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1
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Zhang JH, Xie HX, Li Y, Wang KM, Song Z, Zhu KK, Fang L, Zhang J, Jiang CS. Design, synthesis and biological evaluation of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)hydrazine-1-carboxamide derivatives as α-glucosidase inhibitors. Bioorg Med Chem Lett 2021; 52:128413. [PMID: 34634473 DOI: 10.1016/j.bmcl.2021.128413] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 09/25/2021] [Accepted: 10/05/2021] [Indexed: 11/15/2022]
Abstract
In this present study, a series of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)hydrazine-1-carboxamide derivatives against α-glucosidase were designed and synthesized, and their biological activities were evaluated in vitro and in vivo. Most of the designed analogues exhibited better inhibitory activity than the marketed acarbose, especially the most potent compound 7 with an IC50 value of 9.26 ± 1.84 μM. The direct binding of 7 and 8 with α-glucosidase was confirmed by fluorescence quenching experiments, and the kinetic and molecular docking studies revealed that 7 and 8 inhibited α-glucosidase in a non-competitive manner. Cytotoxicity bioassay indicated compounds 7 and 8 were non-toxic towards LO2 and HepG2 at 100 μM. Furthermore, both compounds were demonstrated to have in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-treated rats.
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Affiliation(s)
- Jin-He Zhang
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China
| | - Hong-Xu Xie
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China
| | - Yue Li
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China
| | - Kai-Ming Wang
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China
| | - Zhiling Song
- College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
| | - Kong-Kai Zhu
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China; College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
| | - Lei Fang
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China
| | - Juan Zhang
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China
| | - Cheng-Shi Jiang
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
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2
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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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3
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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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Sherafati M, Mirzazadeh R, Barzegari E, Mohammadi-Khanaposhtani M, Azizian H, Sadegh Asgari M, Hosseini S, Zabihi E, Mojtabavi S, Ali Faramarzi M, Mahdavi M, Larijani B, Rastegar H, Hamedifar H, Hamed Hajimiri M. Quinazolinone-dihydropyrano[3,2-b]pyran hybrids as new α-glucosidase inhibitors: Design, synthesis, enzymatic inhibition, docking study and prediction of pharmacokinetic. Bioorg Chem 2021; 109:104703. [PMID: 33609917 DOI: 10.1016/j.bioorg.2021.104703] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 12/29/2020] [Accepted: 01/28/2021] [Indexed: 02/08/2023]
Abstract
A series of new quinazolinone-dihydropyrano[3,2-b]pyran derivatives 10A-L were synthesized by simple chemical reactions and were investigated for inhibitory activities against α-glucosidase and α-amylase. New synthesized compounds showed high α-glucosidase inhibition effects in comparison to the standard drug acarbose and were inactive against α-amylase. Among them, the most potent compound was compound 10L (IC50 value = 40.1 ± 0.6 µM) with inhibitory activity around 18.75-fold more than acarboase (IC50 value = 750.0 ± 12.5 µM). This compound was a competitive inhibitor into α-glucosidase. Our obtained experimental results were confirmed by docking studies. Furthermore, the cytotoxicity of the most potent compounds 10L, 10G, and 10N against normal fibroblast cells and in silico druglikeness, ADME, and toxicity prediction of these compounds were also evaluated.
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Affiliation(s)
- Maedeh Sherafati
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Ebrahim Barzegari
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Maryam Mohammadi-Khanaposhtani
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Homa Azizian
- Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
| | | | - Samanesadat Hosseini
- Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ebrahim Zabihi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Somayeh Mojtabavi
- Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Faramarzi
- Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Mahdavi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Rastegar
- Cosmetic Products Research Center, Iranian Food and Drug Administration, MOHE, Tehran, Iran
| | - Haleh Hamedifar
- CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Mir Hamed Hajimiri
- Nano Alvand Company, Avicenna Tech Park, Tehran University of Medical Sciences, Tehran, Iran.
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5
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Spiritos Z, Abdelmalek MF. Metabolic syndrome following liver transplantation in nonalcoholic steatohepatitis. Transl Gastroenterol Hepatol 2021; 6:13. [PMID: 33409407 DOI: 10.21037/tgh.2020.02.07] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 10/16/2019] [Indexed: 12/13/2022] Open
Abstract
Metabolic syndrome is a major clinical disorder involving metabolic dysregulation characterized clinically with features of central obesity, insulin resistance (IR), type 2 diabetes, hypertension, and dyslipidemia. Metabolic syndrome is strongly associated with the rising prevalence nonalcoholic steatohepatitis, a leading indication for orthotopic liver transplantation in the Western world. The presence or recurrence of metabolic syndrome following liver transplantation can contribute to the development and recurrence of nonalcoholic fatty liver disease (NAFLD) in the liver allograft. In this review, we discuss the endogenous and exogenous drivers of post-transplant metabolic syndrome, role of chronic immunosuppression, and the prevalence and clinical significant of post-transplant metabolic syndrome on nonalcoholic steatohepatitis.
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Affiliation(s)
- Zachary Spiritos
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
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6
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Prevalence of cerebrovascular diseases that can cause hemorrhagic stroke in liver transplantation recipients: a 6-year comparative study with 24,681 healthy adults. Neurol Sci 2020; 42:2753-2761. [PMID: 33125597 DOI: 10.1007/s10072-020-04863-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 10/26/2020] [Indexed: 01/20/2023]
Abstract
BACKGROUND AND PURPOSE Cerebrovascular diseases are a leading cause of mortality after liver transplantation (LT). The prevalence of potentially hemorrhagic cerebrovascular diseases (HCVDs) that could cause a hemorrhagic stroke in patients with severe liver diseases has not been reported. We aimed to analyze the underlying prevalence of HCVDs that could lead to hemorrhagic strokes in LT recipients compared with that in previously healthy controls. METHODS A retrospective study with 1,920 consecutive LT recipients and 24,681 adults who underwent a health checkup during the same period was conducted (January 2011-December 2016). The prevalence of cerebral aneurysms (CA), cerebral arteriovenous malformation (AVM), and cavernous malformation (CM) was evaluated using brain imaging, including computed tomography angiography, magnetic resonance imaging, magnetic resonance angiography, and digital subtraction angiography. RESULTS The prevalence of CA and CM were 3.1% and 0.5%, respectively, in the LT group and 3.8% and 0.4%, respectively, in the control group. According to the location of the cerebral artery, paraclinoid internal carotid artery aneurysms (odds ratio [OR] 0.440; P = 0.009) had a lower prevalence in LT recipients than in healthy controls. Anterior communicating artery (OR 3.080; P = 0.002) and superior cerebellar artery (OR 8.767; P = 0.017) aneurysms had a higher prevalence in the LT group than in the control. The prevalence of AVM was significantly higher in LT recipients (0.26%) than in healthy controls (0.06%). CONCLUSION LT recipients showed a different distribution of CA prevalence according to the locations of the cerebral artery and had a higher overall prevalence of AVM than previously healthy controls.
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7
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Lee WG, Wells CI, McCall JL, Murphy R, Plank LD. Prevalence of diabetes in liver cirrhosis: A systematic review and meta-analysis. Diabetes Metab Res Rev 2019; 35:e3157. [PMID: 30901133 DOI: 10.1002/dmrr.3157] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 03/05/2019] [Accepted: 03/19/2019] [Indexed: 12/20/2022]
Abstract
An association between diabetes mellitus (DM) and liver cirrhosis is well-known, but estimates of the prevalence of DM in patients with liver cirrhosis vary widely. A systematic review was undertaken to determine the prevalence of DM in adult patients with liver cirrhosis. The Medline, EMBASE, and Cochrane Library databases were searched for peer-reviewed studies published in English (1979-2017) that investigated the prevalence of diabetes in adult patients with cirrhosis. Pooled estimates of prevalence of DM were determined for all eligible patients and according to aetiology and severity of liver disease. Fifty-eight studies satisfied criteria for inclusion, with 9705 patients included in the pooled prevalence analysis. The overall prevalence of DM was 31%. The prevalence of DM was highest in patients with nonalcoholic fatty liver disease (56%), cryptogenic (51%), hepatitis C (32%), or alcoholic (27%) cirrhosis. For assessing prevalence of DM as a function of severity of liver disease, evaluable data were available only for hepatitis C and hepatitis B cirrhosis. DM may be more prevalent in cirrhosis than previously thought. This has implications for prognosis and treatment in these patients.
