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Leven EA, Li D, Bagiella E, Schiano TD, Tal Grinspan L. Sex-based Differences and Comparative Predictive Value of MELD 3.0 in Simultaneous Liver-Kidney Transplantation Waitlist Outcomes After Standardization of Listing Criteria in the United States. Transplant Direct 2025; 11:e1781. [PMID: 40225741 PMCID: PMC11984772 DOI: 10.1097/txd.0000000000001781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 02/06/2025] [Accepted: 02/10/2025] [Indexed: 04/15/2025] Open
Abstract
Background Sex disparities in solid organ transplantation are well documented. Relative changes in sex-based outcome disparities after the 2017 standardization of simultaneous liver-kidney (SLK) listing criteria in the United States have not been reported. We hypothesized that this policy's objective measures of kidney dysfunction may differentially affect SLK patients by sex and that the use of MELD 3.0 in the SLK population might provide unique benefit to female transplant candidates. Methods Organ Procurement and Transplantation Network data were retrospectively analyzed comparing 2013-2016 with 2018-2021 SLK listings. Waitlist outcomes and Model for End-stage Liver Disease (MELD) 3.0 reclassifications were compared by sex and listing period. Results There were 2626 and 2609 male patients and 1670 and 1919 female patients pre- and post-policy changes, respectively. The proportion of female SLK listings post-policy change (42.4%) was higher than both female SLK listings pre-policy change (38.9%) and female single-organ liver listings post-policy change (36.8%; P < 0.01). A statistically significant interaction between sex and listing group (pre- versus post-policy change) was present in multivariable analysis (P = 0.02). Female patients were more likely to have a higher MELD 3.0 score than the listing MELD/MELD-Na score when the listing MELD score was <30 (P < 0.01). Among all patients who died on the waitlist, female patients were nearly twice as likely to be underrepresented by listing MELD compared with MELD 3.0 (23% female and 13% male patients; P < 0.01). Conclusions Waitlist outcomes were changed differentially between male and female patients after the 2017 SLK policy change. The application of MELD 3.0 to SLK patients is likely to benefit female patients.
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Affiliation(s)
- Emily A. Leven
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Ditian Li
- Department of Population Health, Center for Biostatistics, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Emilia Bagiella
- Department of Population Health, Center for Biostatistics, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Thomas D. Schiano
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Lauren Tal Grinspan
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
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2
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Kojima H, Morinelli TA, Wang Y, Chin JL, Meyer AS, Kao YC, Kadono K, Yao S, Torgerson T, Dery KJ, Bhat A, Reed EF, Kaldas FM, van der Windt DJ, Farmer DG, Kupiec-Weglinski JW, Zhai Y. Group 1 innate lymphoid cells protect liver transplants from ischemia-reperfusion injury via an interferon gamma-mediated pathway. Am J Transplant 2025; 25:969-984. [PMID: 39736469 PMCID: PMC12043423 DOI: 10.1016/j.ajt.2024.11.035] [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: 09/03/2024] [Revised: 11/07/2024] [Accepted: 11/23/2024] [Indexed: 01/01/2025]
Abstract
As important immune regulatory cells, whether innate lymphoid cells (ILCs) are involved in liver transplantation (LT) remains unclear. In a murine orthotopic LT model, we dissected roles of ILCs in liver ischemia-reperfusion injury (IRI). Wild-type (WT) grafts suffered significantly higher IRI in Rag2-γc double knockout (DKO) than Rag2 knockout (KO) recipients, in association with downregulation of group 1 ILCs genes, including interferon gamma. Antibody-mediated ILC depletion or interferon gamma neutralization in Rag2 KO recipients increased, while interferon gamma treatment in DKO recipients reduced, liver graft injuries. At the donor side, grafts from DKO mice or anti-NK1.1-treated WT mice suffered significantly higher IRI, while grafts treated with interferon gamma during cold preservation decreased IRI. Thus, both recipient and donor group 1 ILCs protect liver grafts from IRI. Low-dose interferon gamma upregulated c-FLIP expression in vitro and in vivo and protected hepatocytes from inflammatory cell death. In human liver graft biopsies, single-cell RNA-sequencing analysis revealed group 1 ILCs produce interferon gamma. The c-FLIP levels were positively correlated with interferon gamma in pretransplant biopsies. Grafts with higher c-FLIP were associated with lower caspase-8 activation, IRI gradings, and frequency of early allograft dysfunction post-LT. Our study reveals a novel interferon gamma-mediated cytoprotective role of group 1 ILCs in LT.
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Affiliation(s)
- Hidenobu Kojima
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Thomas A Morinelli
- Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Yue Wang
- Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Jackson L Chin
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA
| | - Aaron S Meyer
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA
| | - Yi-Chu Kao
- Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Kentaro Kadono
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Siyuan Yao
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Taylor Torgerson
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Kenneth J Dery
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Adil Bhat
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Elaine F Reed
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Fady M Kaldas
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Dirk J van der Windt
- Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Douglas G Farmer
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Jerzy W Kupiec-Weglinski
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Yuan Zhai
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
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Walters SM, Richter EW, Lutzker T, Patel S, Vincent AN, Kleiman AM. Perioperative Considerations Regarding Sex in Solid Organ Transplantation. Anesthesiol Clin 2025; 43:83-98. [PMID: 39890324 DOI: 10.1016/j.anclin.2024.06.001] [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: 02/03/2025]
Abstract
Sex plays a pivotal role in all stages of the organ transplant process. In the preoperative phase, sex can affect being listed or considered for a transplant, and sex/size matching of organs is necessary for some organ transplants, thereby affecting organ availability. In the postoperative period, sex has a profound impact on complications as well as graft survival. Sex-related differences in organ transplantation are likely multifactorial related to biological and social characteristics. This article provides an overview of the impact of sex on various types of solid organ transplant, including kidney, pancreas, liver, lung, and heart transplants.
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Affiliation(s)
- Susan M Walters
- Department of Anesthesiology, University of Virginia Health System, PO Box 800710, Charlottesville, VA 22908, USA
| | - Ellen W Richter
- Department of Anesthesiology, Emory University School of Medicine, 1364 Clifton Road Northeast, Atlanta, GA 30322, USA
| | - Tatiana Lutzker
- Department of Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, 900 23rd Street, Northwest, Washington, DC 20037, USA
| | - Suraj Patel
- NYU Anesthesia Associates, 150 55th Street, Brooklyn, NY 11220, USA
| | - Anita N Vincent
- Department of Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, 900 23rd Street, Northwest, Washington, DC 20037, USA
| | - Amanda M Kleiman
- Department of Anesthesiology, University of Virginia Health System, PO Box 800710, Charlottesville, VA 22908, USA.
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Samuel D, De Martin E, Berg T, Berenguer M, Burra P, Fondevila C, Heimbach JK, Pageaux GP, Sanchez-Fueyo A, Toso C. EASL Clinical Practice Guidelines on liver transplantation. J Hepatol 2024; 81:1040-1086. [PMID: 39487043 DOI: 10.1016/j.jhep.2024.07.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 07/30/2024] [Indexed: 11/04/2024]
Abstract
Liver transplantation (LT) is an established life-saving procedure. The field of LT has changed in the past 10 years from several perspectives, with the expansion of indications, transplantation of patients with acute-on-chronic liver failure, evolution of transplant oncology, the use of donations after cardiac death, new surgical techniques, and prioritisation of recipients on the waiting list. In addition, the advent of organ perfusion machines, the recognition of new forms of rejection, and the attention paid to the transition from paediatric to adult patients, have all improved the management of LT recipients. The purpose of the EASL guidelines presented here is not to cover all aspects of LT but to focus on developments since the previous EASL guidelines published in 2016.
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Bilbao I, Lladó L, Cachero A, Campos-Varela I, Colmenero J, Del Hoyo J, Fábrega García E, García-Pajares F, González Diéguez L, González Grande R, Guiberteau Sánchez A, Hernández Oliveros F, Herrero Santos JI, Lorente S, Martín Mateos R, Mesa López MJ, Montero Álvarez JL, Muñoz Codoceo C, Otero Ferreiro A, Otón Nieto E, Rodríguez Soler M, Romero Cristóbal M, Sastre Oliver L, Senosiain Labiano M, Sousa Martín JM, Trapero-Marugán M, Varo E, de la Rosa G, Rodríguez-Perálvarez M. First consensus document of waiting list prioritization for liver transplantation by the Spanish Society of Liver Transplantation (SETH). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:680-689. [PMID: 39267491 DOI: 10.17235/reed.2024.10639/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Spain is worldwide leader in deceased donation rates per million habitants and count on a strong network of twenty-five liver transplant institutions. Although the access to liver transplantation is higher than in other countries, approximately 10% of patients qualifying for liver transplantation in Spain will die in the waiting list or would be excluded due to clinical deterioration. A robust waiting list prioritization system is paramount to grant the sickest patients with the first positions in the waiting list for an earlier access to transplant. In addition, the allocation policy may not create or perpetuate inequities, particularly in a public and universal healthcare system. Hitherto, Spain lacks a unique national allocation system for elective liver transplantation. Most institutions establish their own rules for liver allocation and only two autonomous regions, namely Andalucía and Cataluña, share part of their waiting list within their territory to provide regional priority to patients requiring more urgent transplantation. This heterogeneity is further aggravated by the recently described sex-based disparities for accessing liver transplantation in Spain, and by the expansion of liver transplant indications, mainly for oncological indications, in absence of clear guidance on the optimal prioritization policy. The present document contains the recommendations from the first consensus of waiting list prioritization for liver transplantation issued by the Spanish Society of Liver Transplantation (SETH). The document was supported by all liver transplant institutions in Spain and by the Organización Nacional de Trasplantes (ONT). Its implementation will allow to homogenize practices and to improve equity and outcomes among patients with end-stage liver disease.
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Affiliation(s)
| | | | | | | | | | - Javier Del Hoyo
- Hospital Universitari i Politècnic La Fe. Instituto de Investigación Sanitaria La Fe. CIBERehd
| | | | | | | | | | | | | | | | - Sara Lorente
- Hospital Universitario Lozano Blesa. Instituto de Investigaciones Sanitarias de Aragón (IIS Aragón)
| | - Rosa Martín Mateos
- Hospital Universitario Ramón y Cajal. IRyCIS. Universidad de Alcalá de Henares. CIBERehd
| | | | | | | | | | | | | | - Mario Romero Cristóbal
- Hospital General Universitario e Instituto de Investigación Biomédica Gregorio Marañón. CIBERehd
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Tanaka T, Ross-Driscoll K, Pancholia S, Axelrod D. Body Size Remains the Major Source of Sex Disparity Despite Updated Liver Transplant Allocation Policies. Transplantation 2024; 108:e396-e403. [PMID: 39020468 DOI: 10.1097/tp.0000000000005142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/19/2024]
Abstract
BACKGROUND Efforts to address US liver transplant (LT) access inequities continue, yet disparities linked to candidate traits persist. METHODS Analyzing national registry data pre- and post-Acuity Circle (AC) policy, our study assessed the impact of low body surface area (BSA) on LT waitlist mortality. The outcomes of LT candidates listed in the pre-AC era (n = 39 227) and post-AC (n = 38 443) were compared for patients with low BSA (22.9% pre-AC and 23.3% post-AC). RESULTS Fine-Gray competing risk models highlighted that candidates with low BSA had a lower likelihood of LT both pre-AC (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.92-0.95) and post-AC (HR 0.96; 95% CI, 0.94-0.98), with minimal improvement in waitlist mortality/dropout risk from pre-AC (HR 1.15; 95% CI, 1.09-1.21) to post-AC (HR 1.13; 95% CI, 1.06-1.19). Findings were mostly reaffirmed by Cox regression models incorporating the trajectory of Model for End-stage Liver Disease (MELD) scores as time-dependent covariates. Regions 3, 5, and 7 showed notable LT waitlist disparities among low BSA patients post-AC policy. Causal mediation analysis revealed that low BSA and the difference between MELD-sodium and MELD 3.0 (MELD_D, as a proxy for the potential impact of the introduction of MELD 3.0) largely explained the sex disparity in AC allocation (percent mediated 90.4). CONCLUSIONS LT waitlist disparities for female candidates persist, largely mediated by small body size. Although MELD 3.0 may reduce some disparities, further body size adjustments for in allocation models are justified.
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Affiliation(s)
- Tomohiro Tanaka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
- Center for Access and Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System, Iowa City, IA
- Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, IA
| | - Katherine Ross-Driscoll
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
- Center for Health Services Research, Regenstrief Institute, Indianapolis, IN
| | - Smita Pancholia
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - David Axelrod
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
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7
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Dehne S, Jackson-Gil L, Riede C, Feisst M, Mehrabi A, Michalski CW, Weigand MA, Decker SO, Larmann J. Patient sex and use of tranexamic acid in liver transplantation. Front Med (Lausanne) 2024; 11:1452733. [PMID: 39376656 PMCID: PMC11456493 DOI: 10.3389/fmed.2024.1452733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 09/09/2024] [Indexed: 10/09/2024] Open
Abstract
Background Differences in medical treatment between women and men are common and involve out-of-hospital emergency care, the intensity of pain treatment, and the use of antifibrinolytic treatment in emergency trauma patients. If woman and man receive different antifibrinolytic treatment in highly-standardized major transplant surgery is unknown. Methods We conducted a retrospective cohort study on patients who underwent liver transplantation at Heidelberg University Hospital, Heidelberg, Germany between 2004 and 2017. Logistic regression analyses were performed to determine if sex is associated with the administration of TXA during liver transplantation. Secondary endpoints included venous thrombotic complications, graft failure, mortality, myocardial infarction, hepatic artery thrombosis, and stroke within the first 30 days after liver transplant as well as length of hospital stay and length of intensive care unit stay. Results Out of 779 patients who underwent liver transplantation, 262 patients received TXA. Female sex was not associated with intraoperative administration of TXA [adjusted OR: 0.929 (95% CI 0.654; 1.320), p = 0.681]. The secondary endpoints graft failure (13.2% vs. 8.4%, women vs. men, p = 0.039), pulmonary embolism (3.4% vs. 0.9%, women vs. men, p = 0.012), stroke (1.7% vs. 0.4%, women vs. men, p = 0.049), and deep vein thrombosis (0.8% vs. 0%, women vs. men, p = 0.031) within 30 days after liver transplantation were more frequent in women. Mortality, myocardial infarction, and other secondary endpoints did not differ between groups. However, in women, the use of TXA was associated with a lower rate in thromboembolic complications. Conclusion Our data indicate that different from other scenarios with massive bleeding complications the administration of TXA during liver transplantation is not associated with sex. However, sex is associated with the risk for complications, and in woman TXA might have a preventive effect on the rate of thromboembolic complications. Reasons underlying the observed sex bias rate remain uncertain.
