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Kanbay M, Copur S, Topçu AU, Guldan M, Ozbek L, Gaipov A, Ferro C, Cozzolino M, Cherney DZI, Tuttle KR. An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management. Diabetes Obes Metab 2024; 26:2531-2545. [PMID: 38558257 DOI: 10.1111/dom.15575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/09/2024] [Accepted: 03/09/2024] [Indexed: 04/04/2024]
Abstract
OBJECTIVE Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. METHODS Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. RESULTS PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. DISCUSSION The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.
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Affiliation(s)
- Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - A Umur Topçu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Mustafa Guldan
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Lasin Ozbek
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Abduzhappar Gaipov
- Department of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan
| | - Charles Ferro
- Department of Nephrology, University Hospitals Birmingham and Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - David Z I Cherney
- Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada
| | - Katherine R Tuttle
- Department of Medicine, Division of Nephrology, University of Washington, Seattle, Washington, USA
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Shimada S, Miyake K, Venkat D, Gonzalez H, Moonka D, Yoshida A, Abouljoud M, Nagai S. Clinical characteristics of new-onset diabetes after liver transplantation and outcomes. Ann Gastroenterol Surg 2024; 8:383-393. [PMID: 38707230 PMCID: PMC11066488 DOI: 10.1002/ags3.12775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/21/2023] [Accepted: 12/24/2023] [Indexed: 05/07/2024] Open
Abstract
Background We aimed to identify the characteristics of new-onset diabetes after liver transplantation (LT) (NODAT) and investigate its impacts on post-transplant outcomes. Methods Adult LT patients between 2014 and 2020 who used tacrolimus as initial immunosuppression and survived 3 months at least were evaluated. Patients who developed NODAT within 3 months after LT were classified as NODAT group. Also, patients were further classified as history of diabetes before LT (PHDBT) and non-diabetes (ND) groups. Patient characteristics, post-LT outcomes, and cardiovascular and/or pulmonary complications were compared. Results A total of 83, 225, and 263 patients were classified into NODAT, PHDBT, and ND groups. The proportion of cholestatic liver disease and rejection within 90 days were higher in NODAT group. Mean serum tacrolimus concentration trough level in the first week after LT was 7.12, 6.12, and 6.12 ng/mL (p < 0.001). Duration of corticosteroids was significantly longer in NODAT compared to PHDBD or ND (416, 289, and 228 days, p < 0.001). Three-year graft and patient survival were significantly worse in NODAT than ND (80.5% vs. 95.0%, p < 0.001: 82.0% vs. 95.4%, p < 0.001) but similar to PHDBT. Adjusted risks of 3-year graft loss and patient death using Cox regression analysis were significantly higher in NODAT compared to ND (adjusted hazard ratio [aHR] 3.41, p = 0.004; aHR 3.61, p = 0.004). Incidence rates of cardiovascular or pulmonary complications after LT in NODAT were significantly higher than ND but similar to PHDBT. Conclusion Higher initial tacrolimus concentration and early rejection might be risk factors for NODAT. NODAT was associated with worse post-transplant outcomes.
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Affiliation(s)
- Shingo Shimada
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
| | - Katsunori Miyake
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
| | - Deepak Venkat
- Division of Gastroenterology and HepatologyHenry Ford Health SystemDetroitMichiganUSA
| | - Humberto Gonzalez
- Division of Gastroenterology and HepatologyHenry Ford Health SystemDetroitMichiganUSA
| | - Dilip Moonka
- Division of Gastroenterology and HepatologyHenry Ford Health SystemDetroitMichiganUSA
| | - Atsushi Yoshida
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary SurgeryHenry Ford Health SystemDetroitMichiganUSA
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Fernández-Ramírez A, Olivas-Martinez A, Ruiz-Manriquez J, Kauffman-Ortega E, Moctezuma-Velázquez C, Marquez-Guillen E, Contreras AG, Vilatobá M, González-Flores E, Cruz-Martínez R, Flores-García NC, García-Juárez I. Posttransplantation diabetes mellitus after liver transplant and the impact of family history of diabetes in a Mexican cohort. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:249-257. [PMID: 37858455 DOI: 10.1016/j.rgmxen.2023.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 06/08/2023] [Indexed: 10/21/2023]
Abstract
INTRODUCTION AND AIMS Posttransplantation diabetes mellitus (PTDM) is a serious long-term complication that has a negative impact on graft and patient survival. The purpose of the present study was to describe the incidence of PTDM in a Mexican cohort and evaluate its association with a previous family history of diabetes (FHD). METHODS A retrospective single-center cohort study was conducted on patients undergoing liver transplantation (LT). The primary outcome was time from LT to PTDM. The diagnosis of PTDM was established using the ADA criteria. A mediation analysis that used adjusted Cox regression models and considered pretransplant prediabetes a mediator was performed, to determine the total effect and direct effect of FHD on PTDM. RESULTS A total of 152 patients were included, with a median follow-up time of 41 months; 19.2% (n = 29) had pretransplant diabetes. During the follow-up time, 15% of patients developed PTDM (n = 23), with an incidence rate of 4.71 cases/100 person-years. PTDM was significantly higher in patients with FHD, compared with those with no FHD (8.72 cases/100 person-years vs 2.04 cases/100 person-years, respectively; p = 0.001). The adjusted hazard ratio of PTDM for FHD was 4.14 (95% CI 1.60-10.7), p = 0.005) and 3.48 (95% CI 1.35-9.01, p = 0.010), when further controlled for pretransplant prediabetes. CONCLUSION The occurrence of PTDM was similar to that reported in most international studies. As with type 2 diabetes, family history plays an important role in the development of PTDM, even after accounting for pretransplant prediabetes. Patients with FHD should undergo a stricter metabolic program.
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Affiliation(s)
- A Fernández-Ramírez
- Departamento de Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - A Olivas-Martinez
- Departamento de Bioestadística, Universidad de Washington, Seattle, WA, United States
| | - J Ruiz-Manriquez
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - E Kauffman-Ortega
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - C Moctezuma-Velázquez
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - E Marquez-Guillen
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - A G Contreras
- Departamento de Cirugía y Trasplante, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - M Vilatobá
- Departamento de Cirugía y Trasplante, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - E González-Flores
- Centro de Atención Integral del Paciente con Diabetes (CAIPaDi), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - R Cruz-Martínez
- Departamento de Cirugía y Trasplante, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - N C Flores-García
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - I García-Juárez
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
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Gabrielli F, Golfieri L, Nascimbeni F, Andreone P, Gitto S. Metabolic Disorders in Liver Transplant Recipients: The State of the Art. J Clin Med 2024; 13:1014. [PMID: 38398327 PMCID: PMC10889804 DOI: 10.3390/jcm13041014] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/05/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
Liver transplantation represents a chief therapeutic approach for acute liver failure, end-stage liver disease and hepatocellular carcinoma. Despite witnessing advancements in short- and medium-term survival over recent decades, attributed to refinements in surgical techniques and immunosuppressive protocols, long-term mortality remains impervious to modification. Notably, cardiovascular disease emerges as a predominant cause of mortality among liver transplant recipients. This trend is accentuated by the increasing prominence of non-alcoholic steatohepatitis-related cirrhosis as an indication for liver transplantation. Moreover, the administration of immunosuppressive agents is intricately linked to the degradation of the metabolic profile in liver transplant recipients, thereby contributing to the initiation or exacerbation of cardiovascular risk factors, such as hypertension, diabetes, and dyslipidaemia. In addition, the post-liver transplantation period is marked by a decline in lifestyle quality and a failure to acknowledge the psychological distress experienced by patients throughout the transplant process. These factors can precipitate a deterioration in the patient's metabolic profile, exacerbated by suboptimal therapeutic compliance. This narrative review aims to comprehensively address the principal metabolic disorders intricately associated with liver transplantation.
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Affiliation(s)
- Filippo Gabrielli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Department of Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Lucia Golfieri
- Clinical Psychology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, 40138 Bologna, Italy
| | - Fabio Nascimbeni
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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Park SJ, Yoon JH, Joo I, Lee JM. Newly developed sarcopenia after liver transplantation, determined by a fully automated 3D muscle volume estimation on abdominal CT, can predict post-transplant diabetes mellitus and poor survival outcomes. Cancer Imaging 2023; 23:73. [PMID: 37528480 PMCID: PMC10394977 DOI: 10.1186/s40644-023-00593-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 07/12/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Loss of muscle mass is the most common complication of end-stage liver disease and negatively affects outcomes for liver transplantation (LT) recipients. We aimed to determine the prognostic value of a fully automated three-dimensional (3D) muscle volume estimation using deep learning algorithms on abdominal CT in patients who underwent liver transplantation (LT). METHODS This retrospective study included 107 patients who underwent LT from 2014 to 2015. Serial CT scans, including pre-LT and 1- and 2-year follow-ups were performed. From the CT scans, deep learning-based automated body composition segmentation software was used to calculate muscle volumes in 3D. Sarcopenia was calculated by dividing average skeletal muscle area by height squared. Newly developed-(ND) sarcopenia was defined as the onset of sarcopenia 1 or 2 years after LT in patients without a history of sarcopenia before LT. Patients' clinical characteristics, including post-transplant diabetes mellitus (PTDM) and Model for end-stage liver disease score, were compared according to the presence or absence of sarcopenia after LT. A subgroup analysis was performed in the post-LT sarcopenic group. The Kaplan-Meier method was used for overall survival (OS). RESULTS Patients with ND-sarcopenia had poorer OS than those who did not (P = 0.04, hazard ratio [HR], 3.34; 95% confidence interval [CI] 1.05 - 10.7). In the subgroup analysis for post-LT sarcopenia (n = 94), 34 patients (36.2%) had ND-sarcopenia. Patients with ND-sarcopenia had significantly worse OS (P = 0.002, HR 7.12; 95% CI 2.00 - 25.32) and higher PTDM occurrence rates (P = 0.02, HR 4.93; 95% CI 1.18 - 20.54) than those with sarcopenia prior to LT. CONCLUSION ND-sarcopenia determined by muscle volume on abdominal CT can predict poor survival outcomes and the occurrence of PTDM for LT recipients.
