internal Medicine, Kantonsspital Luzern, Lucerne, Switzerland
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Kaiser T, Kinny-Köster B, Bartels M, Berg T, Scholz M, Engelmann C, Seehofer D, Becker S, Ceglarek U, Thiery J. Cholesterol esterification in plasma as a biomarker for liver function and prediction of mortality. BMC Gastroenterol 2017; 17:57. [PMID: 28427335 PMCID: PMC5397767 DOI: 10.1186/s12876-017-0614-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2016] [Accepted: 04/13/2017] [Indexed: 12/12/2022] Open
Abstract
Background Advanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of these patients suitable biomarkers are essential. The most important biomarkers for liver function are bilirubin and prothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants on the prothrombin time limits its diagnostic value. Aim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs. total cholesterol) as an alternative biomarker for liver synthesis and mortality prediction. Under physiological conditions the CE fraction in blood is closely regulated by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver. Methods One hundred forty-two patients with liver disease clinically considered for orthotopic liver transplant for different indications were enrolled in the study. One patient was excluded because of the intake of a direct oral factor Xa inhibitor which has a strong impact on prothrombin time. Results Results of CE fraction were in good agreement with INR (R2 = 0.73; p < 0.001). In patients who died or survived within three months mean CE fraction was 56% vs. 74% (p < 0.001) and mean INR was 2.0 vs. 1.3 (p < 0.001), respectively. The predictive value of CE fraction for three-month mortality risk was higher compared to INR (p = 0.04). Results for one-year mortality were comparable. Conclusions The cholesterol esterification fraction is a valid biomarker for liver synthesis and allows reliable prediction of mortality. In contrast to INR, it is independent of anticoagulation and other analytical limitations of coagulation tests. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0614-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany.
| | - Benedict Kinny-Köster
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany
| | - Michael Bartels
- Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany
| | - Thomas Berg
- Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Markus Scholz
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University Hospital Leipzig, Leipzig, Germany
| | - Cornelius Engelmann
- Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Daniel Seehofer
- Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany
| | - Susen Becker
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany.,LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany
| | - Uta Ceglarek
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany.,LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany
| | - Joachim Thiery
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany.,LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany
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Abstract
The state of clinical art of the coagulopathy of cirrhosis changed considerably over the last decade. Until 2005, cirrhosis was considered as the epitome of the hemorrhagic coagulopathies and the abnormal hemostasis tests associated with the disease were corrected with infusion of fresh frozen plasma or platelets to minimize the risk of bleeding. Since that time, a great deal of work has been done and there is now a change of paradigm. The prothrombin time once considered as an isolated measure of bleeding risk was rejected, and cirrhosis shifted from a purely hemorrhagic construct to a mixed and thrombosis-prone paradigm. In this article we examine the interesting history of how these conceptual changes came about.
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Hemida K, Al Swaff RE, Shabana SS, Said H, Ali-Eldin F. Prediction of Post-operative Mortality in Patients with HCV-related Cirrhosis Undergoing Non-Hepatic Surgeries. J Clin Diagn Res 2016; 10:OC18-OC21. [PMID: 27891371 DOI: 10.7860/jcdr/2016/22478.8620] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 08/24/2016] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Patients with chronic liver diseases are at great risk for both morbidity and mortality during the post-operative period due to the stress of surgery and the effects of general anaesthesia. AIM The main aim of this study was to evaluate the value of Model for End-stage Liver Disease (MELD) score, as compared to Child-Turcotte-Pugh (CTP) score, for prediction of 30- day post-operative mortality in Egyptian patients with liver cirrhosis undergoing non-hepatic surgery under general anaesthesia. MATERIALS AND METHODS A total of 60 patients with Hepatitis C Virus (HCV) - related liver cirrhosis were included in this study. Sensitivity and specificity of MELD and CTP scores were evaluated for the prediction of post-operative mortality. A total of 20 patients who had no clinical, biochemical or radiological evidence of liver disease were included to serve as a control group. RESULTS The highest sensitivity and specificity for detection of post-operative mortality was detected at a MELD score of 13.5. CTP score had a sensitivity of 75%, a specificity of 96.4%, and an overall accuracy of 95% for prediction of post-operative mortality. On the other side and at a cut-off value of 13.5, MELD score had a sensitivity of 100%, a specificity of 64.0%, and an overall accuracy of 66.6% for prediction of post-operative mortality in patients with HCV- related liver cirrhosis. CONCLUSION MELD score proved to be more sensitive but less specific than CTP score for prediction of post-operative mortality. CTP and MELD scores may be complementary rather than competitive in predicting post-operative mortality in patients with HCV- related liver cirrhosis.
