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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Datrino LN, Boccuzzi ML, Silva RM, Castilho PHBT, Riva WJ, Rocha JS, Tustumi F. Safety and Efficacy of Mycophenolate Mofetil Associated With Tacrolimus for Kidney-pancreas and Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Studies. Transplant Proc 2024; 56:1066-1076. [PMID: 38853029 DOI: 10.1016/j.transproceed.2024.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 05/13/2024] [Accepted: 05/17/2024] [Indexed: 06/11/2024]
Abstract
INTRODUCTION This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney transplants, in comparison with cyclosporine (CyA), azathioprine (AZA), everolimus (EVL), sirolimus (SRL), manitimus (MAN), mizoribine (MZR), and enteric-coated mycophenolate sodium (ECMPS) in combination or monotherapy. METHODS A systematic review and meta-analysis of randomized clinical trials was performed. The outcomes comprised acute rejection, graft loss, and adverse events. RESULTS Thirty studies were included. The main adverse events related to the TAC+MMF scheme were infection (36%; 95%CI: 26%-46%), including cytomegalovirus (CMV) (14%; 95%CI: 8%-20%); anemia (20%; 95%CI: 2%-37%); leukopenia (18%; 95%CI: 3%-33%); nausea (20%; 95%CI: 1%-39%); and diarrhea (26%; 95%CI:13%-40%). TAC+MMF was compared to the schemes AZA+TAC, CyA+AZA, CyA+MMF, CyA+SRL, ECMPS, EVL, MAN+TAC, MMF+SRL, MZR, TAC+AZA, TAC+EVR, TAC+MZR, TAC +SRL and TAC. TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no significant difference was found for graft loss. TAC+MMF was associated with a higher risk of infections than MZR (RD: 0.174; 95%CI: 0.25; 0.323) and TAC monotherapy (RD: 0.07; 95%CI 0.003; 0.138). CONCLUSION Gastrointestinal and hematological adverse events and infections are the most common with TAC+MMF for kidney-pancreas and kidney. TAC+MMF effectively prevents acute cellular rejection, and alternatives with AZA, CyA, SRL, ECMPS, EVL, MAN, and MSR have similar efficacy and safety profiles. TAC monotherapy and MZR may be associated with a lower risk of infections.
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Affiliation(s)
| | - Matheus Lopes Boccuzzi
- Department of Evidenced-based Medicine, Centro Universitário Lusíada, Santos, SP, Brazil
| | - Rafael Matosinho Silva
- Department of Evidenced-based Medicine, Centro Universitário Lusíada, Santos, SP, Brazil
| | | | - Wagner José Riva
- Department of Evidenced-based Medicine, Centro Universitário Lusíada, Santos, SP, Brazil
| | - Jéssica Silva Rocha
- Department of Surgery, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - Francisco Tustumi
- Department of Surgery, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; Department of Gastroenterology, Universidade de São Paulo, São Paulo, SP, Brazil.
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D’Elia JA, Weinrauch LA. Hyperglycemia and Hyperlipidemia with Kidney or Liver Transplantation: A Review. BIOLOGY 2023; 12:1185. [PMID: 37759585 PMCID: PMC10525610 DOI: 10.3390/biology12091185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 08/22/2023] [Indexed: 09/29/2023]
Abstract
Although solid organ transplantation in persons with diabetes mellitus is often associated with hyperglycemia, the risk of hyperlipidemia in all organ transplant recipients is often underestimated. The diagnosis of diabetes often predates transplantation; however, in a moderate percentage of allograft recipients, perioperative hyperglycemia occurs triggered by antirejection regimens. Post-transplant prescription of glucocorticoids, calcineurin inhibitors and mTOR inhibitors are associated with increased lipid concentrations. The existence of diabetes mellitus prior to or following a liver transplant is associated with shorter times of useful allograft function. A cycle involving Smad, TGF beta, m-TOR and toll-like receptors has been identified in the contribution of rejection and aging of allografts. Glucocorticoids (prednisone) and calcineurin inhibitors (cyclosporine and tacrolimus) induce hyperglycemia associated with insulin resistance. Azathioprine, mycophenolate and prednisone are associated with lipogenesis. mTOR inhibitors (rapamycin) are used to decrease doses of atherogenic agents used for immunosuppression. Post-transplant medication management must balance immune suppression and glucose and lipid control. Concerns regarding rejection often override those relative to systemic and organ vascular aging and survival. This review focuses attention on the underlying mechanism of relationships between glycemia/lipidemia control, transplant rejection and graft aging.
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Affiliation(s)
| | - Larry A. Weinrauch
- Kidney and Hypertension Section, E P Joslin Research Laboratory, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; jd'
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A Comprehensive Review on the Risk of Metabolic Syndrome and Cardiovascular Disease after Liver Transplantation. LIVERS 2022. [DOI: 10.3390/livers2020006] [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] [Indexed: 12/20/2022] Open
Abstract
Survival rates after liver transplantation have increased dramatically over the past 20 years. Cardiovascular disease is the most common extra-hepatic cause of mortality in the long-term post liver transplant. This is intimately linked with both the higher pre-existing rates of metabolic syndrome in these patients as well as increased propensity to develop de novo metabolic syndrome post-transplant. This unfavorable metabolic profile that contributes to cardiovascular disease is multifactorial and largely preventable. This review explores metabolic syndrome and cardiovascular disease and their contributory factors post liver transplantation to highlight areas for potential intervention and thus reduce the significant morbidity and mortality of patients due to metabolic syndrome and cardiovascular disease.
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Zorzetti N, Lauro A, Khouzam S, Marino IR. Immunosuppression, Compliance, and Tolerance After Orthotopic Liver Transplantation: State of the Art. EXP CLIN TRANSPLANT 2022; 20:3-9. [PMID: 35384800 DOI: 10.6002/ect.mesot2021.l13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Orthotopic liver transplantation is the treatment of choice for several otherwise irreversible forms of acute and chronic liver diseases. Early implemented immunosuppressant regimens have had disappointing results with high rejection rates. However, new drugs have reduced the daily immunosuppression requirements, thereby improving graft and patient survival as well as kidney function. Liver rejection is a T-cell-driven immune response and is the active target of immunosuppressive agents. Immunosuppressants can be divided into pharmacological or biological drugs: the gold standard is the calcineurin inhibitors, steroids, mycophenolate mofetil, and mechanistic target of rapamycin inhibitors. Compliance with these agents is essential, although they can increase the risk of infections and neoplastic diseases. In some patients, graft tolerance can be achieved. Graft tolerance is defined as the absence of acute and chronic rejection in a graft, with normal function and histology in an immunosuppression-free, fully immunocompetent host, usually as the final result of a successful attempt at immunosuppression withdrawal. The occurrence of immunosuppressive-related complications has led to new protocols aimed at protecting renal function and preventing de novo cancer and dysmetabolic syndrome. The backbone of immunosuppression remains calcineurin inhibitors in association with other drugs, mainly over the short-term period. To avoid rejection and the side effects on renal dysfunction, de novo cancer, and cardiovascular syndrome, optimal long-term immunosuppressive therapy should be tailored in liver transplant recipients.