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Affiliation(s)
- Sae-Jin Park
- Department of Radiology, SMG - SNU Boramae Medical Center, Seoul, Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea.
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Zhang Z, Sun J, Guo M, Yuan X. Progress of new-onset diabetes after liver and kidney transplantation. Front Endocrinol (Lausanne) 2023; 14:1091843. [PMID: 36843576 PMCID: PMC9944581 DOI: 10.3389/fendo.2023.1091843] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/27/2023] [Indexed: 02/11/2023] Open
Abstract
Organ transplantation is currently the most effective treatment for end-stage organ failure. Post transplantation diabetes mellitus (PTDM) is a severe complication after organ transplantation that seriously affects the short-term and long-term survival of recipients. However, PTDM is often overlooked or poorly managed in its early stage. This article provides an overview of the incidence, and pathogenesis of and risk factors for PTDM, aiming to gain a deeper understanding of PTDM and improve the quality of life of recipients.
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Affiliation(s)
- Zhen Zhang
- Department of Urology, The People's Hospital of Linyi, Linyi, Shandong, China
| | - Jianyun Sun
- Department of Gastroenterology, The People's Hospital of Linyi, Linyi, Shandong, China
| | - Meng Guo
- National Key Laboratory of Medical Immunology &Institute of Immunology, Navy Medical University, Shanghai, China
| | - Xuemin Yuan
- Department of Gastroenterology, The People's Hospital of Linyi, Linyi, Shandong, China
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Battistella S, D’Arcangelo F, Grasso M, Zanetto A, Gambato M, Germani G, Senzolo M, Russo FP, Burra P. Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management. Clin Mol Hepatol 2023; 29:S286-S301. [PMID: 36577425 PMCID: PMC10029965 DOI: 10.3350/cmh.2022.0392] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 12/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the fastest growing indication to liver transplantation (LT) in Western Countries, both for end stage liver disease and hepatocellular carcinoma. NAFLD/non-alcoholic steatohepatitis (NASH) is often expression of a systemic metabolic syndrome; therefore, NAFLD/NASH patients require a multidisciplinary approach for a proper pre-surgical evaluation, which is important to achieve a post-transplant outcome comparable to that of other indications to LT. NAFLD/NASH patients are also at higher risk of post-transplant cardiovascular events, diabetes, dyslipidemia, obesity, renal impairment and recurrent NASH. Lifestyle modifications, included diet and physical activity, are key to improve survival and quality of life after transplantation. A tailored immunosuppressive regimen may be proposed in selected patients. Development of new drugs for the treatment of recurrent NASH is awaited.
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Affiliation(s)
- Sara Battistella
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
| | - Francesca D’Arcangelo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
| | - Marco Grasso
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
| | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
| | - Martina Gambato
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
| | - Giacomo Germani
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua,
Italy
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Chaitou AR, Valmiki S, Valmiki M, Zahid M, Aid MA, Fawzy P, Khan S. New-Onset Diabetes Mellitus (NODM) After Liver Transplantation (LT): The Ultimate Non-diabetogenic Immunosuppressive Therapy. Cureus 2022; 14:e23635. [PMID: 35510006 PMCID: PMC9057316 DOI: 10.7759/cureus.23635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 03/29/2022] [Indexed: 11/05/2022] Open
Abstract
New-onset diabetes mellitus (NODM) is a common long-term complication after liver transplantation (LT). It is thought to be drug-induced in most cases, no matter the underlying disease that cause liver failure and indicated transplantation. Standard post-transplantation (PT) immunosuppressive regimens include prolonged use of calcineurin inhibitors (CNIs), namely tacrolimus (TAC), alongside corticosteroids to avoid acute and chronic graft rejection. This combination is well known for its diabetogenicity. Significant differences between the applied regimens stand out concerning the duration and dosages to prevent the metabolic side effects of these drugs in the long run without compromising the graft's survival. Studies were collected after an extensive research of PubMed database for this very specific topic using the following MeSH keywords in multiple combinations: "Liver Transplantation," "Diabetes Mellitus," "NODM," "Tacrolimus," "Cyclosporine A," and "Steroids." In addition, we used the same keywords for regular searches in Google Scholar. Only the relevant English human studies between 2010 and 2020 were collected except for review articles. Duplicates were eliminated using Mendeley software. Twelve relevant studies directly related to the targeted topic were collected and discussed, including five retrospective cohorts, four prospective cohorts, one clinical trial, one prospective pilot, and one case report. Their topics included primarily the factors increasing the risk of new-onset diabetes mellitus after liver transplantation (NODALT), TAC-based immunosuppression and its relative blood levels affecting the possible development of NODALT, the role of cyclosporine in substituting TAC regimen, and the effect of different steroids-avoiding protocols on the prevention of NODALT. The reviewed studies suggested that lowering the serum concentration of tacrolimus (cTAC) throughout the PT period and eliminating the corticosteroids regimen as early as possible, among other measures, can significantly impact the rate of emergence of NODM. This traditional review tackles the most recent studies about NODALT to establish a comprehensive view on this issue and guide clinicians and researchers for the safest immunosuppressive regimen to date, while maintaining a balanced metabolic profile.
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Kotha S, Lawendy B, Asim S, Gomes C, Yu J, Orchanian-Cheff A, Tomlinson G, Bhat M. Impact of immunosuppression on incidence of post-transplant diabetes mellitus in solid organ transplant recipients: Systematic review and meta-analysis. World J Transplant 2021; 11:432-442. [PMID: 34722172 PMCID: PMC8529944 DOI: 10.5500/wjt.v11.i10.432] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 08/27/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Solid organ transplantation is a life-saving intervention for end-stage organ disease. Post-transplant diabetes mellitus (PTDM) is a common complication in solid organ transplant recipients, and significantly compromises long-term survival beyond a year.
AIM To perform a systematic review and meta-analysis to estimate incidence of PTDM and compare the effects of the 3 major immunosuppressants on incidence of PTDM.
METHODS Two hundred and six eligible studies identified 75595 patients on Tacrolimus, 51242 on Cyclosporine and 3020 on Sirolimus. Random effects meta-analyses was used to calculate incidence.
RESULTS Network meta-analysis estimated the overall risk of developing PTDM was higher with tacrolimus (OR = 1.4 95%CI: 1.0–2.0) and sirolimus (OR = 1.8; 95%CI: 1.5–2.2) than with Cyclosporine. The overall incidence of PTDM at years 2-3 was 17% for kidney, 19% for liver and 22% for heart. The risk factors for PTDM most frequently identified in the primary studies were age, body mass index, hepatitis C, and African American descent.
CONCLUSION Tacrolimus tends to exhibit higher diabetogenicity in the short-term (2-3 years post-transplant), whereas sirolimus exhibits higher diabetogenicity in the long-term (5-10 years post-transplant). This study will aid clinicians in recognition of risk factors for PTDM and encourage careful evaluation of the risk/benefit of different immunosuppressant regimens in transplant recipients.
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Affiliation(s)
- Sreelakshmi Kotha
- Department of Gastroenterology, Guy's and St Thomas' Hospital, London SE1 7JD, United Kingdom
| | - Bishoy Lawendy
- Department of Multi-Organ Transplantation, Toronto General Hospital, Toronto M5G 2C4, Canada
| | - Saira Asim
- Multi Organ Transplant Program, Toronto General Hospital, Toronto M5G 2C4, Canada
| | - Charlene Gomes
- Department of Multi-Organ Transplantation, Toronto General Hospital, Toronto M5G 2C4, Canada
| | - Jeffrey Yu
- Department of Multi-Organ Transplantation, Toronto General Hospital, Toronto M5G 2C4, Canada
| | - Ani Orchanian-Cheff
- Department of Multi-Organ Transplantation, Toronto General Hospital, Toronto M5G 2C4, Canada
| | - George Tomlinson
- Dalla Lana School of Public Health, Department of Medicine, University Health Network - Toronto General Hospital, University of Toronto, Toronto M5G 2C4, Canada
| | - Mamatha Bhat
- Multi-organ Transplant, Toronto General Hospital, Toronto M5G 2C4, Canada
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10
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The Underutilization, Adverse Reactions and Efficacy of Statins after Liver Transplant: A Meta-Analysis and Systematic Review. TRANSPLANTOLOGY 2021. [DOI: 10.3390/transplantology2030025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
(1) Background: Treatment of dyslipidemia via statin therapy in the non-liver transplant (LT) population is associated with a mortality benefit; however, the impact of statin therapy in post-LT population is not well-defined. This meta-analysis seeks to investigate the safety and efficacy of statin therapy in post-LT patients. (2) Methods: A systematic literature search on Medline and EMBASE database was conducted. A single-arm proportional meta-analysis and conventional pair-wise meta-analysis were performed to compare different outcomes with a random effects model. (3) Results: A total of 11 studies were included in this study, with 697 LT recipients identified to be on statin therapy. Statins were underutilized with only 32% (95% CI: 0.15–0.52) of 1094 post-LT patients on therapy. The incidence of adverse events of 14% (95% CI: 0.05–0.25) related to statin therapy was low. A significant mortality benefit was noted in patients on statin therapy with HR = 0.282 (95% CI: 0.154–0.517, p < 0.001), and improved lipid profiles post LT. The use of statins also significantly decreased odds of graft rejection (OR = 0.33; 95% CI: 0.15–0.73) and hepatocellular carcinoma (HCC) recurrence (HR = 0.32, 95% CI: 0.11–0.89). (4) Conclusions: Statin therapy is safe and efficacious in post-LT patients. Future studies to evaluate the effects of interactions between statins and immunosuppressant therapy are warranted.
