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Arora A, Sharma P, Kumar A, Acharya S, Sarin SK, Duseja A, Puri P, Shah S, Chawla Y, Rao P, Saraya A, Mohanka R, Singh S, Saighal S, Rela M, Vij V, Asthana S, Shukla A, Bhangui P, Saraf N, Maiwall R, Mandot A, Saraswat V, Madan K, Shalimar, Kapoor D, Anand AC, Gupta S, Varghese J, Mehta N. Indian National Association for the Study of Liver (INASL) Guidance Statements for Determining Futility in Liver Transplantation. J Clin Exp Hepatol 2025; 15:102539. [PMID: 40343081 PMCID: PMC12056968 DOI: 10.1016/j.jceh.2025.102539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 02/24/2025] [Indexed: 05/10/2025] Open
Abstract
Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease; however, with the growing shortage of organ donors, the need to identify futile transplants has become increasingly urgent. Futility in liver transplantation refers to situations where the expected post-transplant survival or quality of life is poor, making the procedure unlikely to yield a meaningful benefit. Various definitions of futility are used across different countries and transplant centers, with criteria often based on clinical factors such as age, comorbidities, MELD score, and functional status. For hepatologists and transplant surgeons, clearer guidelines are essential to make informed decisions and avoid unnecessary transplants that may place patients at risk without improving their prognosis. While some studies have proposed futility scores, there is currently no universal consensus on a standardized definition or set of criteria. This highlights the need for further prospective trials to evaluate the predictors of futility in liver transplantation, aiming to refine decision-making processes, optimize organ allocation, and improve patient outcomes. Future research should focus on the development of universally accepted futility criteria and explore interventions to mitigate the factors contributing to transplant futility.
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Affiliation(s)
- Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - S.K. Acharya
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Ajay Duseja
- Post Institute of Medical Sciences, Chandigarh, India
| | | | - Samir Shah
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | - Y.K. Chawla
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - P.N. Rao
- Asian Institute of Gsstroenterology, Hyderabad, India
| | - Anoop Saraya
- All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Mumbai, India
| | | | | | - Mohamed Rela
- Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Vivek Vij
- Fortis Hospital, Noida, Delhi, India
| | - Sonal Asthana
- Aster CMI Bangalore, Aster RV Bangalore, Aster Whitefield, Bangalore, India
| | - Akash Shukla
- Reliance Foundation Hospital and Research Centre, Mumbai, India
- Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | | | | | - Rakhi Maiwall
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Amit Mandot
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | | | | | - Shalimar
- All India Institute of Medical Sciences, New Delhi, India
| | - Dharmesh Kapoor
- Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
- Yashoda Hospital, Hyderabad, India
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | | | - Joy Varghese
- Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600100, India
| | - Naimish Mehta
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
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Duan Y, Ding L, Gao Z, Wang Y, Cao H, Zhang H, Yao L. Assessing the effectiveness of continuous glucose monitoring compared with conventional monitoring in enhancing surgical outcomes for patients with diabetes: protocol for a multicentre, parallel-arm, randomised, pragmatic trial in China. BMJ Open 2025; 15:e090664. [PMID: 39965943 PMCID: PMC11836829 DOI: 10.1136/bmjopen-2024-090664] [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: 07/01/2024] [Accepted: 02/05/2025] [Indexed: 02/20/2025] Open
Abstract
INTRODUCTION The Comprehensive Complication Index (CCI) is an internationally recognised indicator of postoperative complications. During the perioperative period, patients with diabetes mellitus (DM) or impaired glucose tolerance (IGT) may experience a significant increase in the CCI associated with glucose-related complications and increased mortality. Continuous glucose monitoring (CGM) offers advantages such as portability, accuracy, real-time monitoring and rich information. However, few large-scale studies have investigated the effectiveness and safety of CGM in reducing CCI during major surgeries. METHODS AND ANALYSIS This study is a multicentre, parallel-arm, randomised pragmatic trial to investigate whether CGM improves clinical outcomes in patients with type 1 or type 2 DM or IGT undergoing major surgery relative to conventional monitoring. This study is planned to be conducted in 50 secondary or tertiary hospitals in China. Eligible patients aged 18 years or older with DM or IGT undergoing elective major surgery will be recruited during a baseline screening period of 3 days before surgery. Eligible patients will be randomly assigned to receive CGM or conventional monitoring in a 1:1 ratio. The primary endpoint measure is the CCI score within 30 postoperative days. The margin of superiority is -12.0. A total of 10 168 participants will achieve 90% power to detect a clinically important difference of -13.0 between the means in the primary outcome. This trial includes multiple statistical analysis steps. For the primary outcome, a covariance model will be used to compare the difference in CCI within 30 days postoperatively between the two groups after adjusting for baseline and centre effects. ETHICS AND DISSEMINATION This trial has been approved by the Ethics Committee of Beijing Tsinghua Changgung Hospital (No. 23684-0-02) and its corresponding branch centres. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to a peer-reviewed journal. TRIAL REGISTRATION NUMBER NCT06331923.
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Affiliation(s)
- Yi Duan
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Lin Ding
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Department of Anaesthesiology, Peking University International Hospital, Beijing, China
| | - Zhifeng Gao
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Yutong Wang
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Han Cao
- Medical Data Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Huan Zhang
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Lan Yao
- Department of Anaesthesiology, Peking University International Hospital, Beijing, China
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Li C, Jiang X, Zhang K. A transformer-based deep learning approach for fairly predicting post-liver transplant risk factors. J Biomed Inform 2024; 149:104545. [PMID: 37992791 PMCID: PMC11619923 DOI: 10.1016/j.jbi.2023.104545] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 10/11/2023] [Accepted: 11/13/2023] [Indexed: 11/24/2023]
Abstract
Liver transplantation is a life-saving procedure for patients with end-stage liver disease. There are two main challenges in liver transplant: finding the best matching patient for a donor and ensuring transplant equity among different subpopulations. The current MELD scoring system evaluates a patient's mortality risk if not receiving an organ within 90 days. However, the donor-patient matching should also consider post-transplant risk factors, such as cardiovascular disease, chronic rejection, etc., which are all common complications after transplant. Accurate prediction of these risk scores remains a significant challenge. In this study, we used predictive models to solve the above challenges. Specifically, we proposed a deep learning model to predict multiple risk factors after a liver transplant. By formulating it as a multi-task learning problem, the proposed deep neural network was trained to simultaneously predict the five post-transplant risks and achieve equal good performance by exploiting task-balancing techniques. We also proposed a novel fairness-achieving algorithm to ensure prediction fairness across different subpopulations. We used electronic health records of 160,360 liver transplant patients, including demographic information, clinical variables, and laboratory values, collected from the liver transplant records of the United States from 1987 to 2018. The model's performance was evaluated using various performance metrics such as AUROC and AUPRC. Our experiment results highlighted the success of our multi-task model in achieving task balance while maintaining accuracy. The model significantly reduced the task discrepancy by 39 %. Further application of the fairness-achieving algorithm substantially reduced fairness disparity among all sensitive attributes (gender, age group, and race/ethnicity) in each risk factor. It underlined the potency of integrating fairness considerations into the task-balancing framework, ensuring robust and fair predictions across multiple tasks and diverse demographic groups.
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Affiliation(s)
- Can Li
- Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Xiaoqian Jiang
- Department of Health Data Science and Artificial Intelligence, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Kai Zhang
- Department of Health Data Science and Artificial Intelligence, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
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Mehtani R, Saigal S. Long Term Complications of Immunosuppression Post Liver Transplant. J Clin Exp Hepatol 2023; 13:1103-1115. [PMID: 37975039 PMCID: PMC10643541 DOI: 10.1016/j.jceh.2023.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 06/18/2023] [Indexed: 11/19/2023] Open
Abstract
Improvement in immunosuppression has led to a remarkable improvement in short-term and long-term outcomes post-liver transplant (LT). However, with improvements in long-term survival, complications related to immunosuppressive drugs, either directly or indirectly, have also increased. The adverse events could be drug-specific, class-specific, or generic. Calcineurin inhibitors (cyclosporine and tacrolimus) are the backbone of the immunosuppression after LT and the main culprit associated with most of the complications, including renal failure, post-transplant diabetes mellitus (PTDM), and metabolic syndrome. Steroids are also implicated in the development of diabetes, osteoporosis, and metabolic syndrome post-LT. The development of infections and de novo malignancies (DNMs) is a generic effect linked to the overall cumulative immunosuppression. The development of these complications significantly hampers the quality of life and leads to increased morbidity and mortality post-LT. Thus, it is important to minimize the cumulative immunosuppression dose while simultaneously preventing allograft rejection. This review provides up-to-date, comprehensive knowledge of the complications of long-term immunosuppression post-LT along with associated risk factors and strategies to minimize the risk of complications.
