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1
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Kim J, Joh JW, Lee KW, Choi DL, Wang HJ. Safety and efficacy of early corticosteroid withdrawal in liver transplant recipients: A randomized controlled trial. Ann Hepatobiliary Pancreat Surg 2024; 28:238-247. [PMID: 38484785 PMCID: PMC11128783 DOI: 10.14701/ahbps.23-129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 02/04/2024] [Accepted: 02/04/2024] [Indexed: 05/25/2024] Open
Abstract
Backgrounds/Aims Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. Methods This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Results Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. Conclusions The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.
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Affiliation(s)
- Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, Korea
| | - Hee-Jung Wang
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
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Brodosi L, Petta S, Petroni ML, Marchesini G, Morelli MC. Management of Diabetes in Candidates for Liver Transplantation and in Transplant Recipients. Transplantation 2022; 106:462-478. [PMID: 34172646 PMCID: PMC9904447 DOI: 10.1097/tp.0000000000003867] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/31/2021] [Accepted: 06/02/2021] [Indexed: 11/25/2022]
Abstract
Diabetes is common in patients waitlisted for liver transplantation because of end-stage liver disease or hepatocellular cancer as well as in posttransplant phase (posttransplantation diabetes mellitus). In both conditions, the presence of diabetes severely affects disease burden and long-term clinical outcomes; careful monitoring and appropriate treatment are pivotal to reduce cardiovascular events and graft and recipients' death. We thoroughly reviewed the epidemiology of diabetes in the transplant setting and the different therapeutic options, from lifestyle intervention to antidiabetic drug use-including the most recent drug classes available-and to the inclusion of bariatric surgery in the treatment cascade. In waitlisted patients, the old paradigm that insulin should be the treatment of choice in the presence of severe liver dysfunction is no longer valid; novel antidiabetic agents may provide adequate glucose control without the risk of hypoglycemia, also offering cardiovascular protection. The same evidence applies to the posttransplant phase, where oral or injectable noninsulin agents should be considered to treat patients to target, limiting the impact of disease on daily living, without interaction with immunosuppressive regimens. The increasing prevalence of liver disease of metabolic origin (nonalcoholic fatty liver) among liver transplant candidates, also having a higher risk of noncirrhotic hepatocellular cancer, is likely to accelerate the acceptance of new drugs and invasive procedures, as suggested by international guidelines. Intensive lifestyle intervention programs remain however mandatory, both before and after transplantation. Achievement of adequate control is mandatory to increase candidacy, to prevent delisting, and to improve long-term outcomes.
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Affiliation(s)
- Lucia Brodosi
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Maria L. Petroni
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Giulio Marchesini
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Maria C. Morelli
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Sun J, He Y, Bai L, Wang Z, Cao Z, Shao Y, Zhao J. An Analysis of the Risk Factors for New-Onset Diabetes Mellitus After Liver Transplantation. Int J Gen Med 2021; 14:4783-4792. [PMID: 34466023 PMCID: PMC8402980 DOI: 10.2147/ijgm.s324462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 08/11/2021] [Indexed: 11/23/2022] Open
Abstract
Objective To investigate the risk factors related to new-onset diabetes mellitus (NODM) and the significance of IL-6. Methods A retrospective analysis was conducted on clinical data from 64 patients who received either a living donor liver transplantation or a donation after circulatory death from September 2013 to October 2020 and attended regular follow-up visits for six or more months. During follow-up, patients were randomized into groups and followed up until the completion of the study or the death of the patient. Results The incidence of NODM was 31.25% (n = 20). The median age in the NODM group was 52.15 years (p < 0.01). Age (OR = 1.089; 95% CI: 0.0211-0.1495, p = 0.003) and elevated preoperative IL-6 (OR = 1.122; 95% CI: 0.0619-0.1677, p = 0.029) were found to be independent risk factors for NODM. HBV-induced liver cirrhosis, warm ischemia time (WIT), body mass index (BMI), and high preoperative fasting blood glucose (FBG) were also found to be risk factors for NODM. The recipient had a higher risk of NODM if the donor had a high BMI and poor hepatic function. The concentrations of IL-6, procalcitonin (PCT), FBG, and tacrolimus (TAC) in the first month postoperatively were significantly higher in the NODM group than in the NO-NODM group. The survival rate of the patients was not affected by NODM. Conclusion HBV-induced liver cirrhosis, WIT, BMI, and high preoperative FBG levels are risk factors for NODM, and age and preoperative IL-6 levels are independent risk factors. To a certain extent, higher BMI and poor hepatic function had reference significance for the incidence of NODM. Patients with a high concentration of FBG, IL-6, and TAC in the first month postoperatively had an increased risk of suffering from NODM.