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Affiliation(s)
- Wai Gin Lee
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Cameron I Wells
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - John L McCall
- Section of Surgery, Department of Medical and Surgical Sciences, University of Otago, Dunedin, New Zealand
| | - Rinki Murphy
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
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8
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Gray M, Singh S, Zucker SD. Influence of Type 2 Diabetes Mellitus and Preoperative Hemoglobin A1c Levels on Outcomes of Liver Transplantation. Hepatol Commun 2019; 3:574-586. [PMID: 30976746 PMCID: PMC6442696 DOI: 10.1002/hep4.1323] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/30/2019] [Indexed: 12/28/2022] Open
Abstract
Liver transplant centers often establish hemoglobin A1c (HbA1C) criteria for candidates with type 2 diabetes mellitus (T2DM) based on data from other surgical specialties showing worse outcomes in patients with poor glycemic control. However, because of the reduced reliability of HbA1C in cirrhosis, it is unclear whether pretransplant HbA1C values are predictive of postoperative complications in liver recipients. We retrospectively examined the association between preoperative HbA1C and postoperative outcomes in 173 consecutive patients who underwent liver transplantation at the University of Cincinnati Medical Center between August 2012 and March 2015. Demographic correlates of pretransplant HbA1C included age, T2DM, native Model for End‐Stage Liver Disease, hemoglobin, serum albumin, and nonalcoholic steatohepatitis as the indication for transplantation. No association was identified between pretransplant HbA1C and most outcome measures, including survival, length of stay, reoperation or readmission rates, rejection, bacteremia, and viremia. Significant correlates of HbA1C in liver recipients with diabetes were posttransplant insulin requirement and anastomotic biliary stricture formation. On multivariate analysis, HbA1C was the sole determinant of biliary strictures, with patients in the highest quartile (HbA1C >7.3%) exhibiting a 4‐fold increased risk. Correlation of HbA1C with morning blood glucose levels was much tighter after versus before transplantation. Conclusion: Preoperative HbA1C is predictive of anastomotic biliary stricture formation and the need for insulin following liver transplantation.
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Affiliation(s)
- Meagan Gray
- Division of Gastroenterology and Hepatology University of Alabama at Birmingham Birmingham AL
| | - Sanjeev Singh
- Division of Digestive Diseases University of Cincinnati Medical Center Cincinnati OH
| | - Stephen D Zucker
- Division of Gastroenterology, Hepatology, and Endoscopy Brigham and Women's Hospital Boston MA
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9
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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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10
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He XS, Fu SJ, Zhao Q, Zhu XF, Wang DP, Han M, Ju WQ, Ma Y, Jiao XY, Yuan XP, Hu AB, Guo ZY. A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus. Liver Transpl 2017; 23:1161-1170. [PMID: 28422396 DOI: 10.1002/lt.24774] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2016] [Revised: 03/25/2017] [Accepted: 04/06/2017] [Indexed: 01/13/2023]
Abstract
In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.
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Affiliation(s)
- Xiao-Shun He
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Shun-Jun Fu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Qiang Zhao
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xiao-Feng Zhu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Dong-Ping Wang
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Ming Han
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Wei-Qiang Ju
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Yi Ma
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xing-Yuan Jiao
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xiao-Peng Yuan
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - An-Bin Hu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Zhi-Yong Guo
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
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11
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Abstract
OPINION STATEMENT The long-term survival in liver transplant recipients (LTRs) is currently at an historical high level stemming from improvement in perioperative care, infection control, and immunosuppression medications. However, compared to the general population, LTRs have decreased survival. Metabolic diseases like hypertension, dyslipidemia, type 2 diabetes, and obesity are key determinants of long-term mortality in LTRs. The incidence and prevalence of these metabolic comorbidities is considerably higher in LTRs and likely results from a combination of factors including exposure to chronic immunosuppression, weight gain, and recurrence of chronic liver disease after liver transplantation (LT). Although there is currently little guidance in managing these metabolic conditions post-LT, recommendations are often extrapolated from non-transplant cohorts. In the current review, we explore the relationship between metabolic syndrome and its comorbidities in LTRs.
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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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13
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Xue M, Lv C, Chen X, Liang J, Zhao C, Zhang Y, Huang X, Sun Q, Wang T, Gao J, Zhou J, Yu M, Fan J, Gao X. Donor liver steatosis: A risk factor for early new-onset diabetes after liver transplantation. J Diabetes Investig 2016; 8:181-187. [PMID: 27511316 PMCID: PMC5334314 DOI: 10.1111/jdi.12560] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 07/26/2016] [Accepted: 08/04/2016] [Indexed: 01/01/2023] Open
Abstract
AIMS/INTRODUCTION To investigate whether donor liver steatosis increases the incidence of new-onset diabetes after transplantation (NODAT) in liver transplant recipients. MATERIALS AND METHODS We retrospectively analyzed liver transplant recipients at Zhongshan Hospital, Shanghai, China, from April 2001 to December 2014. The final analysis involved 763 patients. The cumulative incidence of NODAT at 1, 3, 5 and 10 years after liver transplantation was investigated. Furthermore, according to the findings of donor liver biopsy before transplantation, patients were divided into steatotic and non-steatotic donor liver groups, and NODAT incidence was compared between these groups. Multivariate Cox regression was used to explore the risk factors for NODAT in the patients. RESULTS Of the 763 donors, 309 (40.5%) had liver steatosis. At the end of follow up, 130 (42.1%) patients in the steatotic donor liver group developed NODAT, an incidence that exceeded that in the non-steatotic donor liver group (P = 0.001). The cumulative incidence of NODAT among all patients at 1, 3, 5, and 10 years after transplantation was 33, 43, 50 and 56%, respectively. The cumulative incidences of NODAT at 1, 3, 5 and 10 years in the steatotic donor liver group were significantly higher than those in the non-steatotic donor liver group (P = 0.003). Multivariate Cox regression analyses showed that donor liver steatosis was an independent risk factor for NODAT among liver transplant recipients, after other potential risk factors were adjusted for (hazard ratio 1.774, 95% confidence interval: 1.025-3.073; P = 0.041). CONCLUSIONS Donor liver steatosis increases NODAT incidence among liver transplant recipients.
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Affiliation(s)
- Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chenhe Zhao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
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14
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Mikolasevic I, Orlic L, Hrstic I, Milic S. Metabolic syndrome and non-alcoholic fatty liver disease after liver or kidney transplantation. Hepatol Res 2016; 46:841-852. [PMID: 26713425 DOI: 10.1111/hepr.12642] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 11/05/2015] [Accepted: 12/18/2015] [Indexed: 12/12/2022]
Abstract
Transplantation is a definitive treatment option for patients with end-stage liver disease, and for some patients with acute liver failure, hepatocellular carcinoma or end-stage renal disease. Long-term post-transplantation complications have become an important medical issue, and cardiovascular diseases (CVD) are now the leading cause of mortality in liver or kidney transplant recipients. The increased prevalence of metabolic syndrome (MS) likely plays a role in the high incidence of post-transplantation CVD. MS and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), are prevalent among the general population and in pre- and post-transplantation settings. MS components are associated with recurrent or de novo NAFLD in transplant recipients, potentially influencing post-transplantation survival. Moreover, recent data reveal an important association between NAFLD and risk of incident of chronic kidney disease (CKD). Therefore, NAFLD identification could represent an additional clinical feature for improving the stratification of liver and kidney transplant recipients with regards to risks of CVD, CKD and renal allograft dysfunction. All MS components are potentially modifiable; therefore, it is crucial that hepatologists, nephrologists and primary care physicians become more engaged in managing post-transplantation metabolic complications. The present review discusses the recent clinical evidence regarding the importance of MS and its components after liver and kidney transplantation, as well as the link between MS and NAFLD after liver and kidney transplantation.
