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Zelada H, Campana M, Kawai K, Redden D, Agarwal G, Gutierrez OM, Kumar V. Efficacy, Tolerability, and Safety of Glucagon-Like Peptide 1 Receptor Agonists (GLP1-RA) in Kidney Transplant Recipients With Diabetes. Clin Transplant 2025; 39:e70144. [PMID: 40230336 DOI: 10.1111/ctr.70144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 03/05/2025] [Accepted: 03/19/2025] [Indexed: 04/16/2025]
Abstract
INTRODUCTION Uncontrolled diabetes after solid-organ transplantation has been associated with weight gain, high cardiovascular mortality, and transplant rejection. The current standard of care for uncontrolled diabetes after KT is insulin. Recently GLP1-RA have been proposed as an adjuvant medication for those with obesity, but there are concerns for side effects and safety. METHODS Adults (n = 50) with diabetes who underwent KT from at a single academic medical center were included. This is a retrospective study of 25 recipients on insulin ± oral antidiabetic medications who initiated GLP1-RA, and 25 recipients on insulin ± oral agents. Metabolic issues and safety were evaluated before starting GLP1RA, and 6 and 12 months after. The linear mixed effects model was used to evaluate the mean difference in the change in the outcome between the two groups. RESULTS KT participants were on average 56 years of age, 64% male, with T2D. The primary outcome of change in weight 12 months after initiation of GLP1-RA on an average was -10.1 pounds in the GLP1-RA group, compared to +6.0 pounds in the non-GLP1-RA group (p < 0.01), the change in BMI 12 months after initiation of GLP1-RA on an average was -1.7 kg/m2 in the GLP1-RA group compared to +1.1 kg/m2 in the non-GLP1-RA group (p < 0.01), and the change in creatinine 12 months after starting GLP1-RA was on average -0.2 mg/dL in the GLP1-RA group and on average +0.3 mg/dL in the non-GLP1-RA group (p < 0.01). The change in proteinuria 12 months after starting GLP1-RA was on average -128.4 in the GLP1-RA and on average +15.4 mg/dL in the controls (p < 0.01). The rate of GLP1-RA discontinuation was 0%. CONCLUSIONS Well-selected post-kidney transplant participants demonstrated good tolerance for GLP-1RA. Participants who took GLP1-RA had better glycemic control, more weight loss, a decrease in daily insulin requirements, better preservation of kidney function, and reduced proteinuria 7 12 months after initiation of GLP1-RA compared to those who did not. GLP1-RA did not alter tacrolimus levels or doses.
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Affiliation(s)
- Henry Zelada
- Division of Endocrinology Diabetes and Metabolism, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Mario Campana
- Division of Endocrinology Diabetes and Metabolism, Rush University Medical Center, Chicago, Illinois, USA
| | - Kosuke Kawai
- Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - David Redden
- Division of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Gaurav Agarwal
- Division of Nephrology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA
| | - Orlando M Gutierrez
- Division of Nephrology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA
| | - Vineeta Kumar
- Division of Nephrology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA
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O'Donnell JEM, Hastings LA, Briody JN, Chan CL, Colombo C, Douglas TA, Freedman SD, Gonska T, Greenfield JR, Leung DH, Lim AYL, Moran A, Prentice BJ, Putman MS, Trotter M, Tullis E, Westall GP, Verge CF, Wainwright CE, Ooi CY. SHIFTing goals in cystic fibrosis-managing extrapulmonary disease in the era of CFTR modulator therapy; Proceedings of the International Shaping Initiatives and Future Trends (SHIFT) Symposium. Pediatr Pulmonol 2024; 59:1661-1676. [PMID: 39903130 DOI: 10.1002/ppul.26970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 03/06/2024] [Indexed: 02/06/2025]
Abstract
BACKGROUND Cystic fibrosis (CF) is a life-shortening multisystem genetic disease. Although progressive pulmonary disease is the predominant cause of morbidity and mortality, improvements in treatment for CF-related lung disease, with associated increase in longevity, have increased the prevalence of extrapulmonary manifestations1. METHODS To discuss these issues, a multidisciplinary meeting of international leaders and experts in the field was convened in November 2021 at the Shaping Initiatives and Future Trends Symposium with the goal of highlighting shifting management paradigms in CF. The main topics covered were: (1) nutrition and obesity, (2) exocrine pancreas, (3) CF-related diabetes, (4) CF liver disease, (5) CF-related bone disease, and (6) post-lung transplant care. This document summarizes the proceedings, highlighting the key priorities and important research questions that were discussed. RESULTS Improved life expectancy, the advent of cystic fibrosis transmembrane conductance regulator modulators, and the increasing appreciation of the heterogeneity or spectrum of disease are leading to a shift in management for patients with cystic fibrosis. Care should be individualized to ensure that increased longevity is accompanied by improved extra-pulmonary care and reduced morbidity.
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Affiliation(s)
- Jonathan E M O'Donnell
- Department of Gastroenterology, Sydney Children's Hospital, University of New South Wales, Sydney, Australia
- School of Clinical Medicine, Discipline of Pediatrics and Child Health, UNSW Medicine & Health, University of New South Wales, Sydney, Australia
| | - Lucy A Hastings
- Department of Endocrinology, Sydney Children's Hospital Randwick, Sydney Children's Hospitals Network, Sydney, Australia
| | - Julie N Briody
- Nuclear Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
| | - Christine L Chan
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
- Children's Hospital Colorado, Aurora, Colorado, USA
| | - Carla Colombo
- CF Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Tonia A Douglas
- Department of Respiratory and Sleep Medicine, Queensland Children's Hospital, South Brisbane, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Steven D Freedman
- Israel Deaconess Medical Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Tanja Gonska
- Division of Gastroenterology, Hepatology and Nutrition, Dep of Pediatrics, University of Toronto, Toronto, Ontario, Canada
- Research Institute, the Hospital for Sick Children, Toronto, Ontario, Canada
| | - Jerry R Greenfield
- Endocrinology and Diabetes, St Vincent's Hospital Sydney, Darlinghurst, Australia
- School of Clinical Medicine, The University of New South Wales, Sydney, Australia
- Garvan Institute, Sydney, Australia
| | - Daniel H Leung
- Baylor College of Medicine, Houston, Texas, USA
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Adeline Y L Lim
- Department of Respiratory and Sleep Medicine, Queensland Children's Hospital, South Brisbane, Australia
| | | | | | - Melissa S Putman
- Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Michael Trotter
- Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia
| | - Elizabeth Tullis
- St Michael's Hospital, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Glen P Westall
- Lung Transplant Service, Alfred Health, Melbourne, Australia
- Central Clinical School, Monash University, Melbourne, Australia
| | - Charles F Verge
- School of Clinical Medicine, Discipline of Pediatrics and Child Health, UNSW Medicine & Health, University of New South Wales, Sydney, Australia
- Department of Endocrinology, Sydney Children's Hospital Randwick, Sydney Children's Hospitals Network, Sydney, Australia
| | - Claire E Wainwright
- Department of Respiratory and Sleep Medicine, Queensland Children's Hospital, South Brisbane, Australia
- Child Health Research Center (CHRC), The University of Queensland, Brisbane, Australia
| | - Chee Y Ooi
- Department of Gastroenterology, Sydney Children's Hospital, University of New South Wales, Sydney, Australia
- School of Clinical Medicine, Discipline of Pediatrics and Child Health, UNSW Medicine & Health, University of New South Wales, Sydney, Australia
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Lee JE, Jung H, Byun SH, Park JM, Yeo J, Jeon Y, Lee SW, Park SS, Lim DG, Kim SO, Kwak KH. Effect of Dexmedetomidine Preconditioning on Hepatic Ischemia-Reperfusion Injury in Acute Hyperglycemic Rats. Transplant Proc 2023; 55:2478-2486. [PMID: 37867004 DOI: 10.1016/j.transproceed.2023.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 08/08/2023] [Accepted: 09/22/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND Acute hyperglycemia frequently occurs in stressful situations, including liver transplantation or hepatic surgery, which may affect the protective effects of dexmedetomidine preconditioning and increase postoperative mortality. Therefore, this study aimed to investigate the effects of dexmedetomidine on hepatic ischemia-reperfusion injury in acute hyperglycemia. METHODS Thirty-six Sprague-Dawley rats were randomly assigned to 6 groups, including a combination between 2 glycemic (normo- and hyperglycemia) and 3 ischemia-reperfusion conditions (sham, ischemia-reperfusion only, and dexmedetomidine plus ischemia-reperfusion). Dexmedetomidine 70 μg/kg was preconditioned 30 minutes before ischemic injury. After 6 hours of reperfusion, serum aminotransferase levels were measured to confirm the hepatic tissue injury. Furthermore, inflammatory (nuclear factor-κb, tumor necrosis factor-α, and interleukin-6) and oxidative stress markers (malondialdehyde and superoxide dismutase) were detected. RESULTS Ischemia-reperfusion injury significantly increased the serum levels of aminotransferase and inflammatory and oxidative stress markers. These ischemia-reperfusion-induced changes were further exacerbated in hyperglycemia and were significantly attenuated by dexmedetomidine preconditioning. However, the effects of dexmedetomidine in hyperglycemia were lesser than those in normoglycemia (P < .05 for aminotransferases, inflammatory markers, malondialdehyde, and superoxide dismutase). CONCLUSIONS These findings suggest that the protective effects of dexmedetomidine preconditioning may be intact against hepatic ischemia-reperfusion injury in acute hyperglycemia. Although its effects appeared to be relatively reduced, this may be because of the increase in oxidative stress and inflammatory response caused by acute hyperglycemia. To determine whether the effects of dexmedetomidine itself would be impaired in hyperglycemia, further study is needed.
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Affiliation(s)
- Jeong Eun Lee
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Hoon Jung
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Sung-Hye Byun
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Jun-Mo Park
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Jinseok Yeo
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Younghoon Jeon
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - See Woo Lee
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Sung-Sik Park
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Dong Gun Lim
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Si-Oh Kim
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Kyung-Hwa Kwak
- Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
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Caldara R, Tomajer V, Monti P, Sordi V, Citro A, Chimienti R, Gremizzi C, Catarinella D, Tentori S, Paloschi V, Melzi R, Mercalli A, Nano R, Magistretti P, Partelli S, Piemonti L. Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge. Front Immunol 2023; 14:1323439. [PMID: 38077372 PMCID: PMC10701551 DOI: 10.3389/fimmu.2023.1323439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 11/06/2023] [Indexed: 12/18/2023] Open
Abstract
Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes.