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Affiliation(s)
- Rohit Mehtani
- Department of Hepatology, Amrita Institute of Medical Sciences and Research, Faridabad, Haryana – 121001, India
| | - Sanjiv Saigal
- Transplant Hepatology, Centre for Liver and Biliary Sciences, Max Superspecialty Hospital, Saket, New Delhi, India
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Ochoa-Allemant P, Trivedi HD, Saberi B, Bonder A, Fricker ZP. Waitlist and posttransplantation outcomes of lean individuals with nonalcoholic fatty liver disease. Liver Transpl 2023; 29:145-156. [PMID: 37160058 DOI: 10.1002/lt.26531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 05/23/2022] [Accepted: 06/07/2022] [Indexed: 01/25/2023]
Abstract
Lean individuals with nonalcoholic fatty liver disease (NAFLD) represent a subset of patients with a distinct risk factor profile. We assessed the association between body mass index (BMI) on waitlist and postliver transplantation (LT) outcomes among these patients. We retrospectively analyzed the United Network for Organ Sharing data, including adult patients with NAFLD listed for LT between February 27, 2002, and June 30, 2020. We first used competing risk analyses to estimate the association of BMI with waitlist removal due to death or clinical deterioration. We then conducted Kaplan-Meier estimates and Cox regression models to determine the impact of weight change during the waiting list on all-cause mortality and graft failure after LT. Patients with normal weight (BMI 18.5-24.9 kg/m 2 ) suffered higher waitlist removal (adjusted subdistribution hazard ratio 1.26, 95% confidence interval [CI] 1.10-1.43; p = 0.001) compared with patients with obesity class I (BMI 30-34.9 kg/m 2 ). Those who remained at normal weight had higher all-cause mortality (adjusted hazard ratio [aHR] 1.61, 95% CI 1.32-1.96; p <0.001) and graft failure (aHR 1.57, 95% CI 1.32-1.88; p <0.001) than patients with stable obesity. Among patients with normal weight, those with the greatest weight increase (BMI gain ≥3 kg/m 2 ) had lower all-cause mortality (aHR 0.55, 95% CI 0.33-0.93; p = 0.03) and graft failure (aHR 0.49, 95% CI 0.30-0.81; p = 0.01) compared with patients with stable weight (BMI change ≤1 kg/m 2 ). Patients with NAFLD with normal weight have increased waitlist removal and those who remained at normal weight during the waitlist period have worse posttransplantation outcomes. Identifying and addressing factors influencing apparent healthy weight prior to LT are crucial to mitigate poor outcomes.
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Affiliation(s)
- Pedro Ochoa-Allemant
- Department of Internal Medicine , Yale School of Medicine , New Haven , Connecticut , USA
| | - Hirsh D Trivedi
- Liver Center, Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA
| | - Behnam Saberi
- Liver Center, Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA
| | - Alan Bonder
- Liver Center, Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA
| | - Zachary P Fricker
- Liver Center, Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA
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Salman AA, Salman MA, Said M, Elkassar H, El Sherbiny M, Youssef A, Elbaz M, Elmeligui AM, Hassan MB, Omar MG, Samir H, Abdelkader Morad M, Shaaban HED, Youssef M, Moustafa A, Tourky MS, Elewa A, Khalid S, Monazea K, Shawkat M. Albuminuria as a predictor of mortality in type II diabetic patients after living-donor liver transplantation. Ann Med 2022; 54:2598-2605. [PMID: 36164711 PMCID: PMC9521493 DOI: 10.1080/07853890.2022.2124446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 09/02/2022] [Accepted: 09/08/2022] [Indexed: 11/01/2022] Open
Abstract
PURPOSE Diabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection. Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality. This study evaluated albuminuria as a predictor of the outcome of living donor liver transplantation (LDLT) in patients with pre-existing DM. METHODS This retrospective study involved 103 type II diabetic patients with end-stage liver disease who received LDLT. Preoperative spot urine albumin: creatinine ratio was used to determine the degree of albuminuria. The primary outcome measure was the impact of urinary albumin excretion on the 3-year mortality rate after LDLT in this diabetic cohort. RESULTS Hepatitis C virus infection was the main cause of cirrhosis. Albuminuria was detected in 41 patients (39.8%); 15 had macroalbuminuria, while 26 had microalbuminuria. Patients with microalbuminuria were significantly older than those with macroalbuminuria and normal albumin in urine. After 3 years, twenty-four patients (23.3%) died within 3 years after LT. Myocardial infarction was the leading cause of death (25%). Albuminuria was an independent factor affecting 3-year mortality with an odds ratio of 5.17 (95% CI: 1.86-14.35). CONCLUSION Preoperative albuminuria is an independent factor affecting mortality within 3 years after LDLT in type II diabetic patients. Myocardial infarction was the leading cause of death in 25% of cases, followed by hepatocellular carcinoma recurrence, sepsis, and graft failure.KEY MESSAGESDiabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection.Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality.Preoperative albuminuria is a significant predictor of mortality within 3 years after LDLT in diabetic patients.
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Affiliation(s)
| | | | - Mostafa Said
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elkassar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohammad El Sherbiny
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Youssef
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohammed Elbaz
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed M. Elmeligui
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Badr Hassan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mahmoud Gouda Omar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hussien Samir
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Hossam El-Din Shaaban
- Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Youssef
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Moustafa
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Sabry Tourky
- Department of Surgery, Great Western Hospitals NHS Foundation Trust, Swindon, UK
| | - Ahmed Elewa
- General Surgery Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Sadaf Khalid
- General Surgery Department, Royal Free Hospital, London, UK
| | - Khaled Monazea
- General Surgery Department, Assiut Faculty of Medicine for Boys, Al-Azhar University, Cairo, Egypt
| | - Mohamed Shawkat
- Internal Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt
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Liver Transplantation for Budd-Chiari Syndrome in the MELD Era. Transplant Direct 2022; 8:e1407. [PMID: 36398192 PMCID: PMC9666155 DOI: 10.1097/txd.0000000000001407] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 09/09/2022] [Accepted: 09/26/2022] [Indexed: 01/24/2023] Open
Abstract
UNLABELLED To evaluate clinical characteristics and factors associated with survival among liver transplantation (LT) recipients with Budd-Chiari syndrome (BCS), with or without transjugular intrahepatic portosystemic shunt (TIPS), in the post-Model for End-stage Liver Disease era. METHODS We extracted data from the United Network for Organ Sharing database on all adult (≥18 y old) waitlisted candidates and recipients of LT with BCS in the United States between 2002 and 2019. Multivariable Cox regression was used to determine predictors of mortality and hazard ratios (HRs). RESULTS A total of 647 BCS patients were waitlisted between 2002 and 2019. BCS was an indication for LT in 378 (0.2%) of all adult LT recipients during the study period. Of BCS patients who received LT, approximately three-fourths (72.3%) were alive for up to 10 y. We found no significant difference in LT outcomes in BCS patients with or without TIPS. Longer length of hospital stay following LT (HR, 1.32; 95% confidence interval [CI], 1.19-1.47), Black/African American race (HR, 2.24; 95% CI, 1.38-3.64), diabetes (HR, 3.17; 95% CI, 1.62-6.21), donor risk index (HR, 1.44; 95% CI, 1.05-1.99), and lower albumin levels at the time of transplantation (HR, 0.66; 95% CI, 0.50-0.88) were negatively associated with survival after LT. Interestingly, neither the Model for End-stage Liver Disease nor prior TIPS showed a significant association with survival after LT. CONCLUSIONS These findings demonstrate good comparable survival among TIPS versus no TIPS in LT recipients with BCS. The decision for TIPS versus LT should be individualized on a case-by-case basis.
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Okumura K, Lee JS, Dhand A, Sogawa H, Veillette G, John D, Misawa R, Bodin R, Wolf DC, Diflo T, Nishida S. Trends and outcomes of liver transplantation among older recipients in the United States. World J Transplant 2022; 12:259-267. [PMID: 36159074 PMCID: PMC9453296 DOI: 10.5500/wjt.v12.i8.259] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 03/30/2022] [Accepted: 08/01/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The average age of recipients and donors of liver transplantation (LT) is increasing. Although there has been a change in the indications for LT over the years, data regarding the trends and outcomes of LT in the older population is limited.
AIM To assess the clinical characteristics, age-related trends, and outcomes of LT among the older population in the United States.
METHODS We analyzed data from the United Network for Organ Sharing database between 1987-2019. The sample was split into younger group (18-64 years old) and older group (≥ 65 years old).
RESULTS Between 1987-2019, 155758 LT were performed in the United States. During this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased (P < 0.05) with the highest incidence of LT among older population seen in 2019 (1920, 23%). Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group, were non-alcoholic steatohepatitis (16.4% vs 5.9%), hepatocellular carcinoma (14.9% vs 6.9%), acute liver failure (2.5% vs 5.2%), hepatitis C cirrhosis (HCV) (19.2 % vs 25.6%) and acute alcoholic hepatitis (0.13% vs 0.35%). In older recipient group female sex and Asian race were higher, while model for end-stage liver disease (MELD) score and rates of preoperative mechanical ventilation were lower (P < 0.01). Median age of donor, female sex, body mass index (BMI), donor HCV positive status, and donor risk index (DRI) were significantly higher in older group (P < 0.01). In univariable analysis, there was no difference in post-transplant length of hospitalization, one-year, three-year and five-year graft survivals between the two groups. In multivariable Cox-Hazard regression analysis, older group had an increased risk of graft failure during the five-year post-transplant period (hazard ratio: 1.27, P < 0.001). Other risk factors for graft failure among recipients were male sex, African American race, re-transplantation, presence of diabetes, mechanical ventilation at the time of LT, higher MELD score, presence of portal vein thrombosis, HCV positive status, and higher DRI.
CONCLUSION While there is a higher risk of graft failure in older recipient population, age alone should not be a contraindication for LT. Careful selection of donors and recipients along with optimal management of risk factors during the postoperative period are necessary to maximize the transplant outcomes in this population.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Joon Sub Lee
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Abhay Dhand
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Devon John
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Ryosuke Misawa
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Roxana Bodin
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - David C Wolf
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Thomas Diflo
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
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Okumura K, Sogawa H, Samson D, Butler J, Veillette G, John D, Diflo T, Bodin R, Wolf DC, Latifi R, Nishida S. Improving Liver Transplant Outcomes for Hepatitis C Virus Hepatocellular Carcinoma in the Direct-Acting Antiviral Therapy Era. Transplant Proc 2022; 54:1834-1838. [PMID: 35933231 DOI: 10.1016/j.transproceed.2022.03.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 01/27/2022] [Accepted: 03/07/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Direct-acting antiviral (DAA) therapy has transformed the outcomes of liver transplant (LT) with hepatitis C virus (HCV). This study aimed to analyze the effects of DAA treatment for HCV-associated hepatocellular carcinoma (HCC) in LT. METHODS We included patients confirmed with HCC on explant, analyzed data from United Network for Organ Sharing, and defined the pre-DAA era (2012-2013) and DAA era (2014-2016). RESULTS HCV-associated HCC cases totaled 4778 (62%) during the study period. In the DAA era, the median recipient age was older and the median days on the waiting list were longer. For the donor, median age, body mass index, and the rate of HCV significantly increased in the DAA era. In pathology, the median largest tumor size was significantly higher; however, the rate of completed tumor necrosis was significant higher in the DAA era. The 3-year graft/patient survival had significantly improved in the DAA era. In multivariable analysis, the DAA era (hazard ratio, 0.79; 95% confidence interval, 0.68-0.91) had significantly affected the 3-year graft survival. CONCLUSIONS DAA has a significant beneficial effect on LT. In the DAA era, graft survival for HCV-associated HCC has been significantly improving.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - David Samson
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - Jonathan Butler
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - Devon John
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - Thomas Diflo
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - Roxana Bodin
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - David C Wolf
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - Rifat Latifi
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York.
