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Chongo G, Soldera J. Use of machine learning models for the prognostication of liver transplantation: A systematic review. World J Transplant 2024; 14:88891. [PMID: 38576762 PMCID: PMC10989468 DOI: 10.5500/wjt.v14.i1.88891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/08/2023] [Accepted: 12/11/2023] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) is a life-saving intervention for patients with end-stage liver disease. However, the equitable allocation of scarce donor organs remains a formidable challenge. Prognostic tools are pivotal in identifying the most suitable transplant candidates. Traditionally, scoring systems like the model for end-stage liver disease have been instrumental in this process. Nevertheless, the landscape of prognostication is undergoing a transformation with the integration of machine learning (ML) and artificial intelligence models. AIM To assess the utility of ML models in prognostication for LT, comparing their per formance and reliability to established traditional scoring systems. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a thorough and standardized literature search using the PubMed/MEDLINE database. Our search imposed no restrictions on publication year, age, or gender. Exclusion criteria encompassed non-English stu dies, review articles, case reports, conference papers, studies with missing data, or those exhibiting evident methodological flaws. RESULTS Our search yielded a total of 64 articles, with 23 meeting the inclusion criteria. Among the selected studies, 60.8% originated from the United States and China combined. Only one pediatric study met the criteria. Notably, 91% of the studies were published within the past five years. ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values (ranging from 0.6 to 1) across all studies, surpassing the performance of traditional scoring systems. Random forest exhibited superior predictive capa bilities for 90-d mortality following LT, sepsis, and acute kidney injury (AKI). In contrast, gradient boosting excelled in predicting the risk of graft-versus-host disease, pneumonia, and AKI. CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT, marking a significant evolution in the field of prognostication.
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Affiliation(s)
- Gidion Chongo
- Department of Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
| | - Jonathan Soldera
- Department of Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
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2
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de Ferrante HC, van Rosmalen M, Smeulders BML, Vogelaar S, Spieksma FCR. Revising model for end-stage liver disease from calendar-time cross-sections with correction for selection bias. BMC Med Res Methodol 2024; 24:51. [PMID: 38419019 PMCID: PMC10900649 DOI: 10.1186/s12874-024-02176-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 02/07/2024] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND Eurotransplant liver transplant candidates are prioritized by Model for End-stage Liver Disease (MELD), a 90-day waitlist survival risk score based on the INR, creatinine and bilirubin. Several studies revised the original MELD score, UNOS-MELD, with transplant candidate data by modelling 90-day waitlist mortality from waitlist registration, censoring patients at delisting or transplantation. This approach ignores biomarkers reported after registration, and ignores informative censoring by transplantation and delisting. METHODS We study how MELD revision is affected by revision from calendar-time cross-sections and correction for informative censoring with inverse probability censoring weighting (IPCW). For this, we revised UNOS-MELD on patients with chronic liver cirrhosis on the Eurotransplant waitlist between 2007 and 2019 (n = 13,274) with Cox models with as endpoints 90-day survival (a) from registration and (b) from weekly drawn calendar-time cross-sections. We refer to the revised score from cross-section with IPCW as DynReMELD, and compare DynReMELD to UNOS-MELD and ReMELD, a prior revision of UNOS-MELD for Eurotransplant, in geographical validation. RESULTS Revising MELD from calendar-time cross-sections leads to significantly different MELD coefficients. IPCW increases estimates of absolute 90-day waitlist mortality risks by approximately 10 percentage points. DynReMELD has improved discrimination over UNOS-MELD (delta c-index: 0.0040, p < 0.001) and ReMELD (delta c-index: 0.0015, p < 0.01), with differences comparable in magnitude to the addition of an extra biomarker to MELD (delta c-index: ± 0.0030). CONCLUSION Correcting for selection bias by transplantation/delisting does not improve discrimination of revised MELD scores, but substantially increases estimated absolute 90-day mortality risks. Revision from cross-section uses waitlist data more efficiently, and improves discrimination compared to revision of MELD exclusively based on information available at listing.
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Affiliation(s)
- H C de Ferrante
- Department of Mathematics and Computer Science, Eindhoven University of Technology, 5600MB, Eindhoven, PO Box 513, Netherlands.
- Eurotransplant International Foundation, Leiden, the Netherlands.
| | - M van Rosmalen
- Eurotransplant International Foundation, Leiden, the Netherlands
| | - B M L Smeulders
- Department of Mathematics and Computer Science, Eindhoven University of Technology, 5600MB, Eindhoven, PO Box 513, Netherlands
| | - S Vogelaar
- Eurotransplant International Foundation, Leiden, the Netherlands
| | - F C R Spieksma
- Department of Mathematics and Computer Science, Eindhoven University of Technology, 5600MB, Eindhoven, PO Box 513, Netherlands
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3
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Mazumder NR, Fontana RJ. MELD 3.0 in Advanced Chronic Liver Disease. Annu Rev Med 2024; 75:233-245. [PMID: 37751367 DOI: 10.1146/annurev-med-051322-122539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Abstract
The MELD (model for end-stage liver disease) 3.0 score was developed to replace the MELD-Na score that is currently used to prioritize liver allocation for cirrhotic patients awaiting liver transplantation in the United States. The MELD 3.0 calculator includes new inputs from patient sex and serum albumin levels and has new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is expected that use of MELD 3.0 scores will reduce overall waitlist mortality modestly and improve access for female liver transplant candidates. The utility of MELD 3.0 and PELDcre (pediatric end-stage liver disease, creatinine) scores for risk stratification in cirrhotic patients undergoing major abdominal surgery, placement of a transjugular intrahepatic portosystemic shunt, and other interventions requires further study. This article reviews the background of the MELD score and the rationale to create MELD 3.0 as well as potential implications of using this newer risk stratification tool in clinical practice.
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Affiliation(s)
- Nikhilesh R Mazumder
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA; ,
- Gastroenterology Section, Ann Arbor Veterans Affairs Healthcare System, Ann Arbor, Michigan, USA
| | - Robert J Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA; ,
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4
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Zhang W, Jin P, Liu J, Wu Y, Wang R, Zhang Y, Shen Y, Zhang M, Bai X, Fung J, Liang T. Dynamic evaluation based on acute-on-chronic liver failure predicts survival of patients after liver transplantation: a cohort study. Int J Surg 2023; 109:3117-3125. [PMID: 37498133 PMCID: PMC10583902 DOI: 10.1097/js9.0000000000000596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 06/26/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND AND AIMS Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on the Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation (LT) survival. METHODS This study included 637 adults (overall cohort) with benign end-stage liver diseases. The authors compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF-3 were defined as the ACLF-3 cohort ( n =158). The primary outcome was 1-year mortality. ΔMELD and ΔCLIF-OF (Chronic Liver Failure-Organ Failure) represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve. A Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality. RESULTS Patients were grouped into three groups: the deterioration group (D), the stable group (S), and the improvement group (I). The deterioration group (ΔCLIF-OF ≥2) was more likely to receive national liver allocation ( P =0.012) but experienced longer cold ischemia time ( P =0.006) than other groups. The area under the curves for ΔCLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to ΔMELD ( P <0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of the deterioration group were 12.57 (6.72-23.48) for the overall cohort and 7.00 (3.73-13.09) for the ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), ΔCLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while ΔCLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF-3 patients showed a higher survival rate than patients with ACLF-3 in all groups ( P =0.002 for I, P =0.005 for S, and P =0.001 for D). CONCLUSION This was the first ACLF-based dynamic evaluation study. ΔCLIF-OF was a more powerful predictor of post-LT mortality than ΔMELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, ΔCLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and a deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.
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Affiliation(s)
- Wei Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Pingbo Jin
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Junfang Liu
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Yue Wu
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | | | - Yuntao Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Yan Shen
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Min Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - John Fung
- Transplantation Institute, Department of Surgery, University of Chicago, Chicago, Illinois, USA
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
- Key Lab of Combined Multi-organ Transplantation of the Ministry of Health
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
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5
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Silberhumer GR, Györi G, Brugger J, Baumann L, Zehetmayer S, Soliman T, Berlakovich G. MELD-Na Alterations on the Liver Transplant Waiting List and Their Impact on Listing Outcome. J Clin Med 2023; 12:jcm12113763. [PMID: 37297957 DOI: 10.3390/jcm12113763] [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: 03/06/2023] [Revised: 04/19/2023] [Accepted: 05/09/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND Dynamic MELD deterioration (Delta MELD) during waiting time was shown to have significant impact on post-transplant survival. The aim of this study was to analyze the impact of MELD-Na score alterations on waiting list outcomes in liver transplant candidates. METHOD 36,806 patients listed at UNOS for liver transplantation in 2011-2015 were analyzed according to their delisting reasons. Several different MELD-Na alterations during waiting time were analyzed (e.g., maximal change, last change before delisting/transplantation). Outcome estimates were calculated according to MELD-Na scores at listing and Delta MELD. RESULTS Patients who died while on the waiting list showed a significantly higher deterioration in MELD-Na during the waiting time (6.8 ± 8.4 points) than stable patients who remained actively listed (-0.1 ± 5.2 points; p < 0.01). Patients who were considered too healthy for transplantation improved by more than 3 points on average during the waiting time. The mean peak MELD-Na alteration during the waiting time was 10.0 ± 7.6 for patients who died on the waiting list, compared to 6.6 ± 6.1 in the group of patients who finally underwent transplantation. CONCLUSIONS Deterioration of MELD-Na during waiting time and maximal MELD-Na deterioration have a significant negative impact on the liver transplant waiting list outcome.
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Affiliation(s)
- Gerd R Silberhumer
- Department of Transplant Surgery, Medical University of Vienna, 1090 Vienna, Austria
| | - Georg Györi
- Department of Transplant Surgery, Medical University of Vienna, 1090 Vienna, Austria
| | - Jonas Brugger
- Department of CeMSIIS, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria
| | - Lukas Baumann
- Department of CeMSIIS, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria
| | - Sonja Zehetmayer
- Department of CeMSIIS, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria
| | - Thomas Soliman
- Department of Transplant Surgery, Medical University of Vienna, 1090 Vienna, Austria
| | - Gabriela Berlakovich
- Department of Transplant Surgery, Medical University of Vienna, 1090 Vienna, Austria
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Goudsmit BFJ, Braat AE, Tushuizen ME, Coenraad MJ, Vogelaar S, Alwayn IPJ, van Hoek B, Putter H. Development and validation of a dynamic survival prediction model for patients with acute-on-chronic liver failure. JHEP Rep 2021; 3:100369. [PMID: 34765960 PMCID: PMC8570961 DOI: 10.1016/j.jhepr.2021.100369] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/23/2021] [Accepted: 09/22/2021] [Indexed: 12/03/2022] Open
Abstract
Background & Aims Acute-on-chronic liver failure (ACLF) is usually associated with a precipitating event and results in the failure of other organ systems and high short-term mortality. Current prediction models fail to adequately estimate prognosis and need for liver transplantation (LT) in ACLF. This study develops and validates a dynamic prediction model for patients with ACLF that uses both longitudinal and survival data. Methods Adult patients on the UNOS waitlist for LT between 11.01.2016-31.12.2019 were included. Repeated model for end-stage liver disease-sodium (MELD-Na) measurements were jointly modelled with Cox survival analysis to develop the ACLF joint model (ACLF-JM). Model validation was carried out using separate testing data with area under curve (AUC) and prediction errors. An online ACLF-JM tool was created for clinical application. Results In total, 30,533 patients were included. ACLF grade 1 to 3 was present in 16.4%, 10.4% and 6.2% of patients, respectively. The ACLF-JM predicted survival significantly (p <0.001) better than the MELD-Na score, both at baseline and during follow-up. For 28- and 90-day predictions, ACLF-JM AUCs ranged between 0.840-0.871 and 0.833-875, respectively. Compared to MELD-Na, AUCs and prediction errors were improved by 23.1%-62.0% and 5%-37.6% respectively. Also, the ACLF-JM could have prioritized patients with relatively low MELD-Na scores but with a 4-fold higher rate of waiting list mortality. Conclusions The ACLF-JM dynamically predicts outcome based on current and past disease severity. Prediction performance is excellent over time, even in patients with ACLF-3. Therefore, the ACLF-JM could be used as a clinical tool in the evaluation of prognosis and treatment in patients with ACLF. Lay summary Acute-on-chronic liver failure (ACLF) progresses rapidly and often leads to death. Liver transplantation is used as a treatment and the sickest patients are treated first. In this study, we develop a model that predicts survival in ACLF and we show that the newly developed model performs better than the currently used model for ranking patients on the liver transplant waiting list.