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Affiliation(s)
- Rossana Caldara
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Valentina Tomajer
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Paolo Monti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Valeria Sordi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Antonio Citro
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Raniero Chimienti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
| | - Chiara Gremizzi
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Davide Catarinella
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Tentori
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Vera Paloschi
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Raffella Melzi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessia Mercalli
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Rita Nano
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Paola Magistretti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Partelli
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
| | - Lorenzo Piemonti
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
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Zelada H, Recklein CL, McGill JB. Short-term multifactorial intervention (STEMI): An approach using structured blood glucose monitoring (BGM) and conventional therapies in persons with diabetes. J Family Med Prim Care 2023; 12:1412-1416. [PMID: 37649768 PMCID: PMC10465056 DOI: 10.4103/jfmpc.jfmpc_2172_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 04/12/2023] [Accepted: 05/03/2023] [Indexed: 09/01/2023] Open
Abstract
Background Achieving glucose and glycosylated hemoglobin (HbA1c) targets have been shown to reduce long-term microvascular complications of diabetes; however, suboptimal glucose control is common. We tested whether glucose control could be improved within 8 weeks by employing structured blood glucose monitoring (BGM) qid in addition to seven times per day prior to visits for diabetes education and medication management that occurred every 2-4 weeks. Methods This single-center, prospective study was conducted on 78 adults with either type 1 diabetes (T1D) or type 2 diabetes (T2D), HbA1c >8%, and serum creatinine (sCr) <2.0 mg/dl. HbA1c was checked at baseline, Week 2, Week 4, and at Week 8. Patients were evaluated by a physician and a certified diabetes educator (CDE) at baseline, Week 2, and Week 4 for treatment adjustments and lifestyle advice based on a review of BGM done qid plus 7-point profiles conducted before Weeks 2, 4, and 8. Study outcomes were change in HbA1c from baseline to Week 8 and change in mean glucose on the 7-point profile from Week 2 to Week 8. These were compared using one-way repeated measures ANOVA. Results Of the 78 patients, 64.1% had T2D, 50% were women, and 72% were Caucasian. Mean age (±SD) was 51.3.5 ± 11.1 years, and median diabetes duration was 9 (5-17) years. The percentage of patients using insulin increased from 58.9% at baseline to 67.9% at Week 8. The mean (±SD) HbA1c was 9.53% (±1.71) at baseline, declined -1.38% from baseline to week 8 (CI -1.62 to -0.14, P < 0.001). The mean (±SD) glucose on the 7-point profile was 187 (±52) mg/dl at Week 2, and 157 (±5) mg/dl at Week 8. (P < 0.01). Conclusions An intensive glucose optimization program using structured BGM qid plus 7-point profiles, diabetes education, and conventional anti-diabetic therapies was successful in reducing HbA1c by 1.38% over 8 weeks in patients with poor glucose control.
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Affiliation(s)
- Henry Zelada
- Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham Heersink School of Medicine, United States
| | - Carol L. Recklein
- Division of Endocrinology Metabolism and Lipid Research, Washington University School of Medicine in St Louis, United States
| | - Janet B. McGill
- Division of Endocrinology Metabolism and Lipid Research, Washington University School of Medicine in St Louis, United States
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Belfort-DeAguiar R, Lomonaco R, Cusi K. Approach to the Patient With Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab 2023; 108:483-495. [PMID: 36305273 DOI: 10.1210/clinem/dgac624] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 10/13/2022] [Indexed: 01/20/2023]
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes (T2D), causing substantial burden from hepatic and extrahepatic complications. However, endocrinologists often follow people who are at the highest risk of its more severe form with nonalcoholic steatohepatitis or NASH (i.e., T2D or obesity with cardiometabolic risk factors). Endocrinologists are in a unique position to prevent cirrhosis in this population with early diagnosis and treatment. OBJECTIVE This work aims to offer endocrinologists a practical approach for the management of patients with NAFLD, including diagnosis, fibrosis risk stratification, and referral to hepatologists. PATIENTS (1) An asymptomatic patient with obesity and cardiometabolic risk factors, found to have hepatic steatosis; (2) a patient with T2D and NASH with clinically significant liver fibrosis; and (3) a liver transplant recipient with a history of NASH cirrhosis, with significant weight regain and with recurrent NAFLD on the transplanted organ. CONCLUSION NASH can be reversed with proper management of obesity and of T2D. While no agents are currently approved for the treatment of NASH, treatment should include lifestyle changes and a broader use of structured weight-loss programs, obesity pharmacotherapy, and bariatric surgery. Diabetes medications such as pioglitazone and some glucagon-like peptide 1 receptor agonists may also improve liver histology and cardiometabolic health. Sodium-glucose cotransporter-2 inhibitors and insulin may ameliorate steatosis, but their effect on steatohepatitis remains unclear. Awareness by endocrinologists about, establishing an early diagnosis of fibrosis (ie, FIB-4, liver elastography) in patients at high-risk of cirrhosis, long-term monitoring, and timely referral to the hepatologist are all critical to curve the looming epidemic of cirrhosis from NAFLD.
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Affiliation(s)
- Renata Belfort-DeAguiar
- Internal Medicine Department, Endocrinology Section, Yale University, New Haven, Connecticut 06520, USA
| | - Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610, USA
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Effects of Intensive Blood Glucose Control on Surgical Site Infection for Liver Transplant Recipients: A Randomized Controlled Trial. Transplant Proc 2023; 55:170-177. [PMID: 36567173 DOI: 10.1016/j.transproceed.2022.10.062] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 09/07/2022] [Accepted: 10/18/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND The evidence supporting intensive blood glucose control to prevent surgical site infections (SSIs) among liver transplant recipients is insufficient. We aimed to assess the effects of postoperative intensive blood glucose control (IBGC) against standard blood glucose control (SBGC) on the incidence of SSIs among adult liver transplant recipients. METHODS We performed a randomized controlled trial (ClinicalTrials.gov identifier NCT03474666). The IBGC target was 80 to 130 mg/dL, and the SBGC target was below 180 mg/dL. Analyses were made on an intention-to-treat basis. RESULTS Of the 41 recipients enrolled onto the trial, 20 were randomly allocated to the IBGC group and 21 to the SBGC group. There were no significant differences in SSIs among recipients allocated to either group (relative risk [RR], 0.78; 95% confidence interval [CI], 0.21-2.88; P = .69). Mean (SD) blood glucose levels were significantly lower in the IBGC group in the 24-hour period after surgery (145.0 [20.7] mg/dL and 230.2 [51.6] mg/dL; P = .001). While there were fewer episodes of hypoglycemia in the IBGC group, this was not statistically significant. There were no episodes of severe hypoglycemia in either group. Hyperglycemia and severe hyperglycemia were significantly more frequent in the SBGC group (RR, 0.70; 95% CI, 0.52-0.93; P = .001 and RR, 0.07; 95% CI, 0.01-0.48; P = .001, respectively). Length of hospital stay was significantly shorter for recipients in the IBGC group (13.1 [5.5] days vs 19.3 [12.1] days; P = .04). CONCLUSIONS Although this small trial did not find intensive control reduced SSI, it was associated with lower blood glucose levels, fewer episodes of hyperglycemia and severe hyperglycemia, and shorter length of hospital stay.
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Sharma S, Stine JG, Verbeek T, Bezinover D. Management of Patients With Non-alcoholic Steatohepatitis Undergoing Liver Transplantation: Considerations for the Anesthesiologist. J Cardiothorac Vasc Anesth 2022; 36:2616-2627. [PMID: 34391652 DOI: 10.1053/j.jvca.2021.07.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/24/2021] [Accepted: 07/09/2021] [Indexed: 11/11/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) currently affects more than 25% of the world population and is rising. NAFLD can progress to non-alcoholic steatohepatitis that is associated with hepatic inflammation and fibrosis and can result in cirrhosis with subsequent liver failure. Non-alcoholic steatohepatitis (NASH) has now emerged as one of the leading etiologies for a liver transplant among adults in the United States. Given the rising incidence of liver transplants in patients with NASH-related cirrhosis, it is essential for anesthesiologists to be familiar with this condition as well as with NASH-related comorbidities and perioperative complications. Not only is NASH linked to metabolic syndrome, but it also is independently associated with cardiovascular disease, renal and thyroid dysfunction, obstructive sleep apnea (OSA), and a hypercoagulable state. The association with these conditions can affect the perioperative outcome of these patients, particularly because of increased mortality from major adverse cardiovascular events and sepsis. In order to decrease the perioperative morbidity and mortality of patients with NASH undergoing a liver transplant, a multidisciplinary approach to their perioperative management is essential, along with careful preoperative evaluation and aggressive intraoperative and postoperative monitoring. The focus of this review article is to provide a comprehensive overview of challenges associated with liver transplants in patients with NASH and to provide suggestions for appropriate patient selection and perioperative management.
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Affiliation(s)
- Sonal Sharma
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA.
| | - Jonathan G Stine
- Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA; Department of Medicine and Public Health Sciences, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Cancer Institute, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA
| | - Thomas Verbeek
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA; Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA
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Gundling F. Der hepatogene Diabetes – aktueller Stand der Diagnostik und Therapie. JOURNAL FÜR KLINISCHE ENDOKRINOLOGIE UND STOFFWECHSEL 2022; 15:42-52. [DOI: 10.1007/s41969-022-00158-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/23/2022] [Indexed: 01/04/2025]
Abstract
Zusammenfassung
Hintergrund
Patienten mit Leberzirrhose entwickeln häufig Störungen des Glukosemetabolismus wie Glukoseintoleranz oder einen hepatogenen Diabetes, welche neben der hepatozellulären Funktionseinschränkung durch die ausgeprägte Insulinresistenz als Folge der chronischen Lebererkrankung verursacht sind.
Diskussion
Empfehlungen mit Leitliniencharakter zur Diagnostik und Therapie des hepatogenen Diabetes fehlen bislang. Im Hinblick auf basistherapeutische Maßnahmen sollte eine ausreichende Deckung des Energie- und Proteinstoffwechsels gewährleistet sein, da ein Großteil der Zirrhosepatienten mangelernährt ist. Bei der medikamentösen Behandlung des hepatogenen Diabetes muss auf die erhöhte Hypoglykämiegefährdung geachtet werden. Aufgrund der Nebenwirkungen sind Biguanide sowie PPAR-gamma-Liganden bei Leberzirrhose kontraindiziert. Geeignete orale Antidiabetika sind insbesondere Sulfonylharnstoffanaloga und kurz wirksame Sulfonylharnstoffe. Wenn eine suffiziente Diabeteseinstellung mit oralen Antidiabetika nicht gelingt, sollte eine prandiale Insulintherapie mit Insulinen von kurzer Wirkdauer oder kurz wirksamen Insulinanaloga eingesetzt werden.
Schlussfolgerung
Die Optimierung einer diabetischen Stoffwechsellage hat neben der Vermeidung typischer diabetischer Spätkomplikationen eine wichtige Bedeutung für die Vermeidung und Reduzierung von Zirrhose-assoziierten Komplikationen wie z. B. gastrointestinalen Blutungsereignissen, hepatischer Enzephalopathie oder dem Auftreten eines hepatozellulären Karzinoms.