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Affiliation(s)
- Sarah Dehne
- Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Lorena Jackson-Gil
- Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Carlo Riede
- Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Manuel Feisst
- Heidelberg University, Institute of Medical Biometry, Heidelberg, Germany
| | - Arianeb Mehrabi
- Heidelberg University, Medical Faculty Heidelberg, Department of General, Visceral, and Transplantation Surgery, Heidelberg, Germany
| | - Christoph W. Michalski
- Heidelberg University, Medical Faculty Heidelberg, Department of General, Visceral, and Transplantation Surgery, Heidelberg, Germany
| | - Markus A. Weigand
- Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Sebastian O. Decker
- Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Jan Larmann
- Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
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8
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Linge H, Nevermann N, Schmelzle M, Quante M. [Sex differences in hepatobiliary and transplantation surgery]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:715-720. [PMID: 39090449 DOI: 10.1007/s00104-024-02139-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/08/2024] [Indexed: 08/04/2024]
Abstract
Gender-specific differences in hepatobiliary and transplantation surgery are decisive for the diagnosis, treatment and long-term outcomes. Men exhibit a higher risk of late recurrences and cancer-specific death after liver cancer resection. The emphasis on screening recommendations and ensuring equal access to treatment options are vital to minimize disparities. In kidney and liver transplantations, women are less frequently listed and endure longer waiting times, while men dominate the waiting list. Gender-specific disparities in drug compatibility necessitate differentiated dosing. Further studies are needed to ensure equity in transplantation treatment. Individualized treatment considering these differences can enhance treatment outcomes and the quality of life of patients.
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Affiliation(s)
- H Linge
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Deutschland.
| | - N Nevermann
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - M Schmelzle
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - M Quante
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Deutschland
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9
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Cooper KM, Colletta A, Amin D, Herscovici DM, Devuni D. Psychosocial Trauma History Negatively Impacts Liver Transplant Access in Women with Chronic Liver Disease. J Transplant 2024; 2024:2455942. [PMID: 39165271 PMCID: PMC11335414 DOI: 10.1155/2024/2455942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 06/03/2024] [Accepted: 07/22/2024] [Indexed: 08/22/2024] Open
Abstract
Introduction Few studies have evaluated the impact of psychological trauma (mental, emotional, or physical) on liver transplant (LT) candidacy and outcomes. Methods We performed a single center retrospective analysis of patients who completed routine LT evaluation between October 2017 and June 2021. We identified the prevalence of psychological trauma history in men and women LT candidates and evaluated the association between trauma history and LT access. The primary outcome measure was listing for LT. Results A total of 463 patients completed LT evaluation, of which 17% (n = 79) reported a history of trauma: 49 of 159 women and 30 of 304 men. Trauma history was significantly more common in women than in men (31% vs. 10%, p < 0.001). Women with trauma history were less likely to be listed for LT (80% vs. 93%, p = 0.016). Women with trauma history were also more likely to be removed from the LT waitlist (26% vs. 12%, p = 0.045); this persists when excluding patients removed for transfer to another center or for medical improvement (22% vs. 7%, p = 0.020). In contrast, listing for LT (87% vs. 86%, p = 0.973) and waitlist removal (12% vs. 10%, p = 0.766) did not differ in men with and without trauma history. In those that received a LT (n = 107), post-LT relapse, rejection, readmissions, and death did not differ in patients with (n=13)and without (n=94) trauma history. Conclusions Trauma history is associated with reduced access to LT in women but not men with chronic liver disease. Further studies are needed to understand the impact of psychological trauma on LT access and post-LT outcomes.
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Affiliation(s)
| | | | - Dhruval Amin
- Department of MedicineUMass Chan Medical School, Worcester 01655, MA, USA
| | | | - Deepika Devuni
- Department of MedicineUMass Chan Medical School, Worcester 01655, MA, USA
- Division of Gastroenterology and HepatologyUMass Chan Medical School, Worcester 01655, MA, USA
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10
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Reichelt S, Merle U, Klauss M, Kahlert C, Lurje G, Mehrabi A, Czigany Z. Shining a spotlight on sarcopenia and myosteatosis in liver disease and liver transplantation: Potentially modifiable risk factors with major clinical impact. Liver Int 2024; 44:1483-1512. [PMID: 38554051 DOI: 10.1111/liv.15917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 03/07/2024] [Accepted: 03/17/2024] [Indexed: 04/01/2024]
Abstract
Muscle-wasting and disease-related malnutrition are highly prevalent in patients with chronic liver diseases (CLD) as well as in liver transplant (LT) candidates. Alterations of body composition (BC) such as sarcopenia, myosteatosis and sarcopenic obesity and associated clinical frailty were tied to inferior clinical outcomes including hospital admissions, length of stay, complications, mortality and healthcare costs in various patient cohorts and clinical scenarios. In contrast to other inherent detrimental individual characteristics often observed in these complex patients, such as comorbidities or genetic risk, alterations of the skeletal muscle and malnutrition are considered as potentially modifiable risk factors with a major clinical impact. Even so, there is only limited high-level evidence to show how these pathologies should be addressed in the clinical setting. This review discusses the current state-of-the-art on the role of BC assessment in clinical outcomes in the setting of CLD and LT focusing mainly on sarcopenia and myosteatosis. We focus on the disease-related pathophysiology of BC alterations. Based on these, we address potential therapeutic interventions including nutritional regimens, physical activity, hormone and targeted therapies. In addition to summarizing existing knowledge, this review highlights novel trends, and future perspectives and identifies persisting challenges in addressing BC pathologies in a holistic way, aiming to improve outcomes and quality of life of patients with CLD awaiting or undergoing LT.
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Affiliation(s)
- Sophie Reichelt
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital of Bonn, Bonn, Germany
| | - Uta Merle
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Miriam Klauss
- Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christoph Kahlert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Georg Lurje
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Zoltan Czigany
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
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11
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Magadan Álvarez C, Olmos-Martínez JM, González Tolaretxipi E, Lozano Najera A, Toledo Martínez E, Rodríguez Sanjuan JC. Survival analysis of the surgical treatment of hepatocellular carcinoma at a tertiary care center. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:323-331. [PMID: 38789311 DOI: 10.1016/j.rgmxen.2022.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 12/30/2022] [Indexed: 05/26/2024]
Abstract
INTRODUCTION AND AIMS Hepatocellular carcinoma (HCC) is a primary malignant tumor of liver epithelial cells and is the most frequent primary liver cancer. The broadening of transplantation and resectability criteria has made therapeutic decisions more complex. Our aim was to describe the clinical and survival characteristics of patients with HCC treated through resection or liver transplantation at our hospital and identify the presence of factors that enable outcome prediction and facilitate therapeutic decision-making. MATERIALS AND METHODS Patients with HCC that underwent surgery with curative intent at the Hospital Universitario Marqués de Valdecilla, within the time frame of 2007 and 2017, were retrospectively identified. Survival, mortality, disease-free interval, and different outcome-related variables were analyzed. RESULTS Ninety-six patients with a mean follow-up after surgery of 44 months were included. Overall mortality and recurrence were higher in the resection group. Mean survival was 51.4 months in the liver transplantation group and 37.5 months in the resection group, and the disease-free interval was 49.4 ± 37.2 and 27.4 ± 28.7 months, respectively (p = 0.002). The tumor burden score was statistically significant regarding risk for recurrence and specific mortality. CONCLUSIONS There appears to be no patient subgroup in whom the results of surgical resection were superior or comparable to those of transplantation. Tumor burden determination could be a useful tool for patient subclassification and help guide therapeutic decision-making.
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Affiliation(s)
- C Magadan Álvarez
- Servicio de Cirugía General y Aparato Digestivo, Hospital San Agustín, Avilés, Asturias, Spain.
| | - J M Olmos-Martínez
- Servicio de Aparato Digestivo, Hospital Cabueñes, Gijón, Asturias, Spain
| | - E González Tolaretxipi
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain
| | - A Lozano Najera
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain
| | - E Toledo Martínez
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain
| | - J C Rodríguez Sanjuan
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain
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12
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Tejedor M, Neria F, De La Rosa G, Almohalla Álvarez C, Padilla M, Boscà Robledo A, Fundora Suárez Y, Sánchez-Bueno F, Gómez-Bravo MA, Berenguer M. Women Are Also Disadvantaged in Accessing Transplant Outside the United States: Analysis of the Spanish Liver Transplantation Registry. Transpl Int 2024; 37:12732. [PMID: 38773987 PMCID: PMC11106452 DOI: 10.3389/ti.2024.12732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 04/16/2024] [Indexed: 05/24/2024]
Abstract
Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.
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Affiliation(s)
| | - Fernando Neria
- Universidad Francisco de Vitoria, Pozuelo de Alarcón, Spain
| | | | | | | | | | | | | | | | - Marina Berenguer
- Hepatology—Liver Transplantation Unit, IIS La Fe and CIBER-EHD, Hospital Universitari i Politècnic La Fe, Valencia, Spain
- Department of Medicine, Universitat de València, Valencia, Spain
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13
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Toniutto P, Shalaby S, Mameli L, Morisco F, Gambato M, Cossiga V, Guarino M, Marra F, Brunetto MR, Burra P, Villa E. Role of sex in liver tumor occurrence and clinical outcomes: A comprehensive review. Hepatology 2024; 79:1141-1157. [PMID: 37013373 DOI: 10.1097/hep.0000000000000277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 12/06/2022] [Indexed: 04/05/2023]
Abstract
Clinical research on sex-based differences in the manifestations, pathophysiology, and prevalence of several diseases, including those affecting the liver, has expanded considerably in recent years. Increasing evidence suggests that liver diseases develop, progress, and respond to treatment differently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient's sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sex-related inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here, we critically review the main gender-based differences in the molecular mechanisms associated with liver carcinogenesis and the prevalence, prognosis, and treatment of primary and metastatic liver tumors.
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Affiliation(s)
- Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata, Department of Medical Area, University of Udine, Udine, Italy
| | - Sarah Shalaby
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Laura Mameli
- Liver and Pancreas Transplant Center, Azienda Ospedaliera Brotzu Piazzale Ricchi 1, Cagliari, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Departmental Program "Diseases of the Liver and Biliary System," University of Naples "Federico II," Napoli, Italy
| | - Martina Gambato
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Valentina Cossiga
- Department of Clinical Medicine and Surgery, Departmental Program "Diseases of the Liver and Biliary System," University of Naples "Federico II," Napoli, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Departmental Program "Diseases of the Liver and Biliary System," University of Naples "Federico II," Napoli, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | | | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Erica Villa
- Gastroenterology Department, University of Modena and Reggio Emilia, Modena, Italy
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14
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De Simone P, Precisi A, Lai Q, Ducci J, Campani D, Marchetti P, Gitto S. Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2024; 16:1243. [PMID: 38610921 PMCID: PMC11010831 DOI: 10.3390/cancers16071243] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 03/10/2024] [Accepted: 03/19/2024] [Indexed: 04/14/2024] Open
Abstract
To obtain long-term data on the use of everolimus in patients who underwent liver transplantation for hepatocellular carcinoma, we conducted a retrospective, single-center analysis of adult recipients transplanted between 2013 and 2021. Patients on everolimus-incorporating immunosuppression were matched with those on tacrolimus using an inverse probability of treatment weighting methodology. Two propensity-matched groups of patients were thus compared: 233 (45.6%) receiving everolimus versus 278 (54.4%) on tacrolimus. At a median (interquartile range) follow-up of 4.4 (3.8) years after transplantation, everolimus patients showed a reduced risk of recurrence versus tacrolimus (7.7% versus 16.9%; RR = 0.45; p = 0.002). At multivariable analysis, microvascular infiltration (HR = 1.22; p < 0.04) and a higher tumor grading (HR = 1.27; p < 0.04) were associated with higher recurrence rate while being within Milan criteria at transplant (HR = 0.56; p < 0.001), a successful pre-transplant downstaging (HR = 0.63; p = 0.01) and use of everolimus (HR = 0.46; p < 0.001) had a positive impact on the risk of post-transplant recurrence. EVR patients with earlier drug introduction (≤30 days; p < 0.001), longer treatment duration (p < 0.001), and higher drug exposure (≥5.9 ng/mL; p < 0.001) showed lower recurrence rates versus TAC. Based on our experience, everolimus provides a reduction in the relative risk of hepatocellular carcinoma recurrence, especially for advanced-stage patients and those with earlier drug administration, higher drug exposure, and longer time on treatment. These data advocate for early everolimus introduction after liver transplantation to reduce the attrition rate consequent to chronic immunosuppression.