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Affiliation(s)
- Jushan Sun
- Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China
| | - Yibiao He
- Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China
| | - Lei Bai
- Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China
| | - Zhipeng Wang
- Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China
| | - Zhu Cao
- Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China
| | - Yingmei Shao
- Xinjiang Uyghur Autonomous Region Clinical Research Center for Echinococcosis and Hepatobiliary Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China
| | - Jinming Zhao
- Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China
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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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Samji NS, Heda R, Satapathy SK. Peri-transplant management of nonalcoholic fatty liver disease in liver transplant candidates . Transl Gastroenterol Hepatol 2020; 5:10. [PMID: 32190778 PMCID: PMC7061181 DOI: 10.21037/tgh.2019.09.09] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 09/23/2019] [Indexed: 12/12/2022] Open
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly growing, affecting 25% of the world population. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD and affects 1.5% to 6.5% of the world population. Its rising incidence will make end-stage liver disease (ESLD) due to NASH the number one indication for liver transplantation (LT) in the next 10 to 20 years, overtaking Hepatitis C. Patients with NASH also have a high prevalence of associated comorbidities such as type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, and chronic kidney disease (CKD), which must be adequately managed during the peritransplant period for optimal post-transplant outcomes. The focus of this review article is to provide a comprehensive overview of the unique challenges these patients present in the peritransplant period, which comprises the pre-transplant, intraoperative, and immediate postoperative periods.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, USA
| | - Rajiv Heda
- University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA
| | - Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
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The Impact of Preexisting and Post-transplant Diabetes Mellitus on Outcomes Following Liver Transplantation. Transplantation 2019; 103:2523-2530. [DOI: 10.1097/tp.0000000000002757] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Grancini V, Resi V, Palmieri E, Pugliese G, Orsi E. Management of diabetes mellitus in patients undergoing liver transplantation. Pharmacol Res 2019; 141:556-573. [PMID: 30690071 DOI: 10.1016/j.phrs.2019.01.042] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 01/24/2019] [Accepted: 01/24/2019] [Indexed: 02/07/2023]
Abstract
Diabetes is a common feature in cirrhotic individuals both before and after liver transplantation and negatively affects prognosis. Certain aetiological agents of chronic liver disease and loss of liver function per se favour the occurrence of pre-transplant diabetes in susceptible individuals, whereas immunosuppressant treatment, changes in lifestyle habits, and donor- and procedure-related factors contribute to diabetes development/persistence after transplantation. Challenges in the management of pre-transplant diabetes include the profound nutritional alterations characterizing cirrhotic individuals and the limitations to the use of drugs with liver metabolism. Special issues in the management of post-transplant diabetes include the diabetogenic potential of immunosuppressant drugs and the increased cardiovascular risk characterizing solid organ transplant survivors. Overall, the pharmacological management of cirrhotic patients undergoing liver transplantation is complicated by the lack of specific guidelines reflecting the paucity of data on the impact of glycaemic control and the safety and efficacy of anti-hyperglycaemic agents in these individuals.
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Affiliation(s)
- Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Veronica Resi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Eva Palmieri
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
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8
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Hu LS, Chai YC, Zheng J, Shi JH, Zhang C, Tian M, Lv Y, Wang B, Jia A. Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death. World J Gastroenterol 2018; 24:4920-4927. [PMID: 30487701 PMCID: PMC6250918 DOI: 10.3748/wjg.v24.i43.4920] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 10/15/2018] [Accepted: 11/08/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To describe the prevalence of posttransplant metabolic syndrome (PTMS) after donation after cardiac death (DCD) liver transplantation (LT) and the pre- and postoperative risk factors.
METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre- and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-III criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.
RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147 (13.6%). Recipient’s body mass index (P = 0.024), warm ischemia time (WIT) (P = 0.045), and posttransplant hyperuricemia (P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients (P < 0.001). After the 1st mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.
CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.