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10
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Fragoso LVC, Araújo MFMD, Lobo LFDS, Schreen D, Zanetti ML, Damasceno MMC. Bolus versus continuous insulin infusion in immediate postoperative blood glucose control in liver transplantation: pragmatic clinical trial. EINSTEIN-SAO PAULO 2022; 20:eAO6959. [PMID: 35674591 PMCID: PMC9165566 DOI: 10.31744/einstein_journal/2022ao6959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 11/05/2021] [Indexed: 11/05/2022] Open
Abstract
Objective: To analyze the effectiveness and safety of two insulin therapy techniques (continuous and intermittent infusion) in the blood glucose control of people who have undergone liver transplantation, in the immediate postoperative period. Methods: The study was a prospective, open, pragmatic clinical trial with 42 participants, divided into two groups of 21 patients each, in the immediate postoperative period following liver transplantation. Participants in the Experimental Group and Control Group received continuous infusion and bolus insulin, respectively, starting at capillary blood glucose ≥150mg/dL. Results: There were no statistically significant differences in the blood glucose reduction time to reach the target range between the Experimental Group and Control Group in the transplanted patients (p=0.919). No statistically significant differences regarding the presence of low blood glucose (p=0.500) and in the initial blood glucose value (p=0.345) were found. The study identified the final blood glucose value in postoperative intensive care unit lower and statistically significant in the continuous infusion pump group in relation to the Bolus Group (p<0.001). Additionally, the variation of blood glucose reduction was higher and statistically significant in the continuous method group (p<0.05). Conclusion: The continuous infusion method was more effective in the blood glucose control of patients in the postoperative period following liver transplantation. Brazilian Registry of Clinical Trials: RBR-9Y5tbp
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11
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Guidelines for Perioperative Care for Liver Transplantation: Enhanced Recovery After Surgery (ERAS) Recommendations. Transplantation 2022; 106:552-561. [PMID: 33966024 DOI: 10.1097/tp.0000000000003808] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Enhanced Recovery After Surgery (ERAS) is a multimodal, evidence-based, program of care developed to minimize the response to surgical stress, associated with reduced perioperative morbidity and hospital stay. This study presents the specific ERAS Society recommendations for liver transplantation (LT) based on the best available evidence and on expert consensus. METHODS PubMed and ClinicalTrials.gov were searched in April 2019 for published and ongoing randomized clinical trials on LT in the last 15 y. Studies were selected by 5 independent reviewers and were eligible if focusing on each validated ERAS item in the area of adult LT. An e-Delphi method was used with an extended interdisciplinary panel of experts to validate the final recommendations. RESULTS Forty-three articles were included in the systematic review. A consensus was reached among experts after the second round. Patients should be screened for malnutrition and treated whenever possible. Prophylactic nasogastric intubation and prophylactic abdominal drainage may be omitted, and early extubation should be considered. Early oral intake, mobilization, and multimodal-balanced analgesia are recommended. CONCLUSIONS The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the e-Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.
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12
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García-Compeán D, Orsi E, Kumar R, Gundling F, Nishida T, Villarreal-Pérez JZ, Del Cueto-Aguilera ÁN, González-González JA, Pugliese G. Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives. World J Gastroenterol 2022; 28:775-793. [PMID: 35317103 PMCID: PMC8900578 DOI: 10.3748/wjg.v28.i8.775] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/19/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, Fdn IRCCS Ca Granda, Endocrine Unit, Padigl Granelli, Milan 20121, Italy
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Felix Gundling
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Diabetics, Metabolism and Infectious Diseases, Sozialstiftung Bamberg, Bamberg 96049, Germany
| | - Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka 560-8565, Japan
| | | | - Ángel N Del Cueto-Aguilera
- Department of Gastroenterology and Internal Medicine, Faculty of Medicine, University Hospital, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - José A González-González
- Gastroenterology Service and Department of Internal Medicine, University Hospital Dr. José E González and Medical School, Monterrey 64460, Nuevo León, Mexico
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, La Sapienza University, Roma 00161, Italy
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Lee CY, Wu MY, Chan HC, Chen TT, Hsu LY, Wu MS, Cherng YG. The Influence of Diabetes Mellitus on the Risks of End-Stage Kidney Disease and Mortality After Liver Transplantation. Transpl Int 2022; 35:10023. [PMID: 35185375 PMCID: PMC8842258 DOI: 10.3389/ti.2022.10023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 01/10/2022] [Indexed: 11/18/2022]
Abstract
This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research Database, Taiwan, 3,489 patients who received a LT between 1 January 2005, and 31 December 2015, were enrolled in this study and divided into the pre-existing DM, post-LT DM (PLTDM), and without DM groups. All subjects were followed up from 1 year after LT to the index date for ESKD, and the occurrence of death, or until 31 December 2016. Of the 3,489 patients with LT, 1,016 had pre-existing DM, 215 had PLTDM, and 2,258 had no DM pre- or post-LT. The adjusted HRs of ESKD were 1.77 (95% Confidence Interval [CI], .78–3.99) and 2.61 (95% CI, 1.63–4.18) for PLTDM group and pre-existing DM group compared to without DM group, respectively. For the risk of death, the adjusted HRs were 1.05 (95% CI, .72–1.55) and 1.28 (95% CI, 1.04–1.59) for PLTDM group and pre-existing DM group compared to those without DM group, respectively. The sensitivity analysis for the risk of ESKD and death also revealed the consistent result. Pre-existing DM has significant increase the risk of post-LT ESKD and mortality. The role of PLTDM should be explored to explain postoperative morbidity and mortality.
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Affiliation(s)
- Chung-Ying Lee
- Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Mei-Yi Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
| | - Hsiu-Chen Chan
- Department of Pharmacy, Shuang Ho Hospital, New Taipei City, Taiwan
| | - Tzu-Ting Chen
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan
| | - Le-Yin Hsu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Mai-Szu Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yih-Giun Cherng
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- *Correspondence: Yih-Giun Cherng,
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14
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Hartl L, Elias J, Prager G, Reiberger T, Unger LW. Individualized treatment options for patients with non-cirrhotic and cirrhotic liver disease. World J Gastroenterol 2021; 27:2281-2298. [PMID: 34040322 PMCID: PMC8130039 DOI: 10.3748/wjg.v27.i19.2281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/19/2021] [Accepted: 04/25/2021] [Indexed: 02/06/2023] Open
Abstract
The obesity pandemic has led to a significant increase in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). While dyslipidemia, type 2 diabetes mellitus and cardiovascular diseases guide treatment in patients without signs of liver fibrosis, liver related morbidity and mortality becomes relevant for MAFLD's progressive form, non-alcoholic steatohepatitis (NASH), and upon development of liver fibrosis. Statins should be prescribed in patients without significant fibrosis despite concomitant liver diseases but are underutilized in the real-world setting. Bariatric surgery, especially Y-Roux bypass, has been proven to be superior to conservative and/or medical treatment for weight loss and resolution of obesity-associated diseases, but comes at a low but existent risk of surgical complications, reoperations and very rarely, paradoxical progression of NASH. Once end-stage liver disease develops, obese patients benefit from liver transplantation (LT), but may be at increased risk of perioperative infectious complications. After LT, metabolic comorbidities are commonly observed, irrespective of the underlying liver disease, but MAFLD/NASH patients are at even higher risk of disease recurrence. Few studies with low patient numbers evaluated if, and when, bariatric surgery may be an option to avoid disease recurrence but more high-quality studies are needed to establish clear recommendations. In this review, we summarize the most recent literature on treatment options for MAFLD and NASH and highlight important considerations to tailor therapy to individual patient's needs in light of their risk profile.
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Affiliation(s)
- Lukas Hartl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna A-1090, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna A-1090, Austria
| | - Joshua Elias
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, United Kingdom
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, United Kingdom
| | - Gerhard Prager
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna A-1090, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna A-1090, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna A-1090, Austria
| | - Lukas W Unger
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, United Kingdom
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna A-1090, Austria
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15
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Yasodhara A, Dong V, Azhie A, Goldenberg A, Bhat M. Identifying Modifiable Predictors of Long-Term Survival in Liver Transplant Recipients With Diabetes Mellitus Using Machine Learning. Liver Transpl 2021; 27:536-547. [PMID: 37160039 PMCID: PMC8248095 DOI: 10.1002/lt.25930] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 10/01/2020] [Accepted: 10/12/2020] [Indexed: 01/13/2023]
Abstract
Diabetes mellitus (DM) significantly impacts long-term survival after liver transplantation (LT). We identified survival factors for LT recipients who had DM to inform preventive care using machine-learning analysis. We analyzed risk factors for mortality in patients from across the United States using the Scientific Registry of Transplant Recipients (SRTR). Patients had undergone LT from 1987 to 2019, with a follow-up of 6.47 years (standard deviation [SD] 5.95). Findings were validated on a cohort from the University Health Network (UHN) from 1989 to 2014 (follow-up 8.15 years [SD 5.67]). Analysis was conducted with Cox proportional hazards and gradient boosting survival. The training set included 84.67% SRTR data (n = 15,289 patients), and the test set included 15.33% SRTR patients (n = 2769) and data from UHN patients (n = 1290). We included 18,058 adults (12,108 [67.05%] men, average age 54.21 years [SD 9.98]) from the SRTR who had undergone LT and had complete data for investigated features. A total of 4634 patients had preexisting DM, and 3158 had post-LT DM. The UHN data consisted of 1290 LT recipients (910 [70.5%] men, average age 54.0 years [SD 10.4]). Increased serum creatinine and hypertension significantly impacted mortality with preexisting DM 1.36 (95% confidence interval [CI], 1.21-1.54) and 1.20 (95% CI, 1.06-1.35) times, respectively. Sirolimus use increased mortality 1.36 times (95% CI, 1.18-1.58) in nondiabetics and 1.33 times (95% CI, 1.09-1.63) in patients with preexisting DM. A similar effect was found in post-LT DM, although it was not statistically significant (1.38 times; 95% CI, 1.07-1.77; P = 0.07). Survival predictors generally achieved a 0.60 to 0.70 area under the receiver operating characteristic for 5-year mortality. LT recipients who have DM have a higher mortality risk than those without DM. Hypertension, decreased renal function, and sirolimus for maintenance immunosuppression compound this mortality risk. These predisposing factors must be intensively treated and modified to optimize long-term survival after transplant.
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Affiliation(s)
- Angeline Yasodhara
- Department of Computer ScienceUniversity of TorontoTorontoOntarioCanada,Genetics and Genome BiologySickKids Research InstituteTorontoOntarioCanada,Vector InstituteTorontoOntarioCanada
| | - Victor Dong
- Interdepartmental Division of Critical Care MedicineTorontoOntarioCanada
| | - Amirhossein Azhie
- Multi Organ Transplant Program and Division of GastroenterologyUniversity Health NetworkTorontoOntarioCanada
| | - Anna Goldenberg
- Department of Computer ScienceUniversity of TorontoTorontoOntarioCanada,Genetics and Genome BiologySickKids Research InstituteTorontoOntarioCanada,Vector InstituteTorontoOntarioCanada
| | - Mamatha Bhat
- Multi Organ Transplant Program and Division of GastroenterologyUniversity Health NetworkTorontoOntarioCanada,Division of Gastroenterology and HepatologyUniversity Health Network and University of TorontoTorontoOntarioCanada,Division of GastroenterologyUniversity of TorontoTorontoOntarioCanada
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16
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Wilke TJ, Fremming BA, Brown BA, Markin NW, Kassel CA. 2020 Clinical Update in Liver Transplantation. J Cardiothorac Vasc Anesth 2021; 36:1449-1457. [PMID: 33653578 PMCID: PMC7865096 DOI: 10.1053/j.jvca.2021.02.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 02/01/2021] [Indexed: 12/13/2022]
Abstract
The gold standard treatment of end-stage liver disease continues to be liver transplantation (LT). The challenges of LT require skilled anesthesiologists to anticipate physiologic changes associated with end-stage liver disease and surgical considerations that affect multiple organ systems. While on the waiting list, patients may be placed on new anticoagulation medications that can confound already complex coagulopathy in LT patients. Pain management often is an afterthought for such a complex procedure, but appropriate medications can help control pain while limiting opioid medications. Surgical stress and medications for immunosuppression can affect perioperative glucose management in ways that have implications for patient and graft survival. The coronavirus disease 2019 pandemic in 2020 provided a new challenge for anesthesiologists. The uncertainty of the novel respiratory virus challenged providers beyond just LT patients.