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Affiliation(s)
- Paolo De Simone
- Liver Transplant Program, University of Pisa Medical School Hospital, 56124 Pisa, Italy
- Department of Surgical, Medical, Biochemical Pathology and Intensive Care, University of Pisa, 56126 Pisa, Italy;
| | - Arianna Precisi
- Transplant Laboratory, University of Pisa Medical School Hospital, 56126 Pisa, Italy;
| | - Quirino Lai
- AOU Umberto I Policlinico of Rome, Sapienza University of Rome, 00161 Rome, Italy;
| | - Juri Ducci
- Azienda Ospedaliero Universitaria Pisana, 56124 Pisa, Italy;
| | - Daniela Campani
- Department of Surgical, Medical, Biochemical Pathology and Intensive Care, University of Pisa, 56126 Pisa, Italy;
- Department of Pathology, University of Pisa Medical School Hospital, 56124 Pisa, Italy
| | - Piero Marchetti
- Diabetology Unit, University of Pisa Medical School Hospital, 56124 Pisa, Italy;
| | - Stefano Gitto
- Internal Medicine and Liver Unit, University Hospital Careggi, 50134 Florence, Italy;
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
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15
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Andacoglu OM, Dennahy IS, Mountz NC, Wilschrey L, Oezcelik A. Impact of sex on the outcomes of deceased donor liver transplantation. World J Transplant 2024; 14:88133. [PMID: 38576760 PMCID: PMC10989474 DOI: 10.5500/wjt.v14.i1.88133] [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: 10/03/2023] [Revised: 11/01/2023] [Accepted: 12/11/2023] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Data examining the impact of sex on liver transplant (LT) outcomes are limited. It is clear that further research into sex-related differences in transplant patients is necessary to identify areas for improvement. Elucidation of these differences may help to identify specific areas of focus to improve on the organ matching process, as well as the peri- and post-operative care of these patients. AIM To utilize data from a high-volume Eurotransplant center to compare characteristics of male and female patients undergoing liver transplant and assess asso ciation between sex-specific variables with short- and long-term post-transplant outcomes. METHODS A retrospective review of the University of Essen's transplant database was performed with collection of baseline patient characteristics, transplant-related data, and short-term outcomes. Comparisons of these data were made with Shapiro-Wilk, Mann-Whitney U, χ2 and Bonferroni tests applied where app ropriate. A P value of < 0.05 was accepted as statistically significant. RESULTS Of the total 779 LT recipients, 261 (33.5%) were female. Female patients suffered higher incidences of acute liver failure and lower incidences of alcohol-related or viremic liver disease (P = 0.001). Female patients were more likely to have received an organ from a female donor with a higher donor risk index score, and as a high urgency offer (all P < 0.05). Baseline characteristics of male and female recipients were also significantly different. In multivariate hazard regression analysis, recipient lab-Model for End-Stage Liver Disease score and donor cause of death were associated with long-term outcomes in females. Pre-operative diagnosis of hepatocellular carcinoma, age at time of listing, duration of surgery, and units transfused during surgery, were associated with long-term outcomes in males. Severity of complications was associated with long-term outcomes in both groups. Overall survival was similar in both males and females; however, when stratified by age, females < 50 years of age had the best survival. CONCLUSION Female and male LT recipients have different baseline and transplant-related characteristics, with sex-specific variables which are associated with long-term outcomes. Female recipients < 50 years of age demonstrated the best long-term outcomes. Pre- and post-transplant practices should be individualized based on sex-specific variables to optimize long-term outcomes.
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Affiliation(s)
- Oya M Andacoglu
- Division of Transplantation and Advanced Hepatobiliary Surgery, University of Utah, Salt Lake City, UT 84112, United States
- Department of Surgery, University of Essen, Essen D-45122, Germany
| | - Isabel S Dennahy
- Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, United States
| | - Nicole C Mountz
- Department of Surgery, University of Oklahoma College of Medicine, Oklahoma City, OK 73117, United States
| | - Luisa Wilschrey
- Department of Surgery, University of Essen, Essen D-45122, Germany
| | - Arzu Oezcelik
- Department of Surgery, University of Essen, Essen D-45122, Germany
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16
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Chen J, Yang Z, Gao F, Zhou Z, Chen J, Lu D, Wang K, Sui M, Wang Z, Guo W, Lyu G, Qi H, Cai J, Yang J, Zheng S, Xu X. Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma: a multicenter cohort study in China. Cancer Biol Med 2024; 21:j.issn.2095-3941.2023.0453. [PMID: 38425217 PMCID: PMC11033715 DOI: 10.20892/j.issn.2095-3941.2023.0453] [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: 12/05/2023] [Accepted: 01/25/2024] [Indexed: 03/02/2024] Open
Abstract
OBJECTIVE Sex-specific differences are observed in various liver diseases, but the influence of sex on the outcomes of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains to be determined. This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC. METHODS Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed. The associations between donor, recipient, or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching (PSM). The survival associated with different sex-based donor-recipient transplant patterns was further studied. RESULTS Among 3,769 patients enrolled in this study, the 1-, 3-, and 5-year overall survival (OS) rates of patients with HCC after LT were 96.1%, 86.4%, and 78.5%, respectively, in female recipients, and 95.8%, 79.0%, and 70.7%, respectively, in male recipients after PSM (P = 0.009). However, the OS was comparable between recipients with female donors and male donors. Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival (HR = 1.381, P = 0.046). Among the donor-recipient transplant patterns, the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival (P < 0.05). CONCLUSIONS Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients, and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival. Livers from male donors may provide the most benefit to female recipients. Our results indicate that sex should be considered as a critical factor in organ allocation.
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Affiliation(s)
- Jian Chen
- Zhejiang University School of Medicine, Hangzhou 310030, China
| | - Zhe Yang
- Institute of Organ Transplantation, Zhejiang University, Hangzhou 310030, China
- Department of Hepatobiliary and Pancreatic Surgery, Shulan Hospital of Hangzhou, Hangzhou 310006, China
| | - Fengqiang Gao
- Zhejiang University School of Medicine, Hangzhou 310030, China
| | - Zhisheng Zhou
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou 310003, China
| | - Junli Chen
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou 310003, China
| | - Di Lu
- Zhejiang University School of Medicine, Hangzhou 310030, China
| | - Kai Wang
- Zhejiang University School of Medicine, Hangzhou 310030, China
| | - Meihua Sui
- Zhejiang University School of Medicine, Hangzhou 310030, China
| | - Zhengxin Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Guoyue Lyu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, China
| | - Haizhi Qi
- Department of Liver Transplantation, Second Xiangya Hospital, Central South University, Changsha 410008, China
| | - Jinzhen Cai
- Department of Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
| | - Jiayin Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610044, China
| | - Shusen Zheng
- Institute of Organ Transplantation, Zhejiang University, Hangzhou 310030, China
- Department of Hepatobiliary and Pancreatic Surgery, Shulan Hospital of Hangzhou, Hangzhou 310006, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xiao Xu
- Zhejiang University School of Medicine, Hangzhou 310030, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou 310030, China
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou 310003, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
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17
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Cotton JL, Suarez-Pierre A, Breithaupt JJ, Yoeli D, Ziogas IA, Choudhury RA, Nydam TL, Pomposelli JJ, Pomfret EA, Adams MA. Survival following liver transplantation: A population-based nested case-control study. Am J Surg 2024; 228:264-272. [PMID: 38867471 DOI: 10.1016/j.amjsurg.2023.10.039] [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: 08/03/2023] [Revised: 10/04/2023] [Accepted: 10/17/2023] [Indexed: 06/14/2024]
Abstract
BACKGROUND Liver transplantation is the gold standard treatment for end-stage liver disease. This study evaluates post-transplantation survival compared with the general population by quantifying standardized mortality ratios in a nested case-control study. METHODS Controls were noninstitutionalized United States inhabitants from the National Longitudinal Mortality Study. Cases underwent liver transplantation from 1990 to 2007 identified through the Organ Procurement and Transplantation Network database. Propensity matching (5:1, nearest neighbor, caliper 0.1) identified controls based on age, sex, race, and state. The primary endpoint was 10-year survival. RESULTS 62,788 cases were matched to 313,381 controls. The overall standardized mortality ratio was 2.46 (95% CI = 2.44-2.48). The standardized mortality ratio was higher for males (2.59 vs. 2.25) and Hispanic patients (4.80). Younger patients and those transplanted earlier (1990-1995) had higher standardized mortality ratios. CONCLUSIONS Liver recipients have a standardized mortality ratio 2.46 times higher than the general population. Long-term mortality has declined over time.
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Affiliation(s)
- Jake L Cotton
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA.
| | | | - Jason J Breithaupt
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Dor Yoeli
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Ioannis A Ziogas
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Rashikh A Choudhury
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; Colorado Center for Transplantation Care, Research, and Education (CCTCARE) at the University of Colorado Hospital-Anschutz Medical Campus, Aurora, CO, USA
| | - Trevor L Nydam
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; Colorado Center for Transplantation Care, Research, and Education (CCTCARE) at the University of Colorado Hospital-Anschutz Medical Campus, Aurora, CO, USA
| | - James J Pomposelli
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; Colorado Center for Transplantation Care, Research, and Education (CCTCARE) at the University of Colorado Hospital-Anschutz Medical Campus, Aurora, CO, USA
| | - Elizabeth A Pomfret
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; Colorado Center for Transplantation Care, Research, and Education (CCTCARE) at the University of Colorado Hospital-Anschutz Medical Campus, Aurora, CO, USA
| | - Megan A Adams
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; Colorado Center for Transplantation Care, Research, and Education (CCTCARE) at the University of Colorado Hospital-Anschutz Medical Campus, Aurora, CO, USA; Division of Pediatric Transplant Surgery, Children's Hospital of Colorado, Aurora, CO, USA
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18
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Kazemimajd S, Roshanaei G, Tapak L. Spatial inequalities and non-linear association of continuous variables with mortality risk of liver transplantation in Iran: a retrospective cohort study. Sci Rep 2024; 14:404. [PMID: 38172316 PMCID: PMC10764747 DOI: 10.1038/s41598-023-50808-8] [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: 06/25/2023] [Accepted: 12/26/2023] [Indexed: 01/05/2024] Open
Abstract
Liver transplantation is the second most common solid organ transplant and the best option for liver failure. Of course, patient survival after transplantation depends on many risk factors. The aim of this study was to investigate the spatial and non-linear effects of continuous risk factors on patient survival after liver transplantation. This retrospective cohort study (n = 3148) used data on liver transplantation in Iran (2004-2019). A generalized additive model with spatial effects and non-linear effects of age and Model for End-Stage Liver Disease (MELD) score variables by penalized spline was used. The majority of patients were male (63.3%), with a mean (SD) age of 42.65 (13.31) and a mean (SD) MELD score of 24.43 (6.72). The 1, 5, and 10-year survival rates were 88.2%, 84.6%, and 82.5% respectively. The non-linear effect showed a steeper slope of the age effect on the hazard of death after the age of 50 (p < 0.05), and the MELD score had a direct but non-linear relationship with the hazard of death (p < 0.05). In the spatial pattern, the provinces with a greater distance from the transplant center had significantly fewer old patients than other provinces. Also, more distant provinces with an older transplant age had higher post-transplant mortality rates. Our study showed that it is better to take age and MELD score into account in postoperative care. The spatial pattern of mortality risk reflects inequalities in access to transplantation and public health services after transplantation.
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Affiliation(s)
- Somayeh Kazemimajd
- Department of Biostatistics, School of Public Health, Hamadan University of Medical Science, Hamadan, Iran
| | - Ghodratollah Roshanaei
- Department of Biostatistics, School of Public Health and Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Leili Tapak
- Department of Biostatistics, School of Public Health and Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
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19
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Cooper KM, Delk M, Devuni D, Sarkar M. Sex differences in chronic liver disease and benign liver lesions. JHEP Rep 2023; 5:100870. [PMID: 37791378 PMCID: PMC10542645 DOI: 10.1016/j.jhepr.2023.100870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 06/23/2023] [Accepted: 07/01/2023] [Indexed: 10/05/2023] Open
Abstract
The epidemiology, natural history, and therapeutic responses of chronic liver diseases and liver lesions often vary by sex. In this review, we summarize available clinical and translational data on these aspects of the most common liver conditions encountered in clinical practice, including the potential contributions of sex hormones to the underlying pathophysiology of observed differences. We also highlight areas of notable knowledge gaps and discuss sex disparities in access to liver transplant and potential strategies to address these barriers. Given established sex differences in immune response, drug metabolism, and response to liver-related therapies, emerging clinical trials and epidemiological studies should prioritize dedicated analyses by sex to inform sex-specific approaches to liver-related care.