ACLF is a dynamic disease that can rapidly change over time, which greatly influences patient survival without LT. Currently, the MELD-Na score is used to prioritize patients for LT, but MELD-Na underestimates ACLF disease severity. The ACLF joint model (ACLF-JM) was developed to dynamically predict survival. The ACLF-JM significantly outperformed the MELD-Na score for the prediction of mortality on the LT waiting list. The ACLF-JM can be used online to predict survival in individual patients.
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Affiliation(s)
- Ben F J Goudsmit
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands.,Eurotransplant International Foundation, Leiden, The Netherlands
| | - Andries E Braat
- Department of Surgery, Leiden University Medical Center, The Netherlands
| | - Maarten E Tushuizen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands.,Transplant Center, Leiden University Medical Center, The Netherlands
| | - Minneke J Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands
| | - Serge Vogelaar
- Eurotransplant International Foundation, Leiden, The Netherlands
| | - Ian P J Alwayn
- Department of Surgery, Leiden University Medical Center, The Netherlands.,Transplant Center, Leiden University Medical Center, The Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands.,Transplant Center, Leiden University Medical Center, The Netherlands
| | - Hein Putter
- Department of Biomedical Data Sciences, Leiden University Medical Center, The Netherlands
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7
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Goudsmit BFJ, Braat AE, Tushuizen ME, Vogelaar S, Pirenne J, Alwayn IPJ, van Hoek B, Putter H. Joint modeling of liver transplant candidates outperforms the model for end-stage liver disease: The effect of disease development over time on patient outcome. Am J Transplant 2021; 21:3583-3592. [PMID: 34174149 PMCID: PMC8597089 DOI: 10.1111/ajt.16730] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 06/03/2021] [Accepted: 06/21/2021] [Indexed: 01/25/2023]
Abstract
Liver function is measured regularly in liver transplantation (LT) candidates. Currently, these previous disease development data are not used for survival prediction. By constructing and validating joint models (JMs), we aimed to predict the outcome based on all available data, using both disease severity and its rate of change over time. Adult LT candidates listed in Eurotransplant between 2007 and 2018 (n = 16 283) and UNOS between 2016 and 2019 (n = 30 533) were included. Patients with acute liver failure, exception points, or priority status were excluded. Longitudinal MELD(-Na) data were modeled using spline-based mixed effects. Waiting list survival was modeled with Cox proportional hazards models. The JMs combined the longitudinal and survival analysis. JM 90-day mortality prediction performance was compared to MELD(-Na) in the validation cohorts. MELD(-Na) score and its rate of change over time significantly influenced patient survival. The JMs significantly outperformed the MELD(-Na) score at baseline and during follow-up. At baseline, MELD-JM AUC and MELD AUC were 0.94 (0.92-0.95) and 0.87 (0.85-0.89), respectively. MELDNa-JM AUC was 0.91 (0.89-0.93) and MELD-Na AUC was 0.84 (0.81-0.87). The JMs were significantly (p < .001) more accurate than MELD(-Na). After 90 days, we ranked patients for LT based on their MELD-Na and MELDNa-JM survival rates, showing that MELDNa-JM-prioritized patients had three times higher waiting list mortality.
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Affiliation(s)
- Ben F. J. Goudsmit
- Division of TransplantationDepartment of SurgeryLeiden University Medical CentreThe Netherlands,Eurotransplant International FoundationLeidenThe Netherlands,Department of Gastroenterology and HepatologyLeiden University Medical CentreThe Netherlands
| | - Andries E. Braat
- Division of TransplantationDepartment of SurgeryLeiden University Medical CentreThe Netherlands
| | - Maarten E. Tushuizen
- Department of Gastroenterology and HepatologyLeiden University Medical CentreThe Netherlands,Transplant CenterLeiden University Medical CentreThe Netherlands
| | - Serge Vogelaar
- Eurotransplant International FoundationLeidenThe Netherlands
| | - Jacques Pirenne
- Department of Abdominal Transplant SurgeryUniversity Hospitals LeuvenLeuvenBelgium,Eurotransplant Liver Intestine Advisory CommitteeLeuvenBelgium
| | - Ian P. J. Alwayn
- Division of TransplantationDepartment of SurgeryLeiden University Medical CentreThe Netherlands,Transplant CenterLeiden University Medical CentreThe Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and HepatologyLeiden University Medical CentreThe Netherlands,Transplant CenterLeiden University Medical CentreThe Netherlands
| | - Hein Putter
- Department of Biomedical Data SciencesLeiden University Medical CentreThe Netherlands
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8
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Zhao TY, Cong QW, Liu F, Yao LY, Zhu Y. Nonlinear Relationship Between Macrocytic Anemia and Decompensated Hepatitis B Virus Associated Cirrhosis: A Population-Based Cross-Sectional Study. Front Pharmacol 2021; 12:755625. [PMID: 34616304 PMCID: PMC8488205 DOI: 10.3389/fphar.2021.755625] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 09/06/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Mean corpuscular volume (MCV) is major used as an indicator for the differential diagnosis of anemia. Macrocytic anemia in decompensated cirrhosis is common. However, the relationship between macrocytic anemia and decompensated hepatitis B virus (HBV) associated cirrhosis has not been fully addressed. Methods: In this cross-sectional study, a total of 457 patients diagnosed decompensated HBV associated cirrhosis who met all inclusion criteria from 2011 to 2018 were analyzed. Association between macrocytic anemia and the liver damaged (Model for End Stage Liver Disease (MELD) score) were examined using multiple logistic regression analyses and identified using smooth curve fitting. Results: Compared with normocytic anemia, MCV and MELD are significantly positively correlated in macrocytic anemia (p < 0.001). A non-linear relationship of MCV and MELD association was found though the piecewise linear spline models in patients with decompensated HBV associated cirrhosis. MCV positive correlated with MELD when the MCV was greater than 98.2 fl (regression coefficient = 0.008, 95% CI 0.1, 0.4). Conclusion: Macrocytic anemia may be a reliable predictor for mortality because it is closely related to the degree of liver damage in patients with decompensated HBV associated cirrhosis.
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Affiliation(s)
- Tian-Yu Zhao
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qing-Wei Cong
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Fang Liu
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Li-Ying Yao
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ying Zhu
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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9
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Acar Ş, Akyıldız M, Gürakar A, Tokat Y, Dayangaç M. Delta MELD as a predictor of early outcome in adult-to-adult living donor liver transplantation. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:782-789. [PMID: 33361041 DOI: 10.5152/tjg.2020.18761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS An increased post-operative mortality risk has been reported among patients who undergo living donor liver transplantation (LDLT) with higher model for end-stage liver disease (MELD) scores. In this study, we investigated the effect of MELD score reduction on post-operative outcomes in patients with a high MELD (≥20) score by pre-transplant management. MATERIALS AND METHODS We retrospectively analyzed 386 LDLT cases, and patients were divided into low-MELD (<20, n=293) vs. high-MELD (≥20, n=93) groups according to their MELD score at the time of index hospitalization. Patients in the high-MELD group were managed specifically according to a treatment algorithm in an effort to decrease the MELD score. Patients in the high-MELD group were further divided into 2 subgroups: (1) responders (n=34) to pre-transplant treatment with subsequent reduction of the MELD score by a minimum of 1 point vs. (2) non-responders (n=59), whose MELD score remained unchanged or further increased on the day of LDLT. Responders vs. non-responders were compared according to etiology, demographics, and survival.
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Affiliation(s)
- Şencan Acar
- Department of Gastroenterology and Hepatology, Section of Transplant Hepatology, Johns Hopkins University School of Medicine Baltimore, MD, USA;Department of Gastroenterology and Organ Transplantation Center, Sakarya University School of Medicine, Sakarya, Turkey
| | - Murat Akyıldız
- Department of Gastroenterology and Organ Transplantation Center, Koc University School of Medicine, İstanbul, Turkey
| | - Ahmet Gürakar
- Department of Gastroenterology and Hepatology, Section of Transplant Hepatology, Johns Hopkins University School of Medicine Baltimore, MD, USA
| | - Yaman Tokat
- Department of General Surgery and Liver Transplantation Unit, Florence Nightingale Hospital, Istanbul Bilim University, İstanbul, Turkey
| | - Murat Dayangaç
- Department of General Surgery and Liver Transplantation Unit, Medipol Mega University Hospital, İstanbul, Turkey
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10
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Abstract
Risk scoring for patients with cirrhosis has evolved greatly over the past several decades. However, patients with low Model for End-Stage Liver Disease-Sodium scores still suffer from liver-related morbidity and mortality. Unfortunately, it is not clear which of these low Model for End-Stage Liver Disease-Sodium score patients would benefit from earlier consideration of liver transplantation. This article reviews the literature of risk prediction in patients with cirrhosis, identifies which patients may benefit from earlier interventions, such as transplantation, and proposes directions for future research.
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11
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Potluri VS, Sokolich J, Buggs J, Mcclellan W, Rogers E, Barber K, Cocuy K, Kumar A, Bowers V. Outcomes in Hepatocellular Carcinoma Liver Transplantation before and after the Mandated Six-Month Wait Time. Am Surg 2020. [DOI: 10.1177/000313481908500845] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The United Network for Organ Sharing (UNOS) implemented a policy that requires patients with hepatocellular carcinoma seeking liver transplantation to wait six months before being granted Model for End-Stage Liver Disease exception points. We investigated the difference in resource utilization between patients who underwent liver transplantation before and after the present policy. We conducted a retrospective cohort study of adult liver transplants from 2013 to 2018. Patients were classified into prepolicy or postpolicy groups based on 964 days before or after the wait-time policy. We also retrieved national survival outcome data from United Network for Organ Sharing. Differences across compared groups for continuous variables were assessed using the independent sample t test, and the chi-squared test was used for binary variables. We found statistical differences in recipient age ( P = 0.005), days on wait-list ( P = 0.001), sustained viro-logical response ( P < 0.001), and hepatocellular carcinoma recurrence one year posttransplant ( P = 0.04). There were statistically significant differences in the number of treatment days pretransplant and length of transplant admission stay, indicating an increase in resource utilization in the postpolicy group. No statistically significant differences were found between groups in one-year graft or patient survival despite an observed increase in resource utilization by the hepatocellular carcinoma postpolicy group.