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Affiliation(s)
| | - Lidija Orlic
- Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia
| | - Irena Hrstic
- General Hospital Pula, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Sandra Milic
- Departments of Gastroenterology, UHC Rijeka, Rijeka, Croatia
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15
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Xue M, Lv C, Chen X, Huang X, Sun Q, Wang T, Liang J, Zhang Y, He S, Gao J, Zhou J, Yu M, Fan J, Gao X. Effect of interleukin-2 receptor antagonists on new-onset diabetes after liver transplantation: A retrospective cohort study. J Diabetes 2016; 8:579-87. [PMID: 26588180 DOI: 10.1111/1753-0407.12356] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2015] [Revised: 09/28/2015] [Accepted: 11/10/2015] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND The aim of the present retrospective observational study was to examine the effect of interleukin-2 receptor antagonists (IL-2Ra) on new-onset diabetes after transplantation (NODAT) in liver transplant recipients. METHODS Pre- and postoperative clinical data of 781 patients undergoing liver transplantation between April 2001 and December 2014 at Zhongshan Hospital, Fudan University, were analyzed. Patients were divided into two groups depending on the use of IL-2Ra (IL-2Ra and non-IL-2Ra). The cumulative incidence of NODAT was compared between the IL-2Ra and non-IL-2Ra groups and the effect of IL-2Ra on the incidence of NODAT in liver transplant recipients was evaluated. RESULTS Of the 781 patients in the study, 451 received IL-2Ra. During follow-up, 138 (41.8%) and 137 (30.4%) patients in the non-IL-2Ra and IL-2Ra groups, respectively, developed NODAT (P = 0.001). The cumulative incidence of NODAT at 1, 3, 5, and 8 years after transplantation in the IL-2Ra group was 30%, 38%, 45%, and 54%, respectively; these values were substantially lower than corresponding values for the non-IL-2Ra group (P < 0.05). Cox regression analyses showed that IL-2Ra was a protective factor against NODAT development (odds ratio 0.685; 95% confidence interval 0.473-0.991; P = 0.044). This was independent of age, sex, donor type, hepatitis virus infection, body mass index, history of hypertension, preoperative liver function, preoperative fasting plasma glucose, total cholesterol, and total triglyceride levels, severity of liver cirrhosis, acute rejection, initial immunosuppressant regimen type, and postoperative immunosuppressant levels. CONCLUSION In conclusion, IL-2Ra reduces the risk of NODAT in liver transplant recipients.
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Affiliation(s)
- Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Chaoyang Lv
- 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
| | - 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
| | - Yao Zhang
- 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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16
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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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17
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Affiliation(s)
- Gautam Das
- Prince Charles Hospital, Cwm Taf University Health Board; Merthyr Tydfil UK
| | - Hemanth Bolusani
- University Hospital of Wales, Cardiff and Vale University Health Board; Cardiff UK
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18
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Lai HM, Pawar R, Wolf DC, Aronow WS. Impact of Cardiovascular Risk Factors on Long-Term Mortality After Liver Transplantation. Am J Ther 2016; 23:e357-e362. [PMID: 24897624 DOI: 10.1097/mjt.0b013e31829c4c5f] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Immunosuppression with calcineurin inhibitors has contributed to an increased prevalence of hypertension, diabetes, and hypercholesterolemia in patients receiving liver transplantation. This study evaluated the prevalence of cardiovascular risk factors, their management, and long-term mortality after liver transplantation. Medical records were reviewed in 333 adult patients who underwent orthotopic liver transplantation. Data were collected on medical diagnoses before and after transplantation, medication use, and on long-term mortality. The 333 patients in the study included 223 men and 110 women, mean age 59 ± 10 years. The mean follow-up was 50 ± 28 months. After transplantation, there was a high prevalence of hypertension (67%), hypercholesterolemia (46%), diabetes mellitus (42%), and chronic kidney disease (45%). Out of 333 patients in the study, 96 patients (29%) died during follow-up. Stepwise logistic regression was performed to identify the risk factors that might influence long-term mortality outcomes. Based on pretransplant characteristics, positive independent risk factors that increased mortality were age at transplant and hepatitis C. After transplantation, positive predictive factors were diabetes mellitus and cancer. A negative predictive risk factor for mortality was hypercholesterolemia. Analysis of medication after transplantation showed that positive predictive factors were the use of insulin, steroids, and antibiotics. Negative predictors for mortality were tacrolimus and mycophenolate. Our data suggest that diabetes mellitus and hepatitis C play an important role in worsening posttransplant mortality.
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Affiliation(s)
- Hoang M Lai
- 1Division of Cardiology, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY; and 2Division of Gastroenterology and Hepatobiliary Disease, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY
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19
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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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20
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Hara Y, Kawagishi N, Nakanishi W, Tokodai K, Nakanishi C, Miyagi S, Ohuchi N. Prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus before and after adult living donor liver transplantation. Hepatol Res 2015; 45:764-70. [PMID: 25196899 DOI: 10.1111/hepr.12418] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 08/30/2014] [Accepted: 09/02/2014] [Indexed: 02/08/2023]
Abstract
AIM The development of metabolic abnormalities after liver transplantation (LTx) contributes to cardiovascular events and mortality. We analyzed the prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus (DM) after adult living donor liver transplantation. METHODS Fifty-four adult recipients with a minimum follow up of 6 months receiving living donor liver transplantation between 2001 and 2012 at the Tohoku University Hospital were retrospectively analyzed. RESULTS The prevalence of hypertension increased from 18.5% before transplantation to 35.2% post-transplantation, and new-onset hypertension after transplantation was 57.9% of post-transplant hypertension. Univariate analysis showed that risk factors of post-transplant hypertension were age (>50 years, P = 0.0023), pretransplant body mass index (BMI) of 25 or more (P = 0.0123), pretransplant hypertension (P = 0.0012) and cyclosporin A (61.5% vs tacrolimus 25.0%, P = 0.0248). The incidence of obesity, dyslipidemia and DM did not change from before to after transplantation. LTx was curative in 77.8% of cases of pretransplant dyslipidemia and 20% of cases of pretransplant DM. Primary biliary cirrhosis cases comprised 85.7% of cases of pretransplant dyslipidemia that were cured by LTx. In univariate analysis, pretransplant BMI of 25 or more was the only risk factor of post-transplant dyslipidemia (P = 0.0098). The incidence of new-onset DM after transplantation was 20%. Risk factors of post-transplant DM were male sex (P = 0.0156), pretransplant DM (P < 0.0001), alcohol abuse (P = 0.0248) and mycophenolate mofetil (P = 0.0181) by univariate analysis. CONCLUSION The prevalence of hypertension increased after LTx and pretransplant obesity was associated with several post-transplant metabolic abnormalities.
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Affiliation(s)
- Yasuyuki Hara
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Naoki Kawagishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Wataru Nakanishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Kazuaki Tokodai
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Chikashi Nakanishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Shigehito Miyagi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Noriaki Ohuchi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
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Abstract
OBJECTIVE To provide an approach to the care of liver transplant (LT) patients, a growing patient population with unique needs. METHODS A literature search of PubMed for guidelines and review articles using the keywords "liver transplantation", "long term complications" and "medical management" was conducted, resulting in 77 articles. RESULTS As a result of being on immunosuppression, LT recipients are at increased risk of infections and must be screened regularly for metabolic complications and malignancies. DISCUSSION Although immunosuppression is key to maintaining allograft health after transplantation, it comes with its own set of medical issues to follow. Physicians following LT recipients must be aware of the greater risk for hypertension, diabetes, dyslipidemia, renal failure, metabolic bone disease and malignancies in these patients, all of whom require regular monitoring and screening. Vaccination, quality of life, sexual function and pregnancy must be specifically addressed in transplant patients.