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Affiliation(s)
- Trevor J Wilke
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE
| | - Bradley A Fremming
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE
| | - Brittany A Brown
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE
| | - Nicholas W Markin
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE
| | - Cale A Kassel
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE.
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17
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Bari K, Shah SA, Kaiser TE, Cohen RM, Anwar N, Kleesattel D, Sherman KE. Safety and Efficacy of Budesonide for Liver Transplant Immune Suppression: Results of a Pilot Phase 2a Trial. Liver Transpl 2020; 26:1430-1440. [PMID: 32602616 PMCID: PMC7606621 DOI: 10.1002/lt.25837] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/04/2020] [Accepted: 06/19/2020] [Indexed: 02/06/2023]
Abstract
Despite adverse effects like hyperglycemia, new-onset diabetes after transplant (NODAT), and infectious complications, corticosteroid use remains an important part of liver transplantation (LT) immune suppression. Budesonide, a synthetic corticosteroid, undergoes extensive first-pass hepatic metabolism with only 10% systemic bioavailability, providing an opportunity for an improved toxicity-therapeutic ratio. Although effective in the treatment of autoimmune hepatitis, the effects of budesonide for LT immune suppression are unknown. We conducted a single-center phase 2a trial to study the safety and efficacy of budesonide immunosuppressive therapy. From July 2017 to November 2018, 20 patients undergoing a first LT received budesonide tapering doses (from 9 to 3 mg) for 12 weeks. Patients were compared with matched control patients who received prednisone from the same time period. Additionally, both groups received calcineurin inhibitors and mycophenolate mofetil. Outcome measures at week 24 included rates of biopsy-proven acute cellular rejection (ACR), NODAT (hemoglobin A1c >6.4%), and infectious complications. In the budesonide arm, 1 patient developed ACR at week 5 and was removed from the study. Another patient stopped the study drug at week 8 due to persistent nausea. Rates of ACR were similar between the budesonide and control groups (5% versus 5%, P = 1.00). Three patients in the control group developed NODAT versus none in the budesonide group (15% versus 0%; P = 0.23). There were 6 infections in the control group compared with none in the budesonide group (30% versus 0; P = 0.02). These pilot data suggest that budesonide has the potential to be a safe and effective alternative to prednisone for LT immune suppression while reducing steroid-induced infections and NODAT. Randomized controlled trials are required to validate these findings.
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Affiliation(s)
- Khurram Bari
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - Shimul A. Shah
- University of Cincinnati, Division of Transplant Surgery, Department of Surgery, Cincinnati, Ohio
| | - Tiffany E. Kaiser
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - Robert M Cohen
- University of Cincinnati, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cincinnati, Ohio
| | - Nadeem Anwar
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - David Kleesattel
- University of Cincinnati, Department of Internal Medicine, Cincinnati, Ohio
| | - Kenneth E. Sherman
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
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18
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Oliveira RA, Poveda VDB, Tanner J. Perioperative intensive glycemic control for liver transplant recipients to prevent surgical site infection: A systematic review and meta-analysis. Transpl Infect Dis 2020; 22:e13390. [PMID: 32589805 DOI: 10.1111/tid.13390] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 06/15/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND Surgical Site Infections (SSIs) are common among liver transplant recipients and result in adverse patient outcomes. Standard glycemic control is effective in reducing SSIs. Some studies suggest intensive glycemic control reduces the risk of SSI further. METHODS For this systematic review, were searched for studies comparing perioperative intensive and standard glycemic control in liver transplant recipients. Clinical trials registries and reference lists of included studies were also searched. No date or language restrictions were applied. Randomized controlled trials (RCTs) were assessed using Cochrane risk of bias tool and GRADE method. Cohort studies were assessed using the Newcastle-Ottawa Scale. RESULTS Two RCTs and three cohort studies met the inclusion criteria. Low-quality evidence from the two RCTs in a meta-analysis with 264 recipients found it was uncertain whether the risk of SSI was reduced by having intensive glycemic control (Risk Ratio [RR] 1.52, 95% CI 0.66-3.51). However, there was an increased risk of hypoglycemia among recipients having intensive glycemic control (RR 2.34, 95% CI 1.40-3.92) n = 264. Meta-analyses found it uncertain whether secondary outcomes, allograft rejection and death, were reduced among recipients having intensive glycemic control; (RR 0.85, 95% CI 0.48-1.50) and (RR 0.92, 95% CI 0.44-1.95), respectively. The two cohort studies were poor quality and presented conflicting outcomes on the effects of intensive blood glucose control on SSI. CONCLUSION There is insufficient evidence to recommend the use of intensive glycemic control among liver transplant recipients to reduce SSIs.
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Affiliation(s)
| | | | - Judith Tanner
- Faculty of Medicine and Health Sciences, The Queen's Medical Centre, The University of Nottingham, Nottingham, UK
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19
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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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20
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Cotter TG, Charlton M. Nonalcoholic Steatohepatitis After Liver Transplantation. Liver Transpl 2020; 26:141-159. [PMID: 31610081 DOI: 10.1002/lt.25657] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/07/2019] [Indexed: 02/07/2023]
Abstract
Currently, nonalcoholic steatohepatitis (NASH) is the second leading indication for liver transplantation (LT), behind alcohol-related liver disease. After transplant, both recurrent and de novo nonalcoholic fatty liver disease are common; however, recurrence rates of NASH and advanced fibrosis are low. Identification of high-risk groups and optimizing treatment of metabolic comorbidities both before and after LT is paramount to maintaining a healthy allograft, especially with the additional consequences of longterm immunosuppression. In addition, NASH LT recipients are at an increased risk of cardiovascular events and malignancy, and their condition warrants a tailored approach to management. The optimal approach to NASH LT recipients including metabolic comorbidities management, tailored immunosuppression, the role of bariatric surgery, and nutritional and pharmacotherapy of NASH are discussed in this review. Overall, aggressive management of metabolic syndrome after LT via medical and surgical modalities and a minimalist approach to immunosuppression is advised.
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Affiliation(s)
- Thomas G Cotter
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL
| | - Michael Charlton
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL
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Lieber SR, Lee RA, Jiang Y, Reuter C, Watkins R, Szempruch K, Gerber DA, Desai CS, DeCherney GS, Barritt AS. The impact of post-transplant diabetes mellitus on liver transplant outcomes. Clin Transplant 2019; 33:e13554. [PMID: 30927288 DOI: 10.1111/ctr.13554] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 02/26/2019] [Accepted: 03/24/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Post-transplant diabetes mellitus (PTDM) is common after liver transplantation (LT). Yet, how PTDM relates to graft outcomes and survival needs elucidation as more individuals are transplanted for nonalcoholic fatty liver disease (NAFLD). METHODS This single-center, retrospective study of adult LT recipients (2003-2016) identified PTDM incidence and associations with graft steatosis, rejection, and post-LT patient survival. Multivariable analysis investigated predictors of PTDM. Kaplan-Meier curves depicted patient survival 5 years post-LT. RESULTS Among 415 adult LT recipients, 23% had pre-LT DM and 13% were transplanted for NAFLD. PTDM incidence was 34.7%, 46.9%, and 56.2% and overall survival was 90%, 80.9%, and 71.7% at 1, 3, and 5 years, respectively. Over a third of non-NAFLD patients developed PTDM. Half of PTDM cases developed by 6 months and 75% by 12 months. The PTDM group had more rejection episodes compared to no PTDM (31.9% vs 21.8%, P = 0.055), with trends toward worse patient survival 5 years post-LT (log-rank test P = 0.254). Age was the only significant predictor of PTDM. CONCLUSIONS Post-transplant diabetes mellitus occurs rapidly in the post-LT period and is a significant problem for both NAFLD and non-NAFLD LT recipients. Age is a significant risk factor for PTDM. Outcomes trended toward increased rejection and worse survival among PTDM individuals, suggesting the benefit of early strategies targeting glucose control.
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Affiliation(s)
- Sarah R Lieber
- Division of Gastroenterology and Hepatology, Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina
| | - Ruth-Ann Lee
- Department of Pharmacy, UNC Health Care, Chapel Hill, North Carolina
| | - Yue Jiang
- Department of Biostatistics, UNC Gillings School of Public Health, Chapel Hill, North Carolina
| | - Claire Reuter
- Department of Specialty Pharmacy, Ochsner Medical Center, New Orleans, Louisiana
| | - Randall Watkins
- Department of Biostatistics, UNC Gillings School of Public Health, Chapel Hill, North Carolina
| | - Kristen Szempruch
- Department of Pharmacy, UNC Health Care, Chapel Hill, North Carolina
| | - David A Gerber
- Department of Surgery, UNC School of Medicine, Chapel Hill, North Carolina
| | - Chirag S Desai
- Department of Surgery, UNC School of Medicine, Chapel Hill, North Carolina
| | - G Stephen DeCherney
- Division of Endocrinology, Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina
| | - A Sidney Barritt
- Division of Gastroenterology and Hepatology, Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina
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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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Huang CJ, Chang CH, Cheng KW, Chen CL, Wu SC, Shih TH, Yang SC, Lee YE, Huang CE, Jawan B, Wang CH, Juang SE. Correlation Between Blood Transfusion and Blood Glucose Levels in Adult Living Donor Liver Transplantation. Transplant Proc 2018; 50:2645-2647. [PMID: 30401367 DOI: 10.1016/j.transproceed.2018.02.203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 02/19/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND To evaluate the effect of dextrose contained in banked blood products on the changes of blood glucose levels in adult living donor liver transplantation patients retrospectively. METHODS Four hundred seventy-seven patients were divided into a non-blood transfusion (BT) group (G1) and a BT group (G2). The changes in blood glucose levels during the operation were compared using a Mann-Whitney U test, and a P value less than .05 was regarded as significant. RESULTS No significant changes were detected in blood glucose levels after anesthesia, during dissection phase, in the anhepatic phase, or after reperfusion between the groups. Estimated blood loss for G1 (n = 89) and G2 (n = 388) were 718 ± 514 and 5804 ± 877 mL respectively, G1 had no blood transfusion but G2 had received 4350 ± 6230 mL leukocyte-poor red blood cell transfusion, the pre- and end operation hemoglobin for G1 and G2 were 13.2 ± 2.0, 10.2 ± 1.9 and 10.1 ± 1.6, 10.2 ± 1.9 mg/dL respectively, indicating that they were not under or over transfused. CONCLUSION When banked blood products are used to replace ongoing blood loss, the dextrose contained in citrate-phosphate-dextrose-adenine seems to have no effect on the changes in the blood glucose levels of the recipients.