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Affiliation(s)
- Noemi Zorzetti
- From the Department of General Surgery, Ospedale A. Costa, Porretta Terme-Bologna, Italy
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Li XY, Tan HK, Loh YH. New-onset cardiovascular risk factors following liver transplantation: A cohort analysis in Singapore. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2021; 50:548-555. [PMID: 34342335 DOI: 10.47102/annals-acadmedsg.2020632] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
INTRODUCTION The aims of this study were to establish weight change, incidence of non-alcoholic fatty liver disease (NAFLD) and cardiovascular risk factors (CvRF) in liver transplant recipients (LTRs). METHODS Eighty-three patients whose mean (standard deviation [SD]) age was 55.6 (8.4) years (median follow-up 73 months) and who underwent their first liver transplantation (LT) at Singapore General Hospital between February 2006 and March 2017 were included in the study. Anthropometric, clinical and demographic data were collected retrospectively from patients' medical records. Diabetes mellitus (DM), hyperlipidaemia and hypertension were regarded as CvRF. RESULTS Compared to baseline, mean (SD) body weight decreased significantly at 1 month post-LT (60.8kg [11.9] versus 64.3kg [13.7], P<0.001). There was a gradual recovery of body weight thereafter, increasing significantly at year 2 (64.3kg [12.3] vs 61.5kg [13.7], P<0.001) until year 5 (66.9kg [12.4] vs 62.2kg [13.9], P<0.001), respectively. The prevalence of CvRF was significantly higher post-LT. NAFLD occurred in 25.3% of LTRs and it was significantly associated with post-LT DM and hyperlipidaemia. CONCLUSION CvRF increased significantly post-LT, and NAFLD occurred in 25.3% of LTRs. Body weight dropped drastically within the first month post-LT, which then returned to baseline level just before the end of first year. This novel finding suggests that nutritional intervention needs to be tailored and individualised, based on events and time from transplant. Although long-term obesity is a significant problem, aggressive oral or enteral nutritional supplements take precedence in the early and immediate post-LT period, while interventions targeted at metabolic syndrome become necessary after the first year.
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Affiliation(s)
- Xiao Ying Li
- Department of Dietetics, Singapore General Hospital, Singapore
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Tustumi F, de Miranda AA, Silveira S, Fernandes FA, Silva MBDBE, Ernani L, Nacif LS, Coelho FF, Andraus W, Bernardo WM, Herman P, Carneiro-D’Albuquerque LA. Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials. Clinics (Sao Paulo) 2021; 76:e2597. [PMID: 33681947 PMCID: PMC7920399 DOI: 10.6061/clinics/2021/e2597] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 02/03/2021] [Indexed: 11/18/2022] Open
Abstract
A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.
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Affiliation(s)
- Francisco Tustumi
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
- *Corresponding author. E-mail:
| | - Antonio Afonso de Miranda
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Sérgio Silveira
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Felipe Alexandre Fernandes
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Miller Barreto de Brito e Silva
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Lucas Ernani
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Lucas Souto Nacif
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Fabricio Ferreira Coelho
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Wellington Andraus
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Wanderley Marques Bernardo
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Paulo Herman
- Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
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Abstract
INTRODUCTION Liver transplantation is a life-changing event for patients and survival following transplantation has improved significantly since the first transplantation in 1967. Following liver transplantation, patients face a unique set of healthcare management decisions including transplantation-specific complications, recurrence of primary liver disease, as well as metabolic and malignancy concerns related to immunosuppression. As more patients with liver disease receive transplantation and live longer, understanding and managing these patients will require not only transplant specialist but also local subspecialist and primary care physicians. AREAS COVERED This review covers common issues related to the management of patients following liver transplantation including immunosuppression, liver allograft dysfunction, metabolic complications, as well as routine health maintenance such as immunizations and cancer screening. EXPERT OPINION Optimizing medical care for patients following liver transplant will benefit from ensuring all providers, not just transplant specialist, have a basic understanding of the common issues encountered in the post-transplant patient. This review provides an overview of common healthcare concerns and management options for patients following liver transplantation.
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Affiliation(s)
- Nicholas Hoppmann
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
| | - Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
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Becchetti C, Dirchwolf M, Banz V, Dufour JF. Medical management of metabolic and cardiovascular complications after liver transplantation. World J Gastroenterol 2020; 26:2138-2154. [PMID: 32476781 PMCID: PMC7235200 DOI: 10.3748/wjg.v26.i18.2138] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/26/2020] [Accepted: 04/28/2020] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation represents the only curative option for patients with end-stage liver disease, fulminant hepatitis and advanced hepatocellular carcinoma. Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period, long-term survival is hampered by the lack of improvement in survival in the late post transplantation period (over 5 years after transplantation). The main etiologies for late mortality are malignancies and cardiovascular complications. The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components (arterial hypertension, dyslipidemia, obesity, renal injury, etc.). These comorbidities result from a combination of pre-liver transplant features, immunosuppressive agent side-effects, changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle. In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation, as well as proposing management strategies.
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Affiliation(s)
- Chiara Becchetti
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
| | - Melisa Dirchwolf
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
- Hepatology, Hepatobiliary Surgery and Liver Transplant Unit, Hospital Privado de Rosario, Rosario S2000GAP, Santa Fe, Argentina
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Clinical Research, University of Bern, Bern CH-3008, Switzerland
| | - Jean-François Dufour
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
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Sikanderkhel S, Choudhry MW, Valentine V, Al-Dossari G, Khalife WI. Diarrhea-An uncommon presentation of tertiary adrenal insufficiency following heart transplantation. J Card Surg 2017; 32:522-525. [PMID: 28670701 DOI: 10.1111/jocs.13175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Diarrhea following organ transplantation is usually associated with infection and immunosuppression therapy. We describe two patients with diarrhea following orthotopic heart transplantation due to tertiary adrenal insufficiency.
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Affiliation(s)
- Saad Sikanderkhel
- Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - M Waqas Choudhry
- Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Vincent Valentine
- Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama, Birmingham, Alabama
| | - Ghannam Al-Dossari
- Department of Cardiothoracic Surgery, University of Texas Medical Branch, Galveston, Texas
| | - Wissam I Khalife
- Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
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Wei Q, Gao F, Zhuang R, Ling Q, Ke Q, Wu J, Shen T, Zhang M, Zhang M, Xu X, Zheng S. A national report from China Liver Transplant Registry: steroid avoidance after liver transplantation for hepatocellular carcinoma. Chin J Cancer Res 2017; 29:426-437. [PMID: 29142462 DOI: 10.21147/j.issn.1000-9604.2017.05.07] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objective We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods We retrospectively analyzed HCC recipients without steroids after LT (SF group, n=368) based on the China Liver Transplant Registry (CLTR) database. These recipients were matched 1:2 with patients using steroids (S group, n=736) for the same period after LT for HCC, according to propensity scores. Results Multivariate analysis indicates that recipients with younger age [odds ratio (OR), 1.053; P=0.011], preoperative hepatitis B virus (HBV) DNA ≥1,000 copies/mL (OR, 2.597; P=0.004) and beyond Milan criteria (OR, 4.255; P<0.001) were identified as the risk factors associated with tumor recurrence in steroid avoidance recipients after LT. The patients fulfilling the Milan criteria in the SF group presented higher overall and tumor-free survival rates than those in the S group (P<0.05). Multivariate analysis revealed that recipient beyond Milan criteria was an independent prognostic factor for overall survival (OR, 1.690; P<0.001) and tumor-free survival (OR, 2.066; P<0.001). The incidences of new-onset diabetes mellitus (21.20%vs. 33.29%, P<0.001), new-onset hypertension (10.05%vs. 18.61%, P<0.001) and hyperlipidemia (4.08%vs. 7.20%, P=0.042) were significantly lower in the SF group. Conclusions Steroid-free immunosuppression could be safe and feasible for HBV-related HCC patients in LT. Age, HBV DNA level and Milan criteria maybe risk factors associated with tumor recurrence in steroid avoidance recipients. Recipient beyond Milan criteria was an independent prognostic factor and recipient fulfilling Milan criteria can benefit the most from steroid-free immunosuppression.
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Affiliation(s)
- Qiang Wei
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Feng Gao
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Runzhou Zhuang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qi Ling
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qinghong Ke
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jian Wu
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Tian Shen
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Mangli Zhang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Min Zhang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xiao Xu
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
| | - Shusen Zheng
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
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12
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Abstract
Because of troublesome side effects associated with steroid use, many transplant centers have tried to withdraw steroids from stable, solid organ transplant recipients. The objective of this study was to evaluate the ability to wean liver transplant recipients off steroids, depending on both their primary immunosuppressive regimen and their primary disease state. This was a retrospective, single-center review of steroid weaning in adult orthotopic liver transplant recipients. Based on primary immunosuppression, patients could be weaned off steroids similarly if they were taking cyclosporine or tacrolimus (53.9% vs 61.4%). When triple immunosuppressive regimens were compared with dual regimens, a difference was found in ability to wean patients off steroids (52.4% vs 74.5%, P=.001). When steroid weaning was stratified for primary immunosuppression and primary disease state, patients with autoimmune-mediated diseases (autoimmune hepatitis, sclerosing cholangitis, and primary biliary cirrhosis) were less likely to be weaned if they were receiving cyclosporine-based immunosuppressants (36.8% vs 62.2%, P=.03). In conclusion, it appears that a large number of liver transplant recipients can safely be tapered off steroids.