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Affiliation(s)
| | - Julio Sokolich
- Department of Transplant Surgery, Tampa General Medical Group, Tampa, Florida
| | - Jacentha Buggs
- Department of Transplant Surgery, Tampa General Medical Group, Tampa, Florida
| | - William Mcclellan
- Department of Cell and Molecular Biology, University of South Florida, Tampa, Florida
| | - Ebonie Rogers
- Department of Transplant Research, Tampa General Hospital, Tampa, Florida; and
| | - Kristina Barber
- Department of Transplant Surgery, Tampa General Medical Group, Tampa, Florida
| | - Kristal Cocuy
- Department of Transplant Surgery, Tampa General Medical Group, Tampa, Florida
| | - Ambuj Kumar
- Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Victor Bowers
- Department of Transplant Surgery, Tampa General Medical Group, Tampa, Florida
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12
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Piotrowski D, Sączewska-Piotrowska A, Jaroszewicz J, Boroń-Kaczmarska A. Lymphocyte-To-Monocyte Ratio as the Best Simple Predictor of Bacterial Infection in Patients with Liver Cirrhosis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17051727. [PMID: 32155772 PMCID: PMC7084714 DOI: 10.3390/ijerph17051727] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 03/01/2020] [Accepted: 03/04/2020] [Indexed: 12/17/2022]
Abstract
Background and aim: The aim of this study was to assess the diagnostic performance of new morphology-related indices and Child–Turcotte–Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores during hospitalization in predicting the onset of bacterial infection in patients with liver cirrhosis. Material and methods: A total of 171 patients (56.9% males; median age 59 years; total number of hospitalizations 209) with liver cirrhosis were included in this observational study. The diagnosis of cirrhosis was made on the basis of clinical, biochemical, ultrasonic, histological, and endoscopic findings. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), modified aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), Fibrosis-4 index (FIB-4), platelet-to-lymphocyte ratio (PLR), neutrophil-to-monocyte ratio (NMR), and CTP and MELD scores were calculated for the cases of patients with cirrhosis. Results: Bacterial infection was diagnosed in 60 of the 209 (28.7%) hospitalizations of patients with cirrhosis. The most common infections were urinary tract infection (UTI), followed by pneumonia and sepsis. The more severe the liver failure, the greater the bacterial infection prevalence and mortality. Patients with decompensated liver cirrhosis were infected more often than subjects with compensated cirrhosis (50.0% vs. 12.9%, p = 0.003). The calculated MELD score, CTP, NLR, LMR, AAR, monocyte count, and C-reactive protein (CRP) concentration were also related to the bacterial infection prevalence, and mortality areas under the curve (AUC) were 0.629, 0.687, 0.606, 0.715, 0.610, 0.648, and 0.685, respectively. The combined model with two variables (LMR and CTP) had the best AUC of 0.757. The most common bacteria isolated from patients with UTI were Escherichia coli, Enterococcus faecalis, and Klebsiella pneumonia. Gram-negative bacteria were also responsible for spontaneous bacterial peritonitis (SBP), and together with gram-positive streptococci and staphylococci, these microorganisms were isolated from blood cultures of patients with sepsis. Significant differences were found between CTP classification, MELD score, NLR, LMR, AAR, CRP, and PLR in patients with cirrhosis with, or without, bacterial infection. Conclusions: Bacterial infection prevalence is relatively high in patients with liver cirrhosis. Although all analyzed scores, including the LMR, NLR, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), CRP, CTP, and MELD, allowed the prediction of bacterial occurrence, the LMR had the highest clinical utility, according to the area under the curve (AUC) and odds ratio (OR).
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Affiliation(s)
- Damian Piotrowski
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland;
- Correspondence: ; Tel.: +48-501-492-461
| | - Anna Sączewska-Piotrowska
- Department of Labour Market Research and Forecasting, University of Economics, 40-287 Katowice, Poland;
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Anna Boroń-Kaczmarska
- Department of Infectious Diseases, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland;
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13
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Brock GN, Washburn K, Marvin MR. Use of rapid Model for End-Stage Liver Disease (MELD) increases for liver transplant registrant prioritization after MELD-Na and Share 35, an evaluation using data from the United Network for Organ Sharing. PLoS One 2019; 14:e0223053. [PMID: 31581270 PMCID: PMC6776460 DOI: 10.1371/journal.pone.0223053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 09/12/2019] [Indexed: 11/20/2022] Open
Abstract
The Model for End-Stage Liver Disease (MELD) score has been successfully used to prioritize patients on the United States liver transplant waiting list since its adoption in 2002. The United Network for Organ Sharing (UNOS)/Organ Procurement Transplantation Network (OPTN) allocation policy has evolved over the years, and notable recent changes include Share 35, inclusion of serum sodium in the MELD score, and a ‘delay and cap’ policy for hepatocellular carcinoma (HCC) patients. We explored the potential of a registrant’s change in 30-day MELD scores (ΔMELD30) to improve allocation both before and after these policy changes. Current MELD and ΔMELD30 were evaluated using cause-specific hazards models for waitlist dropout based on US liver transplant registrants added to the waitlist between 06/30/2003 and 6/30/2013. Two composite scores were constructed and then evaluated on UNOS data spanning the current policy era (01/02/2016 to 09/07/2018). Predictive accuracy was evaluated using the C-index for model discrimination and by comparing observed and predicted waitlist dropout probabilities for model calibration. After the change to MELD-Na, increased dropout associated with ΔMELD30 jumps is no longer evident at MELD scores below 30. However, the adoption of Share 35 has potentially resulted in discrepancies in waitlist dropout for patients with sharp MELD increases at higher MELD scores. Use of the ΔMELD30 to add additional points or serve as a potential tiebreaker for patients with rapid deterioration may extend the benefit of Share 35 to better include those in most critical need.
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Affiliation(s)
- Guy N. Brock
- Department of Biomedical Informatics and Center for Biostatistics, College of Medicine, The Ohio State University, Columbus, OH, United States of America
- Department of Surgery, Division of Transplantation Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America
- Center for Surgical Health Assessment, Research and Policy (SHARP), Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America
- * E-mail:
| | - Kenneth Washburn
- Department of Surgery, Division of Transplantation Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America
| | - Michael R. Marvin
- Department of Transplantation and Liver Surgery, Geisinger Medical Center, Danville, PA, United States of America
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Cholankeril G, Li AA, Dennis BB, Gadiparthi C, Kim D, Toll AE, Maliakkal BJ, Satapathy SK, Nair S, Ahmed A. Pre-Operative Delta-MELD is an Independent Predictor of Higher Mortality following Liver Transplantation. Sci Rep 2019; 9:8312. [PMID: 31165776 PMCID: PMC6549161 DOI: 10.1038/s41598-019-44814-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 05/14/2019] [Indexed: 12/13/2022] Open
Abstract
Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.
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Affiliation(s)
- George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Andrew A Li
- Department of Internal Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Brittany B Dennis
- Department of Medicine, Saint George's Hospital, University of London, London, UK
| | - Chiranjeevi Gadiparthi
- Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Alice E Toll
- Department of Research, United Network for Organ Sharing, Richmond, VA, USA
| | - Benedict J Maliakkal
- Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Sanjaya K Satapathy
- Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Satheesh Nair
- Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.
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Predictive power of Model for End-Stage Liver Disease and Child-Turcotte-Pugh score for mortality in cirrhotic patients. Clin Exp Hepatol 2018; 4:240-246. [PMID: 30603671 PMCID: PMC6311743 DOI: 10.5114/ceh.2018.80125] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 05/18/2018] [Indexed: 01/28/2023] Open
Abstract
Aim of the study To assess the performance of Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores' kinetics during hospitalization in predicting in-hospital mortality in patients with liver cirrhosis. Material and methods One hundred and seventy-four cases of hospitalized liver cirrhosis patients were selected. The diagnosis of cirrhosis was made based on clinical, biochemical, ultrasonic, histological, and endoscopic findings and results. CTP and MELD scores at admission and ΔCTP and ΔMELD were calculated. Univariate and multivariate logistic regression and receiver-operating characteristic (ROC) curve analysis were performed. In the models, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The area under the ROC curve (AUC) was used to measure the accuracy. For the optimal cutoff point, sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) were calculated. The Kaplan-Meier method was used to construct survival curves, and the log-rank test was used to compare time to death, with respect to MELD and CTP categories. Results Among the assessed scores, the highest area under the ROC curve (AUC) in univariate logistic regression analysis was calculated for ΔMELD ≥ 1, followed by ΔCTP ≥ 1, CTP > 8, and MELD > 17. Based on the selected criteria, multivariate models were created that were characterized by an outstanding ability to predict the in-hospital mortality. Conclusions In-hospital mortality is relatively high in patients with liver cirrhosis. The combination of CTP and MELD scoring methods, combined with their kinetics, allows for the prediction of short-term mortality.
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16
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Yang J, Yan B, Yang L, Li H, Fan Y, Zhu F, Zheng J, Ma X. Macrocytic anemia is associated with the severity of liver impairment in patients with hepatitis B virus-related decompensated cirrhosis: a retrospective cross-sectional study. BMC Gastroenterol 2018; 18:161. [PMID: 30384828 PMCID: PMC6211489 DOI: 10.1186/s12876-018-0893-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 10/23/2018] [Indexed: 12/18/2022] Open
Abstract
Background Macrocytic anemia is common in liver disease. However, its role in hepatitis B virus (HBV)-related decompensated cirrhosis remains unknown. The aim of the present study was to determine the association between macrocytic anemia and the severity of liver impairment in patients with HBV-related decompensated cirrhosis according to the Model for End Stage Liver Disease (MELD) score. Methods A total of 463 participants who fulfilled our criteria were enrolled in this cross-sectional study. Patients were classified into three groups according to anemia types, diagnosed based on their mean corpuscular volume level. Multivariate linear regression analyses were used to determine the association between macrocytic anemia and the MELD score for patients with HBV-related decompensated cirrhosis. Results Patients with macrocytic anemia had evidently higher MELD scores (10.8 ± 6.6) than those with normocytic anemia (8.0 ± 5.5) or microcytic anemia (6.3 ± 5.1). The association remained robust after adjusting for age, gender, smoking, drinking, and total cholesterol (β = 1.94, CI: 0.81–3.07, P < 0.001). Conclusions Macrocytic anemia was found to be associated with the severity of liver impairment and might be a predictor for short-term mortality in patients with HBV-related decompensated cirrhosis.
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Affiliation(s)
- Jian Yang
- Clinical Research Center, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China
| | - Bin Yan
- Clinical Research Center, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China
| | - Lihong Yang
- Clinical Research Center, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China
| | - Huimin Li
- Department of Psychiatry, the First Affiliated Hospital, Xi'an Jiaotong University, No.277 Yanta West Road, Yanta District, Xi'an, 710061, People's Republic of China
| | - Yajuan Fan
- Department of Psychiatry, the First Affiliated Hospital, Xi'an Jiaotong University, No.277 Yanta West Road, Yanta District, Xi'an, 710061, People's Republic of China
| | - Feng Zhu
- Center for Translational Medicine, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China
| | - Jie Zheng
- Clinical Research Center, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China
| | - Xiancang Ma
- Department of Psychiatry, the First Affiliated Hospital, Xi'an Jiaotong University, No.277 Yanta West Road, Yanta District, Xi'an, 710061, People's Republic of China.
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17
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Ascites Neutrophil Gelatinase-Associated Lipocalin Identifies Spontaneous Bacterial Peritonitis and Predicts Mortality in Hospitalized Patients with Cirrhosis. Dig Dis Sci 2017; 62:3487-3494. [PMID: 29098551 DOI: 10.1007/s10620-017-4804-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 10/10/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of both tissue injury and infection. Urine NGAL levels strongly predict acute kidney injury and mortality in patients with cirrhosis, but ascites NGAL is not well characterized. We hypothesized that ascites NGAL level is a marker of spontaneous bacterial peritonitis (SBP) and mortality risk in patients with cirrhosis. METHODS Hospitalized patients with cirrhosis and ascites undergoing diagnostic paracentesis were prospectively enrolled and followed until death or discharge. Patients with secondary peritonitis, prior transplantation, or active colitis were excluded. NGAL was measured in the ascites and serum. Ascites NGAL level was evaluated as a marker of SBP (defined as ascites absolute neutrophil count > 250 cells/mm3) and predictor of in-patient mortality. RESULTS A total of 146 patients were enrolled, and of these, 29 patients (20%) had SBP. Baseline characteristics were similar between subjects with and without SBP. Median (IQR) ascites NGAL was significantly higher in patients with SBP compared to those without SBP (221.3 [145.9-392.9] vs. 139.2 [73.9-237.2], p < 0.01). Sixteen (11%) patients died in the hospital. In the final multivariable model, ascites NGAL (OR 1.02 per 10 units, p < 0.01) remained predictive of in-hospital mortality, controlling for SBP (OR 9.76, p < 0.01) and MELD (OR 1.11, p = 0.01). In ROC analysis, ascites NGAL had an AUC of 0.79 for inhospital mortality, and the final model including ascites NGAL, MELD, and SBP had an AUC of 0.94. CONCLUSIONS Ascites NGAL level may be a biomarker of peritonitis in hospitalized patient with cirrhosis and an independent predictor of short-term in-hospital mortality, even controlling for SBP and MELD.