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22
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Dare AJ, Plank LD, Phillips ARJ, Gane EJ, Harrison B, Orr D, Jiang Y, Bartlett ASJR. Additive effect of pretransplant obesity, diabetes, and cardiovascular risk factors on outcomes after liver transplantation. Liver Transpl 2014; 20:281-90. [PMID: 24395145 DOI: 10.1002/lt.23818] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Accepted: 11/07/2013] [Indexed: 12/31/2022]
Abstract
The effects of pretransplant obesity, diabetes mellitus (DM), coronary artery disease (CAD), and hypertension (HTN) on outcomes after liver transplantation (LT) are controversial. Questions have also been raised about the appropriateness of the body mass index (BMI) for assessing obesity in patients with end-stage liver disease. Both issues have implications for organ allocation in LT. To address these questions, we undertook a cohort study of 202 consecutive patients (2000-2010) undergoing LT at a national center in New Zealand. BMI and body fat percentage (%BF) values (dual-energy X-ray absorptiometry) were measured before transplantation, and the methods were compared. The influence of pretransplant risk variables (including obesity, DM, CAD, and HTN) on the 30-day postoperative event rate, length of hospital stay, and survival were analyzed. There was agreement between the calculated BMI and the measured %BF for 86.0% of the study population (κ coefficient = 0.73, 95% confidence interval = 0.61-0.85), and this was maintained across increasing Model for End-Stage Liver Disease scores. Obesity was an independent risk factor for the postoperative event rate [count ratio (CR) = 1.03, P < 0.001], as was DM (CR = 1.4, P < 0.001). Obesity with concomitant DM was the strongest predictor of the postoperative event rate (CR = 1.75, P < 0.001) and a longer hospital stay (5.81 days, P < 0.01). Independent metabolic risk factors had no effect on 30-day, 1-year, or 5-year patient survival. In conclusion, BMI is an adequate tool for assessing obesity-associated risk in LT. Early post-LT morbidity is highest for patients with concomitant obesity and DM, although these factors do not appear to influence recipient survival.
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Affiliation(s)
- Anna J Dare
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
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23
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Klintmalm GB, Nashan B. The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence. J Transplant 2014; 2014:845438. [PMID: 24719752 PMCID: PMC3955586 DOI: 10.1155/2014/845438] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Revised: 09/20/2013] [Accepted: 09/21/2013] [Indexed: 12/14/2022] Open
Abstract
Despite the success of liver transplantation, long-term complications remain, including de novo malignancies, metabolic syndrome, and the recurrence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). The current mainstay of treatment, calcineurin inhibitors (CNIs), can also worsen posttransplant renal dysfunction, neurotoxicity, and diabetes. Clearly there is a need for better immunosuppressive agents that maintain similar rates of efficacy and renal function whilst minimizing adverse effects. The mammalian target of rapamycin (mTOR) inhibitors with a mechanism of action that is different from other immunosuppressive agents has the potential to address some of these issues. In this review we surveyed the literature for reports of the use of mTOR inhibitors in adult liver transplantation with respect to renal function, efficacy, safety, neurological symptoms, de novo tumors, and the recurrence of HCC and HCV. The results of our review indicate that mTOR inhibitors are associated with efficacy comparable to CNIs while having benefits on renal function in liver transplantation. We also consider newer dosing schedules that may limit side effects. Finally, we discuss evidence that mTOR inhibitors may have benefits in the oncology setting and in relation to HCV-related allograft fibrosis, metabolic syndrome, and neurotoxicity.
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Affiliation(s)
- Goran B. Klintmalm
- Baylor Simmons Transplant Institute, Baylor University Medical Center, 3410 Worth Street, Suite 950, Dallas, TX 75246, USA
| | - Björn Nashan
- Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Eppendorf, Martinistraβe 52, 20246 Hamburg, Germany
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Lankarani KB, Eshraghian A, Nikeghbalian S, Janghorban P, Malek-Hosseini SA. New onset diabetes and impaired fasting glucose after liver transplant: risk analysis and the impact of tacrolimus dose. EXP CLIN TRANSPLANT 2014; 12:46-51. [PMID: 23902591 DOI: 10.6002/ect.2013.0047] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES New onset diabetes mellitus after transplant is one of the major metabolic complications after liver transplant. Development of impaired fasting glucose after liver transplant is thought to be associated with increased risk of cardiovascular mortality and has not been well studied before. The aim of this study was to evaluate incidence and risk factors of new onset diabetes mellitus after transplant and impaired fasting glucose in liver transplant patients. MATERIALS AND METHODS In a cross-sectional study, all adult patients (aged≥18 years) who were transplanted because of chronic liver diseases from June 2002 to September 2010 at Shiraz Liver Transplant Center were evaluated for developing diabetes and impaired fasting glucose. RESULTS Totally, 86 patients (18.81%) were found to have diabetes after liver transplant. Forty patients (27 men and 13 women; 8.75%) developed new onset diabetes mellitus after transplant and 36 patients (7.87%) developed impaired fasting glucose after liver transplant. The mean age of patients with new onset diabetes mellitus after transplant was higher than that of nondiabetic patients (P = .001). Mean fasting plasma glucose before liver transplant was significantly higher in diabetic patients compared with nondiabetic patients (P = .002) (5.20±0.93 mmol/L vs 4.44±0.56 mmol/L) (93.86±16.80 mg/dL vs 80±10.14 mg/dL). Patients with new onset diabetes mellitus after transplant received higher doses of tacrolimus as immunosuppressive medication than nondiabetic patients (P = .001). CONCLUSIONS Fasting plasma glucose before transplant can predict development of new onset diabetes mellitus after transplant. Age and tacrolimus dosage are independent risk factors for new onset diabetes mellitus after transplant in our patients.
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Affiliation(s)
- Kamran Bagheri Lankarani
- Health Policy Research Center, Namazi Hospital, Shiraz University of Medical Science, Shiraz, Iran
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Loria P, Marchesini G, Nascimbeni F, Ballestri S, Maurantonio M, Carubbi F, Ratziu V, Lonardo A. Cardiovascular risk, lipidemic phenotype and steatosis. A comparative analysis of cirrhotic and non-cirrhotic liver disease due to varying etiology. Atherosclerosis 2014; 232:99-109. [PMID: 24401223 DOI: 10.1016/j.atherosclerosis.2013.10.030] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 10/23/2013] [Accepted: 10/24/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Liver regulates lipid metabolism in health and disease states. Nevertheless, the entity of cardiovascular risk (CVR) resulting from dysregulation of lipid metabolism secondary to liver disease is poorly characterized. AIM AND METHODS To review, based on a PubMed literature search, the features and the determinants of serum lipid phenotype and its correlation with hepatic steatosis, insulin resistance (IR) and CVR across the wide spectrum of the most common chronic liver diseases due to different etiologies. RESULTS Alcoholic liver disease (ALD) is associated with steatosis, IR and a typical lipid profile. The relationship between alcohol intake, incident type 2 diabetes (T2D) and CVR describes a J-shaped curve. Non-alcoholic fatty liver disease (NAFLD), and probably nonalcoholic steatohepatitis (NASH) in particular, is associated with IR, atherogenic dyslipidemia and increased CVR independent of traditional risk factors. Moreover, NASH-cirrhosis and T2D contribute to increasing CVR in liver transplant recipients. HBV infection is generally free from IR, steatosis and CVR. HCV-associated dysmetabolic syndrome, featuring steatosis, hypocholesterolemia and IR, appears to be associated with substantially increased CVR. Hyperlipidemia is an almost universal finding in primary biliary cirrhosis, a condition typically spared from steatosis and associated with neither subclinical atherosclerosis nor excess CVR. Finally, little is known on CVR in patients with hepatocellular carcinoma. CONCLUSIONS CVR is increased in ALD, NAFLD and chronic HCV infection, all conditions featuring IR and steatosis. Therefore, irrespective of serum lipid phenotype, hepatic steatosis and IR may be major shared determinants in amplifying CVR in common liver disease due to varying etiology.
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Affiliation(s)
- P Loria
- University of Modena and Reggio Emilia, Italy; Azienda USL MODENA, Italy.
| | | | - F Nascimbeni
- University of Modena and Reggio Emilia, Italy; Azienda USL MODENA, Italy
| | - S Ballestri
- University of Modena and Reggio Emilia, Italy; Azienda USL MODENA, Italy
| | - M Maurantonio
- University of Modena and Reggio Emilia, Italy; Azienda USL MODENA, Italy
| | - F Carubbi
- University of Modena and Reggio Emilia, Italy; Azienda USL MODENA, Italy
| | | | - A Lonardo
- University of Modena and Reggio Emilia, Italy; Azienda USL MODENA, Italy.