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Affiliation(s)
- R W Adams
- Emory University Hospital, Atlanta, Ga., USA
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13
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Tandon M, Singh A, Saluja V, Dubey G, Pandey VK, Pandey CK, Karna ST, Singh SA. Post-operative hypertension, a surrogate marker of the graft function and predictor of survival in living donor liver transplant recipients: A retrospective study. Indian J Anaesth 2016; 60:463-9. [PMID: 27512161 PMCID: PMC4966349 DOI: 10.4103/0019-5049.186016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIMS De novo hypertension (HTN) in liver transplantation recipients is a known entity. We investigated haemodynamic behaviour after a liver transplant to see if it can predict survival to discharge from the hospital. METHODS electronic records of Haemodynamic parameters and laboratory investigations of 95 patients of living donor liver transplant (LDLT) were retrospectively analysed. RESULTS Twenty-three patients were operated for acute liver failure (ALF) and 72 patients for chronic liver disease (CLD). Eight patients of CLD and four of ALF did not survive. CLD patients had statistically significant rise in systolic blood pressure from the post-operative day (POD) 1 to POD 4 and diastolic blood pressure (DBP) from POD 3 to POD 6. Heart rate (HR) significantly decreased from POD 3 to POD 5. Haemodynamic parameters returned to baseline values within 20 days. Diastolic HTN had a positive predictive value of 100% for survival with 100% sensitivity and specificity. Systolic HTN had a positive predictive value of 100% for survival (sensitivity-89%, specificity-100%). ALF patients had a significant decrease in HR from POD 2 to POD 10. Bradycardia (HR ≤60/min) had a positive predictive value of 100% for survival with a sensitivity of 45% and 58% in CLD and ALF, respectively, with a specificity of 100% in both the groups. Non-survivors had no significant change in haemodynamics. In CLD group, International Normalised Ratio had statistically significant, strong negative correlation with DBP. CONCLUSION Haemodynamic pattern of recovery may be used for predicting survival to discharge after LDLT.
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Affiliation(s)
- Manish Tandon
- Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Anshuman Singh
- Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vandana Saluja
- Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Gaurav Dubey
- Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vijay Kant Pandey
- Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chandra Kant Pandey
- Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sunaina Tejpal Karna
- Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shweta A Singh
- Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
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14
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Corticosteroid-Sparing and Optimization of Mycophenolic Acid Exposure in Liver Transplant Recipients Receiving Mycophenolate Mofetil and Tacrolimus. Transplantation 2016; 100:1705-13. [DOI: 10.1097/tp.0000000000001228] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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15
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Jiménez-Pérez M, González-Grande R, Omonte Guzmán E, Amo Trillo V, Rodrigo López JM. Metabolic complications in liver transplant recipients. World J Gastroenterol 2016; 22:6416-6423. [PMID: 27605877 PMCID: PMC4968123 DOI: 10.3748/wjg.v22.i28.6416] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 05/25/2016] [Accepted: 06/13/2016] [Indexed: 02/06/2023] Open
Abstract
The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.
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16
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Abstract
BACKGROUND Liver transplantation is a treatment of choice for both acute and chronic liver failure. Accompanied with the increase of long-term survival rates of recipients, metabolic syndrome and its individual components, including obesity, hyperglycemia, hypertension and hyperlipidemia, have become more frequent post liver transplantation. Here we reviewed the literature concerning the risk factors for the development of metabolic complications in liver recipients. DATA SOURCES PubMed was searched for English-language articles published from January 2000 to June 2015. The search criteria focused on risk factors for metabolic syndrome after liver transplantation. RESULT The risk factors of metabolic syndrome in liver recipients include older age, obesity, pre-transplantation diabetes mellitus, hepatitis C virus infection, certain genetic polymorphisms and the use of immunosuppressive drugs. CONCLUSION Active intervention of the risk factors will reduce the occurrence rate of metabolic syndrome after liver transplantation and improve the recipients' quality of life.
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Affiliation(s)
- Jun Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
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17
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Cuervas-Mons V, Herrero JI, Gomez MA, González-Pinto I, Serrano T, de la Mata M, Fabregat J, Gastaca M, Bilbao I, Varo E, Sánchez-Antolín G, Rodrigo J, Espinosa MD. Impact of tacrolimus and mycophenolate mofetil regimen vs. a conventional therapy with steroids on cardiovascular risk in liver transplant patients. Clin Transplant 2015; 29:667-77. [DOI: 10.1111/ctr.12557] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2015] [Indexed: 01/14/2023]
Affiliation(s)
- Valentín Cuervas-Mons
- Department of Internal Medicine; Liver Transplant Unit; Hospital Puerta de Hierro; Madrid Spain
| | - J. Ignacio Herrero
- Liver Unit; Clínica Universitaria de Navarra; Pamplona Spain
- CIBERehd (Centro de Investigación Biomédica en Red); Instituto de Salud Carlos III (ISCIII); Madrid Spain
| | - Miguel A. Gomez
- Hepatobiliopancreatic Surgery and Transplantation Unit; Hospital Virgen del Rocío; Sevilla Spain
| | | | | | - Manuel de la Mata
- CIBERehd (Centro de Investigación Biomédica en Red); Instituto de Salud Carlos III (ISCIII); Madrid Spain
- Clinical Management Unit of Digestive System; Hepatology Section; Hospital Universitario Reina Sofía; Córdoba Spain
| | - Joan Fabregat
- Hepatobiliopancreatic Surgery and Liver Transplantation Unit; Hospital Universitari de Bellvitge; Barcelona Spain
| | | | - Itxarone Bilbao
- CIBERehd (Centro de Investigación Biomédica en Red); Instituto de Salud Carlos III (ISCIII); Madrid Spain
- Service of Hepatobiliopancreatic Surgery and Liver Transplantation; Hospital Universitario Vall d'Hebrón; Barcelona Spain
| | - Evaristo Varo
- Abdominal Transplantation Unit; Hospital Clínico Universitario de Santiago de Compostela; Santiago de Compostela Spain
| | | | - Juan Rodrigo
- Hepatology and Liver Transplantation Unit; Hospital Regional Universitario de Málaga; Málaga Spain
| | - María Dolores Espinosa
- Hepatology and Liver Transplantation Unit; Service of Digestive System; Hospitales Universitarios de Granada; Granada Spain
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18
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Baron D, Giral M, Brouard S. Reconsidering the detection of tolerance to individualize immunosuppression minimization and to improve long-term kidney graft outcomes. Transpl Int 2015; 28:938-59. [DOI: 10.1111/tri.12578] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 02/03/2015] [Accepted: 04/02/2015] [Indexed: 01/03/2023]
Affiliation(s)
- Daniel Baron
- INSERM; UMR 1064; Nantes France
- CHU de Nantes; ITUN; Nantes France
- Faculté de Médecine; Université de Nantes; Nantes France
| | - Magali Giral
- INSERM; UMR 1064; Nantes France
- CHU de Nantes; ITUN; Nantes France
- Faculté de Médecine; Université de Nantes; Nantes France
| | - Sophie Brouard
- INSERM; UMR 1064; Nantes France
- CHU de Nantes; ITUN; Nantes France
- Faculté de Médecine; Université de Nantes; Nantes France
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19
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Lan X, Liu MG, Chen HX, Liu HM, Zeng W, Wei D, Chen P. Efficacy of immunosuppression monotherapy after liver transplantation: A meta-analysis. World J Gastroenterol 2014; 20:12330-12340. [PMID: 25232269 PMCID: PMC4161820 DOI: 10.3748/wjg.v20.i34.12330] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 02/17/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the advantages and disadvantages of immunosuppression monotherapy after transplantation and the impact of monotherapy on hepatitis C virus (HCV) recurrence.