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18
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Utility of post-liver transplantation MELD and delta MELD in predicting early and late mortality. Eur J Gastroenterol Hepatol 2017; 29:1424-1427. [PMID: 28957872 DOI: 10.1097/meg.0000000000000957] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The performance of early post-liver transplantation (post-LT) model for end-stage liver disease (MELD) or even its dynamic changes over time (ΔMELD) in predicting the mortality after LT is still controversial. AIM The aim of this study was to assess the ability of absolute and ΔMELD calculated at days 7 and 30 after LT to predict 1- and 5-year mortality. PATIENTS AND METHODS Data of 209 consecutive patients who underwent LT in two centers were reviewed. Patients who received LT for hepatocellular carcinoma were excluded, as well as those who did not survive for at least 1 month. MELD and [INCREMENT]MELD were calculated for each patient at 7 and 30 days after LT. RESULTS One hundred fifty-six patients were included, mostly male [104 (66.7%)] with a mean age of 51.9±8.8 years. The main indications for transplantation were decompensated hepatitis C virus-related liver cirrhosis [138 (88.5%)] and hepatitis C and B virus co-infection [10 (6.4%)]. Grafts were obtained from 104 living donors and 52 deceased donors. Survival at 1 and 5 years was 89.7 and 85.9%, respectively, with a mean survival of 52.3±1.5 months. In univariate analysis, both absolute and ΔMELD at postoperative days 7 and 30 significantly predicted 1- and 5-year post-LT mortality. In multivariate analysis, MELD at postoperative day 30 was significantly associated with 1- (odds ratio: 1.24, 95% confidence interval: 1.14-1.35, P<0.0001) and 5-year mortality (odds ratio: 1.23, 95% confidence interval: 1.14-1.33, P<0.0001). The area under the curve for MELD at 30 days post-LT in the prediction of mortality was 0.823 (P=0.01) at 1 year and 0.812 (P<0.001) at 5 years. A cutoff of post-LT day 30 MELD less than 10 could predict mortality with a sensitivity and specificity of 90 and 68.1% at 1 year and 81.3 and 69.7% at 5 years, respectively. CONCLUSION Failure of the MELD score to decline over the first postoperative month to less than 10 is a significant predictor of both early and late post-LT mortality.
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Spengler EK, Hunsicker LG, Zarei S, Zimmerman MB, Voigt MD. Transjugular intrahepatic portosystemic shunt does not independently increase risk of death in high model for end stage liver disease patients. Hepatol Commun 2017; 1:460-468. [PMID: 29404473 PMCID: PMC5721420 DOI: 10.1002/hep4.1053] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 04/14/2017] [Accepted: 04/22/2017] [Indexed: 12/15/2022] Open
Abstract
Physicians often exclude patients with a model for end-stage liver disease (MELD) score ≥ 18 from a transjugular intrahepatic portosystemic shunt (TIPS) procedure due to the concern for higher risk of death. We aimed to determine if TIPS increased the risk of death in these patients. We analyzed the interaction between TIPS and MELD in 106 patients with TIPS and 79 with intractable ascites without TIPS. We performed Cox proportional hazard regression, including both TIPS and MELD as time-dependent covariates together with their interaction, to calculate the impact of TIPS on the risk of death associated with a high MELD score. We found a negative interaction between a high MELD score and a history of TIPS, with potentially important effect sizes. Patients with MELD scores ≥18 had a 51% lower incremental risk of death (lower risk than would be expected from the combined independent risks of MELD and needing/receiving TIPS) associated with TIPS than patients with MELD scores <18 (hazard ratio for TIPS, 0.49; 95% confidence interval, 0.10-2.45) in the first 6 months following TIPS. There was an 80% lower incremental risk of death among patients with a MELD score ≥18 (hazard ratio for TIPS, 0.20; 95% confidence interval, 0.03-1.23) 6 months after the TIPS procedure. Conclusion: Risk of death is associated with underlying disease severity as shown by the MELD score and the need for TIPS, and both history of TIPS and high MELD score independently increased the risk of mortality. However, the risk of death after TIPS was progressively lower than expected as the MELD score increased. (Hepatology Communications 2017;1:460-468).
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Affiliation(s)
- Erin K Spengler
- Division of Gastroenterology and Hepatology Department of Internal Medicine, The University of Iowa Hospitals and Clinics Iowa City IA.,University of Wisconsin, School of Medicine and Public Health Madison WI
| | - Lawrence G Hunsicker
- Division of Nephrology Department of Internal Medicine, The University of Iowa Hospitals and Clinics Iowa City IA
| | - Sanam Zarei
- Carver College of Medicine The University of Iowa Hospitals and Clinics Iowa City IA
| | - M Bridget Zimmerman
- Department of Biostatistics The University of Iowa Hospitals and Clinics Iowa City IA
| | - Michael D Voigt
- Division of Gastroenterology and Hepatology Department of Internal Medicine, The University of Iowa Hospitals and Clinics Iowa City IA
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20
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Machicao VI. Model for End-Stage Liver Disease-Sodium Score: The Evolution in the Prioritization of Liver Transplantation. Clin Liver Dis 2017; 21:275-287. [PMID: 28364813 DOI: 10.1016/j.cld.2016.12.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The adoption of the model of end-stage liver disease (MELD) score as surrogate marker of liver disease severity has been the greatest change in liver allocation. Since its implementation, waiting time has lost significance. The MELD score calculation was later modified to reflect the contribution of hyponatremia in the estimation of mortality risk. However, the MELD score does not capture accurately the risk of mortality of patients with hepatocellular carcinoma (HCC). Therefore the arbitrary assignment of MELD points has been used for HCC patients. The current allocation system still prioritizes transplantation in HCC patients.
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Affiliation(s)
- Victor Ilich Machicao
- Division of Gastroenterology, Hepatology and Nutrition, McGovern Medical School, University of Texas Health Science Center at Houston, 6400 Fannin Street, MSB 4.234, Houston, TX 77030, USA.
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Pannu AK, Bhalla A, Rao C, Singh C. Delta model for end-stage liver disease and delta clinical prognostic indicator as predictors of mortality in patients with viral acute liver failure. Int J Crit Illn Inj Sci 2017; 7:252-255. [PMID: 29291180 PMCID: PMC5737069 DOI: 10.4103/ijciis.ijciis_122_16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Objective: The objective of the study is to compare the model for end-stage liver disease (MELD) with clinical prognostic indicators (CPI) specifically the change in these parameters after 48 h of admission in predicting the mortality in patients with acute liver failure (ALF) due to acute viral hepatitis. Materials and Methods: An open label, investigator-initiated prospective study was conducted that included 41 patients with acute viral hepatitis with ALF. The cases were followed prospectively till death or discharge. The MELD and CPI were calculated at admission and 48 h of admission. Results: Patients having no change or worsening in CPI score, i.e., delta CPI more negative had a higher mortality over the next 48 h compared to patients having an improvement in their respective CPI score. Delta CPI predicted adverse outcome better than the presence of any three CPI on admission (P = 0.019). Patients having no change or a worsening in MELD score, i.e., delta MELD more negative, had a higher mortality in the next 48 h compared to the patients having improvement in their respective MELD score. However, MELD >33 on admission was superior to delta MELD in predicting the adverse outcome (P = 0.019). Conclusion: Among the patients with ALF due to viral hepatitis, delta CPI was found to be superior to delta MELD in predicting the adverse outcome in patients with viral ALF (P < 0.0001).
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Affiliation(s)
- Ashok Kumar Pannu
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Bhalla
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Chelapati Rao
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Charanpreet Singh
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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22
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Ruf AE, Dirchwolf M, Biggins SW, Villamil FG. Revising metrics for aggressiveness assessment in liver transplantation centers. J Hepatol 2016; 65:1066-1067. [PMID: 27476766 DOI: 10.1016/j.jhep.2016.06.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 06/07/2016] [Accepted: 06/28/2016] [Indexed: 12/04/2022]
Affiliation(s)
- Andrés E Ruf
- FUNDIEH (Fundación para la Docencia e Investigación de las Enfermedades del Hígado), Buenos Aires, Argentina; Liver Transplant Unit, British Hospital of Buenos Aires, Buenos Aires, Argentina.
| | - Melisa Dirchwolf
- FUNDIEH (Fundación para la Docencia e Investigación de las Enfermedades del Hígado), Buenos Aires, Argentina
| | - Scott W Biggins
- Division of Gastroenterology and Hepatology, University of Colorado, Denver, CO, USA
| | - Federico G Villamil
- FUNDIEH (Fundación para la Docencia e Investigación de las Enfermedades del Hígado), Buenos Aires, Argentina; Liver Transplant Unit, British Hospital of Buenos Aires, Buenos Aires, Argentina
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23
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Györi GP, Silberhumer GR, Rahmel A, de Vries E, Soliman T, Zehetmayer S, Rogiers X, Berlakovich GA. Impact of dynamic changes in MELD score on survival after liver transplantation - a Eurotransplant registry analysis. Liver Int 2016; 36:1011-7. [PMID: 26814059 DOI: 10.1111/liv.13075] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 01/14/2016] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS With restricted numbers of available organs, futility in liver transplantation has to be avoided. The concept of dynamic changes in MELD score (DeltaMELD) has previously been shown to be a simple tool to identify patients with the greatest risk of death after transplantation. Aim was to validate this concept with the Eurotransplant (ET) database. METHODS A retrospective registry analysis was performed on all patients listed for liver transplantation within ET between 2006 and 2011. Patients <18 years of age, acute liver failure, malignancy and patients listed for retransplantation were excluded. Influence of MELD at listing (MELDon), MELD at transplantation (MELDoff), DeltaMELD, age, sex, underlying disease and time on the waiting list on overall survival after liver transplantation were evaluated. RESULTS A total of 16 821 patients were listed for liver transplantation, 8096 met the inclusion criteria. Age, MELD on and DeltaMELD showed significant influence on survival on the waiting list. Age and DeltaMELD showed influence on survival after liver transplantation, with DeltaMELD>10 showing a 1.6-fold increased risk of death. CONCLUSION The concept of DeltaMELD was validated in a large, prospective data set. It provides a simple tool to identify patients with increased risk of death after liver transplantation and might help improve long-term results.