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New Onset Diabetes Mellitus in Living Donor versus Deceased Donor Liver Transplant Recipients: Analysis of the UNOS/OPTN Database. J Transplant 2013; 2013:269096. [PMID: 24205434 PMCID: PMC3800575 DOI: 10.1155/2013/269096] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2013] [Accepted: 08/22/2013] [Indexed: 02/08/2023] Open
Abstract
New onset diabetes after transplantation (NODAT) occurs less frequently in living donor liver transplant (LDLT) recipients than in deceased donor liver transplant (DDLT) recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52–0.75), P < 0.001). Predictors for NODAT in LDLT recipients were hepatitis C (HCV) and treated acute cellular rejection (ACR). Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications.
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3D co-culturing model of primary pancreatic islets and hepatocytes in hybrid spheroid to overcome pancreatic cell shortage. Biomaterials 2013; 34:3784-94. [PMID: 23433671 DOI: 10.1016/j.biomaterials.2013.02.010] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Accepted: 02/02/2013] [Indexed: 12/29/2022]
Abstract
Here, a spheroidal 3D co-culture model of primary (rat) pancreatic islets and hepatocytes with uniform size and shape was developed using hemispheric concave microwell arrays. We conducted morphological and functional analyses of hybrid spheroids versus mono-cultures of islets or hepatocytes (controls). For the establishment of a 3D hybrid model, a broad range of cell ratios - 1:1, 1:3, 1:5, 1:7, 3:1, 5:1 and 7:1 mixture - of hepatocytes and pancreatic islets were used. As control, each hepatocyte and pancreatic islet were mono-cultured forming 3D spheroids. The transient morphology of spheroid formation in 9 culture models was observed using optical microscopy. Cell viability under these culture environments was assessed, and the morphologies of the outer and inner porous cell-spheroid structures were investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and imaging of stained spheroid sections. The pancreatic islet-specific function of hybrid spheroids was evaluated by measuring insulin secretion and in vivo test by xenotransplantation of encapsulated spheroids in microfibers with a consistent maintenance of normal blood glucose levels over 4 weeks, while liver-specific functions were measured in terms of albumin secretion, urea secretion and cytochrome P450 activity. These diverse observations and evaluations validated the positive and bidirectional effects of co-cultured 3D spheroids. The proposed 3D co-culture model demonstrated that both cells appeared to support each other's functions strongly in spheroids, even though smaller proportions of each cell type was evaluated compared to mono-culture models, suggesting that the proposed model could help overcome the problem of cell shortages in clinical applications.
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Cho MS, Choi HI, Kim IO, Jung SH, Yun TJ, Lee JW, Kim MS, Kim JJ. The clinical course and outcomes of post-transplantation diabetes mellitus after heart transplantation. J Korean Med Sci 2012; 27:1460-7. [PMID: 23255843 PMCID: PMC3524423 DOI: 10.3346/jkms.2012.27.12.1460] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Accepted: 09/13/2012] [Indexed: 12/29/2022] Open
Abstract
The aim of this study was to describe in more detail the predisposition, natural course, and clinical impact of post-transplantation diabetes mellitus (PTDM) after heart transplantation (HT). The characteristics and clinical outcomes of 54 patients with PTDM were compared with those of 140 patients without PTDM. The mean age of PTDM patients was significantly higher than controls (48.9 ± 9.3 vs 38.6 ± 13.3 yr, respectively, P = 0.001), and ischemic heart disease was a more common indication of HT (20.4% [11/54] vs 7.1% [10/140], respectively, P = 0.008). In multivariate analysis, only recipient age (odds ratio, 1.80; 95% confidence interval, 1.35-2.40; P = 0.001) was associated with PTDM development. In 18 patients (33%), PTDM was reversed during the follow-up period, and the reversal of PTDM was critically dependent on the time taken to develop PTDM (1.9 ± 1.0 months in the reversed group vs 14.5 ± 25.3 months in the maintained group, P = 0.005). The 5-yr incidence of late infection (after 6 months) was higher in the PTDM group than in the control group (30.4% ± 7.1% vs 15.4% ± 3.3%, respectively, P = 0.031). However, the 5-yr overall survival rate was not different (92.9% ± 4.1% vs 85.8% ± 3.2%, respectively, P = 0.220). In conclusion, PTDM after HT is reversible in one-third of patients and is not a critical factor in patient survival after HT.
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Affiliation(s)
- Min Soo Cho
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyo-In Choi
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In-Ok Kim
- Organ Transplantation Program, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Ho Jung
- Department of Cardiac Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Jin Yun
- Department of Cardiac Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae-Won Lee
- Department of Cardiac Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Min-Seok Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae-Joong Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Singh S, Watt KD. Long-term medical management of the liver transplant recipient: what the primary care physician needs to know. Mayo Clin Proc 2012; 87:779-90. [PMID: 22763347 PMCID: PMC3498400 DOI: 10.1016/j.mayocp.2012.02.021] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 02/07/2012] [Accepted: 02/16/2012] [Indexed: 12/18/2022]
Abstract
Recognition, management, and prevention of medical complications and comorbidities after liver transplant is the key to improved long-term outcomes. Beyond allograft-related complications, metabolic syndrome, cardiovascular disease, renal dysfunction, and malignancies are leading causes of morbidity and mortality in this patient population. Primary care physicians have an important role in improving outcomes of liver transplant recipients and are increasingly relied on for managing these complex patients. This review serves to assist the primary care physician in the long-term management issues of liver transplant recipients.
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Key Words
- acei, angiotensin converting enzyme inhibitor
- arb, angiotensin receptor blocker
- ckd, chronic kidney disease
- cni, calcineurin inhibitor
- ibd, inflammatory bowel disease
- lt, liver transplant
- mmf, mycophenolate mofetil
- mtor, mammalian target of rapamycin
- nash, nonalcoholic steatohepatitis-related cirrhosis
- olt, orthotopic liver transplant
- psc, primary sclerosing cholangitis
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Affiliation(s)
| | - Kymberly D. Watt
- Correspondence: Address to Kymberly D. Watt, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905
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Kallwitz ER. Metabolic syndrome after liver transplantation: Preventable illness or common consequence? World J Gastroenterol 2012; 18:3627-34. [PMID: 22851856 PMCID: PMC3406416 DOI: 10.3748/wjg.v18.i28.3627] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2012] [Revised: 06/25/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
The metabolic syndrome is common after liver transplant being present in approximately half of recipients. It has been associated with adverse outcomes such as progression of hepatitis C and major vascular events. As the United States population ages and the rate of obesity increases, prevention of the metabolic syndrome in the post-transplant population deserves special consideration. Currently, the metabolic syndrome after transplant appears at least two times more common than observed rates in the general population. Specific guidelines for patients after transplant does not exist, therefore prevention rests upon knowledge of risk factors and the presence of modifiable elements. The current article will focus on risk factors for the development of the metabolic syndrome after transplant, will highlight potentially modifiable factors and propose potential areas for intervention. As in the non-transplant population, behavioral choices might have a major role. Opportunities exist in this regard for health prevention studies incorporating lifestyle changes. Other factors such as the need for immunosuppression, and the changing characteristics of wait listed patients are not modifiable, but are important to know in order to identify persons at higher risk. Although immunosuppression after transplant is unavoidable, the contribution of different agents to the development of components of the metabolic syndrome is also discussed. Ultimately, an increased risk of the metabolic syndrome after transplant is likely unavoidable, however, there are many opportunities to reduce the prevalence.