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Affiliation(s)
- Katherine M. Cooper
- UMass Chan Medical School, Department of Medicine, Division of Gastroenterology/Hepatology, Worcester, MA, United States
| | - Molly Delk
- University of California San Francisco, Department of Medicine, Division of Gastroenterology/Hepatology, San Francisco, CA, United States
| | - Deepika Devuni
- UMass Chan Medical School, Department of Medicine, Division of Gastroenterology/Hepatology, Worcester, MA, United States
| | - Monika Sarkar
- University of California San Francisco, Department of Medicine, Division of Gastroenterology/Hepatology, San Francisco, CA, United States
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20
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Liu M, Li C, Liu J, Wan Q. Risk factors of early bacterial infection and analysis of bacterial composition, distribution and drug susceptibility after cadaveric liver transplantation. Ann Clin Microbiol Antimicrob 2023; 22:63. [PMID: 37525234 PMCID: PMC10391978 DOI: 10.1186/s12941-023-00616-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 07/23/2023] [Indexed: 08/02/2023] Open
Abstract
BACKGROUND This study provided a theoretical basis for the clinical diagnosis and treatment of bacterial infection after liver transplantation through analyzing the pathogenic distribution, drug sensitivity and risk factors of bacterial infection after liver transplantation. METHODS We collected clinical data from 207 recipients undergoing liver transplantation of graft from donation after citizens' death donors in the Third Xiangya Hospital of Central South University from January 2019 to December 2021 and analyzed the composition and distribution of bacterial pathogens, drug resistance and risk factors of infection. RESULTS A total of 90 bacterial infections occurred in 55 recipients within two months after liver transplantation, and the incidence of bacterial infection was 26.6% (55/207). The gram-negative bacteria (46/90, 51.1%) were more prevalent than gram-positive bacteria (44/90, 48.9%). Common sites of infection were the abdominal/biliary tract (26/90, 28.9%), lung (22/90, 22.4%) and urinary tract (22/90, 22.4%). Fourteen cases (6.8%) died after liver transplantation. Klebsiella pneumoniae (17/90, 18.9%) was the most frequent gram-negative bacteria causing infection in liver transplant recipients and 58.7%, 50%, 80.4% and 89.1% of gram-negative bacteria were sensitive to amikacin, minocycline, tigecycline and polymyxin B, respectively. The most common gram-positive bacteria was Enterococcus faecium (30/90, 33.3%) and 97.7%, 100%, 86.4%, 100% and 100% of gram-positive bacteria were sensitive to vancomycin, teicoplanin, daptomycin, tigecycline and linezolid, respectively. Univariate analysis revealed that bacterial infection was associated with female, age (≥ 50 years old), preoperative albumin (≤ 30 g/L), operation duration (≥ 400 min), intraoperative blood loss (≥ 3000 ml) and postoperative ventilator support. Binary Logistic regression analysis showed that female (OR = 3.149, 95% CI: 1.418-6.993, P = 0.005), operation duration (≥ 400 min) (OR = 2.393, 95% CI: 1.202-4.765, P = 0.013) and intraoperative blood loss (≥ 3000 ml) (OR = 2.052, 95% CI: 1.007-4.183, P = 0.048) were independent risk factors for bacterial infection after liver transplantation. CONCLUSION The incidence of early bacterial infection after liver transplantation was high, and the infection sites were mainly abdominal/biliary tract, respiratory tract and urinary tract. The most common pathogenic bacterium was gram-negative bacterium. Our study also identified several independent risk factors for bacterial infection after liver transplantation, including female gender, operation duration of 400 min or more, and intraoperative blood loss of 3000 ml or more. By addressing these risk factors, such as implementing strategies to optimize surgical procedures and minimize blood loss, healthcare professionals can work towards reducing the incidence of bacterial infections following liver transplantation.
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Affiliation(s)
- Min Liu
- Department of Transplant Surgery, the Third Xiangya Hospital, Central South University, 410013, Changsha, China
- Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, the Third Xiangya Hospital, Central South University, 410013, Changsha, China
| | - Cuiying Li
- Department of Transplant Surgery, the Third Xiangya Hospital, Central South University, 410013, Changsha, China
- Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, the Third Xiangya Hospital, Central South University, 410013, Changsha, China
| | - Jing Liu
- Department of Transplant Surgery, the Third Xiangya Hospital, Central South University, 410013, Changsha, China
- Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, the Third Xiangya Hospital, Central South University, 410013, Changsha, China
| | - Qiquan Wan
- Department of Transplant Surgery, the Third Xiangya Hospital, Central South University, 410013, Changsha, China.
- Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, the Third Xiangya Hospital, Central South University, 410013, Changsha, China.
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21
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Binder A, Fenchel J, Lang I, Batra A. The dual role dilemma of liver transplantation health care professionals. BMC Med Ethics 2023; 24:46. [PMID: 37403151 DOI: 10.1186/s12910-023-00923-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 06/20/2023] [Indexed: 07/06/2023] Open
Abstract
BACKGROUND Similar to many other countries, in Germany patients with alcohol-related liver disease are obliged to prove their abstinence before being accepted on a waitlist for liver transplantation. Health care professionals (HCPs) must both treat patients and ensure that patients have proven their abstinence. The aim of this exploratory study was to develop a deeper understanding of how HCPs deal with this dual role. METHODS The study used semi-structured interviews as the source of data. 11 healthcare professionals from ten of the 22 German transplant centers were interviewed. After transcription, a qualitative content analysis was performed. RESULTS We found that these HCPs faced an ethical dilemma, as they must balance the roles of being both a treatment provider (the therapist role) and an assessor (the monitoring role). To solve this dilemma, the strategy seems to be a tendency for the HCPs to take on one dominant role amongst these two roles. HCPs who prefer to take on the therapist role seem to feel burdened by the 6-month abstinence rule and the obligation to monitor their patients. HCPs who prefer to take on the monitoring role tend to have negative assumptions about the patients. HCPs also reported the impression that patients perceive HCPs as more involved in monitoring and less open to the therapeutic role. From this it can be deduced that current regulations and structures lead both to stress for HCPs and to suboptimal therapy for those affected. CONCLUSIONS The results showed that current transplantation guidelines can have a negative impact on both patient care and the burdens on the HCPs. From our point of view, there are various changes that could be made to the current clinical practice that would help solve this dilemma. For instance, integrating other assessment criteria that are more closely adapted to the health status trajectory and psychosocial background of the individual patient would be both possible and would lead to improvements in practice.
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Affiliation(s)
- Annette Binder
- Department of General Psychiatry and Psychotherapy, Addiction Medicine and Addiction Research Section, University Hospital Tuebingen, Tuebingen, Germany.
| | - Julia Fenchel
- Department of General Psychiatry and Psychotherapy, Addiction Medicine and Addiction Research Section, University Hospital Tuebingen, Tuebingen, Germany
| | - Immanuel Lang
- Department of General Psychiatry and Psychotherapy, Addiction Medicine and Addiction Research Section, University Hospital Tuebingen, Tuebingen, Germany
| | - Anil Batra
- Department of General Psychiatry and Psychotherapy, Addiction Medicine and Addiction Research Section, University Hospital Tuebingen, Tuebingen, Germany
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22
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Kim JM, Joo DJ, Hong SK, You YK, Hwang S, Ryu JH, Kim DJ, Yu HC, Nah YW, Kim MS. Outcomes of sexagenarian living liver donors in Korea: A multicenter study. Liver Transpl 2023; 29:698-710. [PMID: 36825584 DOI: 10.1097/lvt.0000000000000104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 01/10/2023] [Indexed: 02/25/2023]
Abstract
The safety of elderly living liver donors and recipient outcomes are always of concern. In the present study, the effects of age in 2 donor groups, a 60+years old group and a 50-59 years old group (referred to as the 60s and 50s donor groups, respectively), on living donor liver transplantation were compared regarding donor safety and recipient outcomes. We retrospectively identified 209 patients 50 years and above of age at 9 centers from 2005 to 2017 in Korea. The 60s donor group represented 10% (n=21) of donor patients. One case in each group was a left liver graft, respectively, and the others were right liver grafts. Postoperative complications were more common in the 60s donor group, but the proportion of Clavien-Dindo grade III in the 60s donor group did not differ from that in the 50s donor group. In-hospital mortality did not occur among donors, and donor mortality was not reported during the observation period. Postoperative total bilirubin and hospitalization in recipients of the 60s donor group were higher and longer than in recipients of the 50s donor group, respectively. Although the cumulative overall survival of the recipients in the 60s donor group was significantly lower than that of the 50s donor group, a difference was not observed in graft survival. Multivariate analysis showed that increased living liver donors age, the coexistence of HCC, and increased intraoperative blood loss during the recipient operation were important predisposing factors for patient death. Present study suggests that highly selected elderly living donors (≥60 y) can safely donate with similar recipient graft survival rates though the recipient overall patient survival is inferior compared to the 50s donor group.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, Seoul, Republic of Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University College of Medicine, Busan, Republic of Korea
| | - Doo Jin Kim
- Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Hee Chul Yu
- Department of Surgery, Chonbuk National University Medical School, Jeonju, Republic of Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
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23
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Chornenkyy Y, Gama AP, Felicelli C, Khurram N, Booth AL, Leventhal JR, Ramsey GE, Yang GY. Alloimmunization Against RBC Antigens Is Not Associated With Decreased Survival in Liver Transplant Recipients. Am J Clin Pathol 2023; 159:255-262. [PMID: 36626677 DOI: 10.1093/ajcp/aqac150] [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: 08/14/2022] [Accepted: 10/25/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Improvement of liver transplantation (LT) outcomes requires better understanding of factors affecting survival. The presence of RBC alloantibodies (RBCAs) on survival in LT recipients was evaluated. METHODS This study was a single-center, retrospective cohort study reviewing transfusion records and all-cause mortality between 2002 and 2021. RESULTS Between 2002 and 2021, 2079 LTs were completed, 1,396 of which met inclusion criteria (1,305 RBCA negative; 91 RBCA positive [6.5%]). The cohorts were similar in age (mean [range], 55.8 [17-79] years vs 56.8 [25-73] years; P = .41, respectively) or sex (RBCA negative, 859 [65%] men and 446 [35%] women vs RBCA positive, 51 [56%] men and 40 [44%] women; P = .0684). Of 132 RBCAs detected, 10 were most common were to E (27.27%), Jka (15.91%), K (9.09%), C (8.33%), M (6.06%), D (5.3%), Fya (4.55%), e (2.27%), c (2.27%), and Jkb (2.27%). Twenty-seven patients (29.7%) had more than 1 RBCA; the most common combinations were C with Jka (7.4%) and E with Dia (7.4%). All-cause mortality was increased in men (men, 14.45 years vs women, 17.27 years; P = .0266) and patients 65 years of age and older (≥65 years of age, 10.21 years vs <64 years of age, 17.22 years; P < .0001). The presence of RBCA (≥1) did not affect all-cause mortality (RBCA negative, 14.17 years vs RBCA positive, 15.29 years; P = .4367). The top 5 causes of death were infection (11.9%), primary malignancy (solid) (10.8%), recurrent malignancy (10.5%), cardiovascular arrest (7.1%), and pulmonary insufficiency/respiratory failure (5.7%). CONCLUSIONS Survival in RBCA-positive LT recipients is no different from that in RBCA-negative LT recipients.
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Affiliation(s)
- Yevgen Chornenkyy
- Department of Pathology, McGaw Medical Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - Alcino Pires Gama
- Department of Pathology, McGaw Medical Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - Christopher Felicelli
- Department of Pathology, McGaw Medical Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - Nigar Khurram
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Adam L Booth
- Department of Pathology, McGaw Medical Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - Joseph R Leventhal
- Department of Surgery, McGaw Medical Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.,Comprehensive Transplant Center, McGaw Medical Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | | | - Guang-Yu Yang
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
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24
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Rodríguez-Perálvarez ML, Gómez-Orellana AM, Majumdar A, Bailey M, McCaughan GW, Gow P, Guerrero M, Taylor R, Guijo-Rubio D, Hervás-Martínez C, Tsochatzis EA. Development and validation of the Gender-Equity Model for Liver Allocation (GEMA) to prioritise candidates for liver transplantation: a cohort study. Lancet Gastroenterol Hepatol 2023; 8:242-252. [PMID: 36528041 DOI: 10.1016/s2468-1253(22)00354-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/19/2022] [Accepted: 10/19/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities. METHODS In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010-20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998-2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessed by Harrell's concordance statistic. FINDINGS 449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell's concordance statistic 0·752 [95% CI 0·700-0·804] vs 0·712 [0·656-0·769]; p=0·001 in the internal validation group and 0·761 [0·703-0·819] vs 0·739 [0·682-0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715-0·818] vs 0·742 [0·686-0·797]; p=0·0058 in the internal validation group and 0·774 [0·720-0·827] vs 0·745 [0·690-0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716-0·888]) and external validation cohorts (0·796 [0·698-0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na. INTERPRETATION GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation. FUNDING Junta de Andalucía and EDRF.
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Affiliation(s)
- Manuel Luis Rodríguez-Perálvarez
- Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, IMIBIC, Córdoba, Spain; Department of Medicine, University of Córdoba, Córdoba, Spain; Centro de investigación biomédica en red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | | | - Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre and Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, The University of Sydney, Sydney, NSW, Australia; Victorian Liver Transplant Unit, Austin Health, Melbourne, VIC, Australia; The University of Melbourne, Melbourne, VIC, Australia
| | - Michael Bailey
- Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; ANZICS Centre for Outcome and Resource Evaluation (CORE), Melbourne, VIC, Australia
| | - Geoffrey W McCaughan
- AW Morrow Gastroenterology and Liver Centre and Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, The University of Sydney, Sydney, NSW, Australia; Liver Injury and Cancer Program, Centenary Institute, Sydney, NSW, Australia
| | - Paul Gow
- Victorian Liver Transplant Unit, Austin Health, Melbourne, VIC, Australia; The University of Melbourne, Melbourne, VIC, Australia
| | - Marta Guerrero
- Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, IMIBIC, Córdoba, Spain; Centro de investigación biomédica en red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - Rhiannon Taylor
- Department of Statistics and Clinical Studies, NHS Blood and Transplant, Stoke Gifford, Bristol, UK
| | - David Guijo-Rubio
- Department of Computer Science and Numerical Analysis, University of Córdoba, Córdoba, Spain; School of Computing Sciences, University of East Anglia, Norwich, UK
| | - César Hervás-Martínez
- Department of Computer Science and Numerical Analysis, University of Córdoba, Córdoba, Spain
| | - Emmanuel A Tsochatzis
- Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
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25
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Tejada S, Martinez-Reviejo R, Nogueira TA, Gómez A, Pont T, Liao X, Zhang Z, Manuel O, Rello J. The effect of sex inequality on solid organ transplantation: A systematic review and meta-analysis. Eur J Intern Med 2023; 109:58-67. [PMID: 36585321 DOI: 10.1016/j.ejim.2022.12.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/14/2022] [Accepted: 12/19/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND Sex disparities are related to biological differences, which may have significant impact on patient and allograft outcomes. The aim was to investigate the impact of sex on clinical and safety outcomes after solid organ transplantation (SOT). METHODS A systematic review and meta-analysis was performed. Observational studies comparing females vs. males after SOT were considered for inclusion after a systematic search of the Pubmed, Cochrane Library, and Web of Science databases conducted from 2016 to 2021. Primary outcome was mortality. PROSPERO register number: CRD42021282615. RESULTS After retrieving 1103 studies, 22 observational studies (1,045,380 subjects) were finally deemed eligible for inclusion. Females accounted 36.3% of SOT recipients, but presented significantly lower mortality (odds ratio (OR): 0.87, 95% confidence interval (CI): 0.83-0.92, I2=78%). In subgroup analyses, mortality was significantly lower in females undergoing liver (OR: 0.89 95%CI: 0.86-0.92, I2=0%) or kidney transplantation (OR: 0.82 95%CI: 0.76-0.89, I2=72%). Male sex was consistently reported as a protective factor against hospital readmission. Among the outcomes, allograft dysfunction was influenced by a combination of donor-recipient sex and age. Data on overall infections were inconclusive. Several reports suggest a higher risk of malignancy among males. CONCLUSIONS Females represent one-third of SOT recipients but have higher survival rates than males after liver and kidney transplantation. The impact on graft dysfunction was heterogeneous. While further research is warranted, our findings should encourage clinicians and researchers to consider sex as a factor when taking decisions regarding SOT management.