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Affiliation(s)
- Khalid Hemida
- Professor, Department of Internal Medicine, Aim Shams University , Cairo, Egypt
| | - Reham Ezzat Al Swaff
- Assistant Professor, Department of Internal Medicine, Aim Shams University , Cairo, Egypt
| | - Sherif Sadek Shabana
- Assistant Professor, Department of Internal Medicine, Aim Shams University , Cairo, Egypt
| | - Hani Said
- Assistant Professor, Department of General Surgery, Aim Shams University , Cairo, Egypt
| | - Fatma Ali-Eldin
- Assistant Professor, Department of Tropical Medicine, Aim Shams University , Cairo, Egypt
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Loftus TJ, Jordan JR, Croft CA, Smith RS, Efron PA, Moore FA, Mohr AM, Brakenridge SC. Emergent laparotomy and temporary abdominal closure for the cirrhotic patient. J Surg Res 2016; 210:108-114. [PMID: 28457316 DOI: 10.1016/j.jss.2016.11.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 10/11/2016] [Accepted: 11/04/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Temporary abdominal closure (TAC) may be performed for cirrhotic patients undergoing emergent laparotomy. The effects of cirrhosis on physiologic parameters, resuscitation requirements, and outcomes following TAC are unknown. We hypothesized that cirrhotic TAC patients would have different resuscitation requirements and worse outcomes than noncirrhotic patients. METHODS We performed a 3-year retrospective cohort analysis of 231 patients managed with TAC following emergent laparotomy for sepsis, trauma, or abdominal compartment syndrome. All patients were initially managed with negative pressure wound therapy (NPWT) TAC with intention for planned relaparotomy and sequential abdominal closure attempts at 24- to 48-h intervals. RESULTS At presentation, cirrhotic patients had higher incidence of acidosis (33% versus 17%) and coagulopathy (87% versus 54%) than noncirrhotic patients. Forty-eight hours after presentation, cirrhotic patients had a persistently higher incidence of coagulopathy (77% versus 44%) despite receiving more fresh frozen plasma (10.8 units versus 4.4 units). Cirrhotic patients had higher NPWT output (4427 mL versus 2375 mL) and developed higher vasopressor infusion rates (57% versus 29%). Cirrhotic patients had fewer intensive care unit-free days (2.3 versus 7.6 days) and higher rates of multiple organ failure (64% versus 34%), in-hospital mortality (67% versus 21%), and long-term mortality (80% versus 34%) than noncirrhotic patients. CONCLUSIONS Cirrhotic patients managed with TAC are susceptible to early acidosis, persistent coagulopathy, large NPWT fluid losses, prolonged vasopressor requirements, multiple organ failure, and early mortality. Future research should seek to determine whether TAC provides an advantage over primary fascial closure for cirrhotic patients undergoing emergency laparotomy.
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Affiliation(s)
- Tyler J Loftus
- Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida
| | - Janeen R Jordan
- Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida
| | - Chasen A Croft
- Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida
| | - R Stephen Smith
- Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida
| | - Philip A Efron
- Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida
| | - Frederick A Moore
- Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida
| | - Alicia M Mohr
- Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida
| | - Scott C Brakenridge
- Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, Florida.
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Kumral D, Caldwell SH, Argo CK. Impact of an Institutional Change in Prothrombin Time Methodology on INR and MELD Scores in Liver Transplant Evaluations. J Clin Lab Anal 2016; 30:968-971. [PMID: 27076282 DOI: 10.1002/jcla.21964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 11/04/2015] [Accepted: 02/09/2016] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Allocation of liver grafts based on the model for end-stage liver disease (MELD) has been questioned because the prothrombin time (PT) measurement in cirrhosis patients changes with different commercially available thromboplastin reagents due to variations in the international sensitivity index (ISI). Our hospital laboratory electively changed the thromboplastin used in the PT/INR from PT-HS (ISI of 1.464) to Recombiplastin (ISI of 0.870). Theoretically, this change may yield lower INR and MELD scores in cirrhosis patients at our institution and thus impact access to organs. METHODS 27 patients listed for liver transplant prior to change in thromboplastin (Cohort A) were compared to 36 patients listed after the change (Cohort B). RESULTS Patients in Cohort A had a mean INR of 1.41 and mean MELD of 13.9 compared to Cohort B with a mean INR of 1.39 and mean MELD of 13.8. Student's t-tests showed no statistically significant difference in INR (p = 0.799) or MELD (p = 0.955) between cohorts. CONCLUSION We expected overall INR and MELD scores to decrease following the change to a thromboplastin with a lower ISI. On the contrary, we found no evidence of a major trend in these values supporting the relative robustness of the MELD.