METHODS: Articles from Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded, including non-English literature identified in these databases, were searched up to January 2013. We included randomized clinical trials comparing various immunosuppression monotherapy and prednisone-based immunosuppression combinations for liver transplantation. The modified Jadad scale score or the Oxford quality scoring system was used. Meta-analyses were performed with weighted random-effects models.
RESULTS: A total of 14 randomized articles including 1814 patients were identified. Eight trials including 1214 patients compared tacrolimus monotherapy (n = 610) vs tacrolimus plus steroids or triple therapy regarding acute rejection and adverse events (n = 604). Five trials, including 285 patients, compared tacrolimus monotherapy (n = 143) vs tacrolimus plus steroids or triple therapy regarding hepatitis C recurrence (n = 142). Four trials including 273 patients compared cyclosporine monotherapy (n = 148) vs cyclosporine and steroids regarding acute rejection and adverse events (n = 125). Two trials including 170 patients compared mycophenolate mofetil monotherapy (n = 86) vs combinations regarding acute rejection (n = 84). There were no significant differences in the acute rejection rates between tacrolimus monotherapy (RR = 1.04, P = 0.620), and cyclosporine monotherapy (RR = 0.89, P = 0.770). Mycophenolate mofetil monotherapy had a significant increase in the acute rejection rate (RR = 4.50, P = 0.027). Tacrolimus monotherapy had no significant effects on the recurrence of hepatitis C (RR = 1.03, P = 0.752). More cytomegalovirus infection (RR = 0.48, P = 0.000) and drug-related diabetes mellitus (RR = 0.54, P = 0.000) were observed in the immunosuppression combination therapy groups.
CONCLUSION: Tacrolimus and cyclosporine monotherapy may be as effective as immunosuppression combination therapy. Mycophenolate mofetil monotherapy was not considerable. Tacrolimus monotherapy does not increase recurrence of HCV.
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20
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Dugast E, Chesneau M, Soulillou JP, Brouard S. Biomarkers and possible mechanisms of operational tolerance in kidney transplant patients. Immunol Rev 2014; 258:208-17. [DOI: 10.1111/imr.12156] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Emilie Dugast
- INSERM UMR 1064; Nantes France
- Centaure; Nantes France
| | - Mélanie Chesneau
- INSERM UMR 1064; Nantes France
- Université de Nantes; Nantes France
| | - Jean-Paul Soulillou
- INSERM UMR 1064; Nantes France
- Centaure; Nantes France
- CHU de Nantes; Nantes France
- Université de Nantes; Nantes France
| | - Sophie Brouard
- INSERM UMR 1064; Nantes France
- Centaure; Nantes France
- CHU de Nantes; Nantes France
- Université de Nantes; Nantes France
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21
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Hu AB, Wu LW, Tai Q, Zhu XF, He XS. Safety and efficacy of four steroid-minimization protocols in liver transplant recipients: 3-year follow-up in a single center. J Dig Dis 2013; 14:38-44. [PMID: 23134408 DOI: 10.1111/1751-2980.12008] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate the safety and efficacy of steroid-minimization therapy in liver transplantation (LT) recipients with hepatitis B virus-related diseases in China. METHODS From March 2000 to June 2007, 502 adult LT recipients, mostly with hepatitis B (HBV)-related diseases, were enrolled in our study. Four study groups were setup according to the steroid-minimization protocols: tacrolimus (TAC) with 6 months steroids withdrawal (6M SW), TAC with 3 months SW (3M SW), TAC with 14 days SW (14d SW), and TAC with basiliximab induction and steroids avoidance (Bas SA). All patients were followed up for at least 36 months after LT. RESULTS There were no significant differences in the overall 3-year survival rates of the patients and graft, and chronic rejection among the four groups (P = 0.092, P = 0.113 and P = 0.684, respectively). There was also no difference in acute rejection within 12 months after LT (P = 0.514). The 3-year recurrence rates of HBV infection and hepatocellular carcinoma (HCC) after LT were significantly different among all the groups (lowest in TAC/Bas SA group; P = 0.037 and P = 0.029, respectively). The overall incidence of infection was significantly higher in the 6M SW group (62.2% vs 56.1% in 3M SW, 30.5% in 14d SW, 20.5% in Bas SA; P < 0.01). By the end of the 3-year follow-up, more than 90% of the surviving patients could safely receive TAC monotherapy. CONCLUSION Bas SA immunosuppressive protocol can be achieved safely in LT and reduce HBV infection and HCC recurrence and side effects of steroids after LT.
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Affiliation(s)
- An Bin Hu
- Department of General Surgery, Organ Transplantation Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
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22
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Braza F, Soulillou JP, Brouard S. Gene expression signature in transplantation tolerance. Clin Chim Acta 2012; 413:1414-8. [DOI: 10.1016/j.cca.2012.04.024] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2011] [Revised: 03/09/2012] [Accepted: 04/18/2012] [Indexed: 01/21/2023]
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Singh S, Watt KD. Long-term medical management of the liver transplant recipient: what the primary care physician needs to know. Mayo Clin Proc 2012; 87:779-90. [PMID: 22763347 PMCID: PMC3498400 DOI: 10.1016/j.mayocp.2012.02.021] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 02/07/2012] [Accepted: 02/16/2012] [Indexed: 12/18/2022]
Abstract
Recognition, management, and prevention of medical complications and comorbidities after liver transplant is the key to improved long-term outcomes. Beyond allograft-related complications, metabolic syndrome, cardiovascular disease, renal dysfunction, and malignancies are leading causes of morbidity and mortality in this patient population. Primary care physicians have an important role in improving outcomes of liver transplant recipients and are increasingly relied on for managing these complex patients. This review serves to assist the primary care physician in the long-term management issues of liver transplant recipients.
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Key Words
- acei, angiotensin converting enzyme inhibitor
- arb, angiotensin receptor blocker
- ckd, chronic kidney disease
- cni, calcineurin inhibitor
- ibd, inflammatory bowel disease
- lt, liver transplant
- mmf, mycophenolate mofetil
- mtor, mammalian target of rapamycin
- nash, nonalcoholic steatohepatitis-related cirrhosis
- olt, orthotopic liver transplant
- psc, primary sclerosing cholangitis
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Affiliation(s)
| | - Kymberly D. Watt
- Correspondence: Address to Kymberly D. Watt, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905
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24
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Kallwitz ER. Metabolic syndrome after liver transplantation: Preventable illness or common consequence? World J Gastroenterol 2012; 18:3627-34. [PMID: 22851856 PMCID: PMC3406416 DOI: 10.3748/wjg.v18.i28.3627] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2012] [Revised: 06/25/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
The metabolic syndrome is common after liver transplant being present in approximately half of recipients. It has been associated with adverse outcomes such as progression of hepatitis C and major vascular events. As the United States population ages and the rate of obesity increases, prevention of the metabolic syndrome in the post-transplant population deserves special consideration. Currently, the metabolic syndrome after transplant appears at least two times more common than observed rates in the general population. Specific guidelines for patients after transplant does not exist, therefore prevention rests upon knowledge of risk factors and the presence of modifiable elements. The current article will focus on risk factors for the development of the metabolic syndrome after transplant, will highlight potentially modifiable factors and propose potential areas for intervention. As in the non-transplant population, behavioral choices might have a major role. Opportunities exist in this regard for health prevention studies incorporating lifestyle changes. Other factors such as the need for immunosuppression, and the changing characteristics of wait listed patients are not modifiable, but are important to know in order to identify persons at higher risk. Although immunosuppression after transplant is unavoidable, the contribution of different agents to the development of components of the metabolic syndrome is also discussed. Ultimately, an increased risk of the metabolic syndrome after transplant is likely unavoidable, however, there are many opportunities to reduce the prevalence.