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Affiliation(s)
- Sofia Tejada
- Centro de Investigación Biomédica En Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain
| | - Raquel Martinez-Reviejo
- Centro de Investigación Biomédica En Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain
| | | | - Aroa Gómez
- Department of Donor & Transplant Coordination, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Teresa Pont
- Department of Donor & Transplant Coordination, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Xuelian Liao
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China; West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Zheng Zhang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Oriol Manuel
- Service of Infectious Diseases, Lausanne University Hospital, Lausanne, Switzerland; Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - Jordi Rello
- Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain; Clinical Research CHU Nîmes, Université de Nîmes-Montpellier, France; Medicine Department, Universitat Internacional de Catalunya (UIC), Sant Cugat, Spain.
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26
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Ochoa-Allemant P, Trivedi HD, Saberi B, Bonder A, Fricker ZP. Waitlist and posttransplantation outcomes of lean individuals with nonalcoholic fatty liver disease. Liver Transpl 2023; 29:145-156. [PMID: 35715982 DOI: 10.1002/lt.26531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 05/23/2022] [Accepted: 06/07/2022] [Indexed: 01/25/2023]
Abstract
Lean individuals with nonalcoholic fatty liver disease (NAFLD) represent a subset of patients with a distinct risk factor profile. We assessed the association between body mass index (BMI) on waitlist and postliver transplantation (LT) outcomes among these patients. We retrospectively analyzed the United Network for Organ Sharing data, including adult patients with NAFLD listed for LT between February 27, 2002, and June 30, 2020. We first used competing risk analyses to estimate the association of BMI with waitlist removal due to death or clinical deterioration. We then conducted Kaplan-Meier estimates and Cox regression models to determine the impact of weight change during the waiting list on all-cause mortality and graft failure after LT. Patients with normal weight (BMI 18.5-24.9 kg/m 2 ) suffered higher waitlist removal (adjusted subdistribution hazard ratio 1.26, 95% confidence interval [CI] 1.10-1.43; p = 0.001) compared with patients with obesity class I (BMI 30-34.9 kg/m 2 ). Those who remained at normal weight had higher all-cause mortality (adjusted hazard ratio [aHR] 1.61, 95% CI 1.32-1.96; p <0.001) and graft failure (aHR 1.57, 95% CI 1.32-1.88; p <0.001) than patients with stable obesity. Among patients with normal weight, those with the greatest weight increase (BMI gain ≥3 kg/m 2 ) had lower all-cause mortality (aHR 0.55, 95% CI 0.33-0.93; p = 0.03) and graft failure (aHR 0.49, 95% CI 0.30-0.81; p = 0.01) compared with patients with stable weight (BMI change ≤1 kg/m 2 ). Patients with NAFLD with normal weight have increased waitlist removal and those who remained at normal weight during the waitlist period have worse posttransplantation outcomes. Identifying and addressing factors influencing apparent healthy weight prior to LT are crucial to mitigate poor outcomes.
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Affiliation(s)
- Pedro Ochoa-Allemant
- Department of Internal Medicine , Yale School of Medicine , New Haven , Connecticut , USA
| | - Hirsh D Trivedi
- Liver Center, Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA
| | - Behnam Saberi
- Liver Center, Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA
| | - Alan Bonder
- Liver Center, Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA
| | - Zachary P Fricker
- Liver Center, Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA
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27
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Moosburner S, Wiering L, Roschke NN, Winter A, Demir M, Gaßner JM, Zimmer M, Ritschl P, Globke B, Lurje G, Tacke F, Schöning W, Pratschke J, Öllinger R, Sauer IM, Raschzok N. Validation of risk scores for allograft failure after liver transplantation in Germany: a retrospective cohort analysis. Hepatol Commun 2023; 7:e0012. [PMID: 36633496 PMCID: PMC9833444 DOI: 10.1097/hc9.0000000000000012] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 09/14/2022] [Indexed: 01/13/2023] Open
Abstract
A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité-Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p<0.001 at 3-month graft survival). Out of these, the BAR score performed best with a c-statistic of 0.6. This a comprehensive comparison of the clinical utility of risk scores after liver transplantation. The EASE score sufficiently predicted 12-month graft and patient survival. Despite a relatively complex calculation, the EASE score provides significant prognostic value for patients and health care professionals in the Eurotransplant region.
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Affiliation(s)
- Simon Moosburner
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
- BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH)
| | - Leke Wiering
- Department of Hepatology and Gastroenterology, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Nathalie N. Roschke
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
| | - Axel Winter
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
| | - Münevver Demir
- Department of Hepatology and Gastroenterology, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Joseph M.G.V. Gaßner
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
- BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH)
| | - Maximilian Zimmer
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
| | - Paul Ritschl
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
- BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH)
| | - Brigitta Globke
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
- BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH)
| | - Georg Lurje
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Wenzel Schöning
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
| | - Johann Pratschke
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
| | - Robert Öllinger
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
| | - Igor M. Sauer
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
| | - Nathanael Raschzok
- Department of Surgery, Experimental Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Universität zu Berlin and Berlin Institute of Health
- BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH)
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Salah M, Montasser IF, El-Gendy HA, Korraa AA, Elewa GM, Dabbous H, Abdelrahman M, Goda MH, Bahaa MM, El Meteini M, Labib HA. Donor gender effect on graft function in adult Egyptian patients undergoing living donor liver transplantation: A single centre study. EGYPTIAN JOURNAL OF ANAESTHESIA 2022; 38:201-210. [DOI: 10.1080/11101849.2022.2060643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 03/20/2022] [Accepted: 03/28/2022] [Indexed: 02/08/2023] Open
Affiliation(s)
- Manar Salah
- Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Iman F. Montasser
- Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hanaa A. El-Gendy
- Department of Anesthesia, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Alaa A. Korraa
- Department of Anesthesia, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Gamal M. Elewa
- Department of Anesthesia, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hany Dabbous
- Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mostafa Abdelrahman
- Department of General Surgery and Liver Transplantation, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Hisham Goda
- Department of General Surgery and Liver Transplantation, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed M. Bahaa
- Department of General Surgery and Liver Transplantation, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud El Meteini
- Department of General Surgery and Liver Transplantation, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Heba A. Labib
- Department of Anesthesia, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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29
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Lonardo A, Mantovani A, Petta S, Carraro A, Byrne CD, Targher G. Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation. Nat Rev Endocrinol 2022; 18:638-650. [PMID: 35840803 DOI: 10.1038/s41574-022-00711-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2022] [Indexed: 11/08/2022]
Abstract
The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major health concern worldwide. NAFLD - specifically its more advanced form, non-alcoholic steatohepatitis (NASH)-related cirrhosis - is now the fastest growing indication for liver transplantation in the USA and Europe. Although the short-term and mid-term overall survival rates of patients who receive a liver transplant for NASH-related cirrhosis are essentially similar to those of patients who receive a transplant for other liver indications, recipients with NASH-related cirrhosis have an increased risk of waiting-list mortality and of developing recurrent liver disease and cardiometabolic complications in the longer term after liver transplantation. This Review provides a brief overview of the epidemiology of NAFLD and NASH and the occurrence of NAFLD or NASH in patients after liver transplantation for NASH and other liver indications. It also discusses the putative metabolic mechanisms underlying the emergence of NAFLD or NASH after liver transplantation as well as optimal therapeutic approaches for recipients of liver transplants, including the management of cardiometabolic comorbidities, tailored immunosuppression, lifestyle changes and pharmacotherapy for NAFLD.
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Affiliation(s)
- Amedeo Lonardo
- Metabolic Syndrome Unit, University of Modena, Modena, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Amedeo Carraro
- Liver Transplant Unit, University of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
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30
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Singh N, Watt KD, Bhanji RA. The fundamentals of sex-based disparity in liver transplantation: Understanding can lead to change. Liver Transpl 2022; 28:1367-1375. [PMID: 35289056 DOI: 10.1002/lt.26456] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 02/21/2022] [Accepted: 03/09/2022] [Indexed: 01/13/2023]
Abstract
Liver transplantation (LT) is the definitive treatment for end-stage liver disease. Unfortunately, women are disadvantaged at every stage of the LT process. We conducted a literature review to increase the understanding of this disparity. Hormonal differences, psychological factors, and Model for End-Stage Liver Disease (MELD) score inequalities are some pretransplantation factors that contribute to this disparity. In the posttransplantation setting, women have differing risk than men in most major outcomes (perioperative complications, rejection, long-term renal dysfunction, and malignancy) and assessing the two groups together is disadvantageous. Herein, we propose interventions including standardized criteria for LT referral, using an alternate MELD, education for support of women, and motivating women to seek living donors. Understanding sex-based differences will allow us to improve access, tailor management, and improve overall outcomes for all patients, particularly women.
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Affiliation(s)
- Noreen Singh
- Division of Gastroenterology (Liver Unit), University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Rahima A Bhanji
- Division of Gastroenterology (Liver Unit), University of Alberta Hospital, Edmonton, Alberta, Canada
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31
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Sealock JM, Ziogas IA, Zhao Z, Ye F, Alexopoulos SP, Matsuoka L, Chen G, Davis LK. Proposing a Sex-Adjusted Sodium-Adjusted MELD Score for Liver Transplant Allocation. JAMA Surg 2022; 157:618-626. [PMID: 35583884 PMCID: PMC9118088 DOI: 10.1001/jamasurg.2022.1548] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 03/05/2022] [Indexed: 01/11/2023]
Abstract
Importance Liver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on 4 laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex. Objective To use laboratory values stored in electronic health records to describe population-level sex differences in all MELD laboratory values (in healthy individuals and patients with liver disease) and propose a sex adjustment. Design, Setting, and Participants A retrospective cohort study was conducted from March 2019 to April 2020 to evaluate sex differences in laboratory values in liver transplant patients, patients with liver disease who did not undergo transplant, and healthy controls. Primary analyses were conducted in Vanderbilt University Medical Center (VUMC)'s deidentified electronic health record system. Replication analyses were conducted in the All of Us Research Program. Simulations of a sex-adjusted sodium-adjusted MELD (MELDNa) score were completed using liver transplant waiting list data from the liver simulated allocation modeling system. Patients who regularly used VUMC with measurements for any MELDNa component laboratory were included in the analyses. Analysis took place from November 2019 to March 2021. Exposures Electronic health record-reported sex. Main Outcomes and Measure Creatinine, bilirubin, international normalized ratio, and sodium levels. Results The VUMC sample was composed of 623 931 individuals (359 976 [57.7%] female) with a median (IQR) age of 44 (23-61) years. All component MELDNa laboratory values and calculated MELDNa scores yielded significant sex differences within VUMC (mean [SD] creatinine: male, 0.99 [0.39] mg/dL; female, 0.79 [0.30] mg/dL; P < .001; bilirubin: male, 0.76 [0.83] mg/dL; female, 0.58 [0.64] mg/dL; P < .001; international normalized ratio of prothrombin rate: male, 1.24 [0.42]; female, 1.20 [0.40]; P < .001; sodium: male, 139.00 [2.36] mEq/L; female, 139.03 [2.28] mEq/L; P < .001), resulting in MELDNa scoring that disadvantaged female individuals. This pattern persisted when the sample was divided into healthy controls, individuals with liver disease who did not undergo transplant, and patients who did undergo liver transplant. Female transplant patients had a greater number of decompensation traits (mean [SD]: male, 1.34 [1.11]; female, 1.60 [1.09]; P = .005), despite having lower MELDNa scores (mean [SD]: male, 21.72 [6.11]; female, 20.21 [6.15]; P = .005), indicating MELDNa scores are not accurately representing disease severity in female individuals. In simulations, the sex-adjusted MELDNa score modestly increased female transplant rate and decreased overall death. Conclusions and Relevance These results demonstrate pervasive sex differences in all laboratory values used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.