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Affiliation(s)
- C-J Huang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-H Chang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - K-W Cheng
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-L Chen
- Department of Surgery and Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - S-C Wu
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - T-H Shih
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - S-C Yang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Y-E Lee
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-E Huang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - B Jawan
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-H Wang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - S-E Juang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Development of a Predictive Model for Hyperglycemia in Nondiabetic Recipients After Liver Transplantation. Transplant Direct 2018; 4:e393. [PMID: 30498770 PMCID: PMC6233666 DOI: 10.1097/txd.0000000000000830] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 07/03/2018] [Indexed: 12/20/2022] Open
Abstract
Background Posttransplant hyperglycemia has been associated with increased risks of transplant rejection, infections, length of stay, and mortality. Methods To establish a predictive model to identify nondiabetic recipients at risk for developing postliver transplant (LT) hyperglycemia, we performed this secondary, retrospective data analysis of a single-center, prospective, randomized, controlled trial of glycemic control among 107 adult LT recipients in the inpatient period. Hyperglycemia was defined as a posttransplant glucose level greater than 200 mg/dL after initial discharge up to 1 month following surgery. Candidate variables with P less than 0.10 in univariate analyses were used to build a multivariable logistic regression model using forward stepwise selection. The final model chosen was based on statistical significance and additive contribution to the model based on the Bayesian Information Criteria. Results Forty-three (40.2%) patients had at least 1 episode of hyperglycemia after transplant after the resolution of the initial postoperative hyperglycemia. Variables selected for inclusion in the model (using model optimization strategies) included length of hospital stay (odds ratio [OR], 0.83; P < 0.001), use of glucose-lowering medications at discharge (OR, 3.76; P = 0.03), donor female sex (OR, 3.18; P = 0.02) and donor white race (OR, 3.62; P = 0.01). The model had good calibration (Hosmer-Lemeshow goodness-of-fit test statistic = 9.74, P = 0.28) and discrimination (C-statistic = 0.78; 95% confidence interval, 0.65-0.81, bias-corrected C-statistic = 0.78). Conclusions Shorter hospital stay, use of glucose-lowering medications at discharge, donor female sex and donor white race are important determinants in predicting hyperglycemia in nondiabetic recipients after hospital discharge up to 1 month after liver transplantation.
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Khowaja A, Alkhaddo JB, Rana Z, Fish L. Glycemic Control in Hospitalized Patients with Diabetes Receiving Corticosteroids Using a Neutral Protamine Hagedorn Insulin Protocol: A Randomized Clinical Trial. Diabetes Ther 2018; 9:1647-1655. [PMID: 29961246 PMCID: PMC6064602 DOI: 10.1007/s13300-018-0468-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Indexed: 01/14/2023] Open
Abstract
INTRODUCTION Hospitalized patients with diabetes receiving corticosteroids are at risk of developing hyperglycemia and related complications. This study evaluated a neutral protamine Hagedorn (NPH) insulin-based protocol in improving glycemic control in hospitalized patients receiving corticosteroids. METHODS This was a randomized, prospective, non-blinded study in an inpatient setting involving patients with diabetes who were hospitalized and receiving prednisone ≥ 10 mg per day or equivalent. High dose corticosteroids group (prednisone > 40 mg/day or equivalent) received NPH insulin 0.3 U/kg between 0600 and 2000 hours if eating or 0.2 U/kg between 2000 and 0600 hours if not eating. Low dose corticosteroids group (prednisone 10-40 mg/day or equivalent) received 0.15 U/kg between 0600 and 2000 hours if eating or 0.1 U/kg between 2000 and 0600 hours if not eating. Primary outcome measure was mean blood glucose level measured pre-meal and at bedtime for days 1-5. RESULTS Mean blood glucose level was lower in the intervention (n = 29) than in the usual care (n = 31) group [226.12 vs. 268.57 mg/dL, respectively, (95% CI for difference - 63.195 to - 21.695), p < 0.0001]. Significant differences in mean glucose level were noted at fasting [170.96 vs. 221.13 mg/dL, respectively, (95% CI for difference - 72.70 to - 27.63), p < 0.0001] and pre-lunch [208 vs. 266.48 mg/dL, respectively, (95% CI for difference - 86.61 to - 30.36), p < 0.0001]. CONCLUSION In hospitalized patients with diabetes receiving corticosteroids, an NPH insulin-based protocol improves glycemic control. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01970241. FUNDING Eli Lilly and Company.
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Affiliation(s)
- Ameer Khowaja
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA.
- Center for Diabetes and Endocrinology, Hennepin Healthcare System, Minneapolis, MN, USA.
| | - Jamil B Alkhaddo
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA
- The Center for Diabetes and Endocrine Health, Allegheny Health Network, Pittsburgh, PA, USA
| | - Zaighum Rana
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA
| | - Lisa Fish
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA
- Center for Diabetes and Endocrinology, Hennepin Healthcare System, Minneapolis, MN, USA
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26
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Ke QH, Huang HT, Ling Q, Liu JM, Dong SY, He XX, Zhang WJ, Zheng SS. New-onset hyperglycemia immediately after liver transplantation: A national survey from China Liver Transplant Registry. Hepatobiliary Pancreat Dis Int 2018; 17:310-315. [PMID: 30108018 DOI: 10.1016/j.hbpd.2018.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 07/25/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND New-onset hyperglycemia (NOH) is a common phenomenon after liver transplantation (LT), but its impact on clinical outcomes has not yet been fully assessed. We aimed to evaluate the etiology and prognosis of NOH within 1 month after LT. METHODS The data of 3339 adult patients who underwent primary LT from donation after citizen death between January 2010 and June 2016 were extracted from China Liver Transplant Registry database and analyzed. NOH was defined as fasting blood glucose ≥7.0 mmol/L confirmed on at least two occasions within the first post-transplant month with or without hypoglycemic agent. RESULTS Of 3339 liver recipients, 1416 (42.4%) developed NOH. Recipients with NOH had higher incidence of post-transplant complications such as graft and kidney failure, infection, biliary stricture, cholangitis, and tumor recurrence in a glucose concentration-dependent manner as compared to non-NOH recipients (P < 0.05). The independent risk factors of NOH were donor warm ischemic time >10 min, cold ischemic time >10 h, anhepatic time >60 min, recipient model for end-stage liver disease score >30, moderate ascites and corticosteroid usage (P < 0.05). Liver enzymes (alanine aminotransferase and gamma-glutamyltranspeptidase) on post-transplant day 7 significantly correlated with NOH (P < 0.001). CONCLUSIONS NOH leads to increased morbidity and mortality in liver recipients. Close surveillance and tight control of blood glucose are desiderated immediately following LT particularly in those with delayed graft function and receiving corticosteroid. Strategic targeting graft ischemic injury may help maintain glucose homeostasis.
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Affiliation(s)
- Qing-Hong Ke
- Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Hai-Tao Huang
- Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qi Ling
- Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Ji-Min Liu
- Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Si-Yi Dong
- China Liver Transplant Registry, Hangzhou 310003, China
| | | | - Wen-Jin Zhang
- Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
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27
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Ramos-Prol A, Hervás-Marín D, Rodríguez-Medina B, Rubio-Almanza M, Berenguer M, Moya-Herraiz Á, Merino-Torres JF. Intensified blood glucose treatment in diabetic patients undergoing a liver transplant: impact on graft evolution at 3 months and at 5 years. J Endocrinol Invest 2018; 41:821-829. [PMID: 29289983 DOI: 10.1007/s40618-017-0810-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 12/14/2017] [Indexed: 01/08/2023]
Abstract
PURPOSE The debate about the impact of intensified hyperglycemia treatment is still ranging. The main objective was to assess whether intensive glycemic control in hospitalized diabetic patients undergoing a liver transplant is associated with a lower rate of graft rejection at 3 months and at 5 years post-transplant. METHODS Cross-sectional study comparing a cohort of patients undergoing liver transplant in 2010 and 2011, in whom an intensive insulin protocol was applied, with a retrospective group of patients undergoing a liver transplant in 2005 and 2006, in whom a conventional insulin protocol was applied. Both diabetics and non-diabetics were compared. As intensive insulin therapy is applied mainly in diabetic patients, it is expected that, when comparing both periods, the treatment would only benefit those patients. RESULTS The logistic regression model showed a statistically significant interaction between the treatment group and the presence of diabetes for the rejection rate 3 months and 5 years post-transplant. At both time points, the intensive insulin treatment group had lower rejection rates in the case of diabetic patients, which did not occur in non-diabetic patients. CONCLUSIONS Our study shows a decrease in the rate of liver graft rejection in diabetic patients undergoing intensive insulin treatment.
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Affiliation(s)
- A Ramos-Prol
- Endocrinology and Nutrition Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
- Unidad Mixta de Investigación de Endocrinología, Nutrición y Dietética, Instituto de Investigación Sanitaria La Fe (Health Research Institute La Fe), Valencia, Spain
- Department of Internal Medicine (Endocrinology and Nutrition), Hospital Francesc de Borja, Gandía, Spain
| | - D Hervás-Marín
- Biostatistics Unit, Health Research Institute La Fe, Valencia, Spain
| | - B Rodríguez-Medina
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - M Rubio-Almanza
- Endocrinology and Nutrition Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
- Unidad Mixta de Investigación de Endocrinología, Nutrición y Dietética, Instituto de Investigación Sanitaria La Fe (Health Research Institute La Fe), Valencia, Spain
| | - M Berenguer
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Á Moya-Herraiz
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - J F Merino-Torres
- Endocrinology and Nutrition Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
- Unidad Mixta de Investigación de Endocrinología, Nutrición y Dietética, Instituto de Investigación Sanitaria La Fe (Health Research Institute La Fe), Valencia, Spain.
