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1
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Codes L, Zapata R, Mendizabal M, Junior ADMF, Restrepo JC, Schiavon LDL, Malbouisson LMS, Andraus W, Gadano A, Padilla-Machaca PM, Villamil A, Stucchi RSB, Castro-Narro GE, Pages J, Terrabuio DRB, Urzúa A, Pessoa MG, Mainardi V, Pedro R, Imventarza O, Gerona S, Wolff R, Abdala E, Tenorio L, Cerda-Reyes E, Cairo F, Uribe M, Bittencourt PL. Latin American association for the study of the liver (ALEH) guidance on postoperative care after liver transplantation. Ann Hepatol 2025; 30:101899. [PMID: 40057036 DOI: 10.1016/j.aohep.2025.101899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/12/2024] [Accepted: 01/01/2025] [Indexed: 03/16/2025]
Abstract
Liver transplantation (LT) is a well-established therapy for patients with decompensated cirrhosis and early-stage hepatocellular carcinoma. Liver transplantation activity varies sharply across Latin American (LATAM) countries due to differences in resources, expertise, and funding and local attitudes toward organ donation and transplantation. This current guidance of postoperative care after LT is the first position paper of the Latin American Association for the Study of the Liver (ALEH) Special Interest Group (SIG), drawing evidence-based recommendations regarding immediate and long-term postoperative care of LT recipients, taking into consideration their applicability in Latin America.
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Affiliation(s)
- Liana Codes
- Hospital Português, Salvador, Bahia, Brazil; Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil.
| | - Rodrigo Zapata
- Unidad de Trasplante hepático, Clínica Alemana/ Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
| | - Manuel Mendizabal
- Unidad de Hepatología y Trasplante de Hígado, Hospital Universitario Austral, Provincia de Buenos Aires, Pilar, Argentina.
| | | | | | | | | | - Wellington Andraus
- Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | | | - P Martin Padilla-Machaca
- Liver Unit, Guillermo Almenara National Hospital, EsSalud, Lima, Perú, and National University of San Marcos, Lima, Perú
| | | | | | - Graciela Elia Castro-Narro
- Unidad de Hepatología y Trasplantes, Hospital Médica Sur, Ciudad de México, México; Servicio de Gastroenterología, Hepatología y Trasplantes, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - Josefina Pages
- Unidad de Hepatología y Trasplante de Hígado, Hospital Universitario Austral, Provincia de Buenos Aires, Pilar, Argentina.
| | | | - Alvaro Urzúa
- Hospital Clínico Universidad de Chile, Santiago, Chile.
| | - Mário Guimarães Pessoa
- Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
| | | | - Rodolpho Pedro
- Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Oscar Imventarza
- Hospital Argerich, Hospital Garrahan, Stalyc Representative, Buenos Aires, Argentina
| | - Solange Gerona
- Hospital Central de Las Fuerzas Armadas, Montevideo, Uruguay
| | - Rodrigo Wolff
- Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Edson Abdala
- Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
| | - Laura Tenorio
- Hospital Nacional Edgardo Rebagliati Martins, Lima, Perú
| | - Eira Cerda-Reyes
- Hospital Central Militar, Escuela Militar de Graduados de Sanidad, Ciudad de México, Mexico
| | | | - Mario Uribe
- Hospital Dr. Luis Calvo Mackenna, Santiago, Chile
| | - Paulo Lisboa Bittencourt
- Hospital Português, Salvador, Bahia, Brazil; Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil.