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Affiliation(s)
- Julia M. Sealock
- Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Ioannis A. Ziogas
- Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Zhiguo Zhao
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Fei Ye
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Sophoclis P. Alexopoulos
- Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Lea Matsuoka
- Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Guanhua Chen
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison
| | - Lea K. Davis
- Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee
- Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
- Department of Medicine and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee
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Gabbay U, Issachar A, Cohen-Naftaly M, Brown M, Nesher E. Gender specific survival rates after deceased donor liver transplantation: A retrospective cohort. Ann Med Surg (Lond) 2022; 79:103933. [PMID: 35860137 PMCID: PMC9289308 DOI: 10.1016/j.amsu.2022.103933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 05/30/2022] [Accepted: 06/02/2022] [Indexed: 11/27/2022] Open
Abstract
Background According to the literature, there are sex allocation inequalities in liver transplantation (LT). Sex disparities in outcomes after LT have been debated. This study aimed to evaluate sex-specific outcomes after LT, specifically short-term mortality and long-term survival rates. Methods A retrospective cohort of the entire LT series from to 2010–2019 in a single center in which the inclusion criteria were adults ≥18 YO age who underwent primary deceased donor LT. Mortality rate was evaluated within 30 days and 6 months. Survival rate was evaluated at 1,3 and 5 years of age. Results A total of 240 primary and deceased donor LTs (153 men and 87 women) were included. Mean age 55.2Y men and 51.6Y women (p = 0.02). Hepatocellular carcinoma (HCC) was the direct indication in 32.7% of the men and only 17.4% of the women. The leading primary liver morbidities were viral hepatitis (B, C, and D) in 38.3% (N = 92) and nonalcoholic steatohepatitis (NASH) in 20.8% (N = 50) of patients. Thirty-day mortality was 14%, which was significantly higher in men (18%) than in women (8%). Survival rates after 5 years were 64.9% and 78.3%, respectively. Multivariate analysis through logistic regression that included age, direct indication, MELD, and primary liver morbidity revealed statistically significant female to male Odds-Ratio of 0.4 in 30 days, 6 m mortality and a statistically significant higher long-term survival. Conclusions Our observations revealed better female outcomes, namely, lower short-term mortality and higher long-term survival. Given the consistency after stratification and given the multivariate analysis, this is unlikely to be attributable to confounders. Such findings suggesting consistently better female outcomes have not been previously reported; hence, multi center study is encouraged.
Gender outcome disparities after liver transplantation (LT) is debated. We present retrospective cohort of 240 consecutive LT in a single center. We found significant lower short-term mortality rates and better long-term survival in women. The outcome disparity was consistent in most underlying liver diseases. We had not identified factors that may confound sex outcome disparity.
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Oliveira MM, Monnet-Aimard A, Bosoi CR, Tremblay M, Rose CF. Sex is associated with differences in oxidative stress and susceptibility to severe hepatic encephalopathy in bile-duct ligated rats. J Neurochem 2022; 162:337-351. [PMID: 35771118 DOI: 10.1111/jnc.15661] [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: 01/18/2022] [Revised: 06/23/2022] [Accepted: 06/26/2022] [Indexed: 11/29/2022]
Abstract
Hepatic encephalopathy (HE) is a debilitating neurological complication of chronic liver disease (CLD). Hyperammonemia plays an important role in HE's pathogenesis, acting synergistically with systemic oxidative stress. During CLD, muscle plays a compensatory role in detoxifying ammonia, and therefore muscle loss leads to an increase in the risk of developing HE. With most animal studies involving males, sex's impact on the development of CLD and associated complications such as HE and muscle loss remains unknown. Therefore, we aimed to identify the impact of sex on CLD, HE, and muscle mass loss in a rodent model of CLD. Liver injury markers, hyperammonemia, oxidative stress, muscle mass and ammonia clearance were measured in female and male bile-duct ligated (BDL) rats. In addition, covert HE was assessed in females while ammonia-precipitated severe HE was assessed in female and male BDL rats, and male BDL rats treated with allopurinol (100mg/kg), an antioxidant (xanthine oxidase inhibitor). Female BDL developed CLD and HE (impaired motor-coordination and night activity) compared to respective SHAM. Hyperammonemia and muscle ammonia clearance were similar between female and male BDL. However, only female BDL rats did not develop muscle loss, brain edema, and short-term memory impairment (vs. female SHAM) and systemic oxidative stress and decreased albumin levels (vs. male BDL). Furthermore, both female BDL and allopurinol-treated male BDL rats were protected against ammonia-induced overt HE. In conclusion, female and male BDL rats develop distinct features of CLD and HE, with systemic oxidative stress playing a pivotal role in the susceptibility to ammonia precipitated overt HE.
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Affiliation(s)
- Mariana M Oliveira
- Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada
| | - Alexis Monnet-Aimard
- Institut de Neurosciences de la Timone, Équipe inVibe, Université Aix-Marseille, France
| | - Cristina R Bosoi
- Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada
| | - Mélanie Tremblay
- Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada
| | - Christopher F Rose
- Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada
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Are MELD and MELDNa Still Reliable Tools to Predict Mortality on the Liver Transplant Waiting List? Transplantation 2022; 106:2122-2136. [PMID: 35594480 DOI: 10.1097/tp.0000000000004163] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Liver transplantation is the only curative treatment for end-stage liver disease. Unfortunately, the scarcity of donor organs and the increasing pool of potential recipients limit access to this life-saving procedure. Allocation should account for medical and ethical factors, ensuring equal access to transplantation regardless of recipient's gender, race, religion, or income. Based on their short-term prognosis prediction, model for end-stage liver disease (MELD) and MELD sodium (MELDNa) have been widely used to prioritize patients on the waiting list for liver transplantation resulting in a significant decrease in waiting list mortality/removal. Recent concern has been raised regarding the prognostic accuracy of MELD and MELDNa due, in part, to changes in recipients' profile such as body mass index, comorbidities, and general condition, including nutritional status and cause of liver disease, among others. This review aims to provide a comprehensive view of the current state of MELD and MELDNa advantages and limitations and promising alternatives. Finally, it will explore future options to increase the donor pool and improve donor-recipient matching.
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Lee O, Kim JM, Kim SJ, Rhu J, Choi GS, Joh JW. Healthy Spouses can be Considered as Living Liver Donors. World J Surg 2022; 46:1474-1484. [PMID: 35316397 DOI: 10.1007/s00268-022-06518-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Spousal donors have gradually been accepted as an alternative living liver donors to alleviate the organ shortage and prevent donations from children. No information is available regarding the effects of spousal donation on donor safety and recipient outcomes. Our purpose in this study was to determine how spousal liver grafts in living donor liver transplantation (LDLT) affect donor safety and recipient outcomes compared with those of LDLT from children. METHODS We retrospectively analyzed 656 patients, including spouses and children, who underwent a right or extended right hepatectomy for living liver donation between January 2009 and December 2018. RESULTS Spouses represented 18.8% (n = 123) of living liver donors. Female donors comprised 78.9% (n = 97) of spousal donors, and the proportion of male donors in the children group was 72.6% (n = 387). The mean donor operation time of the spousal group was shorter than that of the children group (330 min vs. 358 min; P = 0.011), and the complication rate in the spousal group was lower than that in the children group (12.2% vs. 22.9%; P = 0.006). However, there were no differences in severe complication rates, hospitalization, or liver function tests between the 2 groups at 3 months after donor surgery. The overall survival of recipients in the spousal group was not reduced compared to that of recipients in the children group. CONCLUSION The present study suggests that, with careful selection, spousal donation is feasible and safe in LDLT.
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Affiliation(s)
- Okjoo Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.
| | - Sang Jin Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
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Choi JY, Kim JH, Kim JM, Kim HJ, Ahn HS, Joh JW. Outcomes of living liver donors are worse than those of matched healthy controls. J Hepatol 2022; 76:628-638. [PMID: 34785324 DOI: 10.1016/j.jhep.2021.10.031] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 10/12/2021] [Accepted: 10/15/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Donor death is the most serious complication of living liver donation but is reported rarely. We investigated the actual mortality of living liver donors (LLDs) compared with matched control groups based on analysis of the Korean National Health Insurance Services (NHIS) database. METHODS This cohort study included 12,372 LLDs who donated a liver graft between 2002 and 2018, and were registered in the Korean Network for Organ Sharing. They were compared to 3 matched control groups selected from the Korean NHIS and comprising a total of 123,710 individuals: healthy population (Group I); general population without comorbidities (Group II); and general population with comorbidities (Group III). RESULTS In this population, 78.5% of living liver donors were 20-39 years old, and 64.7% of all donors were male. Eighty-nine donors (0.7%) in the LLD group died (68 males and 21 females), a mortality rate (/1,000 person-years) of 0.91 (0.74-1.12). Mortality rate ratio and the adjusted hazard ratio of the LLD group was 2.03 (1.61-2.55) and 1.71 (1.31-2.25) compared to Control Group I, 0.75 (0.60-0.93) and 0.63 (0.49-0.82) compared to Control Group II, and 0.58 (0.46-0.71) and 0.49 (0.39-0.60) compared to Control Group III. LLD group, depression, and lower income were risk factors for adjusted mortality. The incidence of liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the LLD group was significantly higher than in Control Group I. CONCLUSIONS Outcomes of the LLD group were worse than those of the matched healthy control group despite the small number of deaths and medical morbidities in this group. LLDs should receive careful medical attention for an extended period after donation. LAY SUMMARY The incidence of mortality, liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the living liver donor group was significantly higher than in the matched healthy group. Careful donor evaluation and selection processes can improve donor safety and enable safe living donor liver transplantation.
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Affiliation(s)
- Jin Yong Choi
- Department of General Surgery, Myongji Hospital, Goyang, South Korea
| | - Jae Heon Kim
- Department of Urology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - Hyun Jung Kim
- Department of Preventive Medicine, Korea University, Seoul, South Korea.
| | - Hyeong Sik Ahn
- Department of Preventive Medicine, Korea University, Seoul, South Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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37
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Yi SG, Mobley C, Ghobrial RM. Graft and Patient Survival after Liver Transplantation. TEXTBOOK OF LIVER TRANSPLANTATION 2022:433-448. [DOI: 10.1007/978-3-030-82930-8_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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38
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Yoeli D, Choudhury RA, Moore HB, Sauaia A, Simpson MA, Pomfret EA, Nydam TL. Are Hepatitis C Positive Female Liver Transplant Recipients Still at Increased Risk for Graft Failure? Reexamining the Disparity in the Modern Era of Direct-acting Antiviral Agents. Transplantation 2022; 106:129-137. [PMID: 33577252 DOI: 10.1097/tp.0000000000003683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND This study aimed to compare the outcomes of hepatitis C virus (HCV) positive (+) female liver transplant recipients to HCV negative (-) female and HCV+ male recipients before and after the direct-acting-antiviral (DAA) era. METHODS The United Network for Organ Sharing liver transplant database was retrospectively reviewed from 2002 to 2017. The DAA era was defined as ≥2014. RESULTS In the pre-DAA era, HCV+ female recipients had greater risk for graft failure compared with HCV+ male (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.03) and HCV- female (HR, 1.51; 95% CI, 1.43-1.60; P < 0.001) recipients. In the post-DAA era, HCV+ female recipients had lower risk for graft failure compared with HCV+ male recipients (HR, 0.82; 95% CI, 0.70-0.97; P = 0.02) and equivalent outcomes to HCV- female recipients. HCV+ female recipients with graft failure had increased likelihood of graft failure due to disease recurrence compared with HCV+ male recipients in the pre-DAA era (odds ratio, 1.23; 95% CI, 1.08-1.39; P = 0.001) but not in the post-DAA era. CONCLUSIONS Although historically HCV+ female recipients were at disproportionately increased risk for graft failure and disease recurrence, this disparity has been eliminated in the DAA era.
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Affiliation(s)
- Dor Yoeli
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Rashikh A Choudhury
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Hunter B Moore
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Angela Sauaia
- Colorado School of Public Health, University of Colorado Denver, Aurora, CO
| | - Mary Ann Simpson
- Department of Transplantation, Lahey Hospital and Medical Center, Burlington, MA
| | - Elizabeth A Pomfret
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Trevor L Nydam
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
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Epidemiology and Prognostic Significance of Rapid Response System Activation in Patients Undergoing Liver Transplantation. J Clin Med 2021; 10:jcm10235680. [PMID: 34884382 PMCID: PMC8658097 DOI: 10.3390/jcm10235680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/19/2021] [Accepted: 12/01/2021] [Indexed: 11/23/2022] Open
Abstract
Patients undergoing liver transplantation have a high risk of perioperative clinical deterioration. The Rapid Response System is an intensive care unit-based approach for the early recognition and management of hospitalized patients identified as high-risk for clinical deterioration by a medical emergency team (MET). The etiology and prognostic significance of clinical deterioration events is poorly understood in liver transplant patients. We conducted a cohort study of 381 consecutive adult liver transplant recipients from a prospectively collected transplant database (2011–2017). Medical records identified patients who received MET activation pre- and post-transplantation. MET activation was recorded in 131 (34%) patients, with 266 MET activations in total. The commonest triggers for MET activation were tachypnea and hypotension pre-transplantation, and tachycardia post-transplantation. In multivariable analysis, female sex, increasing Model for End-Stage Liver Disease score and hepatorenal syndrome were independently associated with MET activation. The unplanned intensive care unit admission rate following MET activation was 24.1%. Inpatient mortality was 4.2% and did not differ by MET activation status; however, patients requiring MET activation had significantly longer intensive care unit and hospital length of stay and were more likely to require inpatient rehabilitation. In conclusion, liver transplant patients with perioperative complications requiring MET activation represent a high-risk group with increased morbidity and length of stay.