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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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Pollack TA, Illuri V, Khorzad R, Aleppo G, Johnson Oakes D, Holl JL, Wallia A. Risk assessment of the hospital discharge process of high-risk patients with diabetes. BMJ Open Qual 2018; 7:e000224. [PMID: 29862328 PMCID: PMC5976096 DOI: 10.1136/bmjoq-2017-000224] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 03/06/2018] [Accepted: 04/08/2018] [Indexed: 12/15/2022] Open
Abstract
Objectives Describe the application of a risk assessment to identify failures in the hospital discharge process of a high-risk patient group, liver transplant (LT) recipients with diabetes mellitus (DM) and/or hyperglycaemia who require high-risk medications. Design A Failure Modes, Effects and Criticality Analysis (FMECA) of the hospital discharge process of LT recipients with DM and/or hyperglycaemia who required DM education and training before discharge was conducted using information from clinicians, patients and data extraction from the electronic health records (EHR). Failures and their causes were identified and the frequency and characteristics (harm, detectability) of each failure were assigned using a score of low/best (1) to high/worst (10); a Criticality Index (CI=Harm×Frequency) and a Risk Priority Number (RPN=Harm×Frequency×Detection) were also calculated. Setting An academic, tertiary care centre in Chicago, Illinois. Participants Healthcare providers (N=31) including physicians (n= 6), advanced practice providers (n=12), nurses (n=6), pharmacists (n= 4), staff (n=3) and patients (n=6) and caregivers (n=3) participated in the FMECA; EHR data for LT recipients with DM or hyperglycaemia (N=100) were collected. Results Of 78 identified failures, the most critical failures (n=15; RPNs=700, 630, 560; CI=70) were related to variability in delivery of diabetes education and training, care coordination and medication prescribing patterns of providers. Underlying causes included timing of patient education, lack of assessment of patients’ knowledge and industry-level design failures of healthcare products (eg, EHR, insulin pen). Conclusion Most identified critical failures are preventable and suggest the need for the design of interventions, informed by the failures identified by this FMECA, to mitigate safety risks and improve outcomes of high-risk patient populations.
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Affiliation(s)
- Teresa A Pollack
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Vidhya Illuri
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Rebeca Khorzad
- Center for Health Care Studies, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Grazia Aleppo
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Diana Johnson Oakes
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jane L Holl
- Center for Health Care Studies, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Amisha Wallia
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.,Center for Health Care Studies, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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30
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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: 57] [Impact Index Per Article: 8.1] [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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Giráldez E, Varo E, Guler I, Cadarso-Suarez C, Tomé S, Barral P, Garrote A, Gude F. Post-operative stress hyperglycemia is a predictor of mortality in liver transplantation. Diabetol Metab Syndr 2018; 10:35. [PMID: 29713388 PMCID: PMC5909230 DOI: 10.1186/s13098-018-0334-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 04/07/2018] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND A significant association is known between increased glycaemic variability and mortality in critical patients. To ascertain whether glycaemic profiles during the first week after liver transplantation might be associated with long-term mortality in these patients, by analysing whether diabetic status modified this relationship. METHOD Observational long-term survival study includes 642 subjects undergoing liver transplantation from July 1994 to July 2011. Glucose profiles, units of insulin and all variables with influence on mortality are analysed using joint modelling techniques. RESULTS Patients registered a survival rate of 85% at 1 year and 65% at 10 years, without differences in mortality between patients with and without diabetes. In glucose profiles, however, differences were observed between patients with and without diabetes: patients with diabetes registered lower baseline glucose values, which gradually rose until reaching a peak on days 2-3 and then subsequently declined, diabetic subjects started from higher values which gradually decreased across the first week. Patients with diabetes showed an association between mortality and age, Model for End-Stage Liver Disease score (MELD) score and hepatitis C virus; among non-diabetic patients, mortality was associated with age, body mass index, malignant aetiology, red blood cell requirements and parenteral nutrition. Glucose profiles were observed to be statistically associated with mortality among patients without diabetes (P = 0.022) but not among patients who presented with diabetes prior to transplantation (P = 0.689). CONCLUSIONS Glucose profiles during the first week after liver transplantation are different in patients with and without diabetes. While glucose profiles are associated with long-term mortality in patients without diabetes, after adjusting for potential confounding variables such as age, cause of transplantation, MELD, nutrition, immunosuppressive drugs, and units of insulin administered, this does not occur among patients with diabetes.
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Affiliation(s)
- Elena Giráldez
- Intensive Care Unit, Hospital Clínico Universitario de Santiago, Travesia da Choupana s/n, 15706 Santiago, Spain
| | - Evaristo Varo
- Abdominal Transplantation Unit, Hospital Clínico Universitario de Santiago, Santiago, Spain
| | - Ipek Guler
- Biostatistics Unit, Department of Statistics and Operations Research, University of Santiago de Compostela, Santiago, Spain
| | - Carmen Cadarso-Suarez
- Biostatistics Unit, Department of Statistics and Operations Research, University of Santiago de Compostela, Santiago, Spain
| | - Santiago Tomé
- Abdominal Transplantation Unit, Hospital Clínico Universitario de Santiago, Santiago, Spain
| | - Patricia Barral
- Intensive Care Unit, Hospital Clínico Universitario de Santiago, Travesia da Choupana s/n, 15706 Santiago, Spain
| | - Antonio Garrote
- Intensive Care Unit, Hospital Clínico Universitario de Santiago, Travesia da Choupana s/n, 15706 Santiago, Spain
| | - Francisco Gude
- Clinical Epidemiology Unit, Hospital Clínico Universitario de Santiago, Santiago, Spain
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Yoo S, Lee HJ, Lee H, Ryu HG. Association Between Perioperative Hyperglycemia or Glucose Variability and Postoperative Acute Kidney Injury After Liver Transplantation: A Retrospective Observational Study. Anesth Analg 2017; 124:35-41. [PMID: 27749341 DOI: 10.1213/ane.0000000000001632] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Glucose control can be difficult in the intraoperative and immediate postoperative period of liver transplantation. Hyperglycemia and glucose variability have been associated with acute kidney injury (AKI) in critically ill patients. We performed a retrospective study to test the hypothesis that perioperative glucose levels represented by time-weighted average glucose levels and glucose variability are independently associated with the incidence of postoperative AKI in patients undergoing liver transplantation. METHODS On the basis of blood glucose levels during liver transplantation and the initial 48 hours postoperatively, adult liver transplant recipients were classified into 4 groups according to their time-weighted average glucose: normoglycemia (80-200 mg/dL), mild hyperglycemia (200-250 mg/dL), moderate hyperglycemia (250-300 mg/dL), and severe hyperglycemia (>300 mg/dL) group. Patients were also classified into quartiles depending on their glucose variability, defined as the standard deviation of glucose measurements. The primary outcome was postoperative AKI. RESULTS AKI after liver transplantation was more common in the patients with greater perioperative glucose variability (first versus third quartile; OR, 2.47 [95%CI, 1.22-5.00], P = .012; first versus fourth quartile; OR, 2.16 [95% CI, 1.05-4.42], P = .035). CONCLUSIONS Our study suggests that increased perioperative glucose variability, but not hyperglycemia, is independently associated with increased risk of postoperative AKI in liver transplantation recipients.
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Affiliation(s)
- Seokha Yoo
- From the Department of Anesthesiology, Seoul National University Hospital, Seoul, Korea
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33
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Sood S, Haifer C, Yu L, Pavlovic J, Churilov L, Gow PJ, Jones RM, Angus PW, Visvanathan K, Testro AG. A novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation. Liver Transpl 2017; 23:487-497. [PMID: 28133934 DOI: 10.1002/lt.24730] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 11/29/2016] [Accepted: 12/13/2016] [Indexed: 01/13/2023]
Abstract
Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon γ (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. A total of 75 adult transplant recipients were prospectively monitored in a blinded, observational study; 55/75 (73.3%) patients experienced a total of 89 clinical events. Most events occurred within the first month. Low week 1 results were significantly associated with risk of early infection (area under the receiver operating characteristic curve [AUROC], 0.74; P = 0.008). IFNγ ≤ 1.30 IU/mL (likelihood ratio positive, 1.93; sensitivity, 71.4%; specificity, 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ ≤ 1.30 IU/mL. Moreover, an elevated week 1 result was significantly associated with the risk of rejection within the first month after transplant (AUROC, 0.77; P = 0.002), but no episodes of infection. On multivariate logistic regression, IFNγ ≥ 4.49 IU/mL (odds ratio, 4.75) may be an independent predictor of rejection (P = 0.05). In conclusion, low IFNγ suggesting oversuppression is associated with infections, whereas high IFNγ indicating undersuppression is associated with rejection. This assay offers the potential to allow individualization and optimization of immunosuppression that could fundamentally alter the way patients are managed following transplantation. Liver Transplantation 23 487-497 2017 AASLD.
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Affiliation(s)
- Siddharth Sood
- Liver Transplant Unit.,Department of Gastroenterology and Hepatology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.,Innate Immune Laboratory, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia
| | | | - Lijia Yu
- Innate Immune Laboratory, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia
| | | | - Leonid Churilov
- Florey Department of Neuroscience and Mental Health, Austin Health
| | | | | | | | - Kumar Visvanathan
- Innate Immune Laboratory, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia
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Pharmacogenetics of posttransplant diabetes mellitus. THE PHARMACOGENOMICS JOURNAL 2017; 17:209-221. [DOI: 10.1038/tpj.2017.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 12/04/2016] [Accepted: 01/09/2017] [Indexed: 02/08/2023]
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35
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Wallia A, Schmidt K, Oakes DJ, Pollack T, Welsh N, Kling-Colson S, Gupta S, Fulkerson C, Aleppo G, Parikh N, Levitsky J, Norvell JP, Rademaker A, Molitch ME. Glycemic Control Reduces Infections in Post-Liver Transplant Patients: Results of a Prospective, Randomized Study. J Clin Endocrinol Metab 2017; 102:451-459. [PMID: 27875061 PMCID: PMC6283442 DOI: 10.1210/jc.2016-3279] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 11/17/2016] [Indexed: 12/24/2022]
Abstract
CONTEXT Previous studies have shown a relationship between glycemic control and posttransplant morbidity. OBJECTIVE We conducted a prospective randomized controlled trial in postliver transplant patients to evaluate intensive inpatient glycemic control and effects on outcomes to 1 year. RESEARCH DESIGN AND INTERVENTION A total of 164 patients [blood glucose (BG) >180 mg/dL] were randomized into 2 target groups: 82 with a BG of 140 mg/dL and 82 with a BG of 180 mg/dL. Continuous insulin infusions were initiated and then converted to subcutaneous basal bolus insulin therapy by our glucose management service. RESULTS The inpatient mean BG level was significantly different (140 group, 151.4 ± 19.5 mg/dL vs 180 group, 172.6 ± 27.9 mg/dL; P < 0.001). Any infection within 1 year occurred in 35 of the 82 patients (42.7%) in the 140 group and 54 of 82 (65.9%) in the 180 group (P = 0.0046). In a time-to-first infection analysis, being in the 140 group resulted in a hazard ratio of 0.54 (95% confidence interval, 0.35 to 0.83; P = 0.004); the difference between the 2 groups was statistically significant at 1 month (P = 0.008). The number with adjudicated transplant rejection was similar between the 2 groups [17 of 82 (20.7%) and 20 of 82 (24.3%) in the 140 and 180 groups, respectively; P = not significant]. Severe hypoglycemia (BG ≤40 mg/dL) occurred in 3 patients (2 in the 140 group and 1 in the 180 group). However, more patients had moderate hypoglycemia (BG, 41 to 70 mg/dL) in the 140 group [27 of 82 (32.9%) vs 10 of 82 (12.2%) in the 180 group; P = 0.003]. Insulin-related hypoglycemia was not associated with the incidence of severe adverse outcomes. CONCLUSIONS Glycemic control of 140 mg/dL safely resulted in a reduced incidence of infection after transplantation compared with 180 mg/dL, but with an increase in moderate hypoglycemia.