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11
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Lawendy B, Srinathan S, Kotha S, Gomes C, Misra S, Yu J, Orchanian-Cheff A, Tomlinson G, Bhat M. Systematic review and meta-analysis of post-transplant diabetes mellitus in liver transplant recipients. Clin Transplant 2021; 35:e14340. [PMID: 34033142 DOI: 10.1111/ctr.14340] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 04/17/2021] [Accepted: 04/26/2021] [Indexed: 01/04/2023]
Abstract
Post-transplant diabetes mellitus (PTDM) compromises long-term survival in liver transplant (LT) recipients. The aim of this study was to determine incidence of PTDM after LT and risk factors associated with it. A literature search was conducted, and prospective studies that reported on the incidence of PTDM in LT adult patients on tacrolimus, sirolimus, or cyclosporine were included. We performed random effects meta-analyses for the incidence of PTDM stratified by immunosuppressant and time period. Of 9817 articles identified, 26 studies were included in the qualitative analysis and 21 studies were eligible for the quantitative analysis representing 79 559 LT recipients in 32 separate treatment arms. The proportion of patients who developed PTDM by two-three years was 0.15 (95% CI: 0.10-0.24) for cyclosporine, 0.23 (95% CI: 0.14-0.36) for tacrolimus, and 0.27 (95% CI: 0.23-0.30) for sirolimus. CONCLUSION: Our results showed that sirolimus-based immunosuppression was associated with a higher incidence of PTDM than tacrolimus or cyclosporine at two-three years. However, there were only two studies that compared all three drugs which is a limitation of the study and requires more studies with patients on sirolimus. Recipient factors increasing the risk of PTDM are older age, male sex, and high BMI.
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Affiliation(s)
- Bishoy Lawendy
- University of Toronto, Toronto, ON, Canada.,Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Sujitha Srinathan
- Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,University of Ottawa, Ottawa, ON, Canada
| | | | - Charlene Gomes
- Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | | | - Jeffrey Yu
- Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Ani Orchanian-Cheff
- Library and Information Services, University Health Network, Toronto, ON, Canada
| | - George Tomlinson
- Institute of Health Policy, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
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12
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Chin YH, Tan HQM, Ng CH, Tan DJH, Lin SY, Huang DQ, Khoo CM, Muthiah MD. A Time-Based Meta-Analysis on the Incidence of New Onset Diabetes after Liver Transplantation. J Clin Med 2021; 10:jcm10051045. [PMID: 33802465 PMCID: PMC7959476 DOI: 10.3390/jcm10051045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/08/2021] [Accepted: 02/24/2021] [Indexed: 12/29/2022] Open
Abstract
NODAT (new-onset diabetes after transplantation) is an important complication after liver transplant, however, there is variation in the reported incidence of NODAT. Therefore, a meta-analysis was performed to estimate the incidence of NODAT in liver transplant. Electronic databases were searched for articles regarding NODAT incidence after liver transplantation. Incidence of NODAT were analyzed at six different timepoints. Summary statistics were calculated using a generalized linear mixed model in random effects. 28 articles were included and out of a pooled population of 71,257 patients, overall incidence of NODAT was found to be 15.51%, 16.09%, 18.30%, 20.86%, 18.08%, 25.05% for three-months, six-months, one-year, three-year, five-year, and ten-year timepoints respectively. After a sensitivity analysis which only included articles with clear definitions of NODAT, the incidence of NODAT was found to be higher at three-year (21.79%), five-year (25.82%), and ten-year (44.95%) timepoints. Subgroup analysis according to ethnicity found no significant differences for all timepoints. However, studies with predominantly Asian participants generally had a higher incidence of NODAT. In conclusion, this meta-analysis provides a pooled estimate of the incidence of NODAT following liver transplantation. Further studies are required to provide a more comprehensive understanding on how ethnicity can affect the incidence of NODAT.
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Affiliation(s)
- Yip Han Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Hon Qin Marcus Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Correspondence: or (C.H.N.); (M.D.M.)
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
- National University Centre for Organ Transplantation, National University Hospital, Singapore 119074, Singapore
| | - Chin Meng Khoo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
| | - Mark Dhinesh Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
- National University Centre for Organ Transplantation, National University Hospital, Singapore 119074, Singapore
- Correspondence: or (C.H.N.); (M.D.M.)
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13
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Hecking M, Sharif A, Eller K, Jenssen T. Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics. Transpl Int 2021; 34:27-48. [PMID: 33135259 PMCID: PMC7839745 DOI: 10.1111/tri.13783] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/20/2020] [Accepted: 10/29/2020] [Indexed: 12/12/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus-based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium-glucose-linked transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1-RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1-RAs that have not brought forth major concerns, likely indicating that GLP1-RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.
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Affiliation(s)
- Manfred Hecking
- Department of Internal Medicine IIIClinical Division of Nephrology & DialysisMedical University of ViennaViennaAustria
| | - Adnan Sharif
- Department of Nephrology and TransplantationQueen Elizabeth HospitalBirminghamUK
| | - Kathrin Eller
- Clinical Division of NephrologyMedical University of GrazGrazAustria
| | - Trond Jenssen
- Department of Organ TransplantationOslo University HospitalRikshospitaletOsloNorway
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14
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Man Kim J, Hwang S, Lee KW, Lee JG, Ryu JH, Kim BW, Choi DL, You YK, Kim DS, Nah YW, Kang KJ, Cho JY, Hong G, Choi IS, Yu HC, Choi D, Kim MS, The Korean Organ Transplantation Registry Study Group. New-onset diabetes after adult liver transplantation in the Korean Organ Transplantation Registry (KOTRY) study. Hepatobiliary Surg Nutr 2020; 9:425-439. [PMID: 32832494 PMCID: PMC7423540 DOI: 10.21037/hbsn.2019.10.29] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 08/05/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication following liver transplantation (LT). The present study aimed to investigate the incidence of and risk factors for NODAT using the Korean Organ Transplantation Registry (KOTRY) database. METHODS Patients with history of pediatric transplantation (age ≤18 years), re-transplantation, multi-organ transplantation, or pre-existing diabetes mellitus were excluded. A total of 1,919 non-diabetic adult patients who underwent a primary LT between May 2014 and December 2017 were included. Risk factors were identified using Cox regression analysis. RESULTS NODAT occurred in 19.7% (n=377) of adult liver transplant recipients. Multivariate analysis showed steroid use, increased age, and high body mass index (BMI) in recipients, and implantation of a left-side liver graft was closely associated with NODAT in adult LT. In living donor liver transplant (LDLT) patients (n=1,473), open donor hepatectomy in the living donors, steroid use, small for size liver graft (graft to recipient weight ratio ≤0.8), increased age, and high BMI in the recipient were predictive factors for NODAT. The use of antimetabolite and basiliximab induction reduced the incidence of NODAT in adult LT and in adult LDLT. CONCLUSIONS Basiliximab induction, early steroid withdrawal, and antimetabolite therapy may prevent NODAT after adult LT. High BMI or advanced age in liver recipients, open donor hepatectomy in living donors, and small size liver graft can predict the occurrence of NODAT after adult LT or LDLT.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jae-Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
| | - Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Koo Jeong Kang
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
| | - Geun Hong
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
| | - In Seok Choi
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
| | - Hee Chul Yu
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - The Korean Organ Transplantation Registry Study Group
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
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15
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Body Weight Parameters are Related to Morbidity and Mortality After Liver Transplantation: A Systematic Review and Meta-analysis. Transplantation 2020; 103:2287-2303. [PMID: 31283679 DOI: 10.1097/tp.0000000000002811] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Weight gain and obesity are well-known clinical issues in liver transplantation (LTx). However, their impacts on patient outcomes remain unclear, as only the impact of pre-LTx body mass index (BMI) on survival has been meta-analyzed. We summarized and synthesized the evidence on pre- and post-LTx body weight parameters' relations with post-LTx outcomes such as survival, metabolic and cardiovascular comorbidities, and healthcare utilization. METHODS We followed the Cochrane Handbook for Systematic Reviews of Interventions' recommendations. Quality was assessed via a 19-item instrument. Odds ratios and 95% confidence intervals were calculated for outcomes investigated in ≥5 studies. RESULTS Our meta-analysis included 37 studies. Patients with pre-LTx BMI ≥ 30 kg/m and BMI ≥ 35 kg/m had lower overall survival rates than those with pre-LTx normal weight (72.6% and 69.8% versus 84.2%; P = 0.02 and P = 0.03, respectively). Those with pre-LTx BMI ≥ 30 kg/m had worse overall graft survival than normal weight patients (75.8% and 85.4%; P = 0.003). Pre-LTx BMI and pre-LTx overweight were associated with new-onset diabetes (P < 0.001 and P = 0.015, respectively), but post-LTx BMI showed no relationship. No associations were evident with healthcare utilization. CONCLUSIONS Patients with BMI values ≥30 kg/m had worse patient and graft survival than those with normal weight. Few of the reviewed studies examined post-LTx body weight parameters or other relevant outcomes such as cardiovascular comorbidities. High heterogeneity as well as diverse definitions and operationalizations of measurement and outcomes severely impeded comparability.
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16
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Cigrovski Berkovic M, Virovic-Jukic L, Bilic-Curcic I, Mrzljak A. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management. World J Gastroenterol 2020; 26:2740-2757. [PMID: 32550751 PMCID: PMC7284186 DOI: 10.3748/wjg.v26.i21.2740] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/24/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Dubrava, Zagreb 10000, Croatia
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
| | - Lucija Virovic-Jukic
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
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17
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Kelava T, Turcic P, Markotic A, Ostojic A, Sisl D, Mrzljak A. Importance of genetic polymorphisms in liver transplantation outcomes. World J Gastroenterol 2020; 26:1273-1285. [PMID: 32256016 PMCID: PMC7109269 DOI: 10.3748/wjg.v26.i12.1273] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/01/2020] [Accepted: 03/05/2020] [Indexed: 02/06/2023] Open
Abstract
Although, liver transplantation serves as the only curative treatment for patients with end-stage liver diseases, it is burdened with complications, which affect survival rates. In addition to clinical risk factors, contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes. Determination of single nucleotide polymorphisms (SNPs) is one of the most important tools in development of personalized transplant approach. To provide a better insight in recent developments, we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation: Acute cellular rejection, development of new-onset diabetes mellitus and non-alcoholic fatty liver disease, hepatocellular carcinoma recurrence, and tacrolimus concentration variability. Reviewed studies confirmed previously established SNP prognostic factors, such as PNPLA3 rs738409 for non-alcoholic fatty liver disease development, or the role of CYP3A5 rs776746 in tacrolimus concentration variability. They also identified several novel SNPs, with a reasonably strong association, which have the potential to become useful predictors of post-transplant complications. However, as the studies were typically conducted in one center on relatively low-to-moderate number of patients, verification of the results in other centers is warranted to resolve these limitations. Furthermore, of 29 reviewed studies, 28 used gene candidate approach and only one implemented a genome wide association approach. Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.