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Tai CJ, Huang KH, Wang JY, Gau SY, Huang SW, Su KY, Tsai TH, Wu CN, Lee CY. Risk of Incident Post-Transplantation Diabetes Mellitus After Solid Organ Transplantation in Taiwan: A Population-Based Cohort Study. Healthcare (Basel) 2025; 13:523. [PMID: 40077085 PMCID: PMC11898666 DOI: 10.3390/healthcare13050523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 02/20/2025] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
Background: Solid organ transplant (SOT) recipients have an elevated risk of diabetes mellitus (DM). This study investigated the risk of posttransplant DM (PTDM) in a retrospective cohort study. Methods: We analyzed patients aged over 18 years who received an SOT between 2002 and 2013. Each patient was matched with four control individuals by age, sex, insured salary, urbanization level, Charlson's comorbidity index (CCI), and year of inclusion in the study. After matching, the study comprised 6874 patients who underwent an SOT and 27,496 matched general patients as the comparison. The risk of DM among the SOT recipients was assessed using a Cox proportional hazards model after adjustment for all relevant variables. Results: The SOT cohort had a significantly higher risk of DM than general patients (adjusted hazard ratio [aHR], 1.61; 95% confidence interval [CI], 1.51-1.72). Kidney and liver recipients, respectively, had DM incidence rates 1.57 (95% CI, 1.46-1.70) and 1.73 (95% CI, 1.53-1.94) times that of the general patients. Conclusions: SOT recipients had an elevated risk of DM. Among various organ recipients, liver recipients had the highest PTDM risk. Kidney and liver recipients demonstrated the highest DM risk at 6 months after their SOT. The risk of PTDM following an SOT may result in long-term consequences. Hence, we advise the critical need for proper management to mitigate related complications after transplantation.
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Affiliation(s)
- Chih-Jaan Tai
- Department of Otorhinolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung 404327, Taiwan;
- School of Medicine, China Medical University, Taichung 404328, Taiwan
| | - Kuang-Hua Huang
- Department of Health Services Administration, China Medical University, Taichung 406040, Taiwan; (K.-H.H.); (T.-H.T.)
| | - Jiun-Yi Wang
- Department of Healthcare Administration, Asia University, Taichung 413305, Taiwan;
- Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan
| | - Shuo-Yan Gau
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-Y.G.); (S.-W.H.); (K.-Y.S.)
- Department of Business Administration, National Taiwan University, Taipei 106319, Taiwan
| | - Shiang-Wen Huang
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-Y.G.); (S.-W.H.); (K.-Y.S.)
| | - Kun-Yu Su
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-Y.G.); (S.-W.H.); (K.-Y.S.)
| | - Tung-Han Tsai
- Department of Health Services Administration, China Medical University, Taichung 406040, Taiwan; (K.-H.H.); (T.-H.T.)
| | - Chun-Nan Wu
- Department of Pharmacology, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Chien-Ying Lee
- Department of Pharmacology, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
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Alsaqa M, Sierra L, Marenco-Flores A, Parraga X, Barba R, Goyes D, Ozturk NB, Curry MP, Bonder A, Saberi B. Metabolic dysfunction-associated steatotic liver disease correlates with higher lower graft survival in liver transplant recipients with hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00461. [PMID: 39976068 DOI: 10.1097/meg.0000000000002914] [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] [Indexed: 02/21/2025]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment. The changing landscape of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients lacks a thorough description of the outcomes of HCC based on etiology. OBJECTIVE To assess the waitlist (WL) dropout and graft survival in HCC LT candidates based on the etiology of HCC in the post-DAA era. METHODS This retrospective cohort study analyzed United Network Organ Sharing/Organ Procurement Transplant Network data from 2015 to 2022. Graft survival was analyzed using Kaplan-Meier curves, and predictors of WL dropout and graft failure were assessed using multivariate analysis. RESULTS Among LT recipients, etiologies were HCV (53.6%), alcohol-associated liver disease (ALD) (12.0%), metabolic dysfunction-associated steatotic liver disease (MASLD) (16.6%), hepatitis B virus (HBV) (5.6%), and other (12.1%). MASLD and ALD had the highest dropout rates (1-year: 20.4%, 21.7%; 3-year: 58.2%, 51.1%; P < 0.001). Dropout was linked to diabetes, low albumin, high Model of End-Stage Liver Disease, high alpha-fetoprotein, tumor number, and size. MASLD had the worst 1-, 3-, and 5-year graft survival (89.8%, 81.8%, and 74.1%) and higher failure risk than HCV (hazard ratio: 1.143, 95% CI: 1.021-1.281). Diabetes negated MASLD's impact on graft failure but worsened survival for MASLD-HCC compared with HBV and ALD, matching HCV. CONCLUSION MASLD has the highest WL dropout and post-LT graft failure among HCC LT candidates, surpassing HCV in the post-DAA era. The worst graft survival in MASLD-HCC is associated with pre-LT diabetes.