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Proteinuria following sirolimus conversion is associated with deterioration of kidney function in liver transplant recipients. Transplantation 2012; 93:1006-12. [PMID: 22357174 DOI: 10.1097/tp.0b013e31824bbd01] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND The role of sirolimus (SRL) conversion in the preservation of kidney function in liver transplant (LT) recipients with calcineurin inhibitor (CNI) nephrotoxicity is unclear. METHODS Data on 102 LT recipients with deteriorating kidney function after CNI exposure who were later converted to SRL were retrospectively reviewed. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR) at time of conversion and serially thereafter. The primary endpoint was stabilization or improvement of kidney function as assessed by eGFR at last recorded follow-up compared with eGFR at the time of conversion. RESULT After a median (interquartile range) of 3.1 (1.6-4.5) years of follow-up, serum creatinine decreased from 1.9 ± 0.8 to 1.8 ± 0.7 mg/dL (P=0.25) and eGFR increased from 40.8 ± 16.7 to 44.3 ± 20.0 mL/min (P=0.03). During the same time period, 24-hr urinary protein excretion increased from median (interquartile range) of 72 (0-155) to 382 (169-999) mg/day (P=0.0001). Sixty-five (64%) patients achieved the primary endpoint and 37 (36%) experienced deterioration in kidney function. Independent predictors of deterioration of kidney function after SRL conversion were development of proteinuria ≥ 1000 mg/day (odds ratio [OR]: 3.3, confidence interval [CI]: 1.1-9.5 P=0.03), post-LT diabetes (OR: 4.2, CI: 1.6-11.1, P=0.004), and higher eGFR at time of conversion (OR: 1.6, CI: 1.2-2.2, P=0.003). CONCLUSION Improvement or stabilization of kidney function occurred in the majority of LT recipients converted to SRL for CNI nephrotoxicity. Proteinuria ≥ 1000 mg/day, post-LT diabetes, and higher baseline eGFR were independent predictors of kidney function loss after SRL conversion.
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32
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Pretransplant fasting glucose predicts new-onset diabetes after liver transplantation. J Transplant 2012; 2012:614781. [PMID: 22461975 PMCID: PMC3306927 DOI: 10.1155/2012/614781] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2011] [Revised: 10/05/2011] [Accepted: 10/17/2011] [Indexed: 12/27/2022] Open
Abstract
New-onset diabetes after transplantation (NODAT) is common after liver transplant and associated with poorer outcomes. The aim of this study was to identify risk factors for NODAT in liver transplant recipients off corticosteroids. In 225 adult nondiabetic liver transplant recipients, the mean age was 51.7 years, the majority were men (71%), and half had HCV (49%). The mean calculated MELD score at transplantation was 18.7, and 19% underwent living-donor transplant (LDLT). One year after transplantation, 17% developed NODAT, and an additional 16% had impaired fasting glucose. The incidence of NODAT in patients with HCV was 26%. In multivariate analysis, HCV, pretransplant FPG, and LDLT were significant. Each 10 mg/dL increase in pretransplant FPG was associated with a twofold increase in future development of NODAT. The incidence of NODAT after liver transplant in patients off corticosteroids is 17%. Risk factors for developing NODAT include HCV and pretransplant FPG; LDLT is protective.
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Abstract
Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44-58%. The main factors associated with posttransplant MS are posttransplant diabetes, obesity, dyslipidemia, and hypertension. In addition to developing NAFLD, posttransplant MS is associated with increased cardiovascular mortality that is 2.5 times that of the age- and sex-matched individuals. Additionally, the presence of posttransplant MS has been associated with rapid progression to fibrosis in individuals transplanted for HCV cirrhosis. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with posttransplant MS. Until then, early recognition, prevention, and treatment of its components are vital in improving outcomes in liver transplant recipients.
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Stravitz RT, Carl DE, Biskobing DM. Medical management of the liver transplant recipient. Clin Liver Dis 2011; 15:821-43. [PMID: 22032531 DOI: 10.1016/j.cld.2011.08.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Long-term survival of liver transplant recipients has become the rule rather than the exception. As a result, the medical complications of long-term survival, including atherosclerotic cardiovascular disease, metabolic bone disease, and de novo malignancy, have accounted for an increasing proportion of late morbidity and mortality. Risk factors for these complications begin before transplant and are potentially modifiable but are exacerbated by the requirement for immunosuppressive medications after transplantation. Surveillance and early intervention programs administered by transplant hepatologists and other medical subspecialists may improve long-term outcomes in liver transplant recipients by ameliorating risk factors for atherosclerosis, bone fractures, and cancer.
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Affiliation(s)
- R Todd Stravitz
- Section of Hepatology, Division of Gastroenterology, Hepatology, and Nutrition, Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA 23298-0341, USA.
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Anastácio LR, Ferreira LG, Ribeiro HDS, Liboredo JC, Lima AS, Correia MITD. Metabolic syndrome after liver transplantation: prevalence and predictive factors. Nutrition 2011; 27:931-7. [PMID: 21621388 DOI: 10.1016/j.nut.2010.12.017] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Revised: 12/17/2010] [Accepted: 12/20/2010] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Metabolic syndrome (MetS) is a disorder in which obesity, insulin resistance, high blood pressure and dyslipidemia coexist. This study assessed the prevalence of MetS and its associated factors in patients who underwent orthotopic liver transplantation (OLTx). METHODS Post-OLTx patients were assessed for the presence of MetS according to the diagnostic criteria proposed by the International Diabetes Federation (IDF) and National Heart, Lung, and Blood Institute/American Heart Association (NHLBI/AHA). Demographic, socioeconomic, lifestyle, clinical, anthropometric, and dietary variables were collected to identify predictors for MetS using logistic regression analysis. RESULTS Among the 148 patients assessed, the prevalence of MetS was 50% (IDF criteria) and 38.5% (NHLBI/AHA criteria). For both the IDF and the NHLBI/AHA classifications, the independent factors associated with MetS were older age, shorter time since transplantation, and history of excessive weight prior to OLTx. Other predictors for MetS by IDF criteria were alcohol abuse as the indication for OLTx, physical activity reduction as the cause of weight gain after transplantation, and calcium intake below recommended levels. The presence of MetS (NHLBI/AHA) was also associated with decreased intake of potassium, fiber, and folic acid. CONCLUSIONS MetS is highly prevalent among post-OLTx patients and it is predicted by older age, shorter time since transplantation, alcohol abuse as the cause of cirrhosis, excessive weight prior to OLTx, and some potentially modifiable factors such as physical activity reduction after OLTx and low intake of calcium, potassium, fiber, and folic acid.
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Affiliation(s)
- Lucilene Rezende Anastácio
- Adult Health Postgraduate Program, Medical School, Universidade Federal de Minas Gerais, Itauna, Minas Gerais, Brazil.
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Sorice G, Muscogiuri G, Mezza T, Prioletta A, Giaccari A. Metabolic Syndrome in Transplant Patients: An Academic or a Health Burden? Transplant Proc 2011; 43:313-7. [DOI: 10.1016/j.transproceed.2010.09.099] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Chebane L, Tavassoli N, Bagheri H, Montastruc JL. [Drug-induced hyperglycemia: a study in the French pharmacovigilance database]. Therapie 2010; 65:447-58. [PMID: 21144480 DOI: 10.2515/therapie/2010051] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2009] [Accepted: 03/01/2010] [Indexed: 12/28/2022]
Abstract
OBJECTIVE To analyse drugs inducing hyperglycemia by using data reported to the French spontaneous reporting system and recorded in the French PharmacoVigilance Database (FPVD). METHODS All cases with a report of hyperglycemia and/or diabetes in the French database between 1985 and 2008 were included in the study. We estimated the risk of hyperglycemia linked to drugs by the case/non-case method. Cases were reports including hyperglycemia and non cases all other reports. This risk was estimated through calculation of reporting odds ratios (ROR). RESULTS During this period, 1219 reports including the words "hyperglycemia and/or diabetes" were registered (0.34% of the database). This adverse drug reaction occurred 1 fold over 4 in diabetics or as a part of HIV infection. Effect was "serious" in approximatively 50% of cases. We found an increase of risk during exposition with methylprednisolone [ROR=43.5; 95% CI (37.3-50.8)], tacrolimus [ROR=25; 95% CI (17.9-34.8)], olanzapine [ROR=19.9; 95% CI (14.9-26.5)], prednisone [ROR=18.9; 95% CI (15.7-22.8)] or pentamidine [ROR=15.4; 95% CI (8.2-28.3)]. CONCLUSION Drug classes most frequently found in FPVD linked to hyperglycemia are antiretroviral, steroidal anti-inflammatory, second generation neuroleptic, immunosuppressive and diuretic drugs.