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Affiliation(s)
- Georg P Györi
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | | | - Axel Rahmel
- Eurotransplant Foundation, Leiden, the Netherlands
| | | | - Thomas Soliman
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Sonja Zehetmayer
- Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Xavier Rogiers
- Department of Surgery and Transplantation, University Hospital and Medical School, Gent, Belgium
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Cheng XP, Zhao J, Chen Y, Meng FK, Xu B, Yu HW, Meng QH, Liu YM, Zhang SB, Meng S, Zhang JY, Zhang JY, Duan ZP, Zheng SJ. Comparison of the ability of the PDD-ICG clearance test, CTP, MELD, and MELD-Na to predict short-term and medium-term mortality in patients with decompensated hepatitis B cirrhosis. Eur J Gastroenterol Hepatol 2016; 28:444-448. [PMID: 26649802 PMCID: PMC4777221 DOI: 10.1097/meg.0000000000000538] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Accepted: 10/26/2015] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Various methods, including the indocyanine green (ICG) clearance test, the Child-Turcotte-Pugh score (CTP), model for end-stage liver disease (MELD), and MELD combined with serum sodium concentration (MELD-Na), have been used widely in liver function evaluation in patients with end-stage liver disease. In this study, we compared the ability of these methods to predict mortality in patients with decompensated hepatitis B cirrhosis. METHODS A total of 98 patients with decompensated hepatitis B cirrhosis were included in this study and followed up for 12 months. The ICG-derived measurements (ICG-PDR, ICG-R15, EHBF), CTP, MELD, and MELD-Na were obtained within 2 days after patients' admission and patients' survival at 1, 3, 6, and 12 months was recorded. Receiver operating curve was used to evaluate the ability of these methods to predict mortality in these patients with decompensated hepatitis B cirrhosis. RESULTS At 1 month, 3 months, 6 months and 12 months, the cumulative number of deaths and liver transplant recipients was 12 (12.2%), 17 (17.3%), 21 (21.4%) and 25 (25.5%), respectively. The ICG-derived measurements, CTP, MELD, and MELD-Na of nonsurvivors were significantly different compared with that in survivors. All methods yielded viable values in predicting short-term and medium-term prognosis for patients with decompensated hepatitis B cirrhosis, with most area under the curve exceeding 0.8. Moreover, the ICG-derived measurements showed a significant correlation with that of CTP, MELD, and MELD-Na. CONCLUSION All four methods, ICG clearance test, CTP, MELD, and MELD-Na, provided reliable prediction of mortality in patients with decompensated hepatitis B cirrhosis for both short-term and medium-term prognosis.
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Affiliation(s)
- Xiang-Pu Cheng
- aArtificial Liver Center Departments of bUltrasound cEndocrinology and Hepatology dSevere Liver Disease eAutoimmune Liver Disease fGastroenterology gScientific Research, Beijing Youan Hospital, Capital Medical University, Beijing, China
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25
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Gelu-Simeon M, Bayan T, Ostos M, Boufassa F, Teicher E, Steyaert JM, Bertucci I, Anty R, Pageaux GP, Meyer L, Duclos-Vallée JC. MELD Score Kinetics in Decompensated HIV+/HCV+ Patients: A Useful Prognostic Tool (ANRS HC EP 25 PRETHEVIC Cohort Study). Medicine (Baltimore) 2015; 94:e1239. [PMID: 26222860 PMCID: PMC4554127 DOI: 10.1097/md.0000000000001239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
To assess prognostic factors for survival and describe Model for End-Stage liver disease (MELD) dynamics in human immunodeficiency virus+/hepatitis C virus+ (HIV+/HCV+) patients after an initial episode of hepatic decompensation.An HIV+/HCV+ cohort of patients experiencing an initial decompensation episode within the year preceding enrollment were followed prospectively. Clinical and biological data were collected every 3 months. Predictors for survival were identified using Kaplan-Meier curves and Cox models. A 2-slope-mixed linear model was used to estimate MELD score changes as a function of survival.Sixty seven patients were included in 32 centers between 2009 and 2012 (72% male; median age: 48 years [interquartile ratio (IQR):45-52], median follow-up: 22.4 months [range: 0.5-65.3]). Overall survival rates were 86%, 78%, and 59% at 6, 12, and 24 months, respectively. Under multivariate analysis, the MELD score at initial decompensation was predictive of survival, adjusted for age, type of decompensation, baseline CD4 counts, and further decompensation during follow-up as a time-dependent variable. The adjusted hazard ratio of death was 1.32 for a score 3 points higher (95% CI: [1.06-1.63], P = 0.012). MELD score kinetics within the 6 months after initial decompensation differed significantly between non-deceased and deceased patients, with a decreased (-0.49/month; P = 0.016), versus a flat (+0.06/month, P = 0.753) mean change in score.MELD is an effective tool to predict survival in HIV+/HCV+ patients with decompensated cirrhosis. A non-decreasing MELD score within 6 months following this initial decompensation episode may benefit from privileged access to liver transplantation in this poor prognosis population.
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Affiliation(s)
- Moana Gelu-Simeon
- From the AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire (MG-S, MO, ET, J-CD-V); DHU Hepatinov, Villejuif (MG-S, MO, ET, J-CD-V); Inserm, UMR 1018 CESP, Centre de Recherche en Epidémiologie et Santé des Populations (TB, FB, LM); Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre (TB, FB, LM, J-CD-V); École Polytechnique, Laboratoire d'Informatique (LIX), Palaiseau (J-MS); ANRS, Agence Nationale de Recherches sur le Sida et les hépatites virales, Paris (IB); Inserm, UMR 1193, Villejuif (J-CD-V); AP-HP Hôpital de Bicêtre, Service de Médecine Interne, Immunologie Clinique et Maladies Infectieuses, Le Kremlin-Bicêtre (ET); Centre Hospitalier Universitaire de Nice - Hôpital de l'Archet, Service d'Hépato-gastroentérologie, Nice (RA); Université de Nice-Sophia-Antipolis, Faculté de Médecine (RA); Inserm, Unité 1065, Nice (RA); Centre Hospitalier Régional Universitaire de Montpellier - Hôpital Saint-Eloi, Service d'Hépato-Gastroentérologie et Transplantation (G-PP); Université Montpellier 1, Faculté de Médecine, Montpellier (G-PP); CHU de Pointe-à-Pitre, Service d'Hépato-Gastro-Entérologie, Pointe-à-Pitre Cedex, Guadeloupe (MG-S); Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement and Travail (IRSET), Rennes (MG-S); and AP-HP Hôpital Bicêtre, Service de Santé Publique, Le Kremlin-Bicêtre, France (LM)
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26
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Massie AB, Luo X, Alejo JL, Poon AK, Cameron AM, Segev DL. Higher Mortality in registrants with sudden model for end-stage liver disease increase: Disadvantaged by the current allocation policy. Liver Transpl 2015; 21:683-9. [PMID: 25762287 DOI: 10.1002/lt.24102] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Accepted: 02/16/2015] [Indexed: 12/31/2022]
Abstract
Liver allocation is based on current Model for End-Stage Liver Disease (MELD) scores, with priority in the case of a tie being given to those waiting the longest with a given MELD score. We hypothesized that this priority might not reflect risk: registrants whose MELD score has recently increased receive lower priority but might have higher wait-list mortality. We studied wait-list and posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By likelihood maximization, we empirically defined a MELD spike as a MELD increase ≥ 30% over the previous 7 days. At any given time, only 0.6% of wait-list patients experienced a spike; however, these patients accounted for 25% of all wait-list deaths. Registrants who reached a given MELD score after a spike had higher wait-list mortality in the ensuing 7 days than those with the same resulting MELD score who did not spike, but they had no difference in posttransplant mortality. The spike-associated wait-list mortality increase was highest for registrants with medium MELD scores: specifically, 2.3-fold higher (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD score and spikes predicted wait-list mortality risk much better than a model incorporating only the MELD score. Registrants with a sudden MELD increase have a higher risk of short-term wait-list mortality than is indicated by their current MELD score but have no increased risk of posttransplant mortality; allocation policy should be adjusted accordingly.
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Affiliation(s)
- Allan B Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD
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27
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King A, Barton D, Beard HA, Than N, Moore J, Corbett C, Thomas J, Guo K, Guha I, Hollyman D, Stocken D, Yap C, Fox R, Forbes SJ, Newsome PN. REpeated AutoLogous Infusions of STem cells In Cirrhosis (REALISTIC): a multicentre, phase II, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony-stimulating factor (GCSF) mobilised CD133+ bone marrow stem cells in patients with cirrhosis. A study protocol for a randomised controlled trial. BMJ Open 2015; 5:e007700. [PMID: 25795699 PMCID: PMC4368910 DOI: 10.1136/bmjopen-2015-007700] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Liver disease mortality and morbidity are rapidly rising and liver transplantation is limited by organ availability. Small scale human studies have shown that stem cell therapy is safe and feasible and has suggested clinical benefit. No published studies have yet examined the effect of stem cell therapy in a randomised controlled trial and evaluated the effect of repeated therapy. METHODS AND ANALYSIS Patients with liver cirrhosis will be randomised to one of three trial groups: group 1: Control group, Standard conservative management; group 2 treatment: granulocyte colony-stimulating factor (G-CSF; lenograstim) 15 µg/kg body weight daily on days 1-5; group 3 treatment: G-CSF 15 µg/kg body weight daily on days 1-5 followed by leukapheresis, isolation and aliquoting of CD133+ cells. Patients will receive an infusion of freshly isolated CD133+ cells immediately and frozen doses at days 30 and 60 via peripheral vein (0.2×10(6) cells/kg for each of the three doses). Primary objective is to demonstrate an improvement in the severity of liver disease over 3 months using either G-CSF alone or G-CSF followed by repeated infusions of haematopoietic stem cells compared with standard conservative management. The trial is powered to answer two hypotheses of each treatment compared to control but not powered to detect smaller expected differences between the two treatment groups. As such, the overall α=0.05 for the trial is split equally between the two hypotheses. Conventionally, to detect a relevant standardised effect size of 0.8 point reduction in Model for End-stage Liver Disease score using two-sided α=0.05(overall α=0.1 split equally between the two hypotheses) and 80% power requires 27 participants to be randomised per group (81 participants in total). ETHICS AND DISSEMINATION The trial is registered at Current Controlled Trials on 18 November 2009 (ISRCTN number 91288089, EuDRACT number 2009-010335-41). The findings of this trial will be disseminated to patients and through peer-reviewed publications and international presentations.
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Affiliation(s)
- A King
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
| | - D Barton
- NIHR Liver BRU Clinical trials group (EDD), CRUK clinical trials unit, University of Birmingham, Birmingham, UK
| | - H A Beard
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK Cellular and Molecular Therapies, NHS Blood and Transplant, Birmingham, UK
| | - N Than
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - J Moore
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - C Corbett
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - J Thomas
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - K Guo
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - I Guha
- National Institute for Health Research Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - D Hollyman
- Cellular and Molecular Therapies, NHS Blood and Transplant, Birmingham, UK
| | - D Stocken
- Newcastle Clinical Trial Unit, Institute of Health and Society, Newcastle University, Newcastle, UK
| | - C Yap
- NIHR Liver BRU Clinical trials group (EDD), CRUK clinical trials unit, University of Birmingham, Birmingham, UK
| | - R Fox
- NIHR Liver BRU Clinical trials group (EDD), CRUK clinical trials unit, University of Birmingham, Birmingham, UK
| | - S J Forbes
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - P N Newsome
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
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28
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Herden U, Grabhorn E, Briem-Richter A, Ganschow R, Nashan B, Fischer L. Developments in pediatric liver transplantation since implementation of the new allocation rules in Eurotransplant. Clin Transplant 2014; 28:1061-8. [DOI: 10.1111/ctr.12420] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2014] [Indexed: 12/28/2022]
Affiliation(s)
- Uta Herden
- Department of Hepatobiliary and Transplant Surgery; University Medical Centre Hamburg-Eppendorf; Germany
| | - Enke Grabhorn
- Department of Pediatric Hepatology and Liver Transplantation; University Medical Centre Hamburg-Eppendorf; Germany
| | - Andrea Briem-Richter
- Department of Pediatric Hepatology and Liver Transplantation; University Medical Centre Hamburg-Eppendorf; Germany
| | - Rainer Ganschow
- Department of Pediatrics; University Medical Centre Bonn; Germany
| | - Björn Nashan
- Department of Hepatobiliary and Transplant Surgery; University Medical Centre Hamburg-Eppendorf; Germany
| | - Lutz Fischer
- Department of Hepatobiliary and Transplant Surgery; University Medical Centre Hamburg-Eppendorf; Germany
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Abstract
Liver disease is a rising cause of mortality and morbidity, and treatment options remain limited. Liver transplantation is curative but limited by donor organ availability, operative risk and long-term complications. The contribution of bone marrow (BM)-derived stem cells to tissue regeneration has been recognised and there is considerable interest in the potential benefits of BM stem cells in patients with liver disease. In chronic liver disease, deposition of fibrous scar tissue inhibits hepatocyte proliferation and leads to portal hypertension. Although initial reports had suggested transdifferentiation of stem cells into hepatocytes, the beneficial effects of BM stem cells are more likely derived from the ability to breakdown scar tissue and stimulate hepatocyte proliferation. Studies in animal models have yielded promising results, although the exact mechanisms and cell type responsible have yet to be determined. Small-scale clinical studies have quickly followed and, although primarily designed to examine safety and feasibility of this approach, have reported improvements in liver function in treated patients. Well-designed, controlled studies are required to fully determine the benefits of BM stem cell therapy.