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Affiliation(s)
- Dennis Kumral
- Department of Medicine, University of Virginia Health System, Charlottesville, Virginia
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, Virginia
| | - Curtis K Argo
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, Virginia.
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Indocyanine green retention is a potential prognostic indicator after splenectomy and pericardial devascularization for cirrhotic patients. Hepatobiliary Pancreat Dis Int 2016; 15:386-90. [PMID: 27498578 DOI: 10.1016/s1499-3872(16)60114-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Splenectomy and pericardial devascularization (SPD) is an effective treatment of upper gastrointestinal bleeding and hypersplenism in cirrhotic patients with portal hypertension. Indocyanine green retention at 15 minutes (ICGR15) was reported to offer better sensitivity and specificity than the Child-Pugh classification in hepatectomy, but few reports describe ICGR15 in SPD. The present study was to evaluate the prognostic value of ICGR15 for cirrhotic patients with portal hypertension who underwent SPD. METHODS From January 2012 to January 2015, 43 patients with portal hypertension and hypersplenism caused by liver cirrhosis were admitted in our center and received SPD. The ICGR15, Child-Pugh classification, model for end-stage liver disease (MELD) score, and perioperative characteristics were analyzed retrospectively. RESULTS Preoperative liver function assessment revealed that 34 patients were Child-Pugh class A with ICGR15 of 13.6%-43.0% and MELD score of 7-20; 8 patients were class B with ICGR15 of 22.8%-40.7% and MELD score of 7-17; 1 patient was class C with ICGR15 of 39.7% and MELD score of 22. The optimal ICGR15 threshold for liver function compensation was 31.2%, which offered a sensitivity of 68.4% and a specificity of 70.8%. Univariate analysis showed preoperative ICGR15, MELD score, surgical procedure, intraoperative blood loss, and autologous blood transfusion were significantly different between postoperative liver function compensated and decompensated groups. Multivariate regression analysis revealed that ICGR15 was an independent risk factor of postoperative liver function recovery (P=0.020). CONCLUSIONS ICGR15 has outperformed the Child-Pugh classification for assessing liver function in cirrhotic patients with portal hypertension. ICGR15 may be a suitable prognostic indicator for cirrhotic patients after SPD.
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33
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Andriulli A, Tripodi A, Angeli P, Senzolo M, Primignani M, Giannini EG, Riggio O, Colli A, Prati D, Sacerdoti D, Merkel C, Basili S, Ferro D, Villa E, Di Minno G, Caraceni P, Marzioni M, Mannucci PM, Violi F, Piscaglia F, Calvaruso V, De Pietri L, Falcone M, Feltracco P, Grandone E, La Mura V, Licata A, Lucidi C, Maimone S, Marietta M, Morisco F, Napoleone L, Piano S, Raparelli V, Rebulla P, Ribero D, Sartori MT, Scalera A, Schepis F, Siciliano M, Baroni GS, Tufano A, Vitale A, Zuin M. Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference. Dig Liver Dis 2016; 48:455-467. [PMID: 27012444 DOI: 10.1016/j.dld.2016.02.008] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 02/18/2016] [Indexed: 12/11/2022]
Abstract
Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent jury. The statements presented here highlight strengths and weaknesses of current laboratory tests to assess bleeding and thrombotic risk in cirrhotic patients, the pathophysiology of hemostatic perturbations in this condition, and outline the optimal management of bleeding and thrombosis in patients with liver cirrhosis.