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10
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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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11
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Rasaei N, Malekmakan L, Mashayekh M, Gholamabbas G. Chronic Kidney Disease Following Liver Transplant: Associated Outcomes and Predictors. EXP CLIN TRANSPLANT 2022; 21:93-103. [PMID: 36656117 DOI: 10.6002/ect.2022.0288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVES Liver transplant as a life-saving procedure in patients with end-stage liver disease may have some complications such as renal dysfunction. Improved postoperative management and immuno- suppressive therapy have increased long-term survival and thus increased late complications like chronic kidney disease. Our study aimed to investigate outcomes of chronic kidney disease in liver transplant recipients and the incidence, progression rates, and adjustable risk factors of chronic kidney disease after liver transplant. MATERIALS AND METHODS Related studies published in English were elicited from various international sources like the ISI Web of Science, PubMed/Medline, Google Scholar, and Scopus. RESULTS AND CONCLUSIONS Chronic kidney disease as a long-term complication is common in liver transplant recipients whose survival is affected by renal function. Risk assessment of renal function before liver transplant and some nonrenal causes of chronic kidney disease after transplant could help reduce the risks associated with future renal outcomes.
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Affiliation(s)
- Nakisa Rasaei
- From the Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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12
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Zhang X, Hou A, Cao J, Liu Y, Lou J, Li H, Ma Y, Song Y, Mi W, Liu J. Association of Diabetes Mellitus With Postoperative Complications and Mortality After Non-Cardiac Surgery: A Meta-Analysis and Systematic Review. Front Endocrinol (Lausanne) 2022; 13:841256. [PMID: 35721703 PMCID: PMC9204286 DOI: 10.3389/fendo.2022.841256] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 04/12/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Although a variety of data showing that diabetes mellitus (DM) (Type 1 or Type 2) is associated with postoperative complication, there is still a lack of detailed studies that go through the specific diabetic subgroups. The goal of this meta-analysis is to assess the relationship between DM and various complications after non-cardiac surgery. METHODS We searched articles published in three mainstream electronic databases (PubMed, EMBASE, Web of science) before November, 2020. A random effects model was conducted since heterogeneity always exist when comparing results between different types of surgery. RESULTS This paper included 125 studies with a total sample size of 3,208,776 participants. DM was a risk factor for any postoperative complication (Odds ratio (OR)=1.653 [1.487, 1.839]). The risk of insulin-dependent DM (OR=1.895 [1.331, 2.698]) was higher than that of non-insulin-dependent DM (OR=1.554 [1.061, 2.277]) for any postoperative complication. DM had a higher risk of infections (OR=1.537 [1.322, 1.787]), wound healing disorders (OR=2.010 [1.326, 3.046]), hematoma (OR=1.369 [1.120, 1.673]), renal insufficiency (OR=1.987 [1.311, 3.013]), myocardial infarction (OR=1.372 [0.574, 3.278]). Meanwhile, DM was a risk factor for postoperative reoperation (OR=1.568 [1.124, 2.188]), readmission (OR=1.404 [1.274, 1.548]) and death (OR=1.606 [1.178, 2.191]). CONCLUSIONS DM is a risk factor for any postoperative complications, hospitalization and death after non-cardiac surgery. These findings underscore the importance of preoperative risk factor assessment of DM for the safe outcome of surgical patients.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Weidong Mi
- *Correspondence: Jing Liu, ; Weidong Mi,
| | - Jing Liu
- *Correspondence: Jing Liu, ; Weidong Mi,
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13
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Waitlist Mortality and Posttransplant Outcomes in African Americans with Autoimmune Liver Diseases. J Transplant 2021; 2021:6692049. [PMID: 34394979 PMCID: PMC8357471 DOI: 10.1155/2021/6692049] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 02/11/2021] [Accepted: 07/25/2021] [Indexed: 11/17/2022] Open
Abstract
Background Liver transplantation is indicated in end-stage liver disease due to autoimmune diseases. The liver allocation system can be affected by disparities such as decreased liver transplant referrals for racial minorities, especially African Americans that negatively impact the pre- and posttransplant outcomes. Aim To determine differences in waitlist survival and posttransplant graft survival rates between African American and Caucasian patients with autoimmune liver diseases. Study. The United Network for Organ Sharing database was used to identify all patients with autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis who underwent liver transplant from 1988 to 2019. We compared waitlist survival and posttransplant graft survival between Caucasians and African Americans using Kaplan–Meier curves and Cox regression models. We also evaluated the cumulative incidence of death or delisting for deterioration and posttransplant incidence of death and retransplantation using competing risk analysis. Results African Americans were more likely to be removed from the waitlist for death or clinical deterioration (subdistribution hazard ratio (SHR) 1.26, 95% CI 1–1.58, P=0.046) using competing risk analysis. On multivariate Cox regression analysis, there was no difference in posttransplant graft survival among the two groups (hazard ratio (HR) 1.10, 95% CI 0.98–1.23, P=0.081). Conclusions Despite the current efforts to reduce racial disparities, we found that African Americans are more likely to die on the waitlist for liver transplant and are less likely to be transplanted, with no differences in graft survival rates. The persistence of healthcare disparities continues to negatively impact African Americans.
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14
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Thuluvath AJ, Savva Y, Chen PH. Poor Graft and Patient Survival After Liver Transplantation in Sarcoidosis. J Clin Gastroenterol 2021; 54:884-890. [PMID: 33027134 DOI: 10.1097/mcg.0000000000001289] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
GOALS AND BACKGROUND There are limited data on post-liver transplantation (LT) outcomes of patients with sarcoidosis. STUDY We examined the clinical characteristics and post-LT outcomes of patients with sarcoidosis using the United Network for Organ Sharing database from 1985 to 2016 and compared them to patients (entire cohort as well as age, gender, and year of LT-matched counterparts) with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). For the matched design, a conditional logistic regression was used for categorical variables and marginal generalized estimating equation regression models for continuous variables. Survival functions were constructed using the Kaplan-Meier estimator. RESULTS A total of 206 patients with sarcoidosis, transplanted during the study period, were compared with 3933 patients with PBC and 5323 with PSC. In total, 197 patients with sarcoidosis were compared with 576 with PBC and 576 with PSC in the 1:3 matched analysis. The sarcoidosis group had a higher proportion of blacks (53.3%) and a higher prevalence of obesity and type II diabetes mellitus. The graft and patient survival for sarcoidosis patients were lower when compared with unmatched PBC and PSC patients. The results remained unchanged in the matched analysis. At 5-year, patient survival was ~15% lower for the sarcoidosis group when compared with PBC and PSC. In multivariate analysis using matched data, hazard ratios (HRs) for graft (HR=1.68, 95% confidence interval=1.03-2.75, P=0.04), and patient (HR=2.01, confidence interval=1.22-3.34, P<0.01) survival were higher for sarcoidosis. CONCLUSIONS Patients who underwent LT for sarcoidosis had a lower graft and patient survival when compared with those with PBC or PSC. That being said, 66% of patients survived 5 years after transplantation, suggesting that LT is an acceptable option in this population.
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Affiliation(s)
| | - Yulia Savva
- The Institute of Digestive Health and Liver Disease, Mercy Medical Center, Baltimore, MD
| | - Po-Hung Chen
- Department of Medicine
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine
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15
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Alukal JJ, Zhang T, Thuluvath PJ. Outcomes of status 1 liver transplantation for Budd-Chiari Syndrome with fulminant hepatic failure. Am J Transplant 2021; 21:2211-2219. [PMID: 33236517 DOI: 10.1111/ajt.16410] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 10/22/2020] [Accepted: 11/10/2020] [Indexed: 01/25/2023]
Abstract
There is a paucity of data on the outcome of liver transplantation (LT) in Budd-Chiari Syndrome (BCS) patients who are listed as status 1. The objective of our study was to determine patient or graft survival following LT in status 1 BCS patients. We utilized United Network for Organ Sharing (UNOS) database to identify all adult patients (> 18 years of age) listed as status 1 with a primary diagnosis of BCS in the United States from 1998 to 2018, and analyzed their outcomes and compared it to non-status 1 BCS patients. Four hundred and forty-six patients with BCS underwent LT between 1998 and 2018, and of these 55 (12.3%) were listed as status 1. There was no difference in long-term post-liver transplant or "intention-to-treat" survival from the time of listing to death or the last day of follow-up between status 1 and non-status 1 groups. Graft and patient survival at 5 years for status 1 patients were 75% and 82%, respectively. Cox regression analysis showed that patients listed as status 1 (aHR: 0.45, p < .02) were associated with a better survival. BCS patients listed as status 1 have excellent survival following emergency LT.
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Affiliation(s)
- Joseph J Alukal
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA
| | - Talan Zhang
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA
| | - Paul J Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA.,Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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16
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Kathirvel M, Mallick S, Sethi P, Thillai M, Durairaj MS, Nair K, Sunny A, Mathew JS, Varghese CT, Chandran B, Pillai Thankamony Amma BS, Menon RN, Balakrishnan D, Gopalakrishnan U, Surendran S. Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT). HPB (Oxford) 2021; 23:666-674. [PMID: 33032883 DOI: 10.1016/j.hpb.2020.09.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). METHODS We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. RESULTS The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). CONCLUSION Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.