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25
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Wu LW, Guo ZY, Tai Q, Ju WQ, Wang DP, Hu AB, Zhu XF, He XS. Steroid elimination within 24 hours after orthotopic liver transplantation: effectiveness and tolerability. Hepatobiliary Pancreat Dis Int 2012; 11:137-42. [PMID: 22484580 DOI: 10.1016/s1499-3872(12)60138-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Steroids have been the mainstay of immunosuppressive regimen in liver transplantation. However, the use of steroids is associated with various post-transplant complications. This study evaluated the efficacy and safety of reduced immunosuppressive regimen with steroids (steroid elimination within 24 hours post-transplant) in a cohort of Chinese liver transplant recipients. METHODS Seventy-six patients in line with the selection criteria were enrolled in this prospective study. All patients received anti-IL-2 receptor antibody induction and tacrolimus-based maintenance therapy. The recipients were divided into two groups according to the duration of steroid use: 40 transplant in a 3-month withdrawal group and the remaining 36 in a 24-hour elimination group. Recipient survival, post-operative infections, biopsy-proven acute rejection and steroid-resistant acute rejection, non-healing wound, recurrence of hepatitis B virus (HBV) and hepatocellular carcinoma (HCC), de novo diabetes, hyperlipidemia and hypertension were assessed in the two groups. RESULTS There was no significant difference in patient survival, incidence of acute rejection episodes and hyperlipidemia, and recurrence of HBV and HCC between the two groups. However, the incidence rates of post-transplant infection, non-healing wound, de novo diabetes and hypertension were significantly lower in the 24-hour elimination group than in the 3-month withdrawal group (all P values <0.05). CONCLUSION Under anti-IL-2 receptor antibody induction and tacrolimus-based maintainance, steroid elimination within 24 hours post-transplant is associated with reduced steroid-related complications without increasing the risk of rejection.
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Affiliation(s)
- Lin-Wei Wu
- Organ Transplantation Center, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
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26
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Najeed SA, Saghir S, Hein B, Neff G, Shaheen M, Ijaz H, Khan IA. Management of hypertension in liver transplant patients. Int J Cardiol 2011; 152:4-6. [DOI: 10.1016/j.ijcard.2010.12.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2010] [Accepted: 12/04/2010] [Indexed: 12/17/2022]
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27
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Oustecky DH, Riera AR, Rothstein KD. Long-term management of the liver transplant recipient: pearls for the practicing gastroenterologist. Gastroenterol Clin North Am 2011; 40:659-81. [PMID: 21893279 DOI: 10.1016/j.gtc.2011.06.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Liver transplantation is becoming more common and patients are surviving longer after transplantation. Special care must be paid to the long-term management of these patients because they are at increased risk for medical problems, malignancies, and adverse effects from immunosuppression. A stable and continuing relationship must be developed between the physician and the patient to optimize the long-term outcomes for these individuals.
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Affiliation(s)
- David H Oustecky
- Drexel University College of Medicine, Department of Gastroenterology and Hepatology, Mail Stop 913, 219 N. Broad Street, 5th Floor, Philadelphia, PA 19107, USA
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28
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Benítez CE, Puig-Pey I, López M, Martínez-Llordella M, Lozano JJ, Bohne F, Londoño MC, García-Valdecasas JC, Bruguera M, Navasa M, Rimola A, Sánchez-Fueyo A. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation. Am J Transplant 2010; 10:2296-304. [PMID: 20883560 DOI: 10.1111/j.1600-6143.2010.03164.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG-Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard-dose tacrolimus plus steroids;or (b) peritransplant ATG-Fresenius plus reduced-dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end-point was the achievement of very low-dose tacrolimus (every-other-day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end-point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG-Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance-related biomarkers were observed. In conclusion, the use of ATG-Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier: NCT00436722.
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Affiliation(s)
- C E Benítez
- Liver Unit, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
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29
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Desai S, Hong JC, Saab S. Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors, incidence and management. Liver Int 2010; 30:948-57. [PMID: 20500807 DOI: 10.1111/j.1478-3231.2010.02274.x] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND Liver transplantation is the standard of care for acute and chronic causes of end-stage liver disease. Advances in medical therapy and surgical techniques have led to improvement of patient and graft survival rates following orthotopic liver transplantation. However, the prevalence of post-transplant cardiovascular complications has been rising with increased life expectancy after liver transplantation. AIMS To determine the incidences, risk factors, and treatment for hypertension, hyperlipidaemia, diabetes, and obesity in the post-liver transplantation population. METHODS We performed a review of relevant studies available on the PubMed database that provided information on the incidence, risk factors and treatment for cardiovascular complications that develop in the post-liver transplantation population. RESULTS Current immunosuppressive agents have improved patient and graft survival rates. However, long-term exposure to these agents has been associated with development of systemic and metabolic complications including hypertension, hyperlipidaemia, diabetes mellitus and obesity. Cardiovascular disease remains one of the most common causes of death in liver transplant patients with functional grafts. CONCLUSIONS Liver transplant recipients have a higher risk of cardiovascular complications compared with the nontransplant population. Post-transplant cardiac risk stratification and aggressive treatment of cardiovascular complications, including modification of risk factors and tailoring of immunosuppressive regimen, is imperative to prevent serious complications.
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Affiliation(s)
- Shireena Desai
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
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Kaul V, Khurana S, Munoz S. Management of medication noncompliance in solid-organ transplant recipients. BioDrugs 2009; 13:313-26. [PMID: 18034538 DOI: 10.2165/00063030-200013050-00002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
Solid-organ transplantation has emerged as one of the most significant medical advances in the management of end-stage organ disease to date. However, a long term successful outcome after transplantation relies heavily upon the extended, if not lifelong, intake of immunosuppressive medication. Noncompliance with the medication regimen may have devastating effects on the graft and the patient. Furthermore, the effects of noncompliance place an additional burden on the medical resources available and the already scarce organ supply. The magnitude of post-transplant noncompliance and factors associated with noncompliance with various immunosuppressant drugs are reviewed. Patient, physician, social and family relationships interact in a complex manner in the post-transplant scenario and problems here could underlie noncompliance. The paper also includes a review of the methods of evaluating and monitoring noncompliance. Preventive and remedial measures that may help the transplant team to effectively manage this problem are suggested. The multidisciplinary nature of post-transplant patient management and the need for a cohesive approach toward the patient is emphasised. With the identification of patients at higher risk for noncompliance, close monitoring and early intervention, it may be possible to effectively control the effects of noncompliance until newer strategies are developed which permit immunosuppression-free transplantation.
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Affiliation(s)
- V Kaul
- Center for Liver Diseases, Division of Hepatology, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, USA
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31
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Weber NK, Wiseman AC, Trotter JF. Corticosteroid elimination in simultaneous liverâkidney transplantation recipients. Clin Transplant 2009; 23:958-63. [DOI: 10.1111/j.1399-0012.2009.01051.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Campsen J, Zimmerman M, Trotter J, Wachs M, Bak T, Steinberg T, Kaplan M, Kam I. Liver transplantation for primary biliary cirrhosis: results of aggressive corticosteroid withdrawal. Transplant Proc 2009; 41:1707-12. [PMID: 19545712 DOI: 10.1016/j.transproceed.2008.10.095] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2008] [Accepted: 10/06/2008] [Indexed: 10/20/2022]
Abstract
INTRODUCTION A subset of patients with primary biliary cirrhosis (PBC) may require long-term corticosteroid (CS) therapy following liver transplantation (OLT) due to concern over the possibility of recurrence. Our center has attempted to minimize CS use in all of our OLT recipients. In this study, we review our experience in this cohort to determine (1) patient outcome including PBC recurrence following transplantation and (2) the long-term requirement for CS use in PBC patients. METHODS From 1988 to 2006, 1102 OLTs were performed in 1032 adults at the University of Colorado, of which 70 patients (6.8%) with PBC received 74 allografts. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Thirteen potential predictors of CS discontinuation were considered: age, gender, body mass index (BMI), race, type of graft (cadaveric or living donor [LD]), recurrence of PBC, warm ischemia time, and immunosuppressant. RESULTS Overall survival at 5 years was 85%. The 1-, 5-, and 10-year recurrence-free survivals were 90%, 72%, and 54%, respectively. PBC recurred in 18 patients (25.7%). Of these, none received a second transplant due to disease recurrence. At the time of last follow-up, 73% of recipients were steroid free. Independent predictors of CS discontinuation are age (>54; P = .0059) and LD graft type (P = .0008). Conversely, cyclosporine (P = .0007), female gender (P = .0216), and BMI > 31 (P = .0306) were negatively associated with CS withdraw. Importantly, steroid discontinuation did not influence PBC recurrence. CONCLUSIONS While long-term outcomes in PBC patients are favorable, disease recurrence can generally be managed medically without the need for a second transplant. Using an aggressive CS minimization approach, nearly three-quarters of the patients were CS free at the time of last follow-up. Increasing age and LD grafts were associated with successful CS withdraw. Conversely, cyclosporine use, female gender, and increasing BMI were associated with unsuccessful steroid discontinuation.