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34
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The INR is only one side of the coagulation cascade: time to watch the clot. Anaesthesia 2016; 71:613-7. [DOI: 10.1111/anae.13480] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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35
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Agrawal S, Dhiman RK, Limdi JK. Evaluation of abnormal liver function tests. Postgrad Med J 2016; 92:223-34. [DOI: 10.1136/postgradmedj-2015-133715] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 01/04/2016] [Indexed: 12/13/2022]
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36
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Fernandez H, Weber J, Barnes K, Wright L, Levy M. Financial Impact of Liver Sharing and Organ Procurement Organizations' Experience With Share 35: Implications for National Broader Sharing. Am J Transplant 2016; 16:287-91. [PMID: 26372681 DOI: 10.1111/ajt.13436] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Revised: 06/11/2015] [Accepted: 06/24/2015] [Indexed: 01/25/2023]
Abstract
The Share 35 policy for organ allocation, which was adopted in June 2013, allocates livers regionally for candidates with Model for End-Stage Liver Disease scores of 35 or greater. The authors analyzed the costs resulting from the increased movement of allografts related to this new policy. Using a sample of nine organ procurement organizations, representing 17% of the US population and 19% of the deceased donors in 2013, data were obtained on import and export costs before Share 35 implementation (June 15, 2012, to June 14, 2013) and after Share 35 implementation (June 15, 2013, to June 14, 2014). Results showed that liver import rates increased 42%, with an increased cost of 51%, while export rates increased 112%, with an increased cost of 127%. When the costs of importing and exporting allografts were combined, the total change in costs for all nine organ procurement organizations was $11 011 321 after Share 35 implementation. Extrapolating these costs nationally resulted in an increased yearly cost of $68 820 756 by population or $55 056 605 by number of organ donors. Any alternative allocation proposal needs to account for the financial implications to the transplant infrastructure.
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Affiliation(s)
- H Fernandez
- Baylor All Saints Medical Center, Fort Worth, TX
| | - J Weber
- Center of Organ Recovery and Education, Pittsburgh, PA
| | - K Barnes
- Southwest Transplant Alliance, Dallas, TX
| | - L Wright
- Southwest Transplant Alliance, Dallas, TX
| | - M Levy
- Baylor All Saints Medical Center, Fort Worth, TX
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37
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Blasi A. Coagulopathy in liver disease: Lack of an assessment tool. World J Gastroenterol 2015; 21:10062-10071. [PMID: 26401071 PMCID: PMC4572787 DOI: 10.3748/wjg.v21.i35.10062] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2015] [Revised: 05/29/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
There is a discrepancy between the information from clotting tests which have routinely been used in clinical practice and evidence regarding thrombotic and bleeding events in patients with liver disease. This discrepancy leads us to rely on other variables which have been shown to be involved in haemostasis in these patients and/or to extrapolate the behaviour of these patients to other settings in order to decide the best clinical approach. The aims of the present review are as follows: (1) to present the information provided by clotting tests in cirrhotic patients; (2) to present the factors that may influence clotting in these patients; (3) to review the clinical evidence; and (4) to put forward a clinical approach based on the first 3 points.
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Kubilay NZ, Sengel BE, Wood KE, Layon AJ. Biomarkers in Hepatic Disease: A Review Focused on Critically Ill Patients. J Intensive Care Med 2014; 31:104-12. [PMID: 25324195 DOI: 10.1177/0885066614554897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2014] [Accepted: 07/17/2014] [Indexed: 11/15/2022]
Abstract
The ability to make a diagnosis early and appropriately is paramount for the survival of the critically ill ICU patient. Along with the myriad physical examination and imaging modalities available, biomarkers provide a window on the disease process. Herein we review hepatic biomarkers in the context of the critical care patient.