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Affiliation(s)
- Manikandan Kathirvel
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India.
| | - Shweta Mallick
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Pulkit Sethi
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Manoj Thillai
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Madhu S Durairaj
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Krishnanunni Nair
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Aleena Sunny
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Johns S Mathew
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Christi T Varghese
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Biju Chandran
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Binoj S Pillai Thankamony Amma
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Ramachandran N Menon
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Dinesh Balakrishnan
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Unnikrishnan Gopalakrishnan
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
| | - Sudhindran Surendran
- Department of Gastrointestinal Surgery and Solid Organ Transplant, Amrita Institute of Medical Sciences and Research Centre, Amrita University, Kochi, Kerala, India
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17
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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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18
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Li C, Zhang W, Zhao Q, Ye M, Ju W, Wu L, Ma Y, Hu A, Wang G, Zhu X, Guo Z, Wang D, He X. Outcomes of Combined Liver and Pancreas Transplantation: A Review of the SRTR National Database and a Report of the Largest Single Center Series. Front Med (Lausanne) 2020; 7:542905. [PMID: 33195293 PMCID: PMC7605456 DOI: 10.3389/fmed.2020.542905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 08/31/2020] [Indexed: 11/15/2022] Open
Abstract
Purposes: This study was intended to summarize the characteristics and clinical outcome of Liver and Pancreas (LPTx) recipients in the Scientific Registry of Transplant Recipients (SRTR) database vs. the largest series from the First Affiliated Hospital (FAH), Sun Yat-sen University. Methods: The clinical data of 23 patients who underwent LPTx from 2000 to 2016 in the United States and 31 patients who underwent modified LPTx procedure (known as simplified multivisceral transplantation [SMT]) from 2008 to 2017 in our center were reviewed. The indications, surgical techniques, patient and graft survival, and complications were compared between the two groups. Results: All recipients in the FAH group were diagnosed with type 2 diabetes mellitus, while 10 of 23 recipients were diagnosed with type 1 diabetes mellitus in the SRTR group. The 1-, 3-, and 5-year cumulative patient survival rates were 81, 74, and 74% in the FAH group, respectively, and 51, 47, and 37% in the SRTR group, respectively (P = 0.023). No diabetes was observed during follow-up in the FAH group, while the diabetes recurrence rate was 22.2% in the SRTR group (P = 0.03). Conclusion: With multiple techniques modified and indications changed, the SMT procedure yielded a preferable outcome compared to that of the traditional LPTx procedure in records of SRTR. SMT has become a treatment option for patients with end-stage liver disease and concurrent diabetes.
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Affiliation(s)
- Cheukfai Li
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Science, Guangzhou, China
| | - Wei Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Medical Ultrasonics, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiang Zhao
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Maodong Ye
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Weiqiang Ju
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Linwei Wu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yi Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Anbin Hu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guodong Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaofeng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhiyong Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dongping Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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19
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Chung W, Promrat K, Wands J. Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases. World J Hepatol 2020; 12:533-557. [PMID: 33033564 PMCID: PMC7522556 DOI: 10.4254/wjh.v12.i9.533] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/03/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
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Affiliation(s)
- Waihong Chung
- Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Providence, RI 02905, United States.
| | - Kittichai Promrat
- Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI 02908, United States
| | - Jack Wands
- Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
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Man Kim J, Hwang S, Lee KW, Lee JG, Ryu JH, Kim BW, Choi DL, You YK, Kim DS, Nah YW, Kang KJ, Cho JY, Hong G, Choi IS, Yu HC, Choi D, Kim MS. New-onset diabetes after adult liver transplantation in the Korean Organ Transplantation Registry (KOTRY) study. Hepatobiliary Surg Nutr 2020; 9:425-439. [PMID: 32832494 PMCID: PMC7423540 DOI: 10.21037/hbsn.2019.10.29] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 08/05/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication following liver transplantation (LT). The present study aimed to investigate the incidence of and risk factors for NODAT using the Korean Organ Transplantation Registry (KOTRY) database. METHODS Patients with history of pediatric transplantation (age ≤18 years), re-transplantation, multi-organ transplantation, or pre-existing diabetes mellitus were excluded. A total of 1,919 non-diabetic adult patients who underwent a primary LT between May 2014 and December 2017 were included. Risk factors were identified using Cox regression analysis. RESULTS NODAT occurred in 19.7% (n=377) of adult liver transplant recipients. Multivariate analysis showed steroid use, increased age, and high body mass index (BMI) in recipients, and implantation of a left-side liver graft was closely associated with NODAT in adult LT. In living donor liver transplant (LDLT) patients (n=1,473), open donor hepatectomy in the living donors, steroid use, small for size liver graft (graft to recipient weight ratio ≤0.8), increased age, and high BMI in the recipient were predictive factors for NODAT. The use of antimetabolite and basiliximab induction reduced the incidence of NODAT in adult LT and in adult LDLT. CONCLUSIONS Basiliximab induction, early steroid withdrawal, and antimetabolite therapy may prevent NODAT after adult LT. High BMI or advanced age in liver recipients, open donor hepatectomy in living donors, and small size liver graft can predict the occurrence of NODAT after adult LT or LDLT.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jae-Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
| | - Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Koo Jeong Kang
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
| | - Geun Hong
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
| | - In Seok Choi
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
| | - Hee Chul Yu
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - The Korean Organ Transplantation Registry Study Group
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
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21
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Management of metabolic syndrome and cardiovascular risk after liver transplantation. Lancet Gastroenterol Hepatol 2020; 4:731-741. [PMID: 31387736 DOI: 10.1016/s2468-1253(19)30181-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 04/22/2019] [Accepted: 04/23/2019] [Indexed: 12/11/2022]
Abstract
Cardiovascular events are the second most prevalent cause of non-hepatic mortality in liver transplant recipients. The incidence of these events is projected to rise because of the growing prevalence of non-alcoholic steatohepatitis as a transplant indication and the ageing population of liver transplant recipients. Recipients with metabolic syndrome are up to four times more likely to have a cardiovascular event than recipients without, therefore prevention and optimal treatment of the components of metabolic syndrome are key in reducing the risk of these events. Although data on the treatment of metabolic comorbidities specifically in liver transplant recipients are scarce, there is detailed guidance from learned societies that mostly mirrors the guidance for patients at increased cardiovascular risk in the general population. In this Review, we discuss the management of the components of metabolic syndrome following liver transplantation and provide practical stepwise guidance. We also emphasise the need for adequately powered studies for the treatment of metabolic comorbidities in liver transplant recipients.
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Skladaný Ĺ, Mesárošová Z, Bachová B, Stančík M, Dedinská I. Alcohol-Related Liver Disease as a New Risk Factor for Post-transplant Diabetes After Liver Transplantation. Transplant Proc 2019; 51:3369-3374. [DOI: 10.1016/j.transproceed.2019.07.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 06/30/2019] [Accepted: 07/09/2019] [Indexed: 12/19/2022]
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23
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Mark E, Goldsman D, Keskinocak P, Sokol J. Using machine learning to estimate survival curves for patients receiving an increased risk for disease transmission heart, liver, or lung versus waiting for a standard organ. Transpl Infect Dis 2019; 21:e13181. [PMID: 31541522 PMCID: PMC9285951 DOI: 10.1111/tid.13181] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 08/13/2019] [Accepted: 09/15/2019] [Indexed: 12/22/2022]
Abstract
Introduction Over 19% of deceased organ donors are labeled increased risk for disease transmission (IRD) for viral blood‐borne disease transmission. Many potential organ recipients need to decide between accepting an IRD organ offer and waiting for a non–IRD organ. Methods Using machine learning and simulation, we built transplant and waitlist survival models and compared the survival for patients accepting IRD organ offers or waiting for non–IRD organs for the heart, liver, and lung. The simulation consisted of generating 20 000 different scenarios of a recipient either receiving an IRD organ or waiting and receiving a non–IRD organ. Results In the simulations, the 5‐year survival probabilities of heart, liver, and lung recipients who accepted IRD organ offers increased on average by 10.2%, 12.7%, and 7.2%, respectively, compared with receiving a non–IRD organ after average wait times (190, 228, and 223 days, respectively). When the estimated waitlist time was at least 5 days for the liver, and 1 day for the heart and lung, 50% or more of the simulations resulted in a higher chance of 5‐year survival when the patient received an IRD organ versus when the patient remained on the waitlist. We also developed a simple equation to estimate the benefits, in terms of 5‐year survival probabilities, of receiving an IRD organ versus waiting for a non–IRD organ, for a particular set of recipient/donor characteristics. Conclusion For all three organs, the majority of patients are predicted to have higher 5‐year survival accepting an IRD organ offer compared with waiting for a non–IRD organ.