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Affiliation(s)
- J Campsen
- Department of Transplant Surgery, University of Colorado, Aurora, Colorado
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33
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McGuire BM, Rosenthal P, Brown CC, Busch AMH, Calcatera SM, Claria RS, Hunt NK, Korenblat KM, Mazariegos GV, Moonka D, Orloff SL, Perry DK, Rosen CB, Scott DL, Sudan DL. Long-term management of the liver transplant patient: recommendations for the primary care doctor. Am J Transplant 2009; 9:1988-2003. [PMID: 19563332 DOI: 10.1111/j.1600-6143.2009.02733.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient.
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Affiliation(s)
- B M McGuire
- University of Alabama at Birmingham, Birmingham, AL, USA.
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35
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Abstract
Because of the markedly improved short-term results of liver transplantation (LT) and persistently high number of long-term complications, the attention of transplant physicians should be focused on minimizing immunosuppressive therapy as much as possible. Steroid-based immunosuppression is responsible for a substantial post-LT morbidity and mortality, hence, minimization of its use is of utmost importance to improve the quality of life of the successfully transplanted liver recipient. This literature review shows that LT can be performed safely with steroid-minimal immunosuppression without compromising graft and patient survival. The tendency in clinical practice is to move more and more from steroid withdrawal to steroid avoidance protocols.
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Affiliation(s)
- Jan Lerut
- Department of Abdominal and Transplantation Surgery, Université catholique de Louvain, Brussels, Belgium.
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36
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Orthotopic liver transplantation and what to do during follow-up: recommendations for the practitioner. ACTA ACUST UNITED AC 2008; 6:23-36. [PMID: 19029996 DOI: 10.1038/ncpgasthep1312] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2008] [Accepted: 10/01/2008] [Indexed: 12/18/2022]
Abstract
Improvements in surgical technique and the introduction of several new immunosuppressive medications mean that outcome after orthotopic liver transplantation (OLT) has improved continuously over the past 15 years. Given the increasing longevity of patients after OLT, the recognition and prevention of long-term complications after transplantation have become ever more important. With respect to graft function, physicians responsible for the everyday care of patients following transplantation should be particularly aware of the risk of late and chronic rejection episodes and of recurrence of the underlying liver disease. The major challenge of post-transplant care is, however, how best to prevent and manage the long-term adverse effects caused by the immunosuppressive medications prescribed. Screening investigations for early diagnosis of malignancy, strict control of cardiovascular risk factors, preservation of renal function, and prevention of infections are, therefore, fundamental. This Review suggests guidelines for the management of OLT recipients to improve long-term survival, overall outcome and health-related quality of life.
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37
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Campsen J, Zimmerman MA, Trotter JF, Wachs M, Bak T, Steinberg T, Kaplan M, Wright F, Kam I. Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal. Liver Transpl 2008; 14:1281-6. [PMID: 18756454 DOI: 10.1002/lt.21525] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Our center has attempted to minimize corticosteroid (CS) use in all of our orthotopic liver transplantation (OLT) recipients. Because patients with autoimmune hepatitis (AIH) typically require CSs after transplantation, we reviewed our experience in this cohort of patients to determine (1) patient outcomes including recurrent disease and (2) long-term requirements for CS use in AIH patients. From 1988 to 2006, 1102 OLTs were performed in 1032 adult patients at the University of Colorado, of whom 66 (6%) with AIH received 68 allografts. Recurrence was defined by a clinically worsening examination and histological evidence from biopsy. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Twelve potential predictors of CS discontinuation were considered: age, gender, presence of inflammatory bowel disease (IBD), type of graft (cadaver or living donor), recurrence of AIH, warm ischemia time, follow-up time (time since transplant), and immunosuppressants (cyclosporine, tacrolimus, sirolimus, azathioprine, and mycophenolate mofetil). Overall survival at 5 years was 91%. The 1- and 5-year recurrence-free survival was 88% and 59%, respectively. Risk (incidence) of recurrent AIH at 1, 3, and 5 years was 12%, 26%, and 36%, respectively. Disease recurred in 23 of 66 patients or 34.8%. Of the 23 patients who developed recurrent disease, none received a second transplant because of recurrent disease. CSs were withdrawn in 50% of patients at the time of review. Only 2 factors on multivariate analysis were strongly associated negatively with CS withdrawal: (1) an increasing dose of the immunosuppressant and (2) the presence of IBD. Controlling for these other factors, we found that recurrent disease did not strongly influence CS withdrawal. In conclusion, outcomes in AIH patients were quite favorable, and none of the patients required retransplantation for recurrent AIH. With a CS minimization approach, one-half of the patients were able to remain CS-free.
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Affiliation(s)
- Jeffrey Campsen
- Division of Transplant Surgery, University of Colorado Health Sciences Center, Denver, CO 80045, USA
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38
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Chen ZS, He F, Zeng FJ, Jiang JP, Du DF, Liu B. Early steroid withdrawal after liver transplantation for hepatocellular carcinoma. World J Gastroenterol 2007; 13:5273-6. [PMID: 17876900 PMCID: PMC4171311 DOI: 10.3748/wjg.v13.i39.5273] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advanced-stage hepatocellular carcinoma.
METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups.
RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine: 66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L, P < 0.01) were significantly different. These were lower in the steroid-withdrawal group than in the steroid-maintenance group.
CONCLUSION: Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection did not increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased significantly. This may have led to an increase in long-term survival rate.
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Affiliation(s)
- Zhi-Shui Chen
- Institution of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
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39
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Abstract
Liver allograft recipients are at increased risk of death from cerebrovascular and cardiovascular disease. We propose the following strategy of risk-reduction, based on currently available literature. Lifestyle: standard advice should be given (avoidance of smoking, excess alcohol and obesity, adequate exercise, reduction of excess sodium intake). Hypertension: target blood pressure should be 140/90 mmHg or lower, but for those with diabetes or renal disease, 130/80 mmHg or lower. For patients without proteinuria, antihypertensive therapy should be initiated with a calcium channel blocker and for those with proteinuria, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker. If monotherapy fails to achieve adequate response, calcium channel blockers and ACE-inhibitors or angiotensin II receptor blockers should be combined. If hypertension remains uncontrolled, an alpha-blocker may be added. Consideration should be given to changing immunosuppression and avoiding use of calcineurin inhibitors. Diabetes: recipients should be regularly screened for diabetes. For patients with new-onset diabetes after transplant, stepwise therapy should be guided by HbA1c concentrations, as with type II diabetes mellitus. Hyperlipidemia: annual screening of lipid profile should be undertaken, with treatment thresholds and targets based on those advocated for the high risk general population. Dietary intervention is appropriate for all patients. A statin should be considered as the first line treatment to achieve specified targets. In patients receiving a calcineurin inhibitor, Pravastatin should be commenced at a dose of 10 mg/day. In patients receiving other forms of immunosuppression, pravastatin may be commenced at a dose of 20 mg/day. Liver tests should be monitored and patients warned to report myalgia. If monotherapy is inadequate, ezetimibe or a fibrate may be added. Consideration may be given to change in immunosuppression if combination lipid-lowering therapy proves inadequate.