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Affiliation(s)
- Amisha Wallia
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Kathleen Schmidt
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Diana Johnson Oakes
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Teresa Pollack
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Nicholas Welsh
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Susan Kling-Colson
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Suruchi Gupta
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Candice Fulkerson
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Grazia Aleppo
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
| | - Neehar Parikh
- Division of Gastroenterology and Hepatology, Department of Medicine, and
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Department of Medicine, and
| | - J P Norvell
- Division of Gastroenterology and Hepatology, Department of Medicine, and
| | - Alfred Rademaker
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611
| | - Mark E Molitch
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine
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Postoperative Care of the Liver Transplant Recipient. ANESTHESIA AND PERIOPERATIVE CARE FOR ORGAN TRANSPLANTATION 2017. [PMCID: PMC7120127 DOI: 10.1007/978-1-4939-6377-5_29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Glucose Metabolism and Associated Outcome After Pediatric Liver Transplantation. Transplant Proc 2016; 48:2709-2713. [PMID: 27788805 DOI: 10.1016/j.transproceed.2016.08.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 08/03/2016] [Indexed: 11/24/2022]
Abstract
BACKGROUND Despite hypoglycemia and hyperglycemia being frequently observed in the early postoperative phase, information on glucose metabolism after pediatric liver transplantation (pLT) is scarce. METHODS The goal of this retrospective single-center study, which included 46 patients who consecutively underwent 55 liver transplantations, was to gather data on glucose uptake, the prognostic relevance of hyperglycemia, and the safety of insulin administration in patients after pLT. RESULTS In this study population, glucose intake to keep blood sugar levels (BSLs) within the targeted range of 120 to 200 mg/dL (6.7-11.1 mmol/L) increased rapidly over the first few postoperative days and was significantly correlated with graft function. There was no association between a postoperative daily mean BSL >200 mg/dL and specific posttransplant complications (acute rejection, infection, need for retransplantation, and/or death). High postoperative mean 7-day BSLs were associated with poor glucose metabolism and an increase in morbidity and 6-month posttransplant mortality. Hypoglycemia was not observed under insulin administration. CONCLUSIONS With high BSLs being associated with poor glucose metabolism, it is likely that the critical illness itself, in addition to poor graft function, causes the increase in morbidity and mortality, with hyperglycemia serving as a marker.
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38
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Mateo R, Gupta S, Wallia A, Cameron C, Schmidt K, Oakes DJ, Aleppo G, Andrei AC, Wilcox JE, Grady K, Gordon R, Molitch ME. Relationship Between Hyperglycemia and Heart Transplant Rejection. Transplant Proc 2016; 47:2727-31. [PMID: 26680082 DOI: 10.1016/j.transproceed.2015.09.063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Revised: 09/22/2015] [Accepted: 09/30/2015] [Indexed: 12/01/2022]
Abstract
PURPOSE Hyperglycemia increases risks of kidney and liver transplant rejection. To determine whether perioperative and subsequent glycemic control was associated with increased risk of heart transplant rejection over the year after transplantation, we performed a retrospective analysis of glycemic control and rejection rates in heart transplantation patients. METHODS Perioperative glucose levels were analyzed in 157 patients undergoing transplantation at Northwestern Memorial Hospital from June 2005 to December 2012 and compared in patients with and without rejection found on routine follow-up biopsy specimens. RESULTS Grade ≤1R rejection on biopsy was observed in 116 patients and grade ≥2R rejection (grade requiring increased anti-rejection treatment) in 41 patients. Although no significant differences in the preoperative fasting or inpatient mean glucose levels were found, the mean glucose levels from discharge to 1 year trended higher in those with grade ≥2R compared to grade ≤1R (128.8 ± 40.9 versus 142.2 ± 46.6 mg/dL, P = .084). In a multivariable logistic regression model, neither the lowest nor highest quartile of glucose levels had significantly different odds ratios (ORs) for the development of ≥2R compared to the middle 50% glucose levels. Older age (OR 0.96, P = .020) and higher body mass index levels (OR 0.86, P = .004) were significantly associated with lower odds of developing grade ≥2R. CONCLUSIONS Although the glucose trend regarding rejection was not statistically significant, we cannot exclude the possibility that much higher glucose levels would influence rejection rates.
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Affiliation(s)
- R Mateo
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - S Gupta
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - A Wallia
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
| | - C Cameron
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - K Schmidt
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - D J Oakes
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - G Aleppo
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - A-C Andrei
- Division of Cardiac Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - J E Wilcox
- Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - K Grady
- Division of Cardiac Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - R Gordon
- Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - M E Molitch
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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39
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A review of nationwide population study of organ transplantation in Taiwan. ACTA ACUST UNITED AC 2016; 54:70-4. [DOI: 10.1016/j.aat.2016.05.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 05/09/2016] [Accepted: 05/20/2016] [Indexed: 12/20/2022]
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Siddiqui MS, Charlton M. Liver Transplantation for Alcoholic and Nonalcoholic Fatty Liver Disease: Pretransplant Selection and Posttransplant Management. Gastroenterology 2016; 150:1849-62. [PMID: 26971826 DOI: 10.1053/j.gastro.2016.02.077] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 02/12/2016] [Accepted: 02/16/2016] [Indexed: 02/07/2023]
Abstract
Alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease throughout the world. Although they have similar histologic features, a diagnosis of NAFLD requires the absence of significant alcohol use. ALD is seen commonly in patients with a long-standing history of excessive alcohol use, whereas NAFLD is encountered commonly in patients who have developed complications of obesity, such as insulin resistance, hypertension, and dyslipidemia. Lifestyle contributes to the development and progression of both diseases. Although alcohol abstinence can cause regression of ALD, and weight loss can cause regression of NAFLD, many patients with these diseases develop cirrhosis. ALD and NAFLD account for nearly 30% of liver transplants performed in the United States. Patients receiving liver transplants for ALD or NAFLD have similar survival times as patients receiving transplants for other liver disorders. Although ALD and NAFLD recur frequently after liver transplantation, graft loss from disease recurrence after transplantation is uncommon. Cardiovascular disease and de novo malignancy are leading causes of long-term mortality in liver transplant recipients with ALD or NAFLD.
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Affiliation(s)
- M Shadab Siddiqui
- Division of Gastroenterology & Hepatology, Virginia Commonwealth University, Richmond, Virginia
| | - Michael Charlton
- Division of Transplant Hepatology, Intermountain Medical Center, Murry, Utah
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Wallia A, Illuri V, Molitch ME. Diabetes Care After Transplant: Definitions, Risk Factors, and Clinical Management. Med Clin North Am 2016; 100:535-50. [PMID: 27095644 DOI: 10.1016/j.mcna.2016.01.005] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Patients who undergo solid organ transplantation may have preexisting diabetes mellitus (DM), develop new-onset DM after transplantation (NODAT), or have postoperative hyperglycemia that resolves shortly after surgery. Although insulin is usually used to control hyperglycemia in the hospital, following discharge most of the usual diabetes oral and parenteral medications can be used in treatment. However, when there are comorbidities such as impaired kidney or hepatic function, or heart disease, special precautions may be necessary. In addition, drug-drug interactions, such as drugs interacting with CYP3A4 enzyme pathway, require additional consideration because of possible interaction with immunosuppressive drug metabolism.
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Affiliation(s)
- Amisha Wallia
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Vidhya Illuri
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Mark E Molitch
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
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42
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Welsh N, Derby T, Gupta S, Fulkerson C, Oakes DJ, Schmidt K, Parikh ND, Norvell JP, Levitsky J, Rademaker A, Molitch ME, Wallia A. INPATIENT HYPOGLYCEMIC EVENTS IN A COMPARATIVE EFFECTIVENESS TRIAL FOR GLYCEMIC CONTROL IN A HIGH-RISK POPULATION. Endocr Pract 2016; 22:1040-7. [PMID: 27124695 DOI: 10.4158/ep151166.or] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Inpatient hypoglycemia (glucose ≤70 mg/dL) is a limitation of intensive control with insulin. Causes of hypoglycemia were evaluated in a randomized controlled trial examining intensive glycemic control (IG, target 140 mg/dL) versus moderate glycemic control (MG, target 180 mg/dL) on post-liver transplant outcomes. METHODS Hypoglycemic episodes were reviewed by a multidisciplinary team to calculate and identify contributing pathophysiologic and operational factors. A subsequent subgroup case control (1:1) analysis (with/without) hypoglycemia was completed to further delineate factors. A total of 164 participants were enrolled, and 155 patients were examined in depth. RESULTS Overall, insulin-related hypoglycemia was experienced in 24 of 82 patients in IG (episodes: 20 drip, 36 subcutaneous [SQ]) and 4 of 82 in MG (episodes: 2 drip, 2 SQ). Most episodes occurred at night (41 of 60), with high insulin amounts (44 of 60), and during a protocol deviation (51 of 60). Compared to those without hypoglycemia (n = 127 vs. n = 28), hypoglycemic patients had significantly longer hospital stays (13.6 ± 12.6 days vs. 7.4 ± 6.1 days; P = .002), higher peak insulin drip rates (17.4 ± 10.3 U/h vs. 13.1 ± 9.9 U/h; P = .044), and higher peak insulin glargine doses (36.8 ± 21.4 U vs. 26.2 ± 24.3 U; P = .035). In the case-matched analysis (24 cases, 24 controls), those with insulin-related hypoglycemia had higher median peak insulin drip rates (17 U/h vs. 11 U/h; P = .04) and protocol deviations (92% vs. 50%; P = .004). CONCLUSION Peak insulin requirements and protocol deviations were correlated with hypoglycemia. ABBREVIATIONS DM = diabetes mellitus ICU = intensive care unit IG = intensive glycemic control MELD = Model for End-stage Liver Disease MG = moderate glycemic control SQ = subcutaneous.
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Abstract
Hyperglycemia is common following organ transplantation, regardless of the pre-transplant diabetes status. Transient post-transplant hyperglycemia and/or new-onset diabetes after transplantation (NODAT) are common and are associated with increased morbidity and mortality. NODAT and type 2 diabetes share similar characteristics, but the pathophysiology may differ. Immunosuppressive agents and steroids play a key role in the development of NODAT. Glycemic control is challenging in this population due to fluctuating renal/end-organ function, immunosuppressive dosing, nutritional status, and drug-drug interactions. A proactive and multidisciplinary approach is essential, along with flexible protocols to adjust to patient status, type of organ transplanted, and corticosteroid regimens. Insulin is the preferred agent for hospitalized patients and during the early post-transplant period; optimal glycemic control (BG < 180 mg/dl with minimal hypoglycemia [<70 mg/dl]) is desired.
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Affiliation(s)
- Rodolfo J Galindo
- Division of Endocrinology, Diabetes, and Bone Diseases, Icahn School of Medicine at Mount Sinai, Mount Sinai St. Luke's Hospital, 1111 Amsterdam Ave, Babcock Building, 10th floor, Room 1020, New York, NY, 10025, USA.
| | - Amisha Wallia
- Division of Endocrinology, Metabolism and Molecular Medicine, Center for Healthcare Studies, Northwestern University Feinberg School of Medicine, 654 N Michigan Avenue, Suite 530, Chicago, IL, 60611, USA.