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Affiliation(s)
- Tomislav Kelava
- Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Zagreb 10000, Croatia
| | - Petra Turcic
- Department of Pharmacology, Faculty of Pharmacy and Biochemistry of University of Zagreb, Zagreb 10000, Croatia
| | - Antonio Markotic
- Center for Clinical Pharmacology, University Clinical Hospital Mostar, Mostar 88000, Bosnia and Herzegovina
| | - Ana Ostojic
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
| | - Dino Sisl
- Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Medicine, Merkur University Hospital; School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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18
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El-Gendy H, El Agouza IM, Abd Elmoneem HA, Bahaa MM, Salah MM. Evaluation of serum taurine as a prognostic marker for graft function in adult Egyptian patients undergoing living donor liver transplant. EGYPTIAN JOURNAL OF ANAESTHESIA 2020; 36:273-281. [DOI: 10.1080/11101849.2020.1848239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/06/2020] [Accepted: 11/05/2020] [Indexed: 02/08/2023] Open
Affiliation(s)
- Hanaa El-Gendy
- Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | | | - Mohamed M. Bahaa
- Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Manar M. Salah
- Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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19
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Li Y, Han S. Transgastric endoscopic gallbladder polypectomy and cholecystolithiasis: A case report. Exp Ther Med 2019; 19:95-98. [PMID: 31853277 PMCID: PMC6909710 DOI: 10.3892/etm.2019.8195] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 10/11/2019] [Indexed: 12/14/2022] Open
Abstract
As the most common digestive-system disease, cholelithiasis and gallbladder polyps have a high incidence. The most common treatment is laparoscopic cholecystectomy, but there are numerous drawbacks, including stump syndrome. In the present study, a novel treatment, namely transgastric endoscopic gallbladder polypectomy and cholecystolithiasis, was applied. To the best of our knowledge, the present study is the first to report on this application, which can potentially avoid open surgery and associated scars and allows for rapid recovery after surgery, and may therefore be worthy of further development and implementation in clinical practice. It is esteemed that in the future, transgastric endoscopy gallbladder polypectomy and cholecystolithiasis will be considered as a treatment option for certain patients and is subjected to constant improvements.
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Affiliation(s)
- Yang Li
- Gastroenterology Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
| | - Shutang Han
- Gastroenterology Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
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20
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The Impact of Preexisting and Post-transplant Diabetes Mellitus on Outcomes Following Liver Transplantation. Transplantation 2019; 103:2523-2530. [DOI: 10.1097/tp.0000000000002757] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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21
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Roccaro GA, Mitrani R, Hwang WT, Forde KA, Reddy KR. Sustained Virological Response Is Associated with a Decreased Risk of Posttransplant Diabetes Mellitus in Liver Transplant Recipients with Hepatitis C-Related Liver Disease. Liver Transpl 2018; 24:1665-1672. [PMID: 30291672 PMCID: PMC6279473 DOI: 10.1002/lt.25351] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 09/28/2018] [Indexed: 01/13/2023]
Abstract
Posttransplant diabetes mellitus (PTDM), an increasingly recognized complication of solid organ transplantation, is associated with increased morbidity and mortality following liver transplantation (LT). Hepatitis C virus (HCV) infection is a consistent and modifiable risk factor for PTDM. Prior studies have demonstrated improvement in glucose metabolism following sustained virological response (SVR). However, the effect of SVR on the incidence of PTDM has not been previously investigated in a large cohort of LT recipients. We performed a single-center retrospective cohort study of LT recipients with HCV from January 1, 2010 to June 30, 2015 to compare the risk of sustained posttransplant diabetes mellitus (s-PTDM) prior to and following SVR. SVR was treated as a discrete time varying exposure. The s-PTDM was defined as de novo diabetes mellitus following LT of a >6-month duration. Univariate and multivariate Cox proportional hazards models were used to compare crude and adjusted time to s-PTDM prior to and following SVR. There were 256 eligible LT recipients analyzed. Median follow-up was 41.2 months. Overall, 31 (12.1%) and 178 (69.5%) patients achieved SVR prior to LT and following LT, respectively. During follow-up, 71 (27.7%) patients developed s-PTDM. The incidence of s-PTDM was greatest in the first year after LT. After adjustment for potential confounders, SVR was associated with a significantly reduced risk of s-PTDM (HR, 0.40; P = 0.048). In conclusion, eradication of HCV is independently associated with a reduced incidence of s-PTDM. This benefit appears to be most influenced by pre-LT SVR and persists throughout the post-LT period. Given the association between PTDM and posttransplant morbidity and mortality, these data provide another motivator for pre-LT or early post-LT treatment of HCV.
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Affiliation(s)
- Giorgio A. Roccaro
- Division of Gastroenterology, Emory University Medical Center, Atlanta, GA
| | - Robert Mitrani
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA
| | - Wei-Ting Hwang
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Kimberly A. Forde
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA.,Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - K. Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA
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22
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Clinical Profile of Patients With Diabetes Mellitus and Liver Transplantation: Results After a Multidisciplinary Team Intervention. Transplant Proc 2018; 50:784-787. [PMID: 29661438 DOI: 10.1016/j.transproceed.2018.02.042] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Over the years, survival after liver transplantation has increased and metabolic complications are becoming more common, contributing to patients' morbidity and mortality. The objectives of this study were to describe a population of patients with hepatic transplantation and diabetes mellitus (DM), evaluate the frequency of metabolic complications, and assess the impact of a multidisciplinary team on DM management. MATERIALS AND METHODS This was a retrospective study involving interview and medical record analysis of 46 consecutive patients followed at the diabetes mellitus and liver transplantation unit of a tertiary university hospital, all evaluated by a multidisciplinary team. RESULTS Of all patients, 76.1% were men, with a median age 60 years old (interquartile range: 56 to 65 years) and liver transplantation time of 5 years (interquartile range: 0.6-9 years). Hypertension, hypercholesterolemia, hypertriglyceridemia, alcoholism, and smoking were present in 47.8%, 34.8%, 23.9%, 34.8%, and 30.4% of the patients, respectively. The most frequent immunosuppressant in use was tacrolimus (71.1%). Regarding nutritional status, 37.9% of patients were classified as overweight according to body mass index, and 41.2% were considered overweight according to the triceps skin fold. The median glycosylated hemoglobin and weight before and after intervention of the multidisciplinary team in all 46 patients were, respectively, 7.6% (5.7% to 8.8%) versus 6.5% (5.7% to 7.7%); P = .022 and 70.5 kg (64.7 to 82.0 kg) versus 71.6 kg (65.0 to 85.0 kg); P = .18. CONCLUSIONS Hypertension and dyslipidemia were common in transplanted patients with DM. Intervention of the multidisciplinary team resulted in a significant improvement in glycosylated hemoglobin without significant weight gain.
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Castedal M, Skoglund C, Axelson C, Bennet W. Steroid-free immunosuppression with low-dose tacrolimus is safe and significantly reduces the incidence of new-onset diabetes mellitus following liver transplantation. Scand J Gastroenterol 2018; 53:741-747. [PMID: 29688072 DOI: 10.1080/00365521.2018.1463390] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Corticosteroids (CS) are traditionally used as part of the basal immunosuppression (IS) following liver transplantation (LT) but are known to be associated with an increased risk of new-onset diabetes mellitus (NODM), cardiovascular morbidity and mortality. The aim of this study was to retrospectively compare the incidence of transient as well as persistent NODM, rejection rate and patient- and graft survival between patients receiving steroid-based and steroid-free maintenance IS. MATERIALS AND METHODS A total of 238 patients liver transplanted (2008-2011) with deceased donor livers were divided into two groups, one group that received steroid-based IS (tacrolimus (TAC), corticosteroids (CS), ± mycophenolate mofetil (MMF); n = 155) (2008-2011) and another group of non-autoimmune recipients that received steroid-free IS (TAC, MMF; n = 83) according to our new maintenance IS-protocol starting January 2010. The primary and secondary end-points were patient- and graft survival, rejection rates and the incidence of NODM. The median follow-up times were 1248 days and 681 days, respectively. RESULTS The one-year patient- and graft survival in the steroid-based and steroid-free group was 92.7% and 93.3% (ns) and 87.6% and 84.9% (ns), respectively. The incidence of biopsy proven acute rejection (BPAR) was 27.7% in both groups (ns) during follow-up. The overall incidence of persistent NODM in the two groups were 16.8% and 2.9%, respectively (p < .01). CONCLUSIONS The results show that steroid-free low-dose tacrolimus-based IS following LT is safe and decreases the incidence of NODM significantly.
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Affiliation(s)
- M Castedal
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - C Skoglund
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - C Axelson
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - W Bennet
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
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Andrade ARCFD, Cotrim HP, Bittencourt PL, Almeida CG, Sorte NCAB. Nonalcoholic steatohepatitis in posttransplantation liver: Review article. ACTA ACUST UNITED AC 2018; 64:187-194. [PMID: 29641680 DOI: 10.1590/1806-9282.64.02.187] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Accepted: 06/26/2017] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Nonalcoholic steatohepatitis (NASH) associated or not with cirrhosis is the third leading indication for liver transplantation (LT) around the world. After transplants, NASH has a high prevalence and occurs as both recurrent and de novo manifestations. De novo NASH can also occur in allografts of patients transplanted for non-NASH liver disease. OBJECTIVE To evaluate recurrent or de novo NASH in post-LT patients. METHOD A literature review was performed using search engines of indexed scientific material, including Medline (by PubMed), Scielo and Lilacs, to identify articles published in Portuguese and English until August 2016. Eligible studies included: place and year of publication, prevalence, clinical characteristics, risk factors and survival. RESULTS A total of 110 articles were identified and 63 were selected. Most of the studies evaluated recurrence and survival after LT. Survival reached 90-100% in 1 year and 52-100% in 5 years. Recurrence of NAFLD (steatosis) was described in 15-100% and NASH, in 4-71%. NAFLD and de novo NASH were observed in 18-67% and 3-17%, respectively. Metabolic syndrome, diabetes mellitus, dyslipidemia and hypertension were seen in 45-58%, 18-59%, 25-66% and 52-82%, respectively. CONCLUSION After liver transplants, patients present a high prevalence of recurrent and de novo NASH. They also show a high frequence of metabolic disorders. Nevertheless, these alterations seem not to influence patient survival.