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Affiliation(s)
- George Mells
- Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom
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40
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Moench C, Barreiros AP, Schuchmann M, Bittinger F, Thiesen J, Hommel G, Kraemer I, Otto G. Tacrolimus monotherapy without steroids after liver transplantation--a prospective randomized double-blinded placebo-controlled trial. Am J Transplant 2007; 7:1616-23. [PMID: 17511685 DOI: 10.1111/j.1600-6143.2007.01804.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Early steroid withdrawal after liver transplantation (LT) is desirable in order to reduce steroid side effects. Between February 2000 and August 2004, 110 patients after LT were included in this prospective, randomized, double-blind, placebo-controlled trial. Randomization was performed before LT. In all patients, tacrolimus was used without induction therapy. All patients received methylprednisolon for 14 days, thereafter a double-blinded medication containing either placebo (n = 56) or methylprednisolon (n = 54) for 6 months, which was completely stopped thereafter. End points were patient and graft survival, acute and chronic rejection, and incidence of steroid side effects during the first year after LT. One-year patient survival was 85.7% (placebo) and 88.8% (steroid) (p = 0.572). Twenty-seven (48.2%) and 19 (35.2%) patients experienced acute rejection (placebo versus steroid, respectively; p = 0.116). Two patients in the placebo group but none in the steroid group experienced chronic rejection (p = 0.257). The rates of side effects were (placebo versus steroid, respectively): CMV infection 25% versus 33% (p = 0.336), post-transplant diabetes 30% versus 53% (p = 0.024), hypertension 39% versus 52% (p = 0.248), hypercholesterolemia 10% versus 41% (p = 0.002) and hypertriglyceridemia 32% versus 54% (p = 0.046). In conclusion, early steroid withdrawal after LT is feasible under tacrolimus monotherapy without increased rejection rates and with a lower rate of side effects.
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Affiliation(s)
- C Moench
- Department of Transplantation and Hepatobiliarypancreatic Surgery, Johannes Gutenberg University Mainz Hospital, Mainz, Germany.
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41
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Rossi M, Mennini G, Lai Q, Ginanni Corradini S, Drudi F, Pugliese F, Berloco P. Liver transplantation(). J Ultrasound 2007; 10:28-45. [PMID: 23396075 PMCID: PMC3478701 DOI: 10.1016/j.jus.2007.02.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease.The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza).The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center.
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Affiliation(s)
- M. Rossi
- Department of General Surgery and Transplantation “P. Stefanini”, University “La Sapienza”, Rome, Italy
| | - G. Mennini
- Department of General Surgery and Transplantation “P. Stefanini”, University “La Sapienza”, Rome, Italy
| | - Q. Lai
- Department of General Surgery and Transplantation “P. Stefanini”, University “La Sapienza”, Rome, Italy
| | - S. Ginanni Corradini
- Department of Clinical Medicine, Division of Gastroenterology, University “La Sapienza”, Rome, Italy
| | - F.M. Drudi
- Department of Radiology, University “La Sapienza”, Rome, Italy
| | - F. Pugliese
- Department of Anesthesiology, Critical Care Medicine, and the Treatment of Pain, University “La Sapienza”, Rome, Italy
| | - P.B. Berloco
- Department of General Surgery and Transplantation “P. Stefanini”, University “La Sapienza”, Rome, Italy
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42
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Guckelberger O, Byram A, Klupp J, Neumann UP, Glanemann M, Stockmann M, Neuhaus R, Neuhaus P. Coronary event rates in liver transplant recipients reflect the increased prevalence of cardiovascular risk-factors. Transpl Int 2005; 18:967-74. [PMID: 16008748 DOI: 10.1111/j.1432-2277.2005.00174.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Increased prevalence of cardiovascular risk-factors in liver transplant recipients compared with pretransplant and standard population data has been acknowledged. The impact of risk-profiles on cardiovascular event rates or death, however, has not yet been established. Here we evaluate the development of risk-factors during a prospective follow-up of 10 years in 302 patients and compare numbers of coronary events with data from the German Prospective Cardiovascular Münster (PROCAM)-Score population. Prevalence of overweight (17% vs. 27%), hypertension (70% vs. 80%), and diabetes (21% vs. 25%) increased from early to late after transplantation, while elevated serum cholesterol (64% vs. 37%) and triglycerides (40% vs. 21%) became less frequent. Cardiovascular risk-profiles favoring tacrolimus over ciclosporin A based immunosuppression early after transplantation converged over time. Increased risk-scores in liver transplant recipients matched with score standardized event rates in the PROCAM population (ratio: 1.11, 95% CI: 0.53-2.03), nine events were predicted for the transplant population and oppose 10 events observed. Thus, indicating a reflection of increased cardiovascular risk-profiles in corresponding numbers of cardiovascular events.
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Affiliation(s)
- Olaf Guckelberger
- Department of General, Visceral and Transplantation Surgery, Charité- Campus Virchow-Klinikum, Berlin, Germany.
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43
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Angelico M, Gridelli B, Strazzabosco M. Practice of adult liver transplantation in Italy. Recommendations of the Italian Association for the Study of the Liver (A.I.S.F.). Dig Liver Dis 2005; 37:461-7. [PMID: 15893508 DOI: 10.1016/j.dld.2005.03.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2005] [Accepted: 03/01/2005] [Indexed: 12/11/2022]
Abstract
Liver transplantation is an efficient procedure as performed in Italy, yet major differences are present in terms of practice. In an effort to facilitate an homogeneous practice of liver transplantation in Italy, the Italian Association for the Study of Liver Disease has instituted a Commission aimed at providing recommendations on non-urgent liver transplantation in adults, based on current evidence. This nation-wide commission which included experienced hepatologists, surgeons and pathologists with major interest in liver transplantation has drafted a final document in October 2004, approved by the Italian Association for the Study of Liver Governing Board, whose key arguments and main conclusions are summarised in the present paper. The Commission has made specific recommendations on the following topics: the current needs of liver transplantation in Italy; the indications to liver transplantation and re-liver transplantation, with special reference to controversial issues and the minimal listing criteria; the use of marginal donors and the need to optimise donor/recipient matching; the use of living donor liver transplantation; the management of the waiting list and the introduction of Model for End-Stage Liver Disease to define priorities; the clinical management of liver transplantation recipients and disease recurrence; the implementation of audits and outcome monitoring; the training of transplant surgeons and hepatologists and the requirements for Centre accreditation; the pathology of liver transplantation.
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44
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Toyoki Y, Hakamada K, Narumi S, Totsuka E, Nara M, Ono H, Ishizawa Y, Sasaki M. Primary immunosuppression regimen of rapid steroid withdrawal after living related liver transplantation: a single-center experience. Transplant Proc 2005; 36:2279-81. [PMID: 15561218 DOI: 10.1016/j.transproceed.2004.06.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
AIM Corticosteroids have been considered the mainstay of immunosuppressive therapy after liver transplantation. However, the side effects of long-term steroid use such as diabetes, infections, and bone disease, including growth retardation in children, are serious problems. Our immunosuppression regimen includes FK506 and steroid withdrawal by 30 days after transplantation. The aim of this study was to determine the outcomes of liver transplant, using this immunosuppressive regimen. PATIENTS Fifteen primary liver transplant recipients were performed between January 1994 and May 2003 and data were reviewed retrospectively. Eight pediatric and four adult recipients, who had survived more than 3 months after transplantation, were included in this sample. The immunosuppressive regimen consisted of FK 506 (Prograf), initially at doses of 0.03 mg/kg, with dose adjustments to achieve daily trough levels of approximately 10 to 12 ng/mL, and predonisone, initially at 4 mg/kg/d, with a taper and cessation by 30 days when the graft was stable. RESULTS All recipients were successfully withdrawn by 30 days. Acute rejection episodes occurred in three patients, no patient was diagnosed with chronic rejection. The acute rejection-free rate at 5 year was 74.1%. No recipient had diabetes, serious infections or bone disease. CONCLUSION Our primary immunosuppressive regimen of rapid steroid withdrawal is safe with regard to acute and chronic rejection with benefits upon steroid-related side effects.