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Affiliation(s)
- Ethan Mark
- H. Milton Stewart School of Industrial and Systems Engineering Georgia Institute of Technology Atlanta GA USA
| | - David Goldsman
- H. Milton Stewart School of Industrial and Systems Engineering Georgia Institute of Technology Atlanta GA USA
| | - Pinar Keskinocak
- H. Milton Stewart School of Industrial and Systems Engineering Georgia Institute of Technology Atlanta GA USA
| | - Joel Sokol
- H. Milton Stewart School of Industrial and Systems Engineering Georgia Institute of Technology Atlanta GA USA
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24
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Parveez MQ, Ponnappan K, Tandon M, Sharma A, Jain P, Singh A, Pandey CK, Vyas V. Preoperative Glycated Haemoglobin Level and Postoperative Morbidity and Mortality in Patients Scheduled for Liver Transplant. Indian J Endocrinol Metab 2019; 23:570-574. [PMID: 31803599 PMCID: PMC6873256 DOI: 10.4103/ijem.ijem_208_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND There is high prevalence of diabetes mellitus in patients of end stage liver disease and it has been implicated for complications in post-transplant patients. Glycated hemoglobin is now targeted as a modifiable preoperative risk factors for postoperative complications. Data describing the course and severity of postoperative liver transplant complication and their relation with pre-operative glycated hemoglobin level is sparse. In this study, we looked for co-relation between the preoperative HbA1c level and post-operative mortality and morbidity in patients scheduled for liver transplant. MATERIALS AND METHODS Retrospective data in 400 adult patients operated for liver transplant were retrieved. After exclusion, data were analyzed for 224 patients. Patients were divided into two groups on the basis of glycated hemoglobin levels (Group 1 (HbA1C ≥6.5) and Group 2 (HbA1C <6.5)). RESULTS Glycated hemoglobin levels were not associated with postoperative death during stay in intensive care unit, incidence of postoperative cardiovascular, renal, and central nervous complications. No difference was seen between 2 groups for need for renal replacement therapy, incidence of infections, rejection, need for re-exploration surgery and duration of intensive care unit and hospital stay. Glycated hemoglobin cannot predict 30 day survival (Area under curve {AUC} = 0.629, P value 0.05). CONCLUSION Preoperative glycated hemoglobin level is not associated with postoperative morbidity and mortality in patients scheduled for liver transplant. TRIAL REGISTRATION NUMBER CTRI/2018/04/012966.
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Affiliation(s)
- Mohd Qurram Parveez
- Department of Anaesthesiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Karthik Ponnappan
- Department of Anaesthesiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manish Tandon
- Dharamshila Narayana Superspeciality Hospital, New Delhi, India
| | - Ankur Sharma
- Department of Trauma and Emergency (Anaesthesiology), All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Priyanka Jain
- Statistician, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Akhil Singh
- Departments of Anaesthesiology, All India Institute of Medical Sciences, New Delhi, India
| | - Chandra Kant Pandey
- Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Varuna Vyas
- Department of Pediatrics (Endocrinology), All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
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25
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Identifying Predictors of Outcomes in Combined Heart and Liver Transplantation. Transplant Proc 2019; 51:2002-2008. [DOI: 10.1016/j.transproceed.2019.04.038] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 03/24/2019] [Accepted: 04/05/2019] [Indexed: 11/22/2022]
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26
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Hu Y, Yang C, Shen G, Yang S, Cheng X, Cheng F, Rao J, Wang X. Hyperglycemia-Triggered Sphingosine-1-Phosphate and Sphingosine-1-Phosphate Receptor 3 Signaling Worsens Liver Ischemia/Reperfusion Injury by Regulating M1/M2 Polarization. Liver Transpl 2019; 25:1074-1090. [PMID: 30972941 PMCID: PMC6617772 DOI: 10.1002/lt.25470] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 04/04/2019] [Indexed: 12/12/2022]
Abstract
Hyperglycemia aggravates hepatic ischemia/reperfusion injury (IRI), but the underlying mechanism for the aggravation remains elusive. Sphingosine-1-phosphate (S1P) and sphingosine-1-phosphate receptors (S1PRs) have been implicated in metabolic and inflammatory diseases. Here, we discuss whether and how S1P/S1PRs are involved in hyperglycemia-related liver IRI. For our in vivo experiment, we enrolled diabetic patients with benign hepatic disease who had liver resection, and we used streptozotocin (STZ)-induced hyperglycemic mice or normal mice to establish a liver IRI model. In vitro bone marrow-derived macrophages (BMDMs) were differentiated in high-glucose (HG; 30 mM) or low-glucose (LG; 5 mM) conditions for 7 days. The expression of S1P/S1PRs was analyzed in the liver and BMDMs. We investigated the functional and molecular mechanisms by which S1P/S1PRs may influence hyperglycemia-related liver IRI. S1P levels were higher in liver tissues from patients with diabetes mellitus and mice with STZ-induced diabetes. S1PR3, but not S1PR1 or S1PR2, was activated in liver tissues and Kupffer cells under hyperglycemic conditions. The S1PR3 antagonist CAY10444 attenuated hyperglycemia-related liver IRI based on hepatic biochemistry, histology, and inflammatory responses. Diabetic livers expressed higher levels of M1 markers but lower levels of M2 markers at baseline and after ischemia/reperfusion. Dual-immunofluorescence staining showed that hyperglycemia promoted M1 (CD68/CD86) differentiation and inhibited M2 (CD68/CD206) differentiation. Importantly, CAY10444 reversed hyperglycemia-modulated M1/M2 polarization. HG concentrations in vitro also triggered S1P/S1PR3 signaling, promoted M1 polarization, inhibited M2 polarization, and enhanced inflammatory responses compared with LG concentrations in BMDMs. In contrast, S1PR3 knockdown significantly retrieved hyperglycemia-modulated M1/M2 polarization and attenuated inflammation. In conclusion, our study reveals that hyperglycemia specifically triggers S1P/S1PR3 signaling and exacerbates liver IRI by facilitating M1 polarization and inhibiting M2 polarization, which may represent an effective therapeutic strategy for liver IRI in diabetes.
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Affiliation(s)
- Yuanchang Hu
- Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical SciencesNanjingChina
| | - Chao Yang
- Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical SciencesNanjingChina
| | - Gefengqiang Shen
- Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical SciencesNanjingChina
| | - Shikun Yang
- Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical SciencesNanjingChina
| | - Xuyu Cheng
- Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical SciencesNanjingChina
| | - Feng Cheng
- Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical SciencesNanjingChina
| | - Jianhua Rao
- Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical SciencesNanjingChina
| | - Xuehao Wang
- Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical SciencesNanjingChina
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27
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Gray M, Singh S, Zucker SD. Influence of Type 2 Diabetes Mellitus and Preoperative Hemoglobin A1c Levels on Outcomes of Liver Transplantation. Hepatol Commun 2019; 3:574-586. [PMID: 30976746 PMCID: PMC6442696 DOI: 10.1002/hep4.1323] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/30/2019] [Indexed: 12/28/2022] Open
Abstract
Liver transplant centers often establish hemoglobin A1c (HbA1C) criteria for candidates with type 2 diabetes mellitus (T2DM) based on data from other surgical specialties showing worse outcomes in patients with poor glycemic control. However, because of the reduced reliability of HbA1C in cirrhosis, it is unclear whether pretransplant HbA1C values are predictive of postoperative complications in liver recipients. We retrospectively examined the association between preoperative HbA1C and postoperative outcomes in 173 consecutive patients who underwent liver transplantation at the University of Cincinnati Medical Center between August 2012 and March 2015. Demographic correlates of pretransplant HbA1C included age, T2DM, native Model for End‐Stage Liver Disease, hemoglobin, serum albumin, and nonalcoholic steatohepatitis as the indication for transplantation. No association was identified between pretransplant HbA1C and most outcome measures, including survival, length of stay, reoperation or readmission rates, rejection, bacteremia, and viremia. Significant correlates of HbA1C in liver recipients with diabetes were posttransplant insulin requirement and anastomotic biliary stricture formation. On multivariate analysis, HbA1C was the sole determinant of biliary strictures, with patients in the highest quartile (HbA1C >7.3%) exhibiting a 4‐fold increased risk. Correlation of HbA1C with morning blood glucose levels was much tighter after versus before transplantation. Conclusion: Preoperative HbA1C is predictive of anastomotic biliary stricture formation and the need for insulin following liver transplantation.
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Affiliation(s)
- Meagan Gray
- Division of Gastroenterology and Hepatology University of Alabama at Birmingham Birmingham AL
| | - Sanjeev Singh
- Division of Digestive Diseases University of Cincinnati Medical Center Cincinnati OH
| | - Stephen D Zucker
- Division of Gastroenterology, Hepatology, and Endoscopy Brigham and Women's Hospital Boston MA
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28
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Liu A, Galoosian A, Kaswala D, Li AA, Gadiparthi C, Cholankeril G, Kim D, Ahmed A. Nonalcoholic Fatty Liver Disease: Epidemiology, Liver Transplantation Trends and Outcomes, and Risk of Recurrent Disease in the Graft. J Clin Transl Hepatol 2018; 6:420-424. [PMID: 30637220 PMCID: PMC6328728 DOI: 10.14218/jcth.2018.00010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 05/15/2018] [Accepted: 05/31/2018] [Indexed: 02/06/2023] Open
Abstract
In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.
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Affiliation(s)
- Andy Liu
- California Pacific Medical Center, Department of Medicine, San Francisco, CA, USA
| | - Artin Galoosian
- California Pacific Medical Center, Department of Medicine, San Francisco, CA, USA
| | - Dharmesh Kaswala
- California Pacific Medical Center, Division of Gastroenterology and Hepatology, San Francisco, CA, USA
| | - Andrew A. Li
- Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Stanford, CA, USA
| | - Chiranjeevi Gadiparthi
- University of Tennessee Health Science Center, Division of Gastroenterology and Hepatology, Memphis, TN, USA
| | - George Cholankeril
- Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Stanford, CA, USA
| | - Donghee Kim
- Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Stanford, CA, USA
| | - Aijaz Ahmed
- Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Stanford, CA, USA
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29
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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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30
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Diabetes With or Without Hypertension Does Not Affect Graft Survival and All-cause Mortality After Liver Transplant: A Propensity Score Matching Analysis. Transplant Proc 2018; 50:1123-1128. [DOI: 10.1016/j.transproceed.2018.01.045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 01/22/2018] [Indexed: 12/25/2022]
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32
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Li J, Guo QJ, Cai JZ, Pan C, Shen ZY, Jiang WT. Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus. World J Gastroenterol 2017; 23:8104-8108. [PMID: 29259387 PMCID: PMC5725306 DOI: 10.3748/wjg.v23.i45.8104] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 08/27/2017] [Accepted: 09/13/2017] [Indexed: 02/06/2023] Open
Abstract
Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.