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Affiliation(s)
- Nejla Zeynep Kubilay
- The Department of Critical Care Medicine, The Geisinger Health System, Danville, PA, USA Department of Medicine, The Marmara University Teaching and Education Hospital, Istanbul, Turkey
| | - Buket Erturk Sengel
- The Department of Critical Care Medicine, The Geisinger Health System, Danville, PA, USA Department of Medicine, The Marmara University Teaching and Education Hospital, Istanbul, Turkey
| | - Kenneth E Wood
- The Department of Critical Care Medicine, The Geisinger Health System, Danville, PA, USA The Geisinger Medical Center, Danville, PA, USA
| | - A Joseph Layon
- The Department of Critical Care Medicine, The Geisinger Health System, Danville, PA, USA
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Cholongitas E, Arsos G, Goulis J, Birtsou C, Haidich AB, Nakouti T, Chalevas P, Ioannidou M, Karakatsanis K, Akriviadis E. Glomerular filtration rate is an independent factor of mortality in patients with decompensated cirrhosis. Hepatol Res 2014; 44:E145-55. [PMID: 24119148 DOI: 10.1111/hepr.12259] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Revised: 10/03/2013] [Accepted: 10/07/2013] [Indexed: 01/01/2023]
Abstract
AIM Although serum creatinine is included in the Model for End-Stage Liver Disease (MELD) score, it is an inaccurate marker of renal function, namely, of glomerular filtration rate ("true" GFR) in patients with decompensated cirrhosis. Our aim was to investigate the impact of MELD score and "true" GFR as determinants of survival in patients with decompensated cirrhosis. METHODS We included all consecutive patients with decompensated cirrhosis who were admitted to our department. Renal function was assessed by creatinine- and cystatin-based estimated GFR and "true" GFR using (51) Cr-ethylenediaminetetraacetic acid. The independent factors associated with survival were evaluated. The discriminative ability of the prognostic scores (MELD and modifications of MELD score) were evaluated by using the area under the receiver-operator curve (AUC). RESULTS One hundred and ten consecutive patients (77 men, aged 56 ± 12 years); at the end of follow up (8 months; range, 6-18), 92 patients (84%) were alive and 18 (16%) had died. In multivariate analysis, serum bilirubin (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.05-1.26; P = 0.020) and "true" GFR (HR, 0.96; 95% CI, 0.93-0.98; P = 0.003) were the only independent factors significantly associated with the outcome. The derived new prognostic model had high discriminative ability (AUC, 0.90), which was confirmed in the validation sample of 77 patients. CONCLUSION In our cohort of patients with decompensated cirrhosis, "true" GFR and bilirubin were the independent factors of the outcome.
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Affiliation(s)
- Evangelos Cholongitas
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
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Richter S, Polychronidis G, Gotthardt DN, Houben P, Giese T, Sander A, Dörr-Harim C, Diener MK, Schemmer P. Effect of delayed CNI-based immunosuppression with Advagraf® on liver function after MELD-based liver transplantation [IMUTECT]. BMC Surg 2014; 14:64. [PMID: 25178675 PMCID: PMC4160448 DOI: 10.1186/1471-2482-14-64] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 08/20/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND MELD-based allocation for liver transplantation follows the "sickest-patient-first" strategy. The latter patients present with both, decreased immune competence and poor kidney function which is further impaired by immunosuppressants. METHODS/DESIGN In this prospective observational study, 50 patients with de novo low-dose standard Advagraf®-based immunosuppression consisting of Advagraf®, Mycophenolat-mofetil and Corticosteroids after liver transplantation will be evaluated. Advagraf® trough levels of 7-10 μg/l will be reached at the end of the first postoperative week. Immunostatus, infectious complications, graft and kidney function are compared between patients with a pretransplant calculated MELD-score of ≤20 and >20. Each group comprises of 25 consecutive patients. Prior to liver transplantation and on the postoperative days 1, 3 and 7, the patients' graft function (LiMAx test) will be evaluated. On the postoperative days 3, 5 and 7 the patients' immune status will be evaluated by the measurement of their monocytic HLA-DR status.Infectious complications (CMV-reactivation, wound infection, urinary tract infection, and pneumonia), graft- and kidney function will be analysed on day 0, within the first week, and 1, 3, 6, 9 and 12 months after liver transplantation. DISCUSSION This study was designed to assess the effect of a standard low-dose Calcineurin inhibitor-based immunosuppression regime with Advagraf® on the rate of infectious complications, graft and renal function after liver transplantation. TRIAL REGISTRATION The trial is registered at "Clinical Trials" (http://www.clinicaltrials.gov), NCT01781195.
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Affiliation(s)
- Susanne Richter
- Department of General, Visceral and Transplant Surgery, Heidelberg, Germany
| | | | - Daniel N Gotthardt
- Department of Internal Medicine IV, University of Heidelberg, Heidelberg, Germany
| | - Philipp Houben
- Department of General, Visceral and Transplant Surgery, Heidelberg, Germany
| | - Thomas Giese
- Immunology, University of Heidelberg, Heidelberg, Germany
| | - Anja Sander
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | | | - Markus K Diener
- Department of General, Visceral and Transplant Surgery, Heidelberg, Germany
| | - Peter Schemmer
- Department of General, Visceral and Transplant Surgery, Heidelberg, Germany
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Abstract
The success of liver transplantation in the past three decades as a life-saving procedure for patients with end-stage liver disease has led to the ever-increasing disparity between the demands for liver transplantation and the supply of donor liver organs. Donor allocation and distribution remains a challenge and a moral issue as to how these organs can be equitably distributed. This article reviews the evolution of the liver allocation policy and discusses in detail the challenges clinicians face today in this area of medicine.