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Affiliation(s)
| | - Helma P Cotrim
- Medicine and Health Graduate Program, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | | | - Carolina G Almeida
- Medicine and Health Graduate Program, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Ney Christian Amaral Boa Sorte
- Medicine and Health Graduate Program, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
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Peláez-Jaramillo MJ, Cárdenas-Mojica AA, Gaete PV, Mendivil CO. Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment. Diabetes Ther 2018; 9:521-543. [PMID: 29411291 PMCID: PMC6104273 DOI: 10.1007/s13300-018-0374-8] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Indexed: 02/08/2023] Open
Abstract
Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.
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Affiliation(s)
| | | | - Paula V Gaete
- Universidad de los Andes School of Medicine, Bogotá, Colombia
| | - Carlos O Mendivil
- Universidad de los Andes School of Medicine, Bogotá, Colombia.
- Endocrinology Section, Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
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Fabrizi F, Messa P, Martin P, Takkouche B. Hepatitis C Virus Infection and Post-Transplant Diabetes Mellitus among Renal Transplant Patients: A Meta-Analysis. Int J Artif Organs 2018; 31:675-82. [DOI: 10.1177/039139880803100801] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Objective To examine the association between HCV infection and the occurrence of post-transplant diabetes mellitus (PTDM) among renal transplant patients. Design Meta-analysis of observational studies. Data Sources We retrieved studies published in any language by systematically searching Medline, and Embase and by manually examining the references of the original articles, reviews, and monographs retrieved. Review Methods We included cohort and case-control studies reporting relative risk estimates and 95% confidence intervals (CIs) for PTDM occurrence with HCV after renal transplantation. Thirteen studies providing information on a total of 30,099 unique patients were included in our meta-analysis. Results Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates. The pooled relative risk (RR) for PTDM after RT was 2.73 with a 95% confidence interval (CI) of 1.94; 3.83 (10 studies). In a stratified analysis including only large studies (2 studies), the pooled RR was 1.36 (95% CI, 1.21; 1.54). Egger's regression test showed some evidence of publication bias (p=0.0001), but our sensitivity analysis showed that this issue did not meaningfully change the results. Conclusions Our study shows a marked increase of the risk of post-transplant diabetes mellitus in anti-hepatitis C virus-positive renal transplant recipients. The excess risk of death in hepatitis C virus-positive renal transplant recipients may be at least partially attributed to post-transplant diabetes mellitus with its attendant complications.
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Affiliation(s)
- F. Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milan - Italy
| | - P. Messa
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milan - Italy
| | - P. Martin
- Division of Liver Diseases, Mount Sinai School of Medicine, New York City, NY - USA
| | - B. Takkouche
- Department of Preventive Medicine, University School of Medicine, Santiago de Compostela - Spain
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Cen C, Fang HX, Yu SF, Liu JM, Liu YX, Zhou L, Yu J, Zheng SS. Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation. Hepatobiliary Pancreat Dis Int 2017; 16:602-609. [PMID: 29291779 DOI: 10.1016/s1499-3872(17)60069-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Accepted: 08/07/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation (LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients. METHODS A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom MassARRAY. Modified clinical models in predicting NODAT were established and evaluated. RESULTS The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients (56% vs 39%, P=0.014). Dominant model (GG vs GT+TT, P=0.030) and recessive model (GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age (OR=1.048, P=0.004), BMI (OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT (OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT (AUROC=0.743, P<0.001). CONCLUSION ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.
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Affiliation(s)
- Chao Cen
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hai-Xing Fang
- Department of Hepatobiliary Surgery, the First People's Hospital of Fuyang, Hangzhou 311400, China
| | - Song-Feng Yu
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Ji-Min Liu
- Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton CAN L8N 3Z5, Canada
| | - Yuan-Xing Liu
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jun Yu
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Zhang T, Liu Y, Hu Y, Zhang X, Zhong L, Fan J, Peng Z. Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset diabetes mellitus after liver transplantation in a Chinese population. Gene 2017; 627:428-433. [PMID: 28689037 DOI: 10.1016/j.gene.2017.06.060] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Revised: 06/28/2017] [Accepted: 06/30/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUNDS & AIMS New-onset diabetes mellitus (NODM) is a common complication after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphism has been reported to be associated with type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the association of donor and recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences of NODM after LT. METHODS A total of 126 liver transplant patients were enrolled in the study. One single nucleotide polymorphism, SUMO4 rs237025, was genotyped in both donors and recipients. RESULTS Both donor and recipient SUMO4 rs237025 polymorphisms were found to be significantly associated with NODM after LT. In multivariate analysis, recipient age>50 years, tacrolimus trough concentrations>10ng/mL at 1month after LT, donor and recipient rs237025 genetic variant, and the combined donor and recipient rs237025 genetic variant were independent predictive factors of NODM. Area under the receiver operating characteristic curve (AUROC) analysis indicated the higher predictive ability of the model containing combined donor and recipient rs237025 polymorphisms than the clinical model (p=0.046). Furthermore, Kaplan-Meier survival analysis demonstrated that NODM was related to significantly poorer patient survival in comparison with non-NODM patients (p=0.041). CONCLUSIONS Both donor and recipient SUMO4 rs237025 polymorphisms contribute to the development of NODM after LT and NODM is a frequent complication that negatively affects patient survival.
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Affiliation(s)
- Tao Zhang
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuan Liu
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yibo Hu
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xiaoqing Zhang
- Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lin Zhong
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Junwei Fan
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Zhihai Peng
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
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Lin M, Pappas SC. Diabetes, Cirrhosis, and Liver Transplantation. MANAGING GASTROINTESTINAL COMPLICATIONS OF DIABETES 2017:107-115. [DOI: 10.1007/978-3-319-48662-8_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Katsura E, Ichikawa T, Taura N, Miyaaki H, Miuma S, Shibata H, Honda T, Hidaka M, Soyama A, Takeshima F, Eguchi S, Nakao K. Elevated Fasting Plasma Glucose before Liver Transplantation is Associated with Lower Post-Transplant Survival. Med Sci Monit 2016; 22:4707-4715. [PMID: 27909287 PMCID: PMC5138067 DOI: 10.12659/msm.897925] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background The risk of liver cirrhosis is higher among individuals with diabetes mellitus, and a cirrhotic patient with diabetes may have a poorer prognosis after liver transplantation compared to a patient without diabetes. Thus, we evaluated whether fasting plasma glucose prior to receiving a liver transplant was a prognostic factor for post-transplant survival. Material/Methods Ninety-one patients received a living donor liver transplant between November 2005 and December 2012. Patients were considered diabetic if they were prescribed diabetes medications or had impaired glucose tolerance as measured by an oral glucose tolerance test. Each patient was monitored through December 31, 2013, to evaluate prognosis. Results Fasting plasma glucose of at least 100 mg/dL significantly decreased survival following transplant (52% in the high FPG group compared to 78% in the control group, p=0.04), while postprandial hyperglycemia had no effect on survival. Additionally, overall mortality and the incidence of vascular disease were significantly higher among patients with uncontrolled plasma glucose. Impaired fasting plasma glucose was significantly and inversely associated with overall survival in the univariate and multivariate analyses, while creatinine (at least 1 mg/dL) was inversely associated with survival in the univariate analysis. Conclusions Elevated fasting plasma glucose prior to liver transplantation was inversely associated with post-transplant survival. This effect may be due to underlying microangiopathy as a result of uncontrolled diabetes before transplantation. Our data demonstrated the importance of controlled blood glucose prior to liver transplantation.
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Affiliation(s)
- Emi Katsura
- Department of Gastroenterology and Hepatology, Graduate School of
Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Tatsuki Ichikawa
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Nagasaki, Japan
| | - Naota Taura
- Department of Gastroenterology and Hepatology, Graduate School of
Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Graduate School of
Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Graduate School of
Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Hidetaka Shibata
- Department of Gastroenterology and Hepatology, Graduate School of
Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Takuya Honda
- Department of Gastroenterology and Hepatology, Graduate School of
Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Akihiko Soyama
- Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Fuminao Takeshima
- Department of Gastroenterology and Hepatology, Graduate School of
Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Graduate School of
Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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Lonardo A, Ballestri S, Guaraldi G, Nascimbeni F, Romagnoli D, Zona S, Targher G. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - Evidence from three different disease models: NAFLD, HCV and HIV. World J Gastroenterol 2016; 22:9674-9693. [PMID: 27956792 PMCID: PMC5124973 DOI: 10.3748/wjg.v22.i44.9674] [Citation(s) in RCA: 99] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 09/29/2016] [Accepted: 10/30/2016] [Indexed: 02/06/2023] Open
Abstract
Fatty liver, which frequently coexists with necro-inflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease (NAFLD) and chronic infections due to either hepatitis C virus (HCV) or human immunodeficiency virus (HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease (CVD) and type 2 diabetes (T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.