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Affiliation(s)
- Y Toyoki
- Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan.
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45
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Innocenti F, Hepp J, Humeres R, Sanhueza E, Zapata R, Rios H, Suárez L, Sandoval R, Rius M, Zamboni M. Rapid steroid taper and neoral monotherapy in liver transplantation in Chile: a step in the right direction? Transplant Proc 2005; 36:1675-6. [PMID: 15350449 DOI: 10.1016/j.transproceed.2004.06.063] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
UNLABELLED Diabetes, hypercholesterolemia, hypertension, obesity, osteopenia, and increased risk of viral recurrence are among the complications associated with posttransplant steroid use. Steroid withdrawal or rapid taper has been reported to be safe. The aim of this study was to compare the rejection incidence and severity among patients treated with two different steroid taper strategies. METHODS This retrospective study included all the adult liver transplant recipients since the program's inception from 1993 to January 2002. The minimum follow-up was 1 year. Exclusions included patients receiving an immunosupressive regimen other than mycophenolate mofetil, steroids, and Neoral, or suffering an autoimmune etiology, or displaying patient or graft survival less than 1 year. The incidence and severity of rejection episodes were compared between the two groups of steroid taper protocols: group A received methylprednisolone (1 g) intraoperatively with a slow taper to 10 mg prednisone per day at 1 year. Group B received methylprednisolone (2 g) intraoperatively followed by a rapid reduction with intention to withdraw by month 4, continuing on Neoral monotherapy. Rejection diagnosis was made on histological bases. RESULTS One-month and 1-year rejection rates were 47% and 53%, respectively, among the rapid taper group with Neoral monotherapy, which was similar to 60% and 64%, respectively, in the slow taper group. Rejection severity was also comparable between the two groups. CONCLUSIONS Patients treated with a rapid steroid taper protocol followed by Neoral monotherapy or a slow taper protocol showed similar acute rejection incidences and severities. Their survival rates were also comparable. Further study is necessary to evaluate the impact of rapid steroid taper to prevent the complications of steroid use.
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Affiliation(s)
- F Innocenti
- Department of Surgery, Transplant Unit, Clinica Alemana Santiago, Santiago, Chile.
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46
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Steroid withdrawal at day 14 after liver transplantation: a double-blind, placebo-controlled study. Liver Transpl 2004; 10:1454-60. [PMID: 15558584 DOI: 10.1002/lt.20291] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Some clinical studies in liver transplantation have recently reported safety advantages and similar acute rejection rates with early steroid withdrawal. The aim of this study was to evaluate the efficacy and safety of an immunosuppressive regimen with steroid withdrawal at day 14. A multicenter, 1-year, comparative, double blind, placebo-controlled study was performed. Patients undergoing a first cadaveric liver transplantation were recruited and all received basiliximab + cyclosporine + intravenous methylprednisolone. Patients without severe postoperative complications were randomized at day 7 to receive a maintenance regimen with Neoral (cyclosporine) + prednisolone (group 1) or without steroids (Neoral + placebo; group 2), after a 7-day blinded oral steroid tapering period. A total of 174 patients were randomized at day 7 (group 1: n = 90; group 2: n = 84). The incidence of biopsy-confirmed and treated acute rejection at 6 months was 38.1% in group 2 vs. 24.4% in group 1 (P = .03) with a trend for a higher incidence of Grade II / III acute rejection (28.6% vs. 18.9%; P = .12). Changes from baseline were similar with regard to metabolic parameters (glycemia, total cholesterol, and triglycerides). A trend toward a better glucose tolerance was observed, as fewer patients received an antidiabetic treatment in the placebo group (2 vs. 10). In conclusion, this first double-blind, placebo-controlled study of steroid withdrawal at day 14 showed a higher incidence of acute rejection, only balanced by a trend of a lower need of antidiabetic treatment.
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Neal DAJ, Tom BDM, Luan J, Wareham NJ, Gimson AES, Delriviere LD, Byrne CD, Alexander GJM. Is there disparity between risk and incidence of cardiovascular disease after liver transplant? Transplantation 2004; 77:93-9. [PMID: 14724441 DOI: 10.1097/01.tp.0000100685.70064.90] [Citation(s) in RCA: 80] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hypertension and hypercholesterolemia are recognized complications of liver transplantation, but whether they contribute to the development of cardiovascular disease is uncertain. We aimed first to determine the prevalence of risk factors for coronary heart disease (CHD) after liver transplantation and second to study the effect of liver transplantation on the predicted 10-year risk of developing CHD and the incidence of cardiovascular events in comparison with a matched local population. METHODS Data on blood pressure, serum lipids, weight, diabetes mellitus, smoking, and incidence of myocardial infarction (MI) and stroke were obtained retrospectively from the case notes of 181 consecutive adult liver transplant recipients (median follow-up 54 months). The Framingham coronary risk equations were used to calculate the 10-year probability of developing CHD. RESULTS The prevalences of hypertension and hypercholesterolemia after transplantation were 77% and 62%, respectively. The predicted 10-year risk of CHD increased from 6.9% before transplantation to 11.5% at 1 year after transplantation, whereas that of a matched local population was 7%. Compared with a matched nontransplant population, the incidence ratios for MI and stroke were 0.55 (95% confidence interval, 0.01-3.06 ) and 1.45 (95% confidence interval, 0.18-5.22), respectively. No patients died from MI or stroke. CONCLUSIONS Liver transplant recipients have a high prevalence of risk factors for cardiovascular disease, exceeding that of the general population, and have a higher predicted risk of developing CHD. Despite this, there were no deaths from CHD or stroke during the study period.
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Affiliation(s)
- David A J Neal
- Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK
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Ott R, Bussenius-Kammerer M, Reck T, Koch CA, Kissler H, Hohenberger W, Muller V. Impact of changing immunosuppressive monotherapy from Cyclosporin A to Tacrolimus in long-term, stable liver transplant recipients. Transpl Int 2004. [DOI: 10.1111/j.1432-2277.2004.tb00381.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Diem HVT, Sokal EM, Janssen M, Otte JB, Reding R. Steroid withdrawal after pediatric liver transplantation: a long-term follow-up study in 109 recipients. Transplantation 2003; 75:1664-70. [PMID: 12777853 DOI: 10.1097/01.tp.0000063938.49112.c2] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Steroids remain an important component of maintenance immunosuppression in liver transplantation, but when administered for a long period they may be associated with multiple severe side effects, particularly growth suppression in children. This study was conducted to clarify the balance of potential benefits and risks of steroid withdrawal (SW) in pediatric liver transplantation. METHODS Between April 1984 and July 2000, 109 pediatric recipients with SW and at least 12 months of follow-up after SW were retrospectively reviewed and divided into three groups according to the type of anticalcineurin at SW: group I (cyclosporine, n=25), group II (cyclosporine microemulsion, n=25), and group III (tacrolimus, n=59). Steroids were withdrawn after a three-step reduction of steroid dosage (taper down to the substitution dose of 0.25 mg/kg/day, switch to alternate-day therapy, progressive SW). Patients were regularly followed up for clinical and biochemical monitoring. RESULTS Median follow-up was 8.1 (range, 1.6-16.8) years. After SW, neither chronic rejection nor graft nor patient loss occurred. A trend toward lower anticalcineurin trough levels was observed in all groups. Glomerular filtration rate and fasting cholesterol were significantly better in group III (P<0.05). Median height z-score in all patients was -1.1 SD on alternate-day steroids versus -0.2 SD at the time of SW. Height z-score was slightly better in group III (NS). Early SW within 2 years after transplantation allowed a slightly better gain in growth. CONCLUSIONS SW in pediatric liver transplantation is safe and may be beneficial to height outcome. Tacrolimus seems to offer several advantages in the long-term outcome.
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Affiliation(s)
- Hanh Vo Thi Diem
- Pediatric Liver Transplant Program, Saint-Luc University Clinics, Université Catholique de Louvain, Brussels, Belgium
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