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Affiliation(s)
- Jiang Li
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Qing-Jun Guo
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Jin-Zhen Cai
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Cheng Pan
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Zhong-Yang Shen
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Wen-Tao Jiang
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
- Department of Transplant Surgery, Tianjin First Central Hospital, Tianjin 300192, China
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Ramos-Prol A, Hervás-Marín D, García-Castell A, Merino-Torres JF. Outcomes in patients with diabetes 10 years after liver transplantation. J Diabetes 2017; 9:1033-1039. [PMID: 28039959 DOI: 10.1111/1753-0407.12520] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Revised: 12/04/2016] [Accepted: 12/28/2016] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND There are discrepancies between studies regarding the effect of diabetes mellitus on morbidity and mortality in patients undergoing liver transplantation. The aim of the present study was to compare mortality, risk of liver graft rejection, and cardiovascular events in patients with and without diabetes undergoing liver transplantation over a 10-year follow-up period. METHODS A retrospective study was performed on 183 patients who underwent liver transplantation in 2005 and 2006. Mortality and morbidity data were collected until 2016, including information on mortality and survival time, graft rejection and graft survival time, coronary heart disease, stroke, and peripheral arterial ischemia. RESULTS During the follow-up, 41.3% and 27.8% of patients in the groups with and without diabetes, respectively, died. A trend for lower survival time was observed in patients with diabetes, although this effect was not confirmed by the Cox regression model. There was an increased risk of graft rejection in the group with diabetes compared with the group without diabetes ( P < 0.001). In the survival analysis, diabetes was associated with reduced graft survival time ( P = 0.001). Cardiovascular events were also more likely in the group with diabetes ( P = 0.005). CONCLUSIONS In the present study diabetes was associated with a higher risk of liver graft rejection and cardiovascular events. There was also a trend for higher mortality, although the effect was not statistically significant. These findings suggest that patients with diabetes require a more rigorous pretransplant evaluation and closer monitoring after transplantation in order to try to reduce associated complications.
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Affiliation(s)
- Agustín Ramos-Prol
- Department of Internal Medicine (Endocrinology and Nutrition), Francesc de Borja Hospital, Gandía, Spain
- Joint Research Unit of Endocrinology, Nutrition and Clinical Dietetics, Valencia, Spain
| | | | - Alia García-Castell
- Endocrinology and Nutrition Department, University and Polytechnic La Fe Hospital, Valencia, Spain
| | - Juan F Merino-Torres
- Joint Research Unit of Endocrinology, Nutrition and Clinical Dietetics, Valencia, Spain
- Endocrinology and Nutrition Department, University and Polytechnic La Fe Hospital, Valencia, Spain
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He XS, Fu SJ, Zhao Q, Zhu XF, Wang DP, Han M, Ju WQ, Ma Y, Jiao XY, Yuan XP, Hu AB, Guo ZY. A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus. Liver Transpl 2017; 23:1161-1170. [PMID: 28422396 DOI: 10.1002/lt.24774] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2016] [Revised: 03/25/2017] [Accepted: 04/06/2017] [Indexed: 01/13/2023]
Abstract
In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.
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Affiliation(s)
- Xiao-Shun He
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Shun-Jun Fu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Qiang Zhao
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xiao-Feng Zhu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Dong-Ping Wang
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Ming Han
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Wei-Qiang Ju
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Yi Ma
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xing-Yuan Jiao
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Xiao-Peng Yuan
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - An-Bin Hu
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
| | - Zhi-Yong Guo
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People's Republic of China.,Organ Transplantation, Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, People's Republic of China
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Edgerton CA, McGillicuddy JW, DuBay D, Nadig SN. Utilization of the Iliac Artery as Inflow in the Morbidly Obese During Orthotopic Liver Transplantation: A Case Report. Transplant Proc 2017; 49:1624-1627. [PMID: 28838452 DOI: 10.1016/j.transproceed.2017.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 05/13/2017] [Indexed: 11/17/2022]
Abstract
Arterial conduits are a well-recognized technique used in liver transplantation to achieve allograft arterial inflow when conventional hepatic arterial inflow is compromised. Indications for ectopic inflow include native arterial disease at the time of initial transplantation, as well as reconstruction in the setting of thrombotic complications. Although supraceliac or infrarenal aortic reconstructions are preferred approaches, the right common iliac artery represents a viable alternative. We present the case of a morbidly obese patient with occlusive atheromatous plaque at the celiac origin not amenable to preoperative angioplasty who underwent reconstruction with a donor iliac artery conduit to the recipient right common iliac artery. His hepatic arterial inflow remained patent postoperatively with no thrombotic or hemorrhagic complications.
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Affiliation(s)
- C A Edgerton
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston, South Carolina
| | - J W McGillicuddy
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston, South Carolina
| | - D DuBay
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston, South Carolina
| | - S N Nadig
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston, South Carolina.
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Golfieri L, Gitto S, Morelli MC, Pinna AD, Grandi S, Andreone P. Impact of hepatitis C virus infection on health-related quality of life before and after liver transplantation: a multidisciplinary point of view. Expert Rev Anti Infect Ther 2017; 15:759-765. [PMID: 28756716 DOI: 10.1080/14787210.2017.1362334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis C negatively changes patient quality of life even in the absence of advanced liver disease. The specific patterns of quality of life of hepatitis C positive patients waiting for transplant or after surgery are not widely studied. Areas covered: A significant percentage of infected patients show cognitive impairment, fatigue, and/or a 'brain fog', that cannot be explained by the liver disease. Depression can be diagnosed in one third of hepatitis C positive patients. Conflicting data are available regarding the possible role of Model for End-Stage Liver Disease score as predictor of impaired quality of life. In the first period after liver transplant, quality of life tends to increase at the pre-transplant period but in the medium and long-term period, it declines. The recurrence of hepatitis C infection represents a strong predictor of morbidity and mortality and can significantly affect the global quality of life of patients. Expert commentary: Hepatologists, surgeons and psychologists should collaborate to support infected patients in all phases of transplant including the long-term period after surgery. Education and information should be implemented especially regarding the positive role of new direct antivirals.
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Affiliation(s)
- Lucia Golfieri
- a Dipartimento di Psicologia , Università di Bologna , Bologna , Italy
| | - Stefano Gitto
- b Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche , Università di Bologna , Bologna , Italy
- c Programma Dipartimentale Innovazione Terapeutica Epatopatie Croniche Virali (ITEC), Dipartimento Ospedaliero dell'Apparato Digerente , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Maria Cristina Morelli
- d Medicina Interna per il trattamento delle gravi insufficienze d'organo , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Antonio Daniele Pinna
- e Chirurgia Generale e Trapianti , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Silvana Grandi
- a Dipartimento di Psicologia , Università di Bologna , Bologna , Italy
| | - Pietro Andreone
- b Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche , Università di Bologna , Bologna , Italy
- c Programma Dipartimentale Innovazione Terapeutica Epatopatie Croniche Virali (ITEC), Dipartimento Ospedaliero dell'Apparato Digerente , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
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37
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Lin M, Pappas SC. Diabetes, Cirrhosis, and Liver Transplantation. MANAGING GASTROINTESTINAL COMPLICATIONS OF DIABETES 2017:107-115. [DOI: 10.1007/978-3-319-48662-8_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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38
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Karam V, Sebagh M, Rifai K, Yilmaz F, Bhangui P, Danet C, Saliba F, Samuel D, Castaing D, Adam R, Feray C. Quality of life 10 years after liver transplantation: The impact of graft histology. World J Transplant 2016; 6:703-711. [PMID: 28058221 PMCID: PMC5175229 DOI: 10.5500/wjt.v6.i4.703] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 09/06/2016] [Accepted: 09/22/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate the relationship between the state of transplanted liver graft and the recipient quality of life (QOL) of histologically proven lesions in a 10-year post liver transplantation (LT) cohort of patients.
METHODS Seventy-two recipients with a functional first graft at 10 years post-LT underwent liver biopsy and completed a QOL questionnaire. Logistic regression analysis was used to explore associations between histological, clinical and QOL criteria.
RESULTS Ten years after LT, fibrosis was detected in 53% of patients, and affected the general health perception, while ductopenia, present in 36%, affected the well-being (P = 0.05). Hepatic steatosis (HS) was present in 33% of patients and was associated with the worst QOL score on multiple domains. When compared to patients without HS, patients with HS had significantly higher incidence of fibrosis (P = 0.03), hepatitis C virus (HCV) infection (P = 0.007), and more patients had retired from their job (P = 0.03). Recurrent or de novo HCV-associated fibrosis and patient retirement as objective variables, and abdominal pain or discomfort and joint aches or pains as subjective variables, emerged as independent determinants of HS.
CONCLUSION Long-term liver graft lesions, mainly HS presumably as a surrogate marker of HCV infection, may have a substantial impact on QOL 10 years after LT.
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Alvarez-Sotomayor D, Satorres C, Rodríguez-Medina B, Herrero I, de la Mata M, Serrano T, Rodríguez-Perálvarez M, DʼAvola D, Lorente S, Rubín A, Berenguer M. Controlling Diabetes After Liver Transplantation: Room for Improvement. Transplantation 2016; 100:e66-e73. [PMID: 27653229 DOI: 10.1097/tp.0000000000001399] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Diabetes mellitus is a chronic illness with great impact on long-term outcome after liver transplantation (LT). Despite this, the current level of glycemic control and quality of screening strategies for diabetes-associated conditions that are being provided to liver transplant recipients with diabetes have not yet been assessed. METHODS We performed a cross-sectional, multicenter study that included 344 liver transplant recipients and examined the level of glycemic control and its associated factors, as well as the quality of screening strategies for diabetes-associated conditions. RESULTS Seventy-five patients (21.8%) suffered from diabetes before transplantation, and 82 (23.8%) developed diabetes mellitus after transplantation. Adequate glycemic control (HbA1c < 7%) was achieved in 66.7% of the patients. Forty-eight percent of patients underwent regular screening for retinopathy, 47.1% for nephropathy, 4.5% for neuropathy, and 5.7% for foot ulcers. Diabetes was associated with higher frequency of cardiovascular disease and dyslipidemia both before and after LT. Multivariate analysis revealed association between poor glycemic control and arterial hypertension, presence of diabetes before transplantation, elevated GGT, and insulin use. CONCLUSIONS Glycemic control was inadequate in 33.3% of LT recipients with diabetes, and screening protocols for diabetes-associated conditions did not meet the standards for medical care set by the American Diabetes Association in any of the participating centers. Consequently, this study reveals a clear deficiency in the quality of diabetes care provided to patients after LT and, hence, we predict that future progress in this area will have a significant impact on medium-term to long-term outcome of these patients.