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44
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Hyperglycemia during the immediate period following liver transplantation. Future Sci OA 2016; 2:FSO97. [PMID: 28031946 PMCID: PMC5138006 DOI: 10.4155/fsoa-2015-0010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 01/04/2016] [Indexed: 01/14/2023] Open
Abstract
Aim: High blood glucose levels in the hospital are common among transplant recipients. Methods: Retrospective analysis, stratified by diagnosis of pretransplant diabetes mellitus (DM). Results: Of 346 patients, 96 had pretransplant DM (insulin, n = 60; no insulin, n = 36) and 250 did not. Patients with pretransplant DM had higher inpatient mean glucose levels and more hyperglycemia and hypoglycemia (all p < 0.01). For patients without pretransplant DM, the need for insulin at discharge increased 23% for every 5-year age increase (odds ratio: 1.23; 95% CI: 1.06–1.44; p = 0.007) and 51% for every five units of glucose measurements >180 mg/dl (OR: 1.51; 95% CI: 1.23–1.95; p < 0.01). Conclusion: Inpatient hyperglycemia was common in liver transplant recipients. Hospital practitioners must anticipate the need to teach self-management skills to liver transplant recipients. Lay abstract: High blood glucose levels (also known as hyperglycemia) in the hospital are common among patients who have received a transplant. The authors conducted a study to determine how often high blood glucose values occurred in patients who received a liver transplant and found that values were highest in people who had diabetes before the transplant. However, even patients who did not have a history of diabetes had hyperglycemia and needed insulin treatment. Providers caring for these patients in the hospital must be prepared to provide education in diabetes self-management skills to virtually all patients undergoing a liver transplant.
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Jeong SM. Postreperfusion syndrome during liver transplantation. Korean J Anesthesiol 2015; 68:527-39. [PMID: 26634075 PMCID: PMC4667137 DOI: 10.4097/kjae.2015.68.6.527] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 07/31/2015] [Accepted: 08/07/2015] [Indexed: 02/07/2023] Open
Abstract
As surgical and graft preservation techniques have improved and immunosuppressive drugs have advanced, liver transplantation (LT) is now considered the gold standard for treating patients with end-stage liver disease worldwide. However, despite the improved survival following LT, severe hemodynamic disturbances during LT remain a serious issue for the anesthesiologist. The greatest hemodynamic disturbance is postreperfusion syndrome (PRS), which occurs at reperfusion of the donated liver after unclamping of the portal vein. PRS is characterized by marked decreases in mean arterial pressure and systemic vascular resistance, and moderate increases in pulmonary arterial pressure and central venous pressure. The underlying pathophysiological mechanisms of PRS are complex. Moreover, risk factors associated with PRS are not fully understood. Rapid and appropriate treatment with vasopressors, volume replacement, or venesection must be provided depending on the cause of the hemodynamic disturbance when hemodynamic instability becomes profound after reperfusion. The negative effects of PRS on postoperative early morbidity and mortality are clear, but the effect of PRS on postoperative long-term mortality remains a matter of debate.
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Affiliation(s)
- Sung-Moon Jeong
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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46
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Lv C, Zhang Y, Chen X, Huang X, Xue M, Sun Q, Wang T, Liang J, He S, Gao J, Zhou J, Yu M, Fan J, Gao X. New-onset diabetes after liver transplantation and its impact on complications and patient survival. J Diabetes 2015; 7:881-90. [PMID: 25676209 DOI: 10.1111/1753-0407.12275] [Citation(s) in RCA: 41] [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: 11/13/2014] [Revised: 01/13/2015] [Accepted: 01/27/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of the present study was to investigate the incidence and risk factors of new-onset diabetes after transplantation (NODAT) in liver transplant recipients and the influence of NODAT on complications and long-term patient survival. METHODS We examined 438 patients who underwent liver transplantation between April 2001 and December 2008 and were not diabetic before transplantation. RESULTS The mean (± SD) follow-up duration was 2.46 ± 1.62 years. The incidence of NODAT 3, 6, 9, 12, 36, and 60 months after transplantation was 44.24%, 25.59%, 23.08%, 25.17%, 17.86%, and 18.18%, respectively. Multifactor analysis indicated that preoperative fasting plasma glucose (FPG) levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an interleukin-2 receptor (IL-2R) antagonist reduced the risk of NODAT. Compared with the no NODAT group (N-NODAT), the NODAT group had a higher rate of sepsis and chronic renal insufficiency. Mean survival was significantly longer in the N-NODAT than NODAT group. Cox regression analysis showed that pre- and/or postoperative FPG levels, tumor recurrence or metastasis, and renal insufficiency after liver transplantation were independent risk factors of mortality. Pulmonary infection or multisystem failure were specific causes of death in the NODAT group, whereas patients in both groups died primarily from tumor relapse or metastasis. CONCLUSIONS Preoperative FPG levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an IL-2R antagonist reduced the risk of NODAT. Patients with NODAT had reduced survival and an increased incidence of sepsis and chronic renal insufficiency. Significant causes of death in the NODAT group were pulmonary infection and multisystem failure.
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Affiliation(s)
- Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
- Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Shunmei He
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
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47
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Chung HS, Lee S, Kwon SJ, Park CS. Perioperative predictors for refractory hyperglycemia during the neohepatic phase of liver transplantation. Transplant Proc 2015; 46:3474-80. [PMID: 25498075 DOI: 10.1016/j.transproceed.2014.06.078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Accepted: 06/17/2014] [Indexed: 01/15/2023]
Abstract
BACKGROUND Hyperglycemia in the neohepatic phase of liver transplantation (LT) tends to decrease toward completion of the surgical procedure. Refractory hyperglycemia in the neohepatic phase (RH) is influenced by multiple perioperative factors and may be connected to posttransplant outcomes. We attempted to demonstrate the relationship of RH to posttransplant outcomes and to establish a predictive model for RH in living donor liver transplantation (LDLT). METHODS Perioperative data of 211 patients who underwent LDLT from 2009 and 2012 were reviewed, including declines in the blood glucose levels during the neohepatic phase. Perioperative variables including the posttransplant model for end-stage liver disease (MELD) score until day 30 were compared between patients with normal declines in blood glucose and patients with RH. Selected variables after intergroup comparisons were examined by means of multivariate logistic regression to establish a predictive model for RH occurrence. RESULTS The mean blood glucose decline was 22.3 ± 31.5 mg/dL during the neohepatic phase, and 84 of 203 patients (41.4%) had no decline in blood glucose. In intergroup comparisons, preoperative factors associated with RH included sex, Child-Pugh-Turcotte class, MELD score, emergency, liver enzymes, and graft-to-recipient weight ratio. During surgery, surgical time, serum lactate, and arterial pH were associated with RH. After surgery, the RH group showed slower recovery of the MELD score (15.2 versus 11.9 days) and higher MELD scores until day 10 (P < .05). After the multivariate analysis, recipient sex, emergency, surgical time (≤9 h), and the final intraoperative serum lactate level (≥5.0 mmol/L) were included in the predictive model for RH. CONCLUSIONS RH was associated with delayed functional recovery of the liver graft in LT. Recipient sex, emergency, surgical time, and the final intraoperative serum lactate level were identified as predictors of RH. Close monitoring of intraoperative blood glucose in LDLT may be an early prognostic indicator.
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Affiliation(s)
- H S Chung
- Department of Anesthesiology and Pain Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - S Lee
- Department of Anesthesiology and Pain Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - S J Kwon
- Department of Anesthesiology and Pain Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - C S Park
- Department of Anesthesiology and Pain Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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48
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49
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Regelmann MO, Goldis M, Arnon R. New-onset diabetes mellitus after pediatric liver transplantation. Pediatr Transplant 2015; 19:452-9. [PMID: 26032592 DOI: 10.1111/petr.12523] [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] [Accepted: 04/15/2015] [Indexed: 12/28/2022]
Abstract
In the first five yr after liver transplant, approximately one in 10 pediatric recipients will develop NODAT. Factors associated with higher risk for NODAT have been difficult to identify due to lack of uniformity in reporting and data collection. Limited studies have reported higher risk in those who are at an older age at transplant, those with high-risk ethnic backgrounds, and in those with particular underlying conditions, such as CF and primary sclerosing cholangitis. Immunosuppressive medications, including tacrolimus, cyclosporine A, GC, and sirolimus, have been implicated as contributing to NODAT, to varying degrees. Identifying those at highest risk, appropriately screening, and diagnosing NODAT is critical to initiating timely treatment and avoiding potential complications. In the pediatric population, treatment is limited primarily to insulin, with some consideration for metformin. Children with NODAT should be monitored carefully for complications of DM, including microalbuminuria, hypertension, hyperlipidemia, and retinopathy.
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Affiliation(s)
- Molly O Regelmann
- Division of Pediatric Endocrinology & Diabetes, Hall Family Center for Diabetes, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Marina Goldis
- Division of Pediatric Endocrinology & Diabetes, Hall Family Center for Diabetes, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ronen Arnon
- Division of Pediatric Hepatology, Recanati/Miller Transplant Institute, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Tsai MS, Wang YC, Wang HH, Lee PH, Jeng LB, Kao CH. Pre-existing diabetes and risks of morbidity and mortality after liver transplantation: A nationwide database study in an Asian population. Eur J Intern Med 2015; 26:433-8. [PMID: 26048000 DOI: 10.1016/j.ejim.2015.05.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Revised: 04/23/2015] [Accepted: 05/17/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Whether diabetes mellitus (DM) is associated with a higher risk of perioperative mortality and mortality after liver transplantation (LTx) remains unclear. METHODS We compared the risk of postoperative mortality and morbidity in DM and non-DM patients undergoing LTx. We enrolled 558 DM patients who underwent LTx from 2000 to 2010. RESULTS DM was associated with elevated 90-day risk of post-LTx stroke. Otherwise, the DM cohort did not exhibit significantly higher risks of postoperative morbidities, such as septicemia, pneumonia, and wound infection, than the non-DM cohort. Cox proportional hazards regression model showed that patients with DM with coexisting renal manifestations were at a significantly high risk of 30-day and 90-day postoperative mortality. Further comorbidity stratification analysis showed that DM cohort exhibited higher risk of mortality than the non-DM cohort if the patients had liver cancer, or did not have hypertension, ischemic heart disease, and chronic obstructive pulmonary disease. CONCLUSION DM is associated with elevated risk of 90-day post-LTx. Moreover, DM patients with coexisting renal manifestations exhibited an increased postoperative risk of mortality after LTx.
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Affiliation(s)
- Ming-Shian Tsai
- Division of General Surgery, Department of Surgery, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Yu-Chiao Wang
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan
| | - Hsi-Hao Wang
- Division of Nephrology, Department of Internal Medicine, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Po-Huang Lee
- Division of General Surgery, Department of Surgery, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Long-Bin Jeng
- Department of Surgery, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.
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