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Huang DC, Fricker ZP, Alqahtani S, Tamim H, Saberi B, Bonder A. The influence of equitable access policies and socioeconomic factors on post-liver transplant survival. EClinicalMedicine 2021; 41:101137. [PMID: 34585128 PMCID: PMC8452797 DOI: 10.1016/j.eclinm.2021.101137] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 08/27/2021] [Accepted: 09/03/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Survival following liver transplant (LT) is influenced by a variety of factors, including donor risk factors and recipient disease burden and co-morbidities. It is difficult to separate these effects from those of socioeconomic factors, such as income or insurance. The United Network for Organ Sharing (UNOS) created equitable access policies, such as Share 35, to ensure that organs are distributed to individuals with greatest medical need; however, the effect of Share 35 on disparities in post-LT survival is not clear. This study aimed to (1) characterize associations between post-transplant survival and race and ethnicity, income, insurance, and citizenship status, when adjusted for other clinical and demographic factors that may influence survival, and (2) determine if the direction of associations changed after Share 35. METHODS A retrospective, cohort study of adult LT recipients (n = 83,254) from the UNOS database from 2005 to 2019 was conducted. Kaplan-Meier survival graphs and stepwise multivariate cox-regression analyses were performed to characterize the effects of socioeconomic status on post-LT survival, adjusted for recipient and donor characteristics, across the time period and after Share 35. FINDINGS Male sex (HR: 0.93 (95% CI: 0.90-0.96)), private insurance (0.91 (0.88-0.94)), income (0.82 (0.79-0.85)), U.S. citizenship, and Asian (0.81 (0.75-0.88)) or Hispanic (0.82 (0.79-0.86)) race and ethnicity were associated with higher post-transplant survival, after adjustment for clinical and demographic factors (Table 3). These associations were found across the entire time period studied and many persisted after the implementation of Share 35 in 2013 (Table 3; male sex (0.84 (0.79-0.90)), private insurance (0.94 (0.89-1.00)), income (0.82 (0.77-0.89)), and Asian (0.87 (0.73-1.02)) or Hispanic (0.88 (0.81-0.96)) race and ethnicity). INTERPRETATION Recipients' socioeconomic factors at time of transplant may impact long-term post-transplant survival, and a single policy may not significantly alter these structural health inequalities. FUNDING None.
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Key Words
- DDLT, deceased donor living transplant
- DM, diabetes mellitus
- DRI, donor risk index
- HCC, hepatocellular carcinoma
- HCV, hepatitis c virus
- HE, hepatic encephalopathy
- Health disparities
- IQR, interquartile range
- IRB, institutional review board
- LT, liver transplant
- Liver transplant
- MELD, Model for End-Stage Liver Disease
- NAFLD, Non-alcoholic fatty liver disease
- OPTN, Organ Procurement and Transplantation Network
- STAR, Standard Transplant Analysis and Research
- Socioeconomic factors
- UNOS, United Network for Organ Sharing
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Affiliation(s)
- Dora C Huang
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, United States
| | - Zachary P Fricker
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Saleh Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Hani Tamim
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | - Behnam Saberi
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Alan Bonder
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- Corresponding author.
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Cullaro G, Rubin J, Mehta N, Yao F, Verna EC, Lai JC. Sex-based Disparities in Hepatocellular Carcinoma Recurrence After Liver Transplantation. Transplantation 2021; 105:2420-2426. [PMID: 33323764 PMCID: PMC8200371 DOI: 10.1097/tp.0000000000003575] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Women with chronic liver disease have lower rates of hepatocellular carcinoma (HCC) as compared to men; it is unknown if there are sex-based differences in HCC recurrence postliver transplant. METHODS We conducted an analysis of patients who underwent liver transplant for HCC in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2012 through December 31, 2017. RESULTS A total of 12 711 patients underwent liver transplant for HCC: 2909 (23%) women and 9802 (73%) men. Women had significantly lower rates of postliver transplant HCC recurrence than men (4.0% versus 5.4%, P = 0.002). A cox-regression analysis for postliver transplant HCC recurrence highlighted that even after accounting for etiology of cirrhosis, alpha-fetoprotein at liver transplant, tumor diameter, tumor pathology, and vascular invasion, female sex was associated with a 25% lower risk of postliver transplant HCC recurrence (95% confidence interval: 0.57-0.99). There were no interactions between female sex and the following variables: age, type of locoregional therapy, alpha-fetoprotein, donor sex, body mass index, or nonalcoholic steatohepatitis etiology (P > 0.05 for each). CONCLUSIONS This study demonstrates an independent effect of sex on risk for HCC recurrence postliver transplant. Our data highlight an opportunity to better understand HCC tumor biology by investigating the drivers of this sex-based difference in HCC recurrence.
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Affiliation(s)
- Giuseppe Cullaro
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
| | - Jessica Rubin
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
| | - Neil Mehta
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
| | - Francis Yao
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
| | - Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia
University, College of Physicians and Surgeons, New York, NY, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
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Karnam RS, Chen S, Xu W, Chen C, Elangainesan P, Ghanekar A, McGilvray I, Reichman T, Sayed B, Selzner M, Sapisochin G, Galvin Z, Hirschfield G, Asrani SK, Selzner N, Cattral M, Lilly L, Bhat M. Sex Disparity in Liver Transplant and Access to Living Donation. JAMA Surg 2021; 156:1010-1017. [PMID: 34406347 PMCID: PMC8374729 DOI: 10.1001/jamasurg.2021.3586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 05/22/2021] [Indexed: 12/15/2022]
Abstract
Importance The Model for End-stage Liver Disease (MELD)-based organ allocation system has significantly decreased mortality on the transplant waiting list for patients with end-stage liver disease. However, women have remained at a disadvantage with respect to access to deceased donor liver transplant (DDLT) even after introduction of the MELD score for organ allocation. Objective To determine whether availability of living donation in a transplant program can offset inequity in liver transplant (LT) allocation for women. Design, Setting, and Participants This cohort study retrospectively analyzed adult patients listed for LT at the University Health Network in Toronto, Ontario, Canada. Patients included had a potential living donor (pLD) at the moment of listing. This study was performed from November 13, 2012, to May 31, 2019. A total of 1289 listed patients (830 men; 459 women) were analyzed during the study period. Main Outcomes and Measures This study performed survival analysis and competing-risk analysis to delineate how access to livers from living donors was associated with events in women vs men on the transplant waiting list (LT, death, or dropout). Results Of 1289 included patients, 459 (35.6%) were women, and the mean (SD) age was 56.1 (10.0) years at assessment and listing. A total of 783 of 1289 listed patients underwent LT. Among those with no pLD at assessment, there was a higher median (range) Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score at listing (22 [6-50] vs 19 [6-50]; P < .001) and at LT (27 [6-49] vs 20 [6-52]; P < .001) in women receiving DDLT. Women were at a significant disadvantage without a pLD (hazard ratio [HR], 1.29; 95% CI, 1.04-1.60; P = .01); there was no difference in access to LT with availability of a pLD (HR, 0.93; 95% CI, 0.76,-1.14; P = .44). The instantaneous rate of receiving a transplant in men with a pLD was 1.39 times higher than men who did not have a pLD (HR, 1.39; 95% CI; P < .001) and the instantaneous rate of receiving a transplant in women with a pLD was 1.92 times higher than in women who did not (HR, 1.92; 95% CI, 1.51-2.44; P < .001). The HR was 1.38 times higher in women compared with men across the MELD-Na score strata (HR, 1.38; 95% CI, 1.03-1.84; P = .03) and 2.04 times higher when the MELD-Na score was less than 20 (HR, 2.04; 95% CI, 1.31-3.14; P = .001). Conclusions and Relevance These study findings suggest that women can overcome the complex problem of allocation inequity with access to livers from living donors. Women with access only to DDLT were much more unwell than men independent of liver disease at the time of listing, dropout, or LT. Therefore, the wider availability of living donation liver transplant would be helpful in addressing the sex disparity in access to LT in the current MELD-Na era.
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Affiliation(s)
- Ravikiran S. Karnam
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Ramaiah Medical College, Narayana Health, Bengaluru, India
| | - Shiyi Chen
- Department of Biostatistics, Princess Margaret Cancer Research Centre, Toronto, Ontario, Canada
| | - Wei Xu
- Department of Biostatistics, Princess Margaret Cancer Research Centre, Toronto, Ontario, Canada
| | - Catherine Chen
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Praniya Elangainesan
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Anand Ghanekar
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Ian McGilvray
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Trevor Reichman
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Blayne Sayed
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Markus Selzner
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Zita Galvin
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Toronto General Hospital Research Institute, Toronto, Ontario, Canada
| | - Gideon Hirschfield
- Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Toronto General Hospital Research Institute, Toronto, Ontario, Canada
| | | | - Nazia Selzner
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Toronto General Hospital Research Institute, Toronto, Ontario, Canada
| | - Mark Cattral
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Leslie Lilly
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Toronto General Hospital Research Institute, Toronto, Ontario, Canada
| | - Mamatha Bhat
- Multi Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Toronto General Hospital Research Institute, Toronto, Ontario, Canada
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Starlinger P, Ahn JC, Mullan A, Gyoeri GP, Pereyra D, Alva‐Ruiz R, Hackl H, Reiberger T, Trauner M, Santol J, Simbrunner B, Mandorfer M, Berlakovich G, Kamath PS, Heimbach J. The Addition of C-Reactive Protein and von Willebrand Factor to Model for End-Stage Liver Disease-Sodium Improves Prediction of Waitlist Mortality. Hepatology 2021; 74:1533-1545. [PMID: 33786862 PMCID: PMC8518408 DOI: 10.1002/hep.31838] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 02/09/2021] [Accepted: 03/14/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed because of complications of portal hypertension (PH) or infections. von Willebrand factor antigen (vWF-Ag) and C-reactive protein (CRP) are simple, broadly available markers of these processes. APPROACH AND RESULTS We determined whether addition of vWF-Ag and CRP to the Model for End-Stage Liver Disease-Sodium (MELD-Na) score improves risk stratification of patients awaiting LT. CRP and vWF-Ag at LT listing were assessed in two independent cohorts (Medical University of Vienna [exploration cohort] and Mayo Clinic Rochester [validation cohort]). Clinical characteristics, MELD-Na, and mortality on the waiting list were recorded. Prediction of 3-month waiting list mortality was assessed by receiver operating characteristics curve (ROC-AUC). In order to explore potential mechanisms underlying the prognostic utility of vWF-Ag and CRP in this setting, we evaluated their association with PH, bacterial translocation, systemic inflammation, and circulatory dysfunction. In the exploration cohort (n = 269) vWF-Ag and CRP both improved the predictive value of MELD-Na for 3-month waitlist mortality and showed the highest predictive value when combined (AUC: MELD-Na, 0.764; MELD-Na + CRP, 0.790; MELD-Na + vWF, 0.803; MELD-Na + CRP + vWF-Ag, 0.824). Results were confirmed in an independent validation cohort (n = 129; AUC: MELD-Na, 0.677; MELD-Na + CRP + vWF-Ag, 0.882). vWF-Ag was independently associated with PH and inflammatory biomarkers, whereas CRP closely, and MELD independently, correlated with biomarkers of bacterial translocation/inflammation. CONCLUSIONS The addition of vWF-Ag and CRP-reflecting central pathophysiological mechanisms of PH, bacterial translocation, and inflammation, that are all drivers of mortality on the waiting list for LT-to the MELD-Na score improves prediction of waitlist mortality. Using the vWFAg-CRP-MELD-Na model for prioritizing organ allocation may improve prediction of waitlist mortality and decrease waitlist mortality.
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Affiliation(s)
- Patrick Starlinger
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN,Department of SurgeryDivision of General SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Joseph C. Ahn
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMN
| | - Aidan Mullan
- Department of Health Sciences ResearchMayo ClinicRochesterMN
| | - Georg P. Gyoeri
- Department of SurgeryDivision of General SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria,Division of TransplantationDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - David Pereyra
- Department of SurgeryDivision of General SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Roberto Alva‐Ruiz
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Hubert Hackl
- Institute of BioinformaticsBiocenterMedical University of InnsbruckInnsbruckAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Jonas Santol
- Department of SurgeryDivision of General SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Benedikt Simbrunner
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
| | - Gabriela Berlakovich
- Division of TransplantationDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | | | - Julie Heimbach
- Department of SurgeryDivision of Transplantation SurgeryMayo ClinicRochesterMN
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Larivière J, Giard JM, Zuo RM, Massicotte L, Chassé M, Carrier FM. Association between intraoperative fluid balance, vasopressors and graft complications in liver transplantation: A cohort study. PLoS One 2021; 16:e0254455. [PMID: 34242370 PMCID: PMC8270449 DOI: 10.1371/journal.pone.0254455] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 06/26/2021] [Indexed: 01/08/2023] Open
Abstract
Introduction Biliary complications following liver transplantation are common. The effect of intraoperative fluid balance and vasopressors on these complications is unknown. Materials and methods We conducted a cohort study between July 2008 and December 2017. Our exposure variables were the total intraoperative fluid balance and the use of vasopressors on ICU admission. Our primary outcome was any biliary complication (anastomotic and non-anastomotic strictures) up to one year after transplantation. Our secondary outcomes were vascular complications, primary graft non-function and survival. Results We included 562 consecutive liver transplantations. 192 (34%) transplants had a biliary complication, 167 (30%) had an anastomotic stricture and 56 had a non-anastomotic stricture (10%). We did not observe any effect of intraoperative fluid balance or vasopressor on biliary complications (HR = 0.97; 95% CI, 0.93 to 1.02). A higher intraoperative fluid balance was associated with an increased risk of primary graft non-function (non-linear) and a lower survival (HR = 1.40, 95% CI, 1.14 to 1.71) in multivariable analyses. Conclusion Intraoperative fluid balance and vasopressors upon ICU admission were not associated with biliary complications after liver transplantation but may be associated with other adverse events. Intraoperative hemodynamic management must be prospectively studied to further assess their impact on liver recipients’ outcomes.