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Affiliation(s)
- Diego Alvarez-Sotomayor
- 1 Hospital Universitario y Politécnico La Fe, Valencia, Spain.2 Hospitén Clínica Roca, Las Palmas, Spain.3 Clínica Universitaria de Navarra, Pamplona, Spain.4 Instituto de Investigación Sanitaria de Navarra (IdiSNA), CIBEREHD, Estella, Spain.5 Hospital Universitario Reina Sofía, CIBEREHD, Córdoba, Spain.6 Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain., Instituto de Investigación Sanitaria de Aragón, Zaraoza, Spain.7 Hospital Universitario y Politécnico La Fe, Universidad de Valencia, CIBEREHD, Valencia, Spain
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40
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Chang AL, Cortez AR, Bondoc A, Schauer DP, Fitch A, Shah SA, Woodle SE, Diwan T. Metabolic syndrome in liver transplantation: A preoperative and postoperative concern. Surgery 2016; 160:1111-1117. [PMID: 27498302 DOI: 10.1016/j.surg.2016.06.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 06/09/2016] [Accepted: 06/14/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Metabolic syndrome is increasing among patients undergoing liver transplantation. Nonalcoholic steatohepatitis is a manifestation of metabolic syndrome and is an increasingly common cause of end-stage liver disease necessitating orthotopic liver transplantation. We sought to determine the effect of preoperative risk factors on the development of post-transplant metabolic syndrome, complications, readmissions, and mortality. METHODS We conducted a review of 114 orthotopic liver transplantations at our institution from May 2012 to April 2014. RESULTS Patients with (n = 19) and without (n = 95) metabolic syndrome were similar with regard to age, race, and model for end-stage liver disease at time of transplant. Donor and operative factors also were similar between the groups. Preoperative diabetes was found to be associated with an increased rate of readmission (odds ratio 3.45, P = .03). While preoperative metabolic syndrome itself was not a significant predictor of worse outcomes, postoperative metabolic syndrome was associated with significantly greater readmissions in the first year. Major predictors of new onset metabolic syndrome after orthotopic liver transplantation included preoperative diabetes and obesity (odds ratio 8.54 and odds ratio 5.49, P < .01 each). CONCLUSION Efforts to decrease the incidence of postoperative metabolic syndrome after orthotopic liver transplantation may decrease readmissions and improve outcomes, along with decreasing resource utilization.
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Affiliation(s)
- Alex L Chang
- Department of Surgery, Division of Transplantation, CCORE (Cincinnati Collaborative for Obesity Research), University of Cincinnati College of Medicine, Cincinnati, OH
| | - Alexander R Cortez
- Department of Surgery, Division of Transplantation, CCORE (Cincinnati Collaborative for Obesity Research), University of Cincinnati College of Medicine, Cincinnati, OH
| | - Alexander Bondoc
- Department of Surgery, Division of Transplantation, CCORE (Cincinnati Collaborative for Obesity Research), University of Cincinnati College of Medicine, Cincinnati, OH
| | - Daniel P Schauer
- Department of Surgery, Division of Transplantation, CCORE (Cincinnati Collaborative for Obesity Research), University of Cincinnati College of Medicine, Cincinnati, OH
| | - Angela Fitch
- Department of Surgery, Division of Transplantation, CCORE (Cincinnati Collaborative for Obesity Research), University of Cincinnati College of Medicine, Cincinnati, OH
| | - Shimul A Shah
- Department of Surgery, Division of Transplantation, CCORE (Cincinnati Collaborative for Obesity Research), University of Cincinnati College of Medicine, Cincinnati, OH
| | - Steve E Woodle
- Department of Surgery, Division of Transplantation, CCORE (Cincinnati Collaborative for Obesity Research), University of Cincinnati College of Medicine, Cincinnati, OH
| | - Tayyab Diwan
- Department of Surgery, Division of Transplantation, CCORE (Cincinnati Collaborative for Obesity Research), University of Cincinnati College of Medicine, Cincinnati, OH.
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41
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Kuo HT, Lum E, Martin P, Bunnapradist S. Effect of diabetes and acute rejection on liver transplant outcomes: An analysis of the organ procurement and transplantation network/united network for organ sharing database. Liver Transpl 2016; 22:796-804. [PMID: 26850091 DOI: 10.1002/lt.24414] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 01/19/2016] [Accepted: 01/29/2016] [Indexed: 12/18/2022]
Abstract
The effects of diabetic status and acute rejection (AR) on liver transplant outcomes are largely unknown. We studied 13,736 liver recipients from the United Network for Organ Sharing/Organ Procurement Transplant Network database who underwent transplantation between 2004 and 2007 with a functioning graft for greater than 1 year. The association of pretransplant diabetes mellitus (PDM), new-onset diabetes after transplant (NODAT), and AR rates on allograft failure, all-cause mortality, and cardiovascular mortality were determined. To determine the differential and joint effects of diabetic status and AR on transplant outcomes, recipients were further stratified into 6 groups: neither (reference, n = 6600); NODAT alone (n = 2054); PDM alone (n = 2414); AR alone (n = 1448); NODAT and AR (n = 707); and PDM and AR (n = 513). An analysis with hepatitis C virus (HCV) serostatus was also performed (HCV recipients, n = 6384; and non-HCV recipient, n = 5934). The median follow-up was 2537 days. The prevalence of PDM was 21.3%. At 1 year after transplant, the rates of NODAT and AR were 25.5% and 19.4%, respectively. Overall, PDM, NODAT, and AR were associated with increased risks for graft failure (PDM, hazard ratio [HR] = 1.31, P < 0.01; NODAT, HR = 1.11, P = 0.02; AR, HR = 1.28, P < 0.01). A multivariate Cox regression analysis of the 6 recipient groups demonstrated that NODAT alone was not significantly associated with any study outcomes. The presence of PDM, AR, NODAT and AR, and PDM and AR were associated with higher overall graft failure risk and mortality risk. The presence of PDM was associated with higher cardiovascular mortality risk. The analyses in both HCV-positive and HCV-negative cohorts showed a similar trend as in the overall cohort. In conclusion, PDM and AR, but not NODAT, is associated with increased mortality and liver allograft failure. Liver Transplantation 22 796-804 2016 AASLD.
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Affiliation(s)
- Hung-Tien Kuo
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.,Department of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Erik Lum
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Paul Martin
- Division of Hepatology, Center for Liver Diseases, University of Miami School of Medicine, Miami, FL
| | - Suphamai Bunnapradist
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA
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Kia L, Cuttica MJ, Yang A, Donnan EN, Whitsett M, Singhvi A, Lemmer A, Levitsky J. The utility of pulmonary function testing in predicting outcomes following liver transplantation. Liver Transpl 2016; 22:805-11. [PMID: 26929108 DOI: 10.1002/lt.24426] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2015] [Revised: 01/29/2016] [Accepted: 02/20/2016] [Indexed: 02/07/2023]
Abstract
Although pulmonary function tests (PFTs) are routinely performed in patients during the evaluation period before liver transplantation (LT), their utility in predicting post-LT mortality and morbidity outcomes is not known. The aim of this study was to determine the impact of obstructive and/or restrictive lung disease on post-LT outcomes. We conducted a retrospective analysis of patients who had pre-LT PFTs and underwent a subsequent LT (2007-2013). We used statistical analyses to determine independent associations between PFT parameters and outcomes (graft/patient survival, time on ventilator, and hospital/intensive care unit [ICU] length of stay [LOS]). A total of 415 LT recipients with available PFT data were included: 65% of patients had normal PFTs; 8% had obstructive lung disease; and 27% had restrictive lung disease. There was no difference in patient and graft survival between patients with normal, obstructive, and restrictive lung disease. However, restrictive lung disease was associated with longer post-LT time on ventilator and both ICU and hospital LOS (P < 0.05). More specific PFT parameters (diffusing capacity of the lungs for carbon monoxide, total lung capacity, and residual volume) were all significant predictors of ventilator time and both ICU and hospital LOS (P < 0.05). Although pre-LT PFT parameters may not predict post-LT mortality, restrictive abnormalities correlate with prolonged post-LT ventilation and LOS. Efforts to identify and minimize the impact of restrictive abnormalities on PFTs might improve such outcomes. Liver Transplantation 22 805-811 2016 AASLD.
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Affiliation(s)
- Leila Kia
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Michael J Cuttica
- Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Amy Yang
- Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Erica N Donnan
- Departments of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Maureen Whitsett
- Departments of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Ajay Singhvi
- Departments of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Alexander Lemmer
- Departments of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL.,Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
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43
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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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García-Compeán D, González-González JA, Lavalle-González FJ, González-Moreno EI, Villarreal-Pérez JZ, Maldonado-Garza HJ. Hepatogenous diabetes: Is it a neglected condition in chronic liver disease? World J Gastroenterol 2016; 22:2869-2874. [PMID: 26973383 PMCID: PMC4779910 DOI: 10.3748/wjg.v22.i10.2869] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 01/20/2016] [Accepted: 02/20/2016] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) that occurs because of chronic liver disease (CLD) is known as hepatogenous diabetes (HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus (HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.