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Yagi S, Kaido T, Iida T, Yoshizawa A, Okajima H, Uemoto S. New-onset diabetes mellitus after living-donor liver transplantation: association with graft synthetic function. Surg Today 2016; 47:733-742. [PMID: 27837276 DOI: 10.1007/s00595-016-1444-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 09/20/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND PURPOSE It is now known that post-transplant graft function after deceased-donor liver transplantation and living-donor liver transplantation (LDLT) differ; however, there is no report assessing the relationship between graft function and the development of new-onset diabetes mellitus after transplantation (NODAT). We conducted this study to identify the predictive risk factors for NODAT, including graft function after LDLT. METHODS The subjects of this study were 175 adult recipients who underwent LDLT at Kyoto University Hospital between 2006 and 2010, and survived for more than 3 months (median observation period, 1046 days). RESULTS The 1-, 2-, and 3-year incidences of NODAT after LDLT were 26.1, 32.0, and 33.4%, respectively. Pre-transplant diabetes was associated with poor survival (p = 0.0048), whereas NODAT was not associated with patient survival. In the multivariate analysis, recipient age ≥40, a tacrolimus trough level ≥8 ng/mL 3 months after LDLT, and cholinesterase (ChE) <185 IU/L 3 months after LDLT were the independent risk factors for NODAT. CONCLUSIONS Poor graft synthetic function 3 months after LDLT as well as older age of the recipient and a higher tacrolimus concentration were strongly associated with NODAT development after LDLT.
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Affiliation(s)
- Shintaro Yagi
- Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Toshimi Kaido
- Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Taku Iida
- Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Atsushi Yoshizawa
- Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hideaki Okajima
- Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Shinji Uemoto
- Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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Systematic Review and Meta-Analysis of Tacrolimus versus Ciclosporin as Primary Immunosuppression After Liver Transplant. PLoS One 2016; 11:e0160421. [PMID: 27812112 PMCID: PMC5094765 DOI: 10.1371/journal.pone.0160421] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Accepted: 07/19/2016] [Indexed: 01/24/2023] Open
Abstract
Background and Aims Several meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials, but most captured data from randomized controlled trials (RCTs) predating recent improvements in waiting list prioritization, induction protocols and concomitant medications. The present study comprised a systematic review and meta-analysis of ciclosporin and tacrolimus in liver transplant recipients using studies published since January 2000. Methods Searches of PubMed, the Cochrane Library and EMBASE identified RCTs of tacrolimus and ciclosporin as the immunosuppressant in adult primary liver transplant recipients, published between January 2000 and August 6, 2014. A random effects meta-analysis was conducted to evaluate the relative risk of death, graft loss, acute rejection (AR), new-onset diabetes after transplantation (NODAT) and hypertension with tacrolimus relative to ciclosporin at 12 months. Results The literature search identified 11 RCTs comparing ciclosporin with tacrolimus. Relative to ciclosporin, tacrolimus was associated with significantly improved outcomes in terms of patient mortality (risk ratio [RR] with ciclosporin of 1.26; 95% confidence interval [95%CI] 1.01–1.58). Tacrolimus was superior to ciclosporin in terms of hypertension (RR with ciclosporin 1.26; 95%CI 1.07–1.47), but inferior in terms of NODAT (RR with ciclosporin 0.60; 95%CI 0.47–0.77). There were no significant differences between ciclosporin and tacrolimus in terms of graft loss or AR. Conclusions Meta-analysis of RCTs published since 2000 showed tacrolimus to be superior to ciclosporin in terms of patient mortality and hypertension, while ciclosporin was superior in terms of NODAT. No significant differences were identified in terms of graft loss or AR. These findings provide further evidence supporting the use of tacrolimus as the cornerstone of immunosuppressive therapy in liver transplant recipients.
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Pisano G, Fracanzani AL, Caccamo L, Donato MF, Fargion S. Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study. World J Gastroenterol 2016; 22:8869-8882. [PMID: 27833378 PMCID: PMC5083792 DOI: 10.3748/wjg.v22.i40.8869] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/27/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation (OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk (i.e., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT (i.e., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage, which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT.
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Han E, Kim MS, Kim YS, Kang ES. Risk assessment and management of post-transplant diabetes mellitus. Metabolism 2016; 65:1559-69. [PMID: 27621191 DOI: 10.1016/j.metabol.2016.07.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 07/13/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023]
Abstract
The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function.
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Affiliation(s)
- Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center
| | - Myoung Soo Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Yu Seun Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center; Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Liu FC, Lin JR, Chen HP, Tsai YF, Yu HP. Prevalence, predictive factors, and survival outcome of new-onset diabetes after liver transplantation: A population-based cohort study. Medicine (Baltimore) 2016; 95:e3829. [PMID: 27336869 PMCID: PMC4998307 DOI: 10.1097/md.0000000000003829] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
The aim of the present nationwide population-based cohort study was to explore the prevalence, risk factors, and survival outcome of new-onset diabetes (NOD) in recipients after liver transplantation.The National Health Insurance Research Database of Taiwan was searched for ICD-9-codes, 2248 patients who had received liver transplant without pretransplant diabetes from July 1, 1998 to December 31, 2012 were included in the study. The preoperative risks factors were considered and analyzed using logistic regression analysis, following adjustments for age and sex. All patients were followed up until the end of the study or death.The final dataset included 189 patients with NOD and 2059 without diabetes after liver transplantation. The prevalence of NOD was 8.4% and in 64% NOD appeared in the first year after liver transplantation. Preoperative clinical events, alcoholic liver cirrhosis, and hepatic encephalopathy were the most important risk factors for NOD after liver transplantation. The mortality rate was lower in NOD recipients than in non-NOD recipients within 5 years.In this study, we provide evidence that NOD recipients had better 5-year survival outcomes in this clinical population. The most important identifiable predictive factors for NOD after liver transplantation were alcoholic hepatitis, ascites, hepatic coma, and esophageal varices.
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Affiliation(s)
- Fu-Chao Liu
- Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jr-Rung Lin
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Clinical Informatics and Medical Statistics Research Center and Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsiu-Pin Chen
- Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yung-Fong Tsai
- Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Huang-Ping Yu
- Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Kahn A, Reynolds JA, Chakkera HA, Aqel BA, Byrne TJ, Douglas DD, Moss AA, Vargas HE, Carey EJ. Prospective Analysis of Metabolic Parameters in the Detection of Diabetes and Metabolic Syndrome in Liver Transplant Recipients. Metab Syndr Relat Disord 2016; 14:305-10. [PMID: 27164306 DOI: 10.1089/met.2015.0162] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Liver transplant recipients are at increased risk of metabolic complications, including new-onset diabetes mellitus after transplantation (NODAT) and post-transplant metabolic syndrome (PTMS), both of which are associated with decreased patient survival. We prospectively monitored traditional and novel metabolic parameters in nondiabetic liver transplantation (LT) candidates to determine their role in detecting these conditions. METHODS Nondiabetic adults undergoing initial LT were prospectively identified. NODAT and PTMS were defined according to WHO and ATP III criteria. Metabolic measures were collected at pre-LT, 4, and 12 months post-LT. RESULTS Of 49 subjects enrolled, 24.5% were found to be diabetic pre-LT by 2-hr oral glucose tolerance test (OGTT) despite fasting glucose below the diabetic range. Two patients developed NODAT post-LT. A single patient was found to have MS at baseline, while PTMS developed in 26% and 31.3% of patients at 4 and 12 months. Novel metabolic markers did not detect these conditions. CONCLUSIONS Screening OGTT detected pre-LT diabetes in patients with normal fasting glucose. Serial measurement of metabolic parameters allowed earlier detection of PTMS. Novel metabolic parameters did not correspond to post-LT outcomes, but provided a baseline for future study. More frequent and intensive metabolic monitoring appears reasonable, but larger studies are needed to clarify its efficacy.
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Affiliation(s)
- Allon Kahn
- 1 Department of Medicine, Mayo Clinic , Phoenix, Arizona
| | - Justin A Reynolds
- 2 Center for Liver and Hepatobiliary Disease, St. Joseph's Hospital and Medical Center , Phoenix, Arizona
| | | | - Bashar A Aqel
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| | - Thomas J Byrne
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| | - David D Douglas
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| | - Adyr A Moss
- 5 Division of Transplant Surgery, Mayo Clinic , Phoenix, Arizona
| | - Hugo E Vargas
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| | - Elizabeth J Carey
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
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Linder KE, Baker WL, Rochon C, May ST, Sheiner PA, Martin ST. Evaluation of Posttransplantation Diabetes Mellitus After Liver Transplantation: Assessment of Insulin Administration as a Risk Factor. Ann Pharmacother 2016; 50:369-75. [PMID: 26847860 DOI: 10.1177/1060028015627662] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Impaired glucose regulation posttransplantation can affect allograft survival and may lead to the development of posttransplant diabetes mellitus (PTDM). OBJECTIVES The primary purpose of this study is to assess the difference in insulin burden between liver transplant patients who develop PTDM and patients who do not. METHODS This was a single-center, retrospective study. Adult liver transplant recipients transplanted between January 1, 2005, and August 1, 2013, were included. PTDM was defined as: (1) use of an oral antihyperglycemic agent for ≥30 consecutive days after transplant, (2) use of insulin ≥30 consecutive days after transplant, or (3) hemoglobin A1C≥6.5 any time after transplant. RESULTS Of the 114 patients included, 48 (42%) developed PTDM. The average 24-hour insulin requirement on the medical floors was 17.2 ± 14.5 units in the PTDM group and 11.3 ± 12.2 units in the PTDM-free group;P= 0.02. The average blood glucose level on the medical floor was 184.7 ± 31.5 mg/dL in the PTDM group and 169.3 ± 31.4 mg/dL in the PTDM-free group;P= 0.013. Multivariate analysis revealed that experiencing rejection was positively associated with the development of PTDM: adjusted odds ratio (AOR) = 3.237; 95% CI = 1.214-8.633. Basiliximab was negatively associated with the development of PTDM: AOR = 0.182; 95% CI = 0.040-0.836. CONCLUSION Univariate analyses suggest that insulin burden is a positive risk factor for the development of PTDM; this association is lost in multivariate analyses. Rejection was a positive predictor, and use of basiliximab was a negative predictor for the development of PTDM.