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Affiliation(s)
- Leila Chebane
- Laboratoire de Pharmacologie Médicale et Clinique, Unité de Pharmacoépidémiologie EA 3696, Université de Toulouse, Faculté de Médecine, Toulouse, France
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Cardiovascular risk profile of patients with acute liver failure after liver transplantation when compared with the general population. Transplantation 2010; 89:61-8. [PMID: 20061920 DOI: 10.1097/tp.0b013e3181bcd682] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND As opposed to most solid-organ transplant recipients, patients with acute liver failure exhibit a pretransplant health status more comparable with the general population, and any posttransplant cardiovascular risk excess should thus be more attributable to transplantation-related factors alone. METHODS This study compared the cardiovascular risk of 77 consecutive patients with acute liver failure at 5 years after liver transplantation with that of the general population using age, sex, and residence area-standardized prevalence ratios (SPR). RESULTS At least one cardiovascular risk factor developed in 92% of patients. Treated hypertension, observed in 71% of patients at 5 years, was more common among patients than controls (SPR, 2.73; 95% confidence interval [CI], 2.06-3.55), whereas the 61% prevalence of dyslipidemia and 3% prevalence of impaired fasting glucose were significantly less frequent among patients (SPR, 0.69; 95% CI, 0.51-0.92 and SPR, 0.29; 95% CI, 0.04-1.00). The 5-year prevalence of diabetes (10%), overweight (32%), and obesity (13%) deviated nonsignificantly from controls (SPR 1.90, 0.85, and 0.58). Antibody therapy associated with a 1.49-fold increase in the risk of hypertension (95% CI, 1.15-1.94) and a 6.43-fold increase in the risk of diabetes (95% CI, 1.18-34.9). Immunosuppression-type, steroids, acute rejection, retransplantation, or graft steatosis revealed nonsignificant risk alterations. CONCLUSIONS Liver transplantation and associated immunosuppression evidently cause hypertension, and possibly elicit diabetes in susceptible individuals. Conversely, the often reported transplantation-associated increased burden of overweight/obesity and dyslipidemia might relate mostly to other factors.
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Pagadala M, Dasarathy S, Eghtesad B, McCullough AJ. Posttransplant metabolic syndrome: an epidemic waiting to happen. Liver Transpl 2009; 15:1662-70. [PMID: 19938136 DOI: 10.1002/lt.21952] [Citation(s) in RCA: 111] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
With increasing survival after orthotopic liver transplantation (OLT), metabolic syndrome and its individual components, including diabetes mellitus, hypertension, dyslipidemia, and obesity, are increasingly being identified and contributing to cardiovascular complications and late morbidity and mortality. The prevalence of posttransplant metabolic syndrome (PTMS) and its individual components has been found to be higher post-OLT versus a comparable population without OLT. The development of nonalcoholic fatty liver disease (NAFLD) after liver transplantation for non-NAFLD cirrhosis is also being increasingly recognized. A number of predictors have been identified as potential risk factors related to these complications. The pretransplant risk factors include immunosuppression, a higher age at transplant, male gender, a history of smoking, the pretransplant body mass index, pre-OLT diabetes, the etiology of the underlying liver disease that resulted in OLT (hepatitis C, cryptogenic cirrhosis, or alcohol), an increased donor body mass index, and marital status. Although there is an increased risk of cardiovascular events, rejection, and infection among patients with PTMS, the overall impact on long-term survival and mortality remains inconclusive. Strategies to reduce the development of metabolic syndrome after transplantation should include lifestyle modifications involving alterations in diet and increased physical activity. Additional measures that may be potentially beneficial include the use of lipid-lowering agents, the optimal control of blood glucose, and the use of tacrolimus instead of cyclosporine.
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Affiliation(s)
- Mangesh Pagadala
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
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40
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Gökçe S, Durmaz O, Celtik C, Aydoğan A, Baş F, Türkoğlu U, Ozden I, Sökücü S. Investigation of impaired carbohydrate metabolism in pediatric liver transplant recipients. Pediatr Transplant 2009; 13:873-80. [PMID: 19037912 DOI: 10.1111/j.1399-3046.2008.01076.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OGTT was performed in 28 liver transplants maintained with tacrolimus to investigate carbohydrate metabolism and assess risk factors for development of PTDM. None had PTDM that was detected by OGTT. Early PTDM in four cases (14.3%) resolved in follow-up. Five new cases (17.9%) demonstrated DCM (DCM = IGT +/- hyperinsulinemia). Fasting measurements were normal in two hyperinsulinemic cases. With one (20%, p > 0.05) exception none of the children with DCM were overweight or had a family history of diabetes. All five (100%) children with DCM had been given high cumulative dosage of steroids 18 (78.3%)--without DCM (p > 0.05). The median age of children with DCM was greater [4.3 (12.7-18.0) vs. 7.0 (2.3-18.0) yr, p < 0.01] and duration of follow-up longer [5.3 (2.3-7.0) vs. 2.5 (0.7-7.3) yr, p < 0.05]. Four children (80%) with DCM were pubertal (p < 0.05). However, neither age nor duration of follow-up or pubertal stage had significant effect on DCM development. Early PTDM is a transient phenomenon and is not predictive for future development of diabetes. DCM is frequently observed in liver transplanted children. Albeit the children with DCM were given high cumulative dose of steroids, were older, mostly were pubertal, and had longer duration of follow-up, we cannot draw firm conclusions on effects of the risk factors on carbohydrate metabolism because of the small sample size and relatively short duration of follow-up. Unlike fasting measurements, OGTT can detect all children with DCM.
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Affiliation(s)
- Selim Gökçe
- Departments of Pediatric Gastro, Hepatopancreaticobiliary Unit, Istanbul University, Istanbul Medical School, Istanbul, Turkey
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Pageaux GP, Faure S, Bouyabrine H, Bismuth M, Assenat E. Long-term outcomes of liver transplantation: diabetes mellitus. Liver Transpl 2009; 15 Suppl 2:S79-82. [PMID: 19877023 DOI: 10.1002/lt.21913] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
1. Despite methodological problems in estimating the true incidence of new-onset diabetes (NODM), it is generally accepted that this is a common complication of liver transplantation (LT), with the mean reported incidence varying between 7% and 30%. 2. The main predictors of post-LT NODM are ethnicity, a family history of diabetes, age > 45 years, glucose intolerance prior to LT, central obesity, metabolic syndrome, use of corticosteroids over a long period, use of tacrolimus, and hepatitis C infection. 3. NODM is associated with impaired long-term graft function and reduced survival. Diabetes is among the main risk factors for coronary heart disease, cerebrovascular disease, and peripheral occlusive arterial disease in transplant recipients. 4. The management of NODM includes the therapeutic and preventive steps taken in patients with type 2 diabetes. Little information exists on the use of antidiabetic compounds in transplant recipients. Some studies have suggested that LT recipients with NODM may benefit from a conversion to cyclosporine through improved glucose metabolism.
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Affiliation(s)
- Georges-Philippe Pageaux
- Service d'Hépato-Gastroentérologie et Transplantation Hépatique, Centre Hospitalier Universitaire Saint Eloi, Montpellier, France.
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42
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Metabolic syndrome and its components after liver transplantation: incidence, prevalence, risk factors, and implications. Clin Nutr 2009; 29:175-9. [PMID: 19783330 DOI: 10.1016/j.clnu.2009.08.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2008] [Revised: 07/09/2009] [Accepted: 08/14/2009] [Indexed: 01/02/2023]
Abstract
Metabolic syndrome is defined as the mutual existence of obesity, impaired fasting glucose levels, insulin resistance, hypertension, and dyslipidemia. After liver transplantation, patients typically develop these disorders, and even though there has been minimal research focused on the chronic impact of this syndrome on post-liver transplant patients, studies point to an association with major vascular events and fibrosis. The aim of the current work is to review data on the incidence, prevalence, risk factors, and implications of metabolic syndrome and its components in patients who have undergone liver transplantation.
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McGuire BM, Rosenthal P, Brown CC, Busch AMH, Calcatera SM, Claria RS, Hunt NK, Korenblat KM, Mazariegos GV, Moonka D, Orloff SL, Perry DK, Rosen CB, Scott DL, Sudan DL. Long-term management of the liver transplant patient: recommendations for the primary care doctor. Am J Transplant 2009; 9:1988-2003. [PMID: 19563332 DOI: 10.1111/j.1600-6143.2009.02733.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient.
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Affiliation(s)
- B M McGuire
- University of Alabama at Birmingham, Birmingham, AL, USA.