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Affiliation(s)
- Jordan Larivière
- Department of Medicine, Université de Montréal, Montréal, Québec, Canada
| | - Jeanne-Marie Giard
- Department of Medicine—Liver Diseases Division, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
| | - Rui Min Zuo
- Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada
| | - Luc Massicotte
- Department of Anesthesiology, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
| | - Michaël Chassé
- Department of Medicine–Intensive Care Division, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
| | - François Martin Carrier
- Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada
- Department of Medicine–Intensive Care Division, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
- Carrefour de l’innovation, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada
- * E-mail:
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Kim Y, Reddy S, Mouchli M, Summey R, Walsh C, Mir A, Bierle L, Rubio M. Gender-Specific Risk Factors Contributing to Mortality in Patients Hospitalized With Alcoholic Cirrhosis. Cureus 2021; 13:e16271. [PMID: 34377607 PMCID: PMC8349303 DOI: 10.7759/cureus.16271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2021] [Indexed: 11/05/2022] Open
Abstract
Introduction Identification of gender-specific prognostic factors in patients with alcoholic liver cirrhosis (ALC) is integral to understanding disease severity and mortality rates. We gathered data on various widely-used laboratory values and comorbid conditions among male and female patients with ALC after initial hospitalization. These individual risk factors were assessed for their relationship with mortality based on gender. Methods We performed a retrospective observational study of hospitalized patients with either a new or prior diagnosis of ALC from 2008 to 2016 with follow-up through June 2018. The electronic medical record (EMR) was queried for demographics, comorbidities, lab values, and mortality. The cumulative risks of mortality after the first hospitalization were estimated using Kaplan-Meier curves and compared among both genders. Demographic data, lab values, and comorbidities associated with cirrhosis were assessed using multivariate Cox proportional hazard analysis to determine risk factors associated with mortality. Results We identified 247 male patients (mean age 54.19 ± 13.14 years) and 78 female patients (mean age 51.10 ± 11.60 years) hospitalized at Carilion Clinic with a diagnosis of ALC. About 70% (male) and 46% (female) endorsed alcohol use at the time of admission, 10% (male) and 13% (female) endorsed illicit drug use, and 56% (male and female) endorsed tobacco use. The one-, three- and five-year cumulative mortality after the first hospitalization was 43.4%, 53.2%, and 61.6%, respectively for males and 24.1%, 59.0%, and 67.2%, respectively for females. Median survival for younger male patients with ALC (age < 40 years old) after the first hospitalization was significantly different compared to the older male patients (age > 40 years) (p=0.0009), but age was not a significant factor for survival of female patients. Multivariate analysis further shows that illicit drug use, creatinine level at the time of admission, and age > 40 years had the highest hazard ratios for risk of mortality in male patients. For female patients, history of hepatic encephalopathy (HE) and blood urea nitrogen (BUN) level at the time of discharge were both associated with increased risk of mortality, with a history of HE being associated with a higher hazard ratio for risk of mortality. Conclusion Age, illicit drug use, and creatinine level were risk factors associated with mortality for male patients with ALC but not female patients. Hepatic encephalopathy and BUN were risk factors associated with mortality for female patients. The mortality for male patients was about twice the mortality of female patients at one year, but three-year and five-year mortality was higher in female patients.
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Affiliation(s)
- Youseung Kim
- Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, USA
| | - Shravani Reddy
- Gastroenterology and Hepatology, Virginia Tech Carilion School of Medicine, Roanoke, USA
| | - Mohamad Mouchli
- Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland , USA
| | - Robert Summey
- Medicine, University of Pennsylvania, Philadelphia, USA
| | - Chirstopher Walsh
- Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, USA
| | - Adil Mir
- Internal Medicine, Carilion Clinic, Ronaoke , USA
| | - Lindsey Bierle
- Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, USA
| | - Marrieth Rubio
- Gastroenterology and Hepatology, Virginia Tech Carilion School of Medicine, Roanoke, USA
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Kim JM, Kim DG, Kim J, Lee K, Lee KW, Ryu JH, Kim BW, Choi DL, You YK, Kim DS, Nah YW, Kang KJ, Cho JY, Hong G, Yu HC, Moon JI, Choi D, Hwang S, Kim MS. Outcomes after liver transplantation in Korea: Incidence and risk factors from Korean transplantation registry. Clin Mol Hepatol 2021; 27:451-462. [PMID: 33525077 PMCID: PMC8273644 DOI: 10.3350/cmh.2020.0292] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 01/11/2021] [Accepted: 01/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS To analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population. METHODS This study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes. RESULTS A total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±standard deviation age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss. DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence. CONCLUSION This study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Deok Gie Kim
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
| | | | | | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Je Ho Ryu
- Division of Hepato-Biliary-Pancreatic Surgery and liver Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dong-Sik Kim
- Division of HBP Surgery & Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Koo Jeong Kang
- Department of Surgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Jai Young Cho
- Department of Surgery, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea
| | - Geun Hong
- Department of Surgery, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea
| | - Hee Chul Yu
- Department of Surgery, Jeonbuk National University Medical School, Jeonju, Korea
| | - Ju Ik Moon
- Department of Surgery, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, Seoul, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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Hung YC, Chen YW, Rickert CG, Hsu YT, Yeh H, Chang DC. Practitioner availability rather than surgical quality impacts the utilization of liver transplantation for hepatocellular carcinoma. HPB (Oxford) 2021; 23:861-867. [PMID: 33579641 DOI: 10.1016/j.hpb.2020.12.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 12/05/2020] [Accepted: 12/27/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver transplantation (LT) provides better outcome than surgical resection (SR) although both are acceptable surgical options for hepatocellular carcinoma (HCC). It is unclear whether non-clinical factors drive treatment decisions. Our goal is to identify factors that may affect treatment decisions. METHODS Patients aged 18-74 with T2 HCC undergoing either LT or SR in Surveillance, Epidemiology, and End Results Database from 2004 to 2014 were included. Healthcare resources data were analyzed to assess factors that predict utilization of LT versus SR, adjusted for demographic, clinical outcomes, and socioeconomic factors. RESULTS 51% of patients (Total N = 2616) received LT, with a substantial state-level variation in LT rates (0.0%-66.9%). Higher LT center density [OR = 1.04 per 1% increment, P < 0.01], male gender (OR = 1.38, P = 0.02), and numbers of potential donors (OR = 1.19, P = 0.03) were positively associated with LT utilization. Conversely, higher incidence of chronic liver disease/cirrhosis (OR = 0.41 per one additional case per 100,000 populations, P = 0.001) and minority populations were negatively correlated with LT utilization. Notably, short-term surgical outcomes (in-hospital LT & SR mortality) were not associated with LT utilization. CONCLUSION Liver transplant center density and organ availability, but not surgical outcomes, affect utilization of LT. Future studies should focus on increasing availability of resources.
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Affiliation(s)
- Ya-Ching Hung
- Sinai Hospital of Baltimore, Baltimore, MD, USA; Department of Surgery, Massachusetts General Hospital/Harvard Medical, Boston, MA, USA.
| | - Ya-Wen Chen
- Department of Surgery, Massachusetts General Hospital/Harvard Medical, Boston, MA, USA
| | - Charles G Rickert
- Department of Surgery, Massachusetts General Hospital/Harvard Medical, Boston, MA, USA
| | - Yu-Tien Hsu
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, USA
| | - Heidi Yeh
- Department of Surgery, Massachusetts General Hospital/Harvard Medical, Boston, MA, USA
| | - David C Chang
- Department of Surgery, Massachusetts General Hospital/Harvard Medical, Boston, MA, USA
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Low Predictability of Readmissions and Death Using Machine Learning in Cirrhosis. Am J Gastroenterol 2021; 116:336-346. [PMID: 33038139 DOI: 10.14309/ajg.0000000000000971] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 09/02/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Readmission and death in cirrhosis are common, expensive, and difficult to predict. Our aim was to evaluate the abilities of multiple artificial intelligence (AI) techniques to predict clinical outcomes based on variables collected at admission, during hospitalization, and at discharge. METHODS We used the multicenter North American Consortium for the Study of End-Stage Liver Disease (NACSELD) cohort of cirrhotic inpatients who are followed up through 90-days postdischarge for readmission and death. We used statistical methods to select variables that are significant for readmission and death and trained 3 AI models, including logistic regression (LR), kernel support vector machine (SVM), and random forest classifiers (RFC), to predict readmission and death. We used the area under the receiver operating characteristic curve (AUC) from 10-fold crossvalidation for evaluation to compare sexes. Data were compared with model for end-stage liver disease (MELD) at discharge. RESULTS We included 2,170 patients (57 ± 11 years, MELD 18 ± 7, 61% men, 79% White, and 8% Hispanic). The 30-day and 90-day readmission rates were 28% and 47%, respectively, and 13% died at 90 days. Prediction for 30-day readmission resulted in 0.60 AUC for all patients with RFC, 0.57 AUC with LR for women-only subpopulation, and 0.61 AUC with LR for men-only subpopulation. For 90-day readmission, the highest AUC was achieved with kernel SVM and RFC (AUC = 0.62). We observed higher predictive value when training models with only women (AUC = 0.68 LR) vs men (AUC = 0.62 kernel SVM). Prediction for death resulted in 0.67 AUC for all patients, 0.72 for women-only subpopulation, and 0.69 for men-only subpopulation, all with LR. MELD-Na model AUC was similar to those from the AI models. DISCUSSION Despite using multiple AI techniques, it is difficult to predict 30- and 90-day readmissions and death in cirrhosis. AI model accuracies were equivalent to models generated using only MELD-Na scores. Additional biomarkers are needed to improve our predictive capability (See also the visual abstract at http://links.lww.com/AJG/B710).
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Izzy M, Addissie BD, Arab JP, Hilscher MB, Cartee A, Lee DC, Lee Y, Fletcher JG, Keaveny TM, Sanchez W. Triple-Phase Computed Tomography May Replace Dual-Energy X-ray Absorptiometry Scan for Evaluation of Osteoporosis in Liver Transplant Candidates. Liver Transpl 2021; 27:341-348. [PMID: 33098253 DOI: 10.1002/lt.25926] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 09/12/2020] [Accepted: 10/02/2020] [Indexed: 01/13/2023]
Abstract
Assessment of bone density is an important part of liver transplantation (LT) evaluation for early identification and treatment of osteoporosis. Dual-energy X-ray absorptiometry (DXA) is currently the standard clinical test for osteoporosis; however, it may contribute to the appointment burden on LT candidates during the cumbersome evaluation process, and there are limitations affecting its accuracy. In this study, we evaluate the utility of biomechanical analysis of vertebral images obtained during dual-energy abdominal triple-phase computed tomography (TPCT) in diagnosing osteoporosis among LT candidates. We retrospectively reviewed cases evaluated for LT between January 2017 and March 2018. All patients who underwent TPCT within 3 months of DXA were included. The biomechanical computed tomography (BCT) analysis was performed at a centralized laboratory (O.N. Diagnostics, Berkeley, CA) by 2 trained analysts blinded to the DXA data. DXA-based osteoporosis was defined as a T score ≤-2.5 at the hip or spine. BCT-based osteoporosis was defined as vertebral strength ≤4500 N for women or ≤6500 N for men or trabecular volumetric bone mineral density ≤80 mg/cm3 . Comparative data were available for 91 patients who had complete data for both DXA and BCT: 31 women and 60 men, age 54 ± 11 years (mean ± standard deviation), mean body mass index 28 ± 6 kg/m2 . Using DXA as the clinical reference, sensitivity of BCT to detect DXA-defined osteoporosis was 83.3% (20/24 patients) and negative predictive value was 91.7%; specificity and positive predictive value were 65.7% and 46.5%, respectively. BCT analysis of vertebral images on triple-phase computed tomography, routinely obtained during transplant evaluation, can reliably rule out osteoporosis in LT candidates. Patients with suspicion of osteoporosis on TPCT may need further evaluation by DXA.
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Affiliation(s)
- Manhal Izzy
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN
| | - Benyam D Addissie
- Division of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, PA
| | - Juan Pablo Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Moira B Hilscher
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Amanda Cartee
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Harbor, MI
| | | | - Yong Lee
- Department of Radiology, Mayo Clinic, Rochester, MN
| | | | - Tony M Keaveny
- Department of Mechanical Engineering, University of California, Berkeley, CA.,Department of Mechanical Engineering, Department of Bioengineering, University of California, Berkeley, CA
| | - William Sanchez
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Khalili F, Khosravi MB, Sahmeddini MA, Eghbal MH, Kazemi K, Nikeghbalian S, Ghazanfar Tehran S, Khosravi B. The Effect of Perioperative N-acetylcysteine on the Short and Long Term Outcomes in Pediatrics Undergoing Living-Donor Liver Transplantation. Int J Organ Transplant Med 2021; 12:12-20. [PMID: 34987729 PMCID: PMC8717878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND Ischemia-reperfusion injury during transplantation can cause post-operative graft dysfunction. OBJECTIVE To assess the efficacy of N-acetylcysteine in preventing hepatic ischemia-reperfusion injury and post-transplant outcomes. METHODS In this retrospective study on pediatrics undergoing living-donor (from one of their parents) liver transplantation, N-acetylcysteine was administered to one group (n=20) after induction in the donors until graft harvest, and in the recipients during implantation, which was maintained for 19 hours. The second group (n=20) did not receive NAC. Early allograft dysfunction was determined in the presence of alanine aminotransferase or aspartate aminotransferase ≥2000 IU/L and bilirubin ≥10 mg/dL within the first 7 days, and an international normalized ratio ≥1.6 on day 7. Data were collected from a retrospectively maintained database. RESULTS The incidence of post-reperfusion syndrome was lower in N-acetylcysteine group compared with the other group (5% vs. 30%, p=0.037). Serum creatinine level was significantly (p=0.04) different in the N-acetylcysteine group during the second post-operative week (0.14 vs. 0.15 mg/dL). There was no significant difference in the incidence of early allograft dysfunction (21% vs. 14%, p=0.327), and the survival rate (p=0.409). CONCLUSION Peri-operative infusion of N-acetylcysteine in both donor and recipient would effectively prevent post-reperfusion syndrome and renal insufficiency. However, it might not affect the early allograft dysfunction, ICU stay, and mortality. NAC increases the chance of re-operation due to non-surgical bleeding in the first post-operative day.
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Affiliation(s)
- F. Khalili
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - M. B. Khosravi
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - M. A. Sahmeddini
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - M. H. Eghbal
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - K. Kazemi
- Shiraz Organ Transplant Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - S. Nikeghbalian
- Shiraz Organ Transplant Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - S. Ghazanfar Tehran
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - B. Khosravi
- Biostatistics Department, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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