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Affiliation(s)
| | - William L Baker
- University of Connecticut School of Pharmacy, Storrs and Farmington, CT, USA
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Shivaswamy V, Boerner B, Larsen J. Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes. Endocr Rev 2016; 37:37-61. [PMID: 26650437 PMCID: PMC4740345 DOI: 10.1210/er.2015-1084] [Citation(s) in RCA: 215] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM.
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Affiliation(s)
- Vijay Shivaswamy
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Brian Boerner
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Jennifer Larsen
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
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Li Z, Sun F, Hu Z, Xiang J, Zhou J, Yan S, Wu J, Zhou L, Zheng S. New-Onset Diabetes Mellitus in Liver Transplant Recipients With Hepatitis C: Analysis of the National Database. Transplant Proc 2016; 48:138-144. [PMID: 26915859 DOI: 10.1016/j.transproceed.2015.11.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 11/04/2015] [Accepted: 11/18/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND New-onset diabetes mellitus (NODM) after liver transplantation (LT) occurs with increased frequency in recipients with hepatitis C virus (HCV). We compared the incidence and risk factors for NODM in HCV vs non-HCV recipients. METHODS Among 24,956 liver recipients, 18,741 without pretransplantation diabetes were identified. NODM-free survival was analyzed using Kaplan-Meier and log-rank tests, and risk factors for NODM were examined using multivariate Cox regression analysis. RESULTS The overall incidence of NODM was 13.0% at 1 year after LT. At 1, 2, 3, and 5 years after LT, incidence of NODM in HCV recipients was 14.4%, 4.3%, 3.1%, and 3.5%, respectively, compared with 11.9%, 3.5%, 3.2%, and 6.4%, respectively, in non-HCV recipients. HCV recipients had a higher risk of NODM than non-HCV recipients (hazard ratio 1.17 [1.09-1.27], P < .001). Predictors of NODM in HCV recipients were age, body mass index (BMI), tacrolimus and steroid usage at discharge, acute rejection episode, and donor with diabetes mellitus. Risk factors in non-HCV recipients were male recipient, BMI, and recipients with nonalcoholic steatohepatitis diagnosis. CONCLUSIONS HCV recipients have a higher incidence and more risk factors for NODM than non-HCV recipients. Early identification of modifiable risk factors will assist clinical interventions to prevent NODM complications after LT.
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Affiliation(s)
- Z Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - F Sun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Z Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - J Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - J Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - S Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - J Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - L Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - S Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
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Boloori A, Saghafian S, Chakkera HA, Cook CB. Characterization of Remitting and Relapsing Hyperglycemia in Post-Renal-Transplant Recipients. PLoS One 2015; 10:e0142363. [PMID: 26551468 PMCID: PMC4638338 DOI: 10.1371/journal.pone.0142363] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Accepted: 10/21/2015] [Indexed: 01/08/2023] Open
Abstract
Background Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM). Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT). Objective To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications). Methods We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1) immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid), (2) demographic and medical-related risk factors, and (3) inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1) a time-dependent model to analyze the recurrent cases of hyperglycemia and (2) a time-independent model to analyze the first incidence of hyperglycemia. Results Age (P = 0.018), HDL cholesterol (P = 0.010), and the average trough level of tacrolimus (P<0.0001) are significant risk factors associated with the first incidence of hyperglycemia, while age (P<0.0001), non-White race (P = 0.002), BMI (P = 0.002), HDL cholesterol (P = 0.003), uric acid (P = 0.012), and using steroid (P = 0.007) are the significant risk factors for the recurrent cases of hyperglycemia. Discussion This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one) with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature.
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Affiliation(s)
- Alireza Boloori
- Department of Industrial Engineering, School of Computing, Informatics and Decision Systems Engineering, Arizona State University, Tempe, Arizona, United States of America
| | - Soroush Saghafian
- Harvard Kennedy School, Harvard University, Cambridge, Massachusetts, United States of America
- * E-mail:
| | - Harini A. Chakkera
- Division of Nephrology and Transplantation, Mayo Clinic School of Medicine, Scottsdale, Arizona, United States of America
| | - Curtiss B. Cook
- Division of Endocrinology, Mayo Clinic School of Medicine, Scottsdale, Arizona, United States of America
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Lv C, Zhang Y, Chen X, Huang X, Xue M, Sun Q, Wang T, Liang J, He S, Gao J, Zhou J, Yu M, Fan J, Gao X. New-onset diabetes after liver transplantation and its impact on complications and patient survival. J Diabetes 2015; 7:881-90. [PMID: 25676209 DOI: 10.1111/1753-0407.12275] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Revised: 01/13/2015] [Accepted: 01/27/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of the present study was to investigate the incidence and risk factors of new-onset diabetes after transplantation (NODAT) in liver transplant recipients and the influence of NODAT on complications and long-term patient survival. METHODS We examined 438 patients who underwent liver transplantation between April 2001 and December 2008 and were not diabetic before transplantation. RESULTS The mean (± SD) follow-up duration was 2.46 ± 1.62 years. The incidence of NODAT 3, 6, 9, 12, 36, and 60 months after transplantation was 44.24%, 25.59%, 23.08%, 25.17%, 17.86%, and 18.18%, respectively. Multifactor analysis indicated that preoperative fasting plasma glucose (FPG) levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an interleukin-2 receptor (IL-2R) antagonist reduced the risk of NODAT. Compared with the no NODAT group (N-NODAT), the NODAT group had a higher rate of sepsis and chronic renal insufficiency. Mean survival was significantly longer in the N-NODAT than NODAT group. Cox regression analysis showed that pre- and/or postoperative FPG levels, tumor recurrence or metastasis, and renal insufficiency after liver transplantation were independent risk factors of mortality. Pulmonary infection or multisystem failure were specific causes of death in the NODAT group, whereas patients in both groups died primarily from tumor relapse or metastasis. CONCLUSIONS Preoperative FPG levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an IL-2R antagonist reduced the risk of NODAT. Patients with NODAT had reduced survival and an increased incidence of sepsis and chronic renal insufficiency. Significant causes of death in the NODAT group were pulmonary infection and multisystem failure.
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Affiliation(s)
- Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
- Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Shunmei He
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
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Tam N, Zhang C, Lin J, Wu C, Deng R, Liao B, Hu S, Wang D, Zhu X, Wu L, He X. Simultaneous pancreas and kidney transplantation for liver transplant recipients with diabetes and uremia. Clin Res Hepatol Gastroenterol 2015; 39:399-404. [PMID: 25457347 DOI: 10.1016/j.clinre.2014.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Revised: 10/07/2014] [Accepted: 10/09/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVES Chronic kidney disease (CKD) has become a critical problem due to immunosuppressant related nephrotoxicity in liver transplant (LTx) recipients, especially in patients with pre-transplant risk factors. LTx recipients with uraemia and diabetes have poor prognosis even when treated with dialysis and insulin. Simultaneous pancreas and kidney transplantation (SPK) has been proven to be an effective treatment for patients with diabetic uraemia, but rarely performed in patients after LTx. Two cases of SPK after LTx were performed in our centre and we present our experience here. PATIENTS AND METHODS Two patients received LTx because of HBV related liver cirrhosis; both of them had pre-transplant diabetes mellitus (DM), which worsened after the administration of immunosuppressive drugs. These two patients suffered from CKD and developed uraemia due to diabetic nephropathy and immunosuppressive drugs induced renal toxicity years after LTx. They relied on dialysis and insulin injection. SPK were performed years after LTx and the clinical data was retrospectively analyzed. RESULTS SPK was successfully performed in these two patients. Pancreatic fluid drainage was achieved via a side-to-side duodenojejunostomy into the proximal jejunum. No serious surgical complications, including pancreatitis or pancreatic fistula were observed postoperatively. In both cases, kidney and pancreatic grafts were functioning well as evidenced by euglycemia without the need for insulin injections and normal serum-creatinine level 7days after the operation. One of the patients presented with renal graft impairment 1week after the operation. FK506 was tapered and rapamycin was used when the renal graft biopsy indicated drug toxicity. The patient's kidney graft function recovered gradually after the adjustment. Both patients have good function of liver, kidney and pancreas grafts during a 60-month and 30-month period of follow up. CONCLUSIONS SPK could serve as an effective option for patients with diabetes and uremia after LTx. Perioperative management, especially the immunosuppressive strategy is crucial to improve the outcome of this procedure.
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Affiliation(s)
- Ngalei Tam
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Hepatobiliary surgery department, the University of Hong Kong, Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Chuanzhao Zhang
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jianwei Lin
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Chenglin Wu
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ronghai Deng
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Bing Liao
- Pathology Department, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shuiqing Hu
- Department of Clinical Laboratories, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Dongping Wang
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xiaofeng Zhu
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Linwei Wu
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
| | - Xiaoshun He
- Organ Transplantation Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
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Li DW, Lu TF, Hua XW, Dai HJ, Cui XL, Zhang JJ, Xia Q. Risk factors for new onset diabetes mellitus after liver transplantation: A meta-analysis. World J Gastroenterol 2015; 21:6329-6340. [PMID: 26034369 PMCID: PMC4445111 DOI: 10.3748/wjg.v21.i20.6329] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Revised: 10/16/2014] [Accepted: 12/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the risk factors for new-onset diabetes mellitus (NODM) after liver transplantation by conducting a systematic review and meta-analysis.
METHODS: We electronically searched the databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to December 2013 to identify relevant studies reporting risk factors for NODM after liver transplantation. Two authors independently assessed the trials for inclusion and extracted the data. Discrepancies were resolved in consultation with a third reviewer. All statistical analyses were performed with the RevMan5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated using either a fixed effects or a random effects model, based on the presence (I2 < 50%) or absence (I2 > 50%) of significant heterogeneity.