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Affiliation(s)
- Andrew King
- NIHR Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
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30
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Wang LY, Fan YC, Zhao J, Gao S, Sun FK, Han J, Yang Y, Wang K. Elevated expression of tumour necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 mRNA in peripheral blood mononuclear cells is associated with disease progression of acute-on-chronic hepatitis B liver failure. J Viral Hepat 2014; 21:64-73. [PMID: 24329858 DOI: 10.1111/jvh.12116] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Accepted: 03/30/2013] [Indexed: 12/30/2022]
Abstract
Aberrant immunity response contributes to the pathogenesis of acute-on-chronic hepatitis B liver failure. Tumour necrosis factor-α-induced protein-8 like-2 (TIPE2) is a recently identified molecular to maintain immune homoeostasis, but its role in acute-on-chronic hepatitis B liver failure (ACHBLF) is unknown. We detected TIPE2 mRNA levels in peripheral blood mononuclear cells (PBMCs) from 56 patients with ACHBLF, 60 chronic hepatitis B patients, 24 healthy controls and analysed its role in disease severity and prognosis. TIPE2 mRNA expression in patients with ACHBLF was higher than that of patients with chronic infection or healthy controls. In patients with ACHBLF, TIPE2 mRNA level was positively correlated with serum total bilirubin, international normalized ratio and model for end-stage liver disease scores. Furthermore, the level of TIPE2 mRNA was significantly higher in nonsurvivors than survivors in patients with ACHBLF. The mRNA level of TIPE2 gradually decreased week by week in survivors accompanied by recovery from patients with ACHBLF, while its expression sustained at high levels in nonsurvivors. TIPE2 mRNA level after lipopolysaccharide (LPS) stimulation ex vivo in patients with ACHBLF was higher compared with controls and patients with chronic infection. Meanwhile, cytokines ex vivo secreted were measured as a marker of immune activation. After LPS stimulation, interleukin (IL)-6 and tumour necrosis factor (TNF)-α mRNA expression were reduced in patients with ACHBLF, and a significantly negative correlation was found between TIPE2 and TNF-α mRNA levels. In conclusion, our results identified the potential role of TIPE2 in predicting disease progression and prognosis in patients with ACHBLF by negative regulating of cell-mediated immunity.
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Affiliation(s)
- L-Y Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
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31
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Kim HJ, Lee HW. Important predictor of mortality in patients with end-stage liver disease. Clin Mol Hepatol 2013; 19:105-15. [PMID: 23837134 PMCID: PMC3701842 DOI: 10.3350/cmh.2013.19.2.105] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Accepted: 05/23/2013] [Indexed: 12/13/2022] Open
Abstract
Prognosis is an essential part of the baseline assessment of any disease. For predicting prognosis of end-stage liver disease, many prognostic models were proposed. Child-Pugh score has been the reference for assessing the prognosis of cirrhosis for about three decades in end-stage liver disease. Despite of several limitations, recent large systematic review showed that Child-Pugh score was still robust predictors and it's components (bilirubin, albumin and prothrombin time) were followed by Child-Pugh score. Recently, Model for end-stage liver disease (MELD) score emerged as a "modern" alternative to Child-Pugh score. The MELD score has been an important role to accurately predict the severity of liver disease and effectively assess the risk of mortality. Due to several weakness of MELD score, new modified MELD scores (MELD-Na, Delta MELD) have been developed and validated. This review summarizes the current knowledge about the prognostic factors in end-stage liver disease, focusing on the role of Child-Pugh and MELD score.
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Affiliation(s)
- Hyung Joon Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
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33
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Tsuang WM, Vock DM, Copeland CAF, Lederer DJ, Palmer SM. An acute change in lung allocation score and survival after lung transplantation: a cohort study. Ann Intern Med 2013; 158:650-7. [PMID: 23648947 PMCID: PMC3819715 DOI: 10.7326/0003-4819-158-9-201305070-00004] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Lung transplantation is an effective treatment for patients with advanced lung disease. In the United States, lungs are allocated on the basis of the lung allocation score (LAS), a composite measure of transplantation urgency and utility. Clinical deteriorations result in increases to the LAS; however, whether the trajectory of the LAS has prognostic significance is uncertain. OBJECTIVE To determine whether an acute increase in the LAS before lung transplantation is associated with reduced posttransplant survival. DESIGN Retrospective cohort study of adult lung transplant recipients listed for at least 30 days between 4 May 2005 (LAS implementation) and 31 December 2010 in the United Network for Organ Sharing registry. An acute increase in the LAS was defined as an LAS change (LASΔ) greater than 5 units between the 30 days before and the time of transplantation. Multivariable Cox proportional hazard models were used to examine the relationship between an LASΔ >5 and posttransplant graft survival. SETTING All U.S. lung transplantation centers. PATIENTS 5749 lung transplant recipients. MEASUREMENTS Survival time after lung transplantation. RESULTS 702 (12.2%) patients experienced an LASΔ >5. These patients had significantly worse posttransplant survival (hazard ratio, 1.31 [95% CI, 1.11 to 1.54]; P = 0.001]) after adjustment for the LAS at transplantation (LAS-T) and other clinical covariates. The effect of an LASΔ >5 was independent of the LAS-T, underlying diagnosis, center volume, or donor characteristics. LIMITATION Analysis was based on center-reported data. CONCLUSION An acute increase in LAS before transplantation is associated with posttransplant survival after adjustment for LAS-T. Further emphasis on serial assessment of the LAS could improve the ability to offer accurate prediction of survival after transplantation. PRIMARY FUNDING SOURCE National Institutes of Health.
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Affiliation(s)
- Wayne M Tsuang
- Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina; University of Minnesota School of Public Health, Minneapolis, Minnesota; and College of Physicians and Surgeons and Mailman School of Public Health, Columbia University, New York, New York
| | - David M Vock
- Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina; University of Minnesota School of Public Health, Minneapolis, Minnesota; and College of Physicians and Surgeons and Mailman School of Public Health, Columbia University, New York, New York
| | - C Ashley Finlen Copeland
- Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina; University of Minnesota School of Public Health, Minneapolis, Minnesota; and College of Physicians and Surgeons and Mailman School of Public Health, Columbia University, New York, New York
| | - David J Lederer
- Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina; University of Minnesota School of Public Health, Minneapolis, Minnesota; and College of Physicians and Surgeons and Mailman School of Public Health, Columbia University, New York, New York
| | - Scott M Palmer
- Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina; University of Minnesota School of Public Health, Minneapolis, Minnesota; and College of Physicians and Surgeons and Mailman School of Public Health, Columbia University, New York, New York
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34
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Garonzik-Wang JM, James NT, Arendonk KJV, Gupta N, Orandi BJ, Hall EC, Massie AB, Montgomery RA, Dagher NN, Singer AL, Cameron AM, Segev DL. The aggressive phenotype revisited: utilization of higher-risk liver allografts. Am J Transplant 2013; 13:936-942. [PMID: 23414232 DOI: 10.1111/ajt.12151] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2012] [Revised: 09/30/2012] [Accepted: 11/05/2012] [Indexed: 01/25/2023]
Abstract
Organ shortage has led to increased utilization of higher risk liver allografts. In kidneys, aggressive center-level use of one type of higher risk graft clustered with aggressive use of other types. In this study, we explored center-level behavior in liver utilization. We aggregated national liver transplant recipient data between 2005 and 2009 to the center-level, assigning each center an aggressiveness score based on relative utilization of higher risk livers. Aggressive centers had significantly more patients reaching high MELDs (RR 2.19, 2.33 and 2.28 for number of patients reaching MELD>20, MELD>25 and MELD>30, p<0.001), a higher organ shortage ratio (RR 1.51, 1.60 and 1.51 for number of patients reaching MELD>20, MELD>25 and MELD>30 divided by number of organs recovered at the OPO, p<0.04), and were clustered within various geographic regions, particularly regions 2, 3 and 9. Median MELD at transplant was similar between aggressive and nonaggressive centers, but average annual transplant volume was significantly higher at aggressive centers (RR 2.27, 95% CI 1.47-3.51, p<0.001). In cluster analysis, there were no obvious phenotypic patterns among centers with intermediate levels of aggressiveness. In conclusion, highwaitlist disease severity, geographic differences in organ availability, and transplant volume are the main factors associated with the aggressive utilization of higher risk livers.
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Affiliation(s)
- J M Garonzik-Wang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - N T James
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - K J Van Arendonk
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - N Gupta
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - B J Orandi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - E C Hall
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Surgery, Georgetown University, Washington, DC, USA
| | - A B Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - R A Montgomery
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - N N Dagher
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - A L Singer
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - A M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - D L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA
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35
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Abstract
Model for end-stage liver disease (MELD) score, initially developed to predict survival following transjugular intrahepatic portosystemic shunt was subsequently found to be accurate predictor of mortality amongst patents with end-stage liver disease. Since 2002, MELD score using 3 objective variables (serum bilirubin, serum creatinine, and institutional normalized ratio) has been used worldwide for listing and transplanting patients with end-stage liver disease allowing transplanting sicker patients first irrespective of the wait time on the list. MELD score has also been shown to be accurate predictor of survival amongst patients with alcoholic hepatitis, following variceal hemorrhage, infections in cirrhosis, after surgery in patients with cirrhosis including liver resection, trauma, and hepatorenal syndrome (HRS). Although, MELD score is closest to the ideal score, there are some limitations including its inaccuracy in predicting survival in 15-20% cases. Over the last decade, many efforts have been made to further improve and refine MELD score. Until, a better score is developed, liver allocation would continue based on the currently used MELD score.