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Zhang F, Zhuge Y, Zou X, Zhang M, Peng C, Li Z, Wang T. Different scoring systems in predicting survival in Chinese patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic shunt. Eur J Gastroenterol Hepatol 2014; 26:853-860. [PMID: 24915489 DOI: 10.1097/meg.0000000000000134] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) is an established minimal-invasive procedure to treat complications of portal hypertension, and several scoring systems have been used to help choose suitable patients. However, its accuracy remains controversial. AIM To compare the performance of the Child-Turcotte-Pugh (CTP) classification system, model for end-stage liver disease (MELD) score, Emory score, Bonn TIPS early mortality (BOTEM) score, and serum bilirubin and platelet count (SB/PLT model) in predicting survival in Chinese patients with liver cirrhosis undergoing TIPS. PATIENTS AND METHODS The clinical data of patients undergoing TIPS in our department were retrospectively analyzed to compare the five scoring systems on the basis of survival after TIPS. RESULTS A cohort of 159 patients was analyzed. The survival curves showed a statistical significance between classification B and C of CTP (χ=9.451, P=0.002), between MELD less than 10 and MELD at least 10 (χ=10.099, P=0.001), and between low-risk and moderate-risk groups of the Emory score (χ=4.656, P=0.031), indicating a better discriminatory ability. By ROC curves and a logistic regression model, the MELD score and the CTP system had better power to predict 3-, 12-, and 24-month survival. The MELD score and the CTP classification system had smaller values of -2 Ln(L), Akaike Information criterion, and Schwarz-Bayesian criterion, respectively. CONCLUSION The MELD score and the CTP classification system provide better prognostic stratification for a cohort of Chinese patients with advanced cirrhosis undergoing TIPS. However, the MELD score is not significantly superior to the CTP system.
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Affiliation(s)
- Feng Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests. Eur Radiol 2014; 24:2482-90. [PMID: 25030459 DOI: 10.1007/s00330-014-3291-x] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Revised: 06/03/2014] [Accepted: 06/25/2014] [Indexed: 12/22/2022]
Abstract
OBJECTIVES To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. METHODS Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. RESULTS Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). CONCLUSIONS Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. KEY POINTS • Relative enhancement (RLE) of Gd-EOB-DTPA is related to biochemical liver function tests. • Correlation of RLE with bilirubin, ALT, AST, GGT, INR and MELD Score is reverse. • The correlation of relative liver enhancement with prothrombin time is positive. • AST, ALT, GLDH, prothrombin time, INR and MELD Score correlate with pre-contrast liver-spleen contrast ratio. • Such biomarkers may help to evaluate liver function.
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Lee HJ, Kim JE, Lee HY, Lim HS, Kim HK. Significance of local international sensitivity index systems for monitoring warfarin and liver function. Am J Clin Pathol 2014; 141:542-50. [PMID: 24619756 DOI: 10.1309/ajcp2ry1pirrpuow] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
OBJECTIVES Use of a local calibrator has been recommended for standardization of the international normalized ratio (INR) and international sensitivity index (ISI). We investigated the performance of two commercial local calibrators for warfarin monitoring and determined the significance of liver-specific INR. METHODS ISI values were determined using the World Health Organization (WHO) method and two commercial local calibrators. Liver-specific ISI was determined using plasma samples from patients with liver cirrhosis and normal controls. RESULTS In warfarin monitoring, the two local ISIs determined by the two local calibrators showed better consistency than uncorrected ISI, although they were inferior to the ISIs calibrated using the WHO method. Alternative calibration using calibration plasma from patients with liver cirrhosis instead of warfarinized plasma reduced the INR variability. CONCLUSIONS Local ISI determined by a commercial local calibrator improved INR standardization among thromboplastins. The alternative ISI calibration using liver-specific calibration plasma is expected to reduce INR variability for the evaluation of liver function.