RESULTS: Twenty studies with 4580 patients were included in the meta-analysis, all of which were retrospective. The meta-analysis identified the following significant risk factors: hepatitis C virus (HCV) infection (OR = 2.68; 95%CI: 1.92-3.72); a family history of diabetes (OR = 1.69, 95%CI: 1.09-2.63, P < 0.00001); male gender (OR = 1.53; 95%CI: 1.24-1.90; P < 0.0001); impaired fasting glucose (IFG; OR = 3.27; 95%CI: 1.84-5.81; P < 0.0001); a family history of diabetes (OR = 1.69; 95%CI: 1.09-2.63; P = 0.02); use of tacrolimus (OR = 1.34; 95%CI: 1.03-1.76; P = 0.03) and body mass index (BMI)(WMD = 1.19, 95%CI: 0.69-1.68, P < 0.00001). Other factors, such as hepatitis B virus infection and alcoholism, were not found to be associated with the incidence of NODM.
CONCLUSION: The study showed that HCV infection, IFG, a family history of diabetes, male gender, tacrolimus and BMI are risk factors for NODM after liver transplantation.
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Guillaud O, Boillot O, Sebbag L, Walter T, Bouffard Y, Dumortier J. Cardiovascular risk 10 years after liver transplant. EXP CLIN TRANSPLANT 2015; 12:55-61. [PMID: 24471725 DOI: 10.6002/ect.2013.0208] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVES We sought to evaluate the frequency of cardiovascular risk factors in a cohort of patients 10 years after a liver transplant, and to assess their 10-year risk of fatal cardiovascular disease using Systematic COronary Risk Evaluation (SCORE) charts. MATERIALS AND METHODS Between January 1990 and June 1996, one hundred eighty-nine adults underwent a first liver transplant in our center. Fifty-nine patients (31%) died before reaching their tenth year, and 115 patients were available with complete clinical data at 10 years. RESULTS The main indications for liver transplant were alcoholic (38%) and viral cirrhosis (40%). The median age of patients was 56 (range, 29-73 y), 80% were men, 23% were obese, 16% were active smokers, 18% were diabetic, 40% had hypercholesterolemia, and 77% had hypertension. Before the tenth year after transplant, 6 deaths were because of cardiovascular diseases, which represents the third cause of late death (> 1 year after liver transplant). After liver transplant, 5% of the surviving patients underwent ischemic cardiovascular events during the first decade. At a 10-year assessment, the median estimated 10-year risk of fatal cardiovascular disease was 1% (range, 0%-9%) and 10% of the patients had a high risk (ie, SCORE ≥ 5%). CONCLUSIONS Our results suggest that the frequency of cardiovascular events is relatively low after a liver transplant, even if most of the patients had 1 or more cardiovascular risk factors. Nevertheless, clinicians should perform a similar evaluation 15 or 20 years after the liver transplant because cardiovascular risk exponentially increases with age.
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Affiliation(s)
- Olivier Guillaud
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, Lyon
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Younossi Z, Stepanova M, Saab S, Trimble G, Mishra A, Henry L. The association of hepatitis C virus infection and post-liver transplant diabetes: data from 17 000 HCV-infected transplant recipients. Aliment Pharmacol Ther 2015; 41:209-17. [PMID: 25413020 DOI: 10.1111/apt.13027] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Revised: 09/08/2014] [Accepted: 10/23/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) is associated with metabolic manifestations including insulin resistance and diabetes through various mechanisms. Whether HCV infection is associated with an increased risk of post-transplant diabetes in liver transplant recipients is unclear. AIM To assess the association of HCV infection with post-transplant diabetes. METHODS All liver transplant recipients infected with hepatitis C (exposed) and hepatitis B (HBV) (controls) with post-transplant follow-up from the Scientific Registry of Transplant Recipients (2003-2012) were included. RESULTS A total of 17 121 HCV patients and 1450 HBV controls were included in this observational study. Subjects with HCV were more likely to be overweight and obese at transplant, but the rate of pre-transplant diabetes of 13.7% was similar to HBV (P > 0.05). Post-transplant, 32.5% of HCV patients and 27.5% of HBV patients had diabetes (P < 0.0001). This difference was observed starting as early as 6 months post-transplant: 22.5% HCV and 18.9% HBV (P = 0.0043). With longer follow-up, both the cumulative and incidental risks of developing post-transplant diabetes were consistently higher in HCV patients. In particular, by 5 years post-transplant, both the relative risk of having diabetes [1.18 (1.08-1.29), P = 0.0002] and the hazard ratio for time to developing diabetes [1.27 (1.15-1.41), P < 0.0001] were significantly higher in HCV patients compared to HBV patients. In multivariate analysis, after adjustment for confounders including the use of immunosuppressants, hepatitis C infection was independently associated with developing post-transplant diabetes: aHR = 1.55 (1.34-1.79), P < 0.0001. CONCLUSION Hepatitis C infection is associated with a higher risk of post-transplant diabetes that persists up to 5 years post-transplant.
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Affiliation(s)
- Z Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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Tripon S, Francoz C, Albuquerque A, Paradis V, Boudjema H, Voitot H, Belghiti J, Valla D, Durand F. Interactions between virus-related factors and post-transplant ascites in patients with hepatitis C and no cirrhosis: role of cryoglobulinemia. Transpl Int 2014; 28:162-9. [PMID: 25267442 DOI: 10.1111/tri.12466] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Revised: 06/02/2014] [Accepted: 09/21/2014] [Indexed: 12/11/2022]
Abstract
Refractory ascites may appear in liver transplant recipients with recurrence of hepatitis C virus infection, even in the absence of advanced fibrosis. The mechanisms are unclear. The aim was to determine whether post-transplant cryoglobulinemia could be a predisposing factor for ascites in this population. Retrospective data of 82 liver transplant recipients with HCV recurrence surviving more than 1 year were collected. Cryoglobulinemia was systematically tested after transplantation. All patients had 1-year protocol biopsy with assessment of sinusoidal distension, perisinusoidal fibrosis, and centrolobular necrosis. Additional biopsies were performed when needed. Fourteen of 82 patients (17%) developed refractory ascites. When ascites appeared, fibrosis was stage F0-F1 in 36% and F2-F3 in 57%. Factors independently associated with post-transplant ascites were pretransplant refractory ascites (P = 0.001), fibrosis ≥stage 2 at 1 year (P = 0.002), perisinusoidal fibrosis at 1 year (P = 0.02), and positive cryoglobulinemia (P = 0.02). Patients with ascites had a significantly worse prognosis compared to those without ascites. Refractory ascites may occur in liver transplant recipients with HCV recurrence in the absence of advanced fibrosis. The finding that both positive cryoglobulinemia and perisinusoidal fibrosis at 1 year were significantly associated with ascites suggests that liver microangiopathy is involved in the mechanisms of HCV-related ascites.
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Affiliation(s)
- Simona Tripon
- Hepatology and Liver Intensive Care, Hospital Beaujon, Clichy, France
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Dumortier J, Boillot O, Scoazec JY. Natural history, treatment and prevention of hepatitis C recurrence after liver transplantation: Past, present and future. World J Gastroenterol 2014; 20:11069-11079. [PMID: 25170196 PMCID: PMC4145750 DOI: 10.3748/wjg.v20.i32.11069] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 03/07/2014] [Accepted: 06/23/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV)-related liver disease, including cirrhosis and hepatocellular carcinoma is the main indication for liver transplantation (LT) worldwide. Post-transplant HCV re-infection is almost universal and results in accelerated progression from acute hepatitis to chronic hepatitis, and liver cirrhosis. Comprehension and treatment of recurrent HCV infection after LT have been major issues for all transplant hepatologists and transplant surgeons for the last decades. The aim of this paper is to review the evolution of our knowledge on the natural history of HCV recurrence after LT, including risk factors for disease progression, and antiviral therapy. We will focus our attention on possible ways (present and future) to improve the final long-term results of LT for HCV-related liver disease.
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Abstract
Advances in pharmacologic immunosuppression are responsible for the excellent outcomes experienced by recipients of liver transplants. However, long-term follow-up of these patients reveals an increasing burden of morbidity and mortality that is attributable to these drugs. The authors summarize the agents used in contemporary liver transplantation immunosuppression protocols and discuss the emerging trend within the community to minimize or eliminate these agents from use. The authors present recently published data that may provide the foundation for immunosuppression minimization or tolerance induction in the future and review studies that have focused on the utility of biomarkers in guiding immunosuppression management.
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Parvizi Z, Azarpira N, Kohan L, Darai M, Kazemi K, Parvizi MM. Association between E23K variant in KCNJ11 gene and new-onset diabetes after liver transplantation. Mol Biol Rep 2014; 41:6063-9. [PMID: 24996284 DOI: 10.1007/s11033-014-3483-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Accepted: 06/17/2014] [Indexed: 12/24/2022]
Abstract
New-onset diabetes after transplantation (NODAT) is an important complication after solid organ transplantation. NODAT is a polygenic disease and KCNJ11 E23K polymorphism is considered as a diabetes-susceptibility gene. The present study aimed to assess the association between KCNJ11 (rs5219) variants and the risk of developing NODAT after liver transplantation. This study was conducted on 120 liver transplant recipients who had received tacrolimus-based immunosuppressive drugs. The liver transplant recipients were divided into an new onset diabetes mellitus (NODM) and a non-NODM group. The NODAT group consisted of 60 patients who developed diabetes in the first 6 months after transplantation, while the non-NODAT group included 60 patients who remained euglycemic. The patients were genotyped using polymerase chain reaction-restriction fragment length polymorphism and the incidence of NODAT was compared between the two groups. Nongenetic risk factors including donor gender and cold ischemia time, and recipient (MELD score, presence of viral hepatitis, acute rejection and steroid pulse therapy) were also considered. The KCNJ11 KK variant was associated with an increased risk for NODAT with respective odds ratio of 6.03 (95 % confidence interval 2.37-15.4; P < 0.001]. Donor age and male sex, recipient age as well as fasting plasma glucose before transplantation were significantly different between NODAT and non-NODAT groups (P < 0.05). The prednisolone daily dosage was significantly higher in the NODAT group (P = 0.01). These patients received pulse of methyl prednisolone for treatment of acute rejection. This study showed that polymorphisms in KCNJ11 might predispose the patients treated by tacrolimus to development of NODAT after liver transplantation.
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Affiliation(s)
- Zahra Parvizi
- Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Zand Street, 7193711351, Shiraz, Iran
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