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Lai HM, Pawar R, Wolf DC, Aronow WS. Impact of Cardiovascular Risk Factors on Long-Term Mortality After Liver Transplantation. Am J Ther 2016; 23:e357-e362. [PMID: 24897624 DOI: 10.1097/mjt.0b013e31829c4c5f] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Immunosuppression with calcineurin inhibitors has contributed to an increased prevalence of hypertension, diabetes, and hypercholesterolemia in patients receiving liver transplantation. This study evaluated the prevalence of cardiovascular risk factors, their management, and long-term mortality after liver transplantation. Medical records were reviewed in 333 adult patients who underwent orthotopic liver transplantation. Data were collected on medical diagnoses before and after transplantation, medication use, and on long-term mortality. The 333 patients in the study included 223 men and 110 women, mean age 59 ± 10 years. The mean follow-up was 50 ± 28 months. After transplantation, there was a high prevalence of hypertension (67%), hypercholesterolemia (46%), diabetes mellitus (42%), and chronic kidney disease (45%). Out of 333 patients in the study, 96 patients (29%) died during follow-up. Stepwise logistic regression was performed to identify the risk factors that might influence long-term mortality outcomes. Based on pretransplant characteristics, positive independent risk factors that increased mortality were age at transplant and hepatitis C. After transplantation, positive predictive factors were diabetes mellitus and cancer. A negative predictive risk factor for mortality was hypercholesterolemia. Analysis of medication after transplantation showed that positive predictive factors were the use of insulin, steroids, and antibiotics. Negative predictors for mortality were tacrolimus and mycophenolate. Our data suggest that diabetes mellitus and hepatitis C play an important role in worsening posttransplant mortality.
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Affiliation(s)
- Hoang M Lai
- 1Division of Cardiology, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY; and 2Division of Gastroenterology and Hepatobiliary Disease, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY
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Grancini V, Trombetta M, Lunati ME, Zimbalatti D, Boselli ML, Gatti S, Donato MF, Resi V, D'Ambrosio R, Aghemo A, Pugliese G, Bonadonna RC, Orsi E. Contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes: Role of severity of liver disease. J Hepatol 2015; 63:1484-90. [PMID: 26297917 DOI: 10.1016/j.jhep.2015.08.011] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Revised: 07/19/2015] [Accepted: 08/03/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS This study evaluated the contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes. METHODS One-hundred and sixty cirrhotic patients with normal fasting plasma glucose (FPG), three with impaired fasting glucose and seven with untreated diabetes mellitus (DM) underwent an extended oral glucose tolerance test (OGTT). The OGTT data were analyzed with a Minimal Model to estimate dynamic (derivative) control (DC) and static (proportional) control (PC) of β-cell function, and with the Oral Glucose Insulin Sensitivity (OGIS)-2h index to estimate insulin sensitivity. RESULTS Twenty-six patients (15.6%) had normal glucose tolerance (NGT), 60 (35.8%) had impaired glucose tolerance (IGT), and 84 (48.6%) had DM. DC was significantly reduced in DM vs. NGT and IGT patients. PC was significantly impaired in DM and IGT vs. NGT patients and in DM vs. IGT subjects. The OGIS-2h index was significantly reduced to a similar extent in DM and IGT vs. NGT patients. Patients with Child-Pugh class B and C cirrhosis had reduced DC and PC, but not OGIS-2h values, as compared with subjects in class A. Moreover, Child-Pugh class/score was an independent predictor of β-cell function even after adjustment for glucose tolerance. CONCLUSIONS Abnormalities of glucose tolerance occur frequently in cirrhosis even in patients with normal FPG, thereby supporting the importance of performing an OGTT. Transition from IGT to DM is driven primarily by β-cell dysfunction. Insulin secretion worsens in parallel with the severity of liver disease, thus suggesting a detrimental effect of liver failure on pancreatic islets on its own.
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Affiliation(s)
- Valeria Grancini
- Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Maddalena Trombetta
- Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy
| | - Maria Elena Lunati
- Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Dario Zimbalatti
- Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Maria Linda Boselli
- Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy
| | - Stefano Gatti
- General Surgery Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Maria Francesca Donato
- A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Veronica Resi
- Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Roberta D'Ambrosio
- A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Alessio Aghemo
- A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
| | - Riccardo C Bonadonna
- Department of Clinical and Experimental Medicine, University of Parma, and Division of Endocrinology, Azienda Ospedaliera Universitaria, Parma, Italy
| | - Emanuela Orsi
- Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
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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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Yue S, Zhou H, Zhu J, Rao J, Busuttil RW, Kupiec-Weglinski JW, Lu L, Zhai Y. Hyperglycemia and liver ischemia reperfusion injury: a role for the advanced glycation endproduct and its receptor pathway. Am J Transplant 2015; 15:2877-87. [PMID: 26112980 PMCID: PMC9438741 DOI: 10.1111/ajt.13360] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2014] [Revised: 04/17/2015] [Accepted: 04/19/2015] [Indexed: 01/25/2023]
Abstract
Although pretransplant diabetes is a risk factor for mortality post-liver transplant, the underlying mechanism has not been fully defined. In a murine liver partial warm ischemia model, we addressed the question of how diabetes/hyperglycemia impacted tissue inflammatory injuries against ischemia reperfusion (IR), focusing on the advanced glycation endproduct (AGE) and its receptor (RAGE) pathway. Our results showed that hepatocellular injury was exacerbated in streptozotocin-induced diabetic mice against IR, in association with hyper-inflammatory immune activation in livers. Serum levels of AGEs, but not HMGB1, were increased in diabetic mice in response to liver IR. Both RAGE antagonist peptides and small interfering RNA alleviated liver injuries and inhibited inflammatory immune activation against IR in diabetic, but not normal, mice. Kupffer cells (KCs)/macrophages, but not hepatocytes, from diabetic mice expressed significantly higher levels of RAGE, leading to their hyper-inflammatory responsiveness to both TLR ligands and AGEs. In vitro, hyperglycemia increased macrophage RAGE expression and enhanced their TLR responses. Our results demonstrated that activation of the AGE-RAGE signaling pathway in KCs was responsible for hyper-inflammatory immune responses and exacerbated hepatocellular injuries in diabetic/hyperglycemic hosts against liver IR.
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Affiliation(s)
- Shi Yue
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA
| | - Haoming Zhou
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA,Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Jianjun Zhu
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA,Liver Surgery, Renji Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Jianhua Rao
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA,Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Ronald W. Busuttil
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA
| | - Jerzy W. Kupiec-Weglinski
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA
| | - Ling Lu
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yuan Zhai
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA
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Singhal A, Wilson GC, Wima K, Quillin RC, Cuffy M, Anwar N, Kaiser TE, Paterno F, Diwan TS, Woodle ES, Abbott DE, Shah SA. Impact of recipient morbid obesity on outcomes after liver transplantation. Transpl Int 2015; 28:148-55. [PMID: 25363625 DOI: 10.1111/tri.12483] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 09/25/2014] [Accepted: 10/24/2014] [Indexed: 12/28/2022]
Abstract
The aim of this study was to analyze the impact of morbid obesity in recipients on peritransplant resource utilization and survival outcomes. Using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 12 445 patients who underwent liver transplantation (LT) between 2007 and 2011 and divided them into two cohorts based on recipient body mass index (BMI; <40 vs. ≥40 kg/m²). Recipients with BMI ≥40 comprised 3.3% (n = 416) of all LTs in the studied population. There were no significant differences in donor characteristics between two groups. Recipients with BMI ≥40 were significant for being female, diabetic, and with NASH cirrhosis. Patients with a BMI ≥40 had a higher median MELD score, limited physical capacity, and were more likely to be hospitalized at LT. BMI ≥40 recipients had higher post-LT length of stay and were less often discharged to home. With a median follow-up of 2 years, patient and graft survival were equivalent between the two groups. In conclusion, morbidly obese LT recipients appear sicker at time of LT with an increase in resource utilization but have similar short-term outcomes.
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Affiliation(s)
- Ashish Singhal
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
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50
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Hoehn RS, Singhal A, Wima K, Sutton JM, Paterno F, Steve Woodle E, Hohmann S, Abbott DE, Shah SA. Effect of pretransplant diabetes on short-term outcomes after liver transplantation: a national cohort study. Liver Int 2015; 35:1902-9. [PMID: 25533420 DOI: 10.1111/liv.12770] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Accepted: 12/15/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS We sought to analyse the effect of pretransplant diabetes on post-operative outcomes and resource utilization following liver transplantation. METHODS A retrospective cohort study was designed using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases. We identified 12 442 patients who underwent liver transplantation at 63 centres from 2007-2011 and separated cohorts of patients with diabetes (n = 2971; 24%) and without (n = 9471; 76%) at the time of transplant. We analysed transplant related outcomes and short-term survival. RESULTS Diabetic recipients were more likely to be male (70% vs 67%), non-white (32% vs 26%), older (age ≥60; 41% vs 28%), and have a higher BMI (29 vs 27; P < 0.001). More diabetic patients were on haemodialysis (10% vs 7%), had cirrhosis caused by NASH (24% vs 9%; P < 0.001), and received liver allografts from older donors (≥ 60 years; 19% vs 15%) with a higher donor risk index (>1.49; 46% vs 42%; P < 0.001). Post-transplant, diabetic recipients had longer hospital length of stay (10 vs 9 days), higher peri-transplant mortality (5% vs 4%) and 30-day readmission rates (41% vs 37%), were less often discharged to home (83% vs 87%; P < 0.05), and had inferior graft and patient survival. Liver transplant was more expensive for type 1 vs type 2 diabetics ($105 078 vs $100 624, P < 0.001). Poorly controlled diabetic recipients were less likely discharged home following transplant (75% vs 82%, P < 0.01). CONCLUSIONS This national study indicates that pretransplant diabetes is associated with inferior post-operative outcomes and increased resource utilization after liver transplantation.
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Affiliation(s)
- Richard S Hoehn
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Ashish Singhal
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Koffi Wima
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Jeffrey M Sutton
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Flavio Paterno
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - E Steve Woodle
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Sam Hohmann
- University Health Consortium and Department Health Systems Management, Rush University, Chicago, IL, USA
| | - Daniel E Abbott
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Shimul A Shah
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
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