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Affiliation(s)
- Hwa Jeen Lee
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Ji-Eun Kim
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Yeon Lee
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hae Sook Lim
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Kyung Kim
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Kaiser T, Kinny-Köster B, Bartels M, Parthaune T, Schmidt M, Thiery J. Impact of different creatinine measurement methods on liver transplant allocation. PLoS One 2014; 9:e90015. [PMID: 24587188 PMCID: PMC3937403 DOI: 10.1371/journal.pone.0090015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Accepted: 01/29/2014] [Indexed: 12/12/2022] Open
Abstract
Introduction The model for end-stage liver disease (MELD) score is used in many countries to prioritize organ allocation for the majority of patients who require orthotopic liver transplantation. This score is calculated based on the following laboratory parameters: creatinine, bilirubin and the international normalized ratio (INR). Consequently, high measurement accuracy is essential for equitable and fair organ allocation. For serum creatinine measurements, the Jaffé method and enzymatic detection are well-established routine diagnostic tests. Methods A total of 1,013 samples from 445 patients on the waiting list or in evaluation for liver transplantation were measured using both creatinine methods from November 2012 to September 2013 at the university hospital Leipzig, Germany. The measurements were performed in parallel according to the manufacturer’s instructions after the samples arrived at the institute of laboratory medicine. Patients who had required renal replacement therapy twice in the previous week were excluded from analyses. Results Despite the good correlation between the results of both creatinine quantification methods, relevant differences were observed, which led to different MELD scores. The Jaffé measurement led to greater MELD score in 163/1,013 (16.1%) samples with differences of up to 4 points in one patient, whereas differences of up to 2 points were identified in 15/1,013 (1.5%) samples using the enzymatic assay. Overall, 50/152 (32.9%) patients with MELD scores >20 had higher scores when the Jaffé method was used. Discussion Using the Jaffé method to measure creatinine levels in samples from patients who require liver transplantation may lead to a systematic preference in organ allocation. In this study, the differences were particularly pronounced in samples with MELD scores >20, which has clinical relevance in the context of urgency of transplantation. These data suggest that official recommendations are needed to determine which laboratory diagnostic methods should be used when calculating MELD scores.
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Affiliation(s)
- Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany
- * E-mail:
| | - Benedict Kinny-Köster
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany
| | - Michael Bartels
- Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Tanja Parthaune
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany
| | | | - Joachim Thiery
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany
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Northup PG, Caldwell SH. Coagulation in liver disease: a guide for the clinician. Clin Gastroenterol Hepatol 2013; 11:1064-74. [PMID: 23506859 DOI: 10.1016/j.cgh.2013.02.026] [Citation(s) in RCA: 163] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Revised: 02/18/2013] [Accepted: 02/20/2013] [Indexed: 02/06/2023]
Abstract
The human hemostasis system is complex and poorly understood after decades of intense scientific study. Despite multiple defects in routine coagulation laboratory studies in patients with chronic liver disease, there is growing evidence that these patients are effectively "rebalanced" with regard to procoagulant and anticoagulant activity and that most of these patients remain in a tenuous but balanced state of hemostasis. A major difficulty in the assessment of these patients is that there are no established laboratory tests that accurately reflect the changes in both the procoagulant and anticoagulant systems; therefore, routine laboratory testing is misleading to the clinician and may prompt inappropriate or risky therapies with little real benefit to the patient. The international normalized ratio is an example of this type of misleading test. Although the international normalized ratio is inextricably linked to prognosis and severity of protein synthetic dysfunction in acute and chronic liver disease, it is a very poor marker for bleeding risk and should not be used in isolation for this purpose. Coagulation disorders are critical in the management of frequent clinical scenarios such as esophageal variceal bleeding, invasive and percutaneous procedures, portal vein thrombosis, venous thromboembolism, and acute liver failure. This article summarizes the pathophysiology of hemostasis in liver disease, describes the strengths and weaknesses of various laboratory tests in assessment of these patients, and outlines the optimal management of hemostasis for some common clinical scenarios. Further research is needed for proper understanding of hemostasis in liver disease to optimally and safely manage these complex patients.
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Affiliation(s)
- Patrick G Northup
- Division of Gastroenterology and Hepatology, Center for the Study of Coagulation in Liver Disease, University of Virginia, Charlottesville, Virginia, USA.