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Key Words
- AH, alcoholic hepatitis
- BAR, balance risk
- CTP, Child–Pugh–Turcotte
- Cirrhosis
- DFI, discriminate function index
- EDC, extended donor criteria
- ESLD, end-stage liver disease
- FHF, fulminant hepatic failure
- GFR, glomerular filtration rate
- HVPG, hepatic venous pressure gradient
- LT, liver transplantation
- Liver transplantation
- MDRD, modification of diet in renal disease
- MELD
- MELD, model for end-stage liver disease
- MLP, multi-layer perceptron
- QALY, quality adjusted life years
- SLK, simultaneous liver kidney transplantation
- SOFA, sequential organ failure assessment
- SOFT, survival outcomes following transplantation
- TIPS, transjugular intrahepatic portosystemic
- UKELD, UK end stage liver disease score
- UNOS, United Network for Organ Sharing
- VH, variceal hemorrhage
- deMELD, drop-out equivalent MELD
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Affiliation(s)
| | - Patrick S. Kamath
- Address for correspondence: Patrick S. Kamath, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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36
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Bennink RJ, Tulchinsky M, de Graaf W, Kadry Z, van Gulik TM. Liver function testing with nuclear medicine techniques is coming of age. Semin Nucl Med 2012; 42:124-37. [PMID: 22293167 DOI: 10.1053/j.semnuclmed.2011.10.003] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver function is a broad term, as the organ participates in a multitude of different physiological and biochemical processes, including metabolic, synthetic, and detoxifying functions. However, it is the function of the hepatocyte that is central to sustaining normal life and dealing with disease states. When the liver begins to fail in severely ill patients, it forecasts a terminal outcome. However, unlike the glomerular filtration rate which clearly quantifies the key renal function, at most practice sites, there is no clinically available quantitative test for liver function. Although it is commonplace to assess indirect evidence of that function (by measuring blood levels of its end products and by-products) and to detect an acute injury (by following rising transaminases), a widely available test that would directly measure hepatocellular function is lacking. This article reviews current knowledge on liver function studies and focuses on those nuclear medicine tests available to study the whole liver and regional liver function. The clinical application driving these tests, prediction of remnant liver function after partial hepatectomy for primary liver malignancy or metastatic disease, is addressed here in detail. The test was recently validated for this specific application and was shown to be better than the current standard of practice (computed tomography volumetry), particularly in patients with hepatic comorbidities like cirrhosis, steatosis, or cholestasis. Furthermore, early assessment of regional liver function increase after preoperative portal vein embolization becomes possible with this technology. The limiting factor to a wider acceptance of this test is based on the lack of clinical software that would allow calculation of liver function parameters. This article provides information that enables a clinical nuclear medicine facility to provide this test using readily available equipment. Furthermore, it addresses emerging clinical applications that are under investigation.
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Affiliation(s)
- Roelof J Bennink
- Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Györi GP, Silberhumer GR, Zehetmayer S, Kern B, Hetz H, Soliman T, Steininger R, Mühlbacher F, Berlakovich GA. Dynamic changes in MELD score not only predict survival on the waiting list but also overall survival after liver transplantation. Transpl Int 2012; 25:935-40. [DOI: 10.1111/j.1432-2277.2012.01519.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Yang Y, Deng L, Li X, Shi Z, Chen D, Chen X, Li M, Ma L. Evaluation of the prognosis of fulminant viral hepatitis in late pregnancy by the MELD scoring system. Eur J Clin Microbiol Infect Dis 2012; 31:2673-8. [PMID: 22569645 DOI: 10.1007/s10096-012-1613-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Accepted: 03/20/2012] [Indexed: 12/14/2022]
Abstract
The purpose of this paper was to analyze the prognosis of women with fulminant viral hepatitis in late pregnancy (FVHILP) by the Model for End-Stage Liver Disease (MELD) scoring system. A retrospective study involving patients admitted to two tertiary hospitals between January 1, 1994 and June 30, 2011 was undertaken. The relations between MELD scores and change of MELD score over time (ΔMELD) and prognosis during hospitalization were analyzed. Among the 54 patients with FVHILP, the MELD scores on admission were significantly higher in the non-survival group than those in the survival group (p < 0.05). Among the 26 FVHILP patients who underwent cesarean section, the MELD scores before and after cesarean section were both significantly higher in the non-survival group (p < 0.05). The ΔMELD scores (before operation and three days after operation) significantly increased in the non-survival group (p < 0.05). The concordance (c-statistic) values were all greater than 0.8. The MELD scoring system shows excellent short-term predictive value for the prognosis of FVHILP.
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Affiliation(s)
- Y Yang
- Department of Obstetrics and Gynecology, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China
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David G, French B, Abt P, Feng S, Cameron AM. Increasing disparity in waitlist mortality rates with increased model for end-stage liver disease scores for candidates with hepatocellular carcinoma versus candidates without hepatocellular carcinoma. Liver Transpl 2012; 18:434-43. [PMID: 22271656 PMCID: PMC3319293 DOI: 10.1002/lt.23394] [Citation(s) in RCA: 110] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Candidates with hepatocellular carcinoma (HCC) within the Milan criteria (MC) receive standardized Model for End-Stage LIver Disease (MELD) exception points because of the projected risk of tumor expansion beyond the MC. Exception points at listing are meant to be equivalent to a 15% rusj if 90-day mortality, with additional points granted every 3 months, equivalent to a 10% increased morality risk. We analyzed the United Network for Organ Sharing database (January 1, 2005 to May 31, 2009) to compare the 90-day waitlist outcomes of HCC candidates and non-HCC candidates with similar MELD scores. Two hundred fifty-nine HCC candidates (4.1%) who were initially listed with 22 MELD exception points were removed because of death or clinical deterioration within 90 days of listing, whereas 283 non-HCC candidates (11.0%) with initial laboratory MELD scores of 21 to 23 were removed. Ninety-three HCC candidates (4.6%) with 25 exception points (after 3-6 months of waiting) were removed because of death or clinical deterioration within 90 days, whereas 805 non-HCC candidates (17.3%) with laboratory MELD scores of 24 to 26 were removed. Twenty HCC candidates (3.0%) with 28 exception points (after 6-9 months of waiting) were removed for death or clinical deterioration within 90 days, whereas 646 non-HCC candidates (23.6%) with laboratory MELD scores of 27 to 29 were removed. In multivariate logistic regression models, HCC candidates had significantly lower 90-day odds of waitlist removal for death or clinical deterioration (P < 0.001). Over time, the risk of waitlist removal for death or clinical deterioration was unchanged for HCC candidates (P = 0.17), whereas it increased significantly for non-HCC candidates. The current allotment of HCC exception points should be re-evaluated because of the stable risk of waitlist dropout for these candidates.
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Affiliation(s)
- Goldberg David
- Department of Medicine, Division of Gastroenterology, University of Pennsylvania,Clinical Center for Epidemiology and Biostatistics
| | - Benjamin French
- Clinical Center for Epidemiology and Biostatistics,Leonard Davis Institute for Health Economics, University of Pennsylvania
| | - Peter Abt
- Department of Surgery, Division of Transplantation, University of Pennsylvania
| | - Sandy Feng
- Department of Surgery, Division of Transplant Surgery, University of California San Francisco
| | - Andrew M Cameron
- The Johns Hopkins University Comprehensive Transplant Center, Johns Hopkins University School of Medicine
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Wang LY, Meng QH, Zou ZQ, Fan YC, Han J, Qi ZX, Ge J, Xu AL, Wang SK, Wang K. Increased frequency of circulating Th17 cells in acute-on-chronic hepatitis B liver failure. Dig Dis Sci 2012; 57:667-674. [PMID: 21984439 DOI: 10.1007/s10620-011-1930-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Accepted: 09/20/2011] [Indexed: 12/16/2022]
Abstract
BACKGROUND T helper (Th) 17 cells participate in the pathogenesis of liver diseases but their exact role in acute-on-chronic hepatitis B liver failure (ACHBLF) still remains obscure. AIMS This present study was aimed to characterize the circulating Th17 cells and to analyze their association with disease progression in ACHBLF. METHODS This retrospective study consisted of 40 ACHBLF patients, 40 chronic hepatitis B (CHB) patients and 20 healthy controls. The frequency of peripheral Th17 cells and IL-17 mRNA level in peripheral blood mononuclear cells (PBMCs) were estimated by flow cytometry and relative quantitative real-time polymerase chain reaction. RESULTS We found that the frequency of peripheral Th17 cells, as well as the level of IL-17 mRNA in PBMCs, was significantly increased in ACHBLF patients compared with CHB patients and healthy controls. In ACHBLF patients, the frequency of Th17 cells was positively correlated with serum total bilirubin (r = 0.392, P = 0.012) and model for end-stage liver disease scores (r = 0.383, P = 0.015), but negatively correlated with prothrombin activity (r = -0.317, P = 0.046). The same trend was observed as for relative expression of IL-17. Furthermore, the frequency of Th17 cells and IL-17 mRNA level were significantly elevated in non-survivors compared with survivors in ACHBLF patients. CONCLUSIONS These results suggested that Th17 cells as well as IL-17 might be related with disease severity and prognosis in ACHBLF patients.
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Affiliation(s)
- Li-Yuan Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, 250012 Jinan, China
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Ripoll C, Lastra P, Rincón D, Catalina V, Bañares R. Comparison of MELD, HVPG, and their changes to predict clinically relevant endpoints in cirrhosis. Scand J Gastroenterol 2012; 47:204-11. [PMID: 22242615 DOI: 10.3109/00365521.2011.645500] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
AIM Identification of predictors in the natural history of cirrhosis is based on determinations at a fixed time point. However, changes of these predictors may offer more information. To evaluate the predictive value of Model for End Stage Liver Disease (MELD) and hepatic venous pressure gradient (HVPG) and their changes in cirrhosis. METHODS Patients with repeat HVPG measurements between January 2000 and December 2008 were considered for inclusion. Patients were followed until decompensation/death or July 2009. Multivariate Cox regression was used to analyze the predictive value of a single measurement of MELD and HVPG, and changes between measurements. Compensated and decompensated patients were analyzed separately. RESULTS One hundred and seventeen patients were included (51 compensated, 66 decompensated). Median time between measurements and follow-up was 13 (2-24) and 11 (6-38) months in compensated and 8 (1-16) and 10 (3-21) months in decompensated patients, respectively. Fifteen compensated patients developed decompensation while twelve decompensated patients died. On multivariate analysis, MELD (HR 1.12 (95% CI 1-1.24)) and HVPG (HR 1.16 (95% CI 1.04-1.29)) were independent predictors of decompensation in compensated, while MELD (HR 1.18 (95% CI 1.09-1.27)) was the only predictor of death in the decompensated. CONCLUSION Single and repeat measurements of MELD and HVPG are associated to outcomes in cirrhosis. Use of repeat measurements does not seem to add further information.
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Affiliation(s)
- Cristina Ripoll
- Digestive Diseases Department, Hospital General Universitario Gregorio Marañón, Liver and Transplant Unit, CiberEHD, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
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Abstract
The Model for End-stage Liver Disease (MELD) score is the basis for allocation of liver allografts for transplantation in the United States. The MELD score, as an objective scale of disease severity, is also used in the management of patients with chronic liver disease in the nontransplant setting. Several models have been proposed to improve the MELD score. The authors believe that the MELD score is, by design, continually evolving and lends itself to continued refinement and improvement to serve as a metric to optimize organ allocation in the future.
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Affiliation(s)
- Sumeet K Asrani
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - W. Ray Kim
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
- Corresponding Author, W Ray Kim, 200 First Street SW, Rochester, Minnesota 55905, fax: 507-538-3974, telephone: 507-538-0254,
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Basto ST, Villela-Nogueira CA, Tura BR, Coelho HSM, Ribeiro J, Fernandes ESM, Schmal AF, Victor L, Luiz RR, Perez RM. Risk factors for long-term mortality in a large cohort of patients wait-listed for liver transplantation in Brazil. Liver Transpl 2011; 17:1013-1020. [PMID: 21604358 DOI: 10.1002/lt.22344] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver donor shortage and long waiting times are observed in many liver transplant programs worldwide. The aim of this study was to evaluate the wait list in a developing country, before and after the introduction of the MELD scoring system. In addition, the MELD score ability to predict mortality in this setting was assessed. A single-center retrospective study of patients wait-listed for liver transplantation between 1997 and 2010 was undertaken. There were 1339 and 762 patients on the list in pre-MELD and MELD era, respectively. A competitive risk analysis was performed to assess age, gender, disease diagnosis, serum sodium, MELD, Child-Pugh, ABO type, and body mass index. Also, MELD score predictive ability at 3, 6, 12, and 24 months after list enrollment was evaluated. The overall mortality rates on waiting list were 31.0% and 28.1% (P = 0.16), and the median waiting times were 412 and 952 days (P < 0.001), in pre and MELD eras, respectively. The competitive risk analysis yielded the following significant P values for both eras: HCC (0.03 and <0.001), MELD (<0.001 and 0.002), sodium level (0.002 and <0.001), and Child-Pugh (0.02 and <0.001). The MELD mortality predictions at 3, 6, 12, and 24 months were similar. In conclusion, in a liver transplant program with long waiting times, the MELD system introduction did not improve mortality rate. In either pre and MELD eras, HCC diagnosis, serum sodium, Child-Pugh, and MELD were significant predictors of prognosis. Short- and long-term MELD based mortality predictions were similarly accurate. Strategies for increasing the liver donor pool should be implemented to improve mortality.