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Combined En-bloc Liver-Pancreas Transplantation in Patients With Liver Cirrhosis and Insulin-Dependent Type 2 Diabetes Mellitus. Transplantation 2009; 87:542-5. [DOI: 10.1097/tp.0b013e3181949cce] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Froud T, Baidal DA, Faradji R, Cure P, Mineo D, Selvaggi G, Kenyon NS, Ricordi C, Alejandro R. Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes. Transplantation 2008; 86:1695-701. [PMID: 19104407 PMCID: PMC2759396 DOI: 10.1097/tp.0b013e31819025e5] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Only a minority of islet transplant recipients maintain insulin independence at 5 years under the Edmonton protocol of immunosuppression. New immunosuppressive strategies are required to improve long-term outcomes. MATERIALS AND METHODS Three subjects with unstable type 1 diabetes mellitus underwent islet transplantation with alemtuzumab induction and sirolimus-tacrolimus maintenance for 3 months and then sirolimus-mycophenolic acid maintenance thereafter. Follow-up was more than 2 years. Comparison was with 16 historical subjects transplanted under the Miami version of the Edmonton protocol. RESULTS Insulin independence was achieved in 2 of 3 alemtuzumab and 14 of 16 historical subjects. Those who did not achieve insulin independence only received a single islet infusion. Insulin-independence rates remained unchanged in the alemtuzumab group, but decreased from 14 of 16 (88%) to 6 of 16 (38%) in the historical group over 2 years. Insulin requirements increased in the historical group while remaining stable in the alemtuzumab group. Comparison of functional measures at 3 months suggested better engraftment with alemtuzumab (P=NS). Further comparison of alemtuzumab versus historical groups, up to 24 months, demonstrated significantly better: Mixed meal stimulation index (24 months, 1.0+/-0.08 [n=3] vs. 0.5+/-0.06 pmol/mL [n=6], P<0.01), mixed meal peak C-peptide (24 months, 5.0+/-0.5 [n=3] vs. 3.1+/-0.3 nmol/mL [n=6], P<0.05), HbA1c (24 months, 5.4+/-0.15 [n=3] vs. 6.3+/-0.12 pmol/mL [n=10], P<0.01). Administration of alemtuzumab was well tolerated. There was no increased incidence of infections in alemtuzumab subjects despite profound, prolonged lymphocyte depletion. CONCLUSIONS Islet transplantation with alemtuzumab induction was well tolerated and resulted in improved short- and long-term outcomes. Further investigation is underway for validation.
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Affiliation(s)
- Tatiana Froud
- Clinical Islet Transplant Program, Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
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Chen T, Jia H, Li J, Chen X, Zhou H, Tian H. New onset diabetes mellitus after liver transplantation and hepatitis C virus infection: meta-analysis of clinical studies. Transpl Int 2008; 22:408-15. [PMID: 19207185 DOI: 10.1111/j.1432-2277.2008.00804.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
New onset diabetes mellitus (NODM) postliver transplantation (LT) is very common and may negatively affect patient and graft survival, but its causative mechanism is still unclear. This study was to analyze the connection between Hepatitis C virus (HCV) infection and NODM after LT by systematically reviewing published medical literature. We electronically searched databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to January 2008. Only retrospective studies could be identified. Seven of them were subjected to the meta-analysis. Analysis was performed by using revman 4.2 software. We found that HCV increased the prevalence of NODM [OR 2.46; 95%CI (1.44, 4.19)]. Then, we further analyzed the association between HCV and persistent-NODM (P-NODM) after LT. The result showed that prevalence of P-NODM was higher in HCV-positive group than in HCV-negative group with marginally statistical significance [OR = 1.39; 95%CI (1.06, 1.83)]. The present meta-analysis based on retrospective studies suggested a significant relationship between HCV and NODM after LT, and it seems that HCV infection might also increase the prevalence of P-NODM. Multicenter, large sized prospective studies are still needed to further confirm these results.
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Affiliation(s)
- Tao Chen
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China
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47
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Hanouneh IA, Feldstein AE, McCullough AJ, Miller C, Aucejo F, Yerian L, Lopez R, Zein NN. The significance of metabolic syndrome in the setting of recurrent hepatitis C after liver transplantation. Liver Transpl 2008; 14:1287-93. [PMID: 18756451 DOI: 10.1002/lt.21524] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Although hyperinsulinemia and its associated metabolic syndrome (MS) have been implicated in the progression of hepatic fibrosis in hepatitis C virus (HCV) patients, little is known about the consequences of MS after orthotopic liver transplantation (OLT). The aim of this study was to assess the association between MS and fibrosis progression in patients with recurrent HCV after OLT. We identified all OLT/HCV patients (1998-2005) with at least 2 post-OLT liver biopsies. MS was defined with Adult Treatment Panel III criteria at 1 year post-OLT. The Ludwig-Batts scoring system was used to stage all biopsies (408 biopsies from 95 patients). The first biopsy that showed progression post-OLT was used for the time-to-progression analysis. Univariable and multivariable logistic regression analysis was performed to identify factors associated with fibrosis progression. MS was present in 50% of patients. Average follow-up to last available biopsy was 24 +/- 17 months, during which 72% of subjects had fibrosis progression. The overall median rate of fibrosis progression was 0.08 units per month (Q25, Q75: 0.0, 0.17). By univariable analysis, high HCV RNA at 4 months post-OLT (P < 0.001), diabetes (P = 0.046), cytomegalovirus infection (P = 0.006), and MS (P = 0.049) were associated with progression of fibrosis. In multivariable analysis, MS was independently associated with progression of fibrosis beyond 1 year after OLT (odds ratio = 6.3, P = 0.017). A high viral load at 4 months post-OLT (odds ratio = 1.1, P = 0.004) and steroid therapy for acute rejection (odds ratio = 1.9, P = 0.05) were independently associated with fibrosis progression. In conclusion, MS, a potentially modifiable disease, is common and is strongly associated with long-term fibrosis progression in the setting of recurrent HCV after OLT.
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Affiliation(s)
- Ibrahim A Hanouneh
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, USA
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48
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Abstract
As patient survival after solid organ transplantation continues to improve, comorbidites associated with chronic hyperglycemia will assume increasing importance in limiting outcomes and quality of life. New-onset diabetes mellitus commonly occurs in the posttransplant setting and is associated with multiple complications including graft loss, cardiovascular disease, infection, and death. Furthermore, recent studies have begun to highlight the very high posttransplant prevalence and the significant cardiovascular implications of the prediabetic states of impaired fasting glucose and impaired glucose tolerance, indicating that the overall burden of transplantation-associated hyperglycemia is far greater than previously appreciated. Shared and distinct pathogenic factors and clinical repercussions exist among the organ-specific transplant scenarios. Diabetogenic immunosuppressive agents are common to all organ transplant settings, whereas glucose regulation is also strained by the restoration of failed hepatic and renal function. The atherogenic properties of hyperglycemia are particularly significant in the kidney transplant population, which has a marked predisposition to cardiovascular disease, whereas accelerated cardiac allograft vasculopathy and liver fibrosis have been associated with hyperglycemia in the heart and liver transplant settings, respectively. Aggressive screening will effectively detect transplant-associated hyperglycemia, whereas risk factor modification, lifestyle intervention and, where appropriate, drug therapy, may decrease its impact. Topics of future investigation should include the use of emerging diabetes therapies and avenues for the prevention and reversal of transplant-associated hyperglycemia.
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Affiliation(s)
- Roy D Bloom
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Verna EC, Brown RS. Hepatitis C and liver transplantation: enhancing outcomes and should patients be retransplanted. Clin Liver Dis 2008; 12:637-59, ix-x. [PMID: 18625432 DOI: 10.1016/j.cld.2008.03.010] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatitis C (HCV)-related end-stage liver disease is the most common indication for liver transplantation. Safe expansion of the donor pool with improved rates of deceased donation and more widespread use of living and extended criteria donation are likely to decrease wait list mortality. In addition, improved antiviral treatments and a better understanding of the delicate balance between under- and over-immunosuppression in this population are needed. Finally, when recurrent advanced fibrosis occurs, the criteria for patient selection for retransplantation remain widely debated. This article reviews the literature on these topics and the work being done in each area to maximize outcomes in patients receiving transplants for HCV-related cirrhosis.
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Affiliation(s)
- Elizabeth C Verna
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
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