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Affiliation(s)
- Liang-Shuo Hu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi-Chao Chai
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jie Zheng
- Clinical Research Center, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jian-Hua Shi
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Chun Zhang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Min Tian
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi Lv
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Bo Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Ai Jia
- Department of Gastroenterology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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Paka P, Lieber SR, Lee RA, Desai CS, Dupuis RE, Barritt AS. Perioperative glucose management and outcomes in liver transplant recipients: A qualitative systematic review. World J Transplant 2018; 8:75-83. [PMID: 29988867 PMCID: PMC6033739 DOI: 10.5500/wjt.v8.i3.75] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 02/20/2018] [Accepted: 04/01/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the relationship between post-liver transplantation (LT) glycemic control and LT outcomes. METHODS A qualitative systematic review on relevant prospective interventions designed to control glucose levels including insulin protocols. Studies investigating an association between glycemic control and post-LT outcomes such as mortality, graft rejection, and infection rate were reviewed. PubMed, EMBASE, and other databases were searched through October 2016. RESULTS Three thousands, six hundreds and ninety-two patients from 14 studies were included. Higher mortality rate was seen when blood glucose (BG) ≥ 150 mg/dL (P = 0.05). BG ≥ 150 mg/dL also led to higher rates of infection. Higher rates of graft rejection were seen at BG > 200 mg/dL (P < 0.001). Mean BG ≥ 200 mg/dL was associated with more infections (P = 0.002). Nurse-initiated protocols and early screening strategies have shown a reduction in negative post-LT outcomes. CONCLUSION Hyperglycemia in the perioperative period is associated with poor post-LT outcomes. Only a few prospective studies have designed interventions aimed at managing post-LT hyperglycemia, post-transplant diabetes mellitus (PTDM) and their impact on post-LT outcomes.
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Affiliation(s)
- Prani Paka
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States
| | - Sarah R Lieber
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, United States
| | - Ruth-Ann Lee
- Division of Abdominal Transplant, Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, United States
| | - Chirag S Desai
- Division of Abdominal Transplant, Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, United States
| | - Robert E Dupuis
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States
| | - Alfred Sidney Barritt
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, United States
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10
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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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11
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Ling Q, Xie H, Li J, Liu J, Cao J, Yang F, Wang C, Hu Q, Xu X, Zheng S. Donor Graft MicroRNAs: A Newly Identified Player in the Development of New-onset Diabetes After Liver Transplantation. Am J Transplant 2017; 17:255-264. [PMID: 27458792 PMCID: PMC5215980 DOI: 10.1111/ajt.13984] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 07/17/2016] [Accepted: 07/18/2016] [Indexed: 01/25/2023]
Abstract
New-onset diabetes after liver transplantation (NODALT) is a frequent complication with an unfavorable outcome. We previously demonstrated a crucial link between donor graft genetics and the risk of NODALT. We selected 15 matched pairs of NODALT and non-NODALT liver recipients using propensity score matching analysis. The donor liver tissues were tested for the expression of 10 microRNAs (miRNAs) regulating human hepatic glucose homeostasis. The biological functions of potential target genes were predicted using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Both miR-103 and miR-181a were significantly highly expressed in the NODALT group as compared to the non-NODALT group. The predicted target genes (e.g. Irs2, Pik3r1, Akt2, and Gsk3b) were involved in glucose import and the insulin signaling pathway. We also observed dysregulation of miRNAs (e.g. let-7, miR-26b, miR-145, and miR-183) in cultured human hepatocytes treated with tacrolimus or high glucose, the two independent risk factors of NODALT identified in this cohort. The hepatic miRNA profiles altered by tacrolimus or hyperglycemia were associated with insulin resistance and glucose homeostatic imbalance as revealed by enrichment analysis. The disease susceptibility miRNA expressive pattern could be imported directly from the donor and consolidated by the transplant factors.