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Affiliation(s)
- Samanta T Basto
- Division of Hepatology, Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
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Barber K, Madden S, Allen J, Collett D, Neuberger J, Gimson A. Elective liver transplant list mortality: development of a United Kingdom end-stage liver disease score. Transplantation 2011; 92:469-476. [PMID: 21775931 DOI: 10.1097/tp.0b013e318225db4d] [Citation(s) in RCA: 128] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Prediction of short-term survival probability is important in the selection and allocation of patients for liver transplantation, and the Mayo End-Stage Liver Disease (MELD) score has been used in these contexts. The aim of this study was to develop and validate a model for estimation of short-term prognosis of patients selected for elective liver transplantation in the United Kingdom. METHODS A modeling dataset was based on 1103 adult patients registered for a first elective liver transplant in the United Kingdom between April 1, 2003, and March 31, 2006, and a validation dataset based on 452 patients registered between April 1, 2006, and March 31, 2007. The final model (United Kingdom End-Stage Liver Disease) included international normalized ratio, serum creatinine, bilirubin, and sodium. RESULTS The model, based on the modeling dataset, accurately predicted mortality on the transplant list in the validation dataset and proved to be a better predictor than MELD or MELD-Na. The United Kingdom End-Stage Liver Disease score was not associated with overall posttransplant survival but was associated with both the duration of intensive care unit stay and overall initial hospital stay. CONCLUSION This model, developed specifically for patients awaiting liver transplantation, provides a useful tool for the selection of patients for liver transplantation and the allocation of donor livers.
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Affiliation(s)
- Kerri Barber
- NHS Blood and Transplant, Stoke Gifford, Bristol, United Kingdom.
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Huang K, Hu JH, Wang HF, He WP, Chen J, Duan XZ, Zhang AM, Liu XY. Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure. World J Gastroenterol 2011; 17:3448-3452. [PMID: 21876637 PMCID: PMC3160571 DOI: 10.3748/wjg.v17.i29.3448] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Revised: 11/08/2010] [Accepted: 11/15/2010] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed. Their general conditions and survival were analyzed by survival analysis and Cox regression analysis. RESULTS A total of 190 patients were included in this study. The overall 1-year survival rate was 57.6%. Patients not treated with antiviral drugs had a significantly higher mortality [relative risk (RR) = 0.609, P = 0.014]. The highest risk of death in patients with ACLF was associated with hepatorenal syndrome (HRS) (RR = 2.084, P =0.026), while other significant factors were electrolyte disturbances (RR = 2.062, P = 0.010), and hepatic encephalopathy (HE) (RR = 1.879, P < 0.001). CONCLUSION Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate. HRS, electrolyte disturbances, and HE also affect patient survival.
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The MELD score in patients awaiting liver transplant: strengths and weaknesses. J Hepatol 2011; 54:1297-306. [PMID: 21145851 DOI: 10.1016/j.jhep.2010.11.008] [Citation(s) in RCA: 115] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2010] [Revised: 11/10/2010] [Accepted: 11/12/2010] [Indexed: 12/14/2022]
Abstract
Adoption of the Model for End-stage Liver Disease (MELD) to select and prioritize patients for liver transplantation represented a turning point in organ allocation. Prioritization of transplant recipients switched from time accrued on the waiting list to the principle of "sickest first". The MELD score incorporates three simple laboratory parameters (serum creatinine and bilirubin, and INR for prothrombin time) and stratifies patients according to their disease severity in an objective and continuous ranking scale. Concordance statistics have demonstrated its high accuracy in stratifying patients according to their risk of dying in the short-term (three months). Further validations of MELD as a predictor of survival at various temporal end-points have been obtained in independent patient cohorts with a broad spectrum of chronic liver disease. The MELD-based liver graft allocation policy has led to a reduction in waitlist new registrations and mortality, shorter waiting times, and an increase in transplants, without altering overall graft and patient survival rates after transplantation. MELD limitations are related either to the inter-laboratory variability of the parameters included in the score, or to the inability of the formula to predict mortality accurately in specific settings. For some conditions, such as hepatocellular carcinoma, widely accepted MELD corrections have been devised. For others, such as persistent ascites and hyponatremia, attempts to improve MELD's predicting power are currently underway, but await definite validation.
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Prediction value of model for end-stage liver disease scoring system on prognosis in the acute on chronic liver failure patients with plasma exchange treatment. ASAIO J 2011; 56:475-8. [PMID: 20613491 DOI: 10.1097/mat.0b013e3181e6bf13] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Hepatitis B virus-related acute-on-chronic liver failure (AoCLF) is associated with a high mortality rate. Plasma exchange (PE) is useful to bridge patients with AoCLF to liver transplantation or recovery. The aim of this study was to analyze the impact of the model for end-stage liver disease (MELD) score on 30-day survival in patients with AoCLF treated with PE or conventional medications and to evaluate the therapeutic effectiveness of PE. In this study, 62 enrolled patients with AoCLF who received PE treatment were compared with 131 patients treated with conventional medications. The MELD scores were calculated according to the original formula, and the 30-day survival in patients was recorded. The 30-day survival rate of the patients who received PE versus controls was 41.9% versus 25.2% (p < 0.05). The 30-day survival rate of patients in the PE group (50.0%) with a MELD score from 20 to 30 was higher than that of the control group (31.7%, p < 0.05); for MELD scores more than 30, there was no significant difference in two groups (8.3% vs. 0%, p > 0.05). PE seems to be efficacious and safe for the treatment of patients with AoCLF and significantly increased the survival rates of patients with a MELD score of 20-30.
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Abstract
There are three possible policies for prioritization for liver transplantation: medical urgency, utility and transplant benefit. The first is based on the severity of cirrhosis, using Child-Turcotte-Pugh score and, more recently, the Model for End-stage Liver Disease (MELD) score, or variants of MELD, for allocation. Although prospectively developed and validated, the MELD score has several limitations, including interlaboratory variations for measurement of serum creatinine and international normalized ratio of prothrombin time, and a systematic adverse female gender bias. Adjustments to the original MELD equation and new scoring systems have been proposed to overcome these limitations; incorporation of serum sodium improves its predictive accuracy. The MELD score poorly predicts outcomes after liver transplantation due to the absence of donor factors incorporated into the scoring system. Several utility models are based on donor and recipient characteristics. Combined poor recipient and donor characteristics lead to very poor outcomes, which in a utility system would be considered unacceptable. Finally, transplant benefit models rank patients according to the net survival benefit that they would derive from transplantation. However, complex statistical models are required, and unmeasured characteristics may unduly affect the models. Well-designed prospective studies and simulation models are necessary to establish the optimal allocation system in liver transplantation.
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Affiliation(s)
- Evangelos Cholongitas
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippocration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece
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Yang YW, Wu CH, Hu RH, Ho MC, Tsai MK, Wu YM, Lee PH. Longitudinal assessment of prognostic factors for patients with hepatorenal syndrome in a tertiary center. Hepatol Int 2010; 4:507-10. [PMID: 20827408 DOI: 10.1007/s12072-010-9180-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Accepted: 02/26/2010] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Hepatorenal syndrome (HRS) is one of the serious complications in patients with advanced cirrhosis and ascites. In tertiary centers, most patients were classified as having type 1 HRS for their rapid progressive diseases. However, no significant predictors have been assessed previously for patients with type 1 HRS. In addition to the initial model of end-stage liver disease (MELD) scores and biochemistry parameters, we want to further investigate the prognostic importance of changes in MELD scores and biochemistry parameters over time for patients with type 1 HRS. MATERIALS AND METHODS Data from type 1 HRS patients were incorporated, including their demographic, clinical progression, all recording biochemical parameters, therapeutic methods, and outcomes. RESULTS A total of 103 patients were included in our study. According to the definition of the International Ascites Club, 67 patients (or 65%) had type 1 HRS whereas 36 (or 35%) had type 2 HRS. According to the multivariate COX proportional hazards regression model, either initial biochemistry parameters or MELD scores were not significantly associated with prognosis. By time-dependent proportional hazards model, each point elevated in creatinine (CRE) and total bilirubin (TBI) levels during the admission increased mortality risk by 29 and 4%, respectively. Increasing albumin level during the admission showed its protective value. Changes in MELD score simple during the admission, which were calculated by CRE and TBI [3.8 × log (bilirubin (mg/dl)] + 9.6 × log [Creatinine (mg/dl) + 6.43], were significant predictor for patients with type 1 HRS. CONCLUSION In patients with type 1 HRS, changes in TBI, CRE, and albumin level during the admission were associated with prognosis. Changes in MELD score simple is superior to initial and changes in MELD scores to predict prognosis in patients with type 1 HRS.
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Novelli G, Rossi M, Ferretti G, Pugliese F, Travaglia D, Guidi S, Novelli S, Lai Q, Morabito V, Berloco PB. Predictive parameters after molecular absorbent recirculating system treatment integrated with model for end stage liver disease model in patients with acute-on-chronic liver failure. Transplant Proc 2010; 42:1182-1187. [PMID: 20534256 DOI: 10.1016/j.transproceed.2010.03.095] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The aim of study was to highlight parameters that in association with Model for End-stage Liver Disease (MELD) provide predictive criteria for long-term survival after treatment with the Molecular Adsorbent Recirculating System (MARS). Two homogenous groups were studied: one treated with standard medical therapy (SMT) and the other, with MARS. MATERIALS AND METHODS Twenty acute-on-chronic liver failure patients on the waiting list for liver transplantation and affected by alcoholic cirrhosis with similar MELD scores (20-29) were evaluated for 7 days from inclusion and for 6-month survival. Ten patients (seven males and three females) were treated with MARS. Their mean age was 48.5 years (range = 35-61). The number of MARS applications was six for 6 consecutive days, and the length of the applications was 8 hours. Ten other patients (seven males and three females) were treated with SMT, including prophylaxis against bacterial infections and judicious use of diuretics. The precipitating factors were also treated appropriately. The mean age of the patients was 51 years (range = 37-64). All the variables that were significant upon univariate analysis were enrolled in a receiver operating characteristic analysis, with the intention to detect predictive parameters for patient death at 6 months. We considered a significant area under curve (AUC) value to be greater than 0.5. RESULTS Among 11 patients who died within 6 months there were in the MARS group and eight in the SMT group: the 3- and 6-month patient survival rates were 90% and 70% versus 30% and 20% in the two groups, respectively. Nine measures resulted in an AUC > 0.5: DeltaMELD; interleukin (IL)-8; IL-6; tumor necrosis factor- alpha, MELD score; creatinine, bilirubin international normalized ratio (INR) and cardiac index. DeltaMELD and postoperative IL-8 concentrations showed better results (AUC = 0.899), followed by postoperative creatinine (AUC = 0.879), postoperative cardiac index (AUC = 0.833), and postoperative INR (AUC = 0.818). Postoperative creatinine showed the best sensitivity (100%), while IL-8, the best specificity (88.9%). CONCLUSION A combination of biochemical and clinical variables probably represent the best way to predict the survival of patients, allowing physicians to select the best therapies for each patient.
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Affiliation(s)
- G Novelli
- Dipartimento P Stefanini Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Rome, Italy.
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