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Magnusson M, Sten-Linder M, Bergquist A, Rajani R, Kechagias S, Fischler B, Németh A, Lindahl TL. The international normalized ratio according to Owren in liver disease: interlaboratory assessment and determination of international sensitivity index. Thromb Res 2013; 132:346-51. [PMID: 23993902 DOI: 10.1016/j.thromres.2013.05.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Revised: 04/28/2013] [Accepted: 05/07/2013] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The international normalized ratio (INR) is used to prioritize liver disease patients for transplantation. Previous studies have shown high interlaboratory variability in Quick-based INR determinations in samples of patients with liver disease. We assessed Owren-based INR reagents for analyzing INR in patients with liver disease. Further, we determined the difference between international sensitivity index (ISI) for patients on vitamin K antagonists (ISIVKA) and ISI for patients with liver disease (ISIliver). PATIENTS AND METHODS Twenty patients with liver disease were included, 10 with INR 1.8-3.6 (group A1) and 10 with INR 1.2-1.5 (group C1). Plasma from these patients was analyzed for Owren-based INR in eight Swedish laboratories using either of following reagents: SPA+, Owrens PT or Nycotest PT. To determine ISI liver, the reference thromboplastin RBT/05 and additional 41 patients with liver disease and 20 normal controls were included. ISIVKA was determined according to the WHO procedure. The difference between the ISIVKA and ISIliver was calculated. RESULTS The coefficients of variance for the Owren based INR methods were 6.2% in group A1, 3.9 % in group C1 and 5.3% for all patients. The difference between ISIVKA and ISIliver were -0.4%, -0.7% and -0.2% for SPA+, Owrens PT and Nycotest PT respectively. CONCLUSIONS Interlaboratory variation in INR analyses according to Owren in patients with liver disease is low and the difference between ISIVKA and ISIliver is below 10% with this method. ISIVKA can therefore be used in the INR calibration, for the Owren reagents studied, when analyzing plasma from patients with liver disease.
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Affiliation(s)
- Maria Magnusson
- CLINTEC, Karolinska Institutet, Division of Pediatrics, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
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Silveira F, Silveira FP, Macri MM, Nicoluzzi JEL. [Analysis of liver waiting list mortality in Paraná, Brazi: what shall we do to face organ shortage?]. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2013; 25:110-3. [PMID: 23381754 DOI: 10.1590/s0102-67202012000200010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2011] [Accepted: 02/13/2012] [Indexed: 01/15/2023]
Abstract
BACKGROUND Orthotopic liver transplantation is the best therapeutic modality for patients with end stage of liver disease. Minimization of death, while waiting for the procedure, involves accurate priorization according to clinical status and appropriate allocation of donor livers. AIM The mortality analysis in the liver waiting list in Paraná state, PR, Brazil. METHODS Were analyzed the data on all patients (n = 65) who were registered on the liver waiting list during a 32 months period in the state of Paraná, southern Brazil. RESULTS The death rated in waiting list was 41,5% (n = 27). No statistic difference was observed regarding the MELD/MELD-Na scores between the group who died (19,88/21,6) and not died (17,28/19,47). MELD-Na predicted a higher mortality, especially in the subgroup of patients with intermediate severity of disease (class B) predicted by the CTP score. CONCLUSION It´s critical the shortage of donor organs in our region, waiting list mortality rate far exceeds the inherent risk of a liver transplant, especially among patients with lower MELD scores. It´s desirable to use an aggressive protocol of expanded criteria donors, split liver and living donor transplant.
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Affiliation(s)
- Fábio Silveira
- Trabalho realizado Instituto para Cuidadodo Fígado (www.icfigado.org), Curitiba, PR, Brazil.
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Let's go down the correct path(way). Anesthesiology 2013; 118:1237. [PMID: 23612138 DOI: 10.1097/aln.0b013e318289bb69] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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50
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Venous thromboembolism in cirrhosis: a review of the literature. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2013; 26:905-8. [PMID: 23248793 DOI: 10.1155/2012/175849] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Although hemorrhage has traditionally been regarded as the most significant hemostatic complication of liver disease, there is increasing recognition that hypercoagulability is a prominent aspect of cirrhosis. Identifying markers of coagulability and monitoring anticoagulation therapy in the setting of cirrhosis is problematic. The bleeding risk of venous thromboembolism (VTE) prophylaxis and treatment in patients with chronic liver disease is unclear and there are currently no recommendations to guide practice in this regard. In the present report, the mechanism of coagulation disturbance in chronic liver disease is reviewed with an examination of the evidence for an increased VTE risk in cirrhosis. Finally, the available evidence is assessed for prophylaxis and therapy of VTE in chronic liver disease, and the role it may play in decreasing clinical decompensation and improving survival.
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