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Affiliation(s)
- Q. Ling
- Department of SurgeryCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
- Key Lab of Combined Multi‐Organ TransplantationMinistry of Public HealthHangzhouChina
| | - H. Xie
- Key Lab of Combined Multi‐Organ TransplantationMinistry of Public HealthHangzhouChina
| | - J. Li
- Department of SurgeryCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
| | - J. Liu
- Department of SurgeryCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
- Department of Pathology and Molecular MedicineFaculty of Health SciencesMcMaster UniversityHamiltonOntarioCanada
| | - J. Cao
- Key Lab of Combined Multi‐Organ TransplantationMinistry of Public HealthHangzhouChina
| | - F. Yang
- Department of SurgeryCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
| | - C. Wang
- Department of SurgeryCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
| | - Q. Hu
- Key Lab of Combined Multi‐Organ TransplantationMinistry of Public HealthHangzhouChina
| | - X. Xu
- Department of SurgeryCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
- Key Lab of Combined Multi‐Organ TransplantationMinistry of Public HealthHangzhouChina
| | - S. Zheng
- Department of SurgeryCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
- Key Lab of Combined Multi‐Organ TransplantationMinistry of Public HealthHangzhouChina
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Ling Q, Xu X, Xie H, Wang K, Xiang P, Zhuang R, Shen T, Wu J, Wang W, Zheng S. New-onset diabetes after liver transplantation: a national report from China Liver Transplant Registry. Liver Int 2016; 36:705-712. [PMID: 26681557 DOI: 10.1111/liv.13042] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 12/04/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND/AIMS New-onset diabetes after transplantation (NODAT) is a serious complication of liver transplantation (LT). The present study aimed to investigate the risk factors of NODAT by a national survey using the China Liver Transplant Registry database. PATIENTS A total of 10 204 non-pre-existing diabetic patients undergone primary LT between January 2000 and December 2013 were included. Risk factors were identified by logistic regression analysis. RESULTS NODAT occurred in 24.3% of liver recipients with a median follow-up time of 2.6 years, and was associated with a significantly lower patient survival. NODAT increased not only diabetes related complications (e.g., infection, kidney failure) but also biliary stricture and cholangitis. NODAT patients who received hypoglycaemic treatment had a worse prognosis and a higher hepatocellular carcinoma recurrence compared with those without treatment. New-onset hyperglycaemia (<30 days) was the major predictor of NODAT. Other risk factors included cold ischaemia time >9 h, recipient age >50 years, body mass index >25 kg/m(2) , other hepatitis (mainly hepatitis C), post-transplant intensive care unit stay >15 days, cytomegalovirus infection and corticosteroid at discharge. CONCLUSIONS The incidence of NODAT in China is similar to that in Western countries. However, the NODAT-related complications are more common and severer in China compared with those in Western countries. The major risk factors are different.
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Affiliation(s)
- Qi Ling
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haiyang Xie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kai Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Penghui Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Runzhou Zhuang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian Shen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Ling Q, Xu X, Wang B, Li L, Zheng S. The Origin of New-Onset Diabetes After Liver Transplantation: Liver, Islets, or Gut? Transplantation 2016; 100:808-813. [PMID: 26910326 DOI: 10.1097/tp.0000000000001111] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
New-onset diabetes is a frequent complication after solid organ transplantation. Although a number of common factors are associated with the disease, including recipient age, body mass index, hepatitis C infection, and use of immunosuppressive drugs, new-onset diabetes after liver transplantation (NODALT) has the following unique aspects and thus needs to be considered its own entity. First, a liver graft becomes the patient's primary metabolic regulator after liver transplantation, but this would not be the case for kidney or other grafts. The metabolic states, as well as the genetics of the graft, play crucial roles in the development of NODALT. Second, dysfunction of the islets of Langerhans is common in cirrhotic patients and would be exacerbated by immunosuppressive agents, particularly calcineurin inhibitors. On the other hand, minimized immunosuppressive protocols have been widely advocated in liver transplantation because of liver tolerance (immune privilege). Third and last, through the "gut-liver axis," graft function is closely linked to gut microbiota, which is now considered an important metabolic organ and known to independently influence the host's metabolic homeostasis. Liver transplant recipients present with specific gut microbiota that may be prone to trigger metabolic disorders. In this review, we proposed 3 possible sites for the origin of NODALT, which are liver, islets, and gut, to help elucidate the underlying mechanism of NODALT.
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Affiliation(s)
- Qi Ling
- 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China. 3 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Xia Q. New-onset diabetes after liver transplantation: Enough attention required! J Diabetes 2015; 7:774-6. [PMID: 25802101 DOI: 10.1111/1753-0407.12285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Affiliation(s)
- Qiang Xia
- Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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