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Affiliation(s)
- Marwan Alsaqa
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Leandro Sierra
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Ana Marenco-Flores
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Ximena Parraga
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Romelia Barba
- Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Daniela Goyes
- Division of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut and
| | - N Begum Ozturk
- Department of Internal Medicine, Beaumont Hospital, Royal Oak, Michigan, USA
| | - Michael P Curry
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Alan Bonder
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Behnam Saberi
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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AlShahrani AN, Al-Khlaiwi T, Meo SA, Siddiqui IA, Alghanem B, Almourfi F. Endocannabinoid and hematological responses to pre- and post-therapeutic exercises in liver transplant patients. AMERICAN JOURNAL OF CLINICAL AND EXPERIMENTAL IMMUNOLOGY 2024; 13:259-271. [PMID: 39839347 PMCID: PMC11744344 DOI: 10.62347/fnlx9490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 12/17/2024] [Indexed: 01/23/2025]
Abstract
Endocannabinoids (eCBs) play a crucial role in regulating the pathophysiological progression of chronic liver disease through hepatic cannabinoid receptor 2 (CB2). According to the literature, various treatment options are available for liver disease patients, including transplantation and physical activity both before and after the procedure. The aim of this study is to assess the response of endocannabinoids to pre- and post-therapeutic exercises in liver transplant patients (LTx). This analytical case-control longitudinal study was conducted on patients aged 18-70 at King Fahad Specialist Hospital in Dammam, Saudi Arabia. Participants were divided into two groups: an intervention group of LTx patients (n = 26) and a control group of end-stage liver disease patients (n = 23) who were not candidates for liver transplantation (LT). Blood samples were collected before the initiation of preoperative exercises, one month before LT, and three months after LT following postoperative exercises. The median arachidonoyl ethanolamide (AEA) levels in the control group were comparatively higher after therapeutic exercises compared to before; however, the Wilcoxon signed-rank test showed no significant differences (P = 0.212). In the LTx group, the median difference in AEA between pre- and post-therapeutic exercises was marginally significant (P = 0.091). Additionally, the Wilcoxon signed-rank test revealed a highly significant increase in median 2-arachidonoylglycerol (2-AG) levels after therapeutic exercises compared to before in the LTx group (P = 0.049), while the control group showed no significant change in post- vs. pre-therapeutic exercise median 2-AG levels (P = 0.346). The study's findings revealed an increased concentration of 2-AG after therapeutic exercises in LTx patients but not in the control group, while AEA levels were elevated after therapeutic exercises in both groups. The effect of post-therapeutic exercises on hematological and biochemical markers was significant between the control and LTx groups, particularly concerning platelet count, total bilirubin, total protein, albumin/globulin ratio, international normalized ratio, and calcium levels.
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Affiliation(s)
| | - Thamir Al-Khlaiwi
- Department of Physiology, College of Medicine, King Saud UniversityRiyadh, Saudi Arabia
| | - Sultan Ayoub Meo
- Department of Physiology, College of Medicine, King Saud UniversityRiyadh, Saudi Arabia
| | - Intisar Ahmad Siddiqui
- Department of Dental Education, College of Dentistry, Imam Abdulrahman Bin Faisal UniversityDammam, Saudi Arabia
| | - Bandar Alghanem
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard Health AffairsRiyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health SciencesRiyadh, Saudi Arabia
| | - Feras Almourfi
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard Health AffairsRiyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health SciencesRiyadh, Saudi Arabia
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Chen S, Bowen DG, Liu K, Vidot H. Hypomagnesaemia, an independent risk factor for the development of post-transplant diabetes mellitus in liver and renal transplant recipients? A systematic review. J Hum Nutr Diet 2024; 37:1407-1419. [PMID: 39073157 DOI: 10.1111/jhn.13354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/21/2024] [Accepted: 07/09/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Post-transplantation diabetes mellitus (PTDM) is common after solid organ transplantation. In the past decade, there has been increasing interest in the association between hypomagnesaemia and the development of PTDM. This systematic review aimed to investigate the current knowledge regarding the association between hypomagnesaemia and PTDM in adult liver and renal transplant recipients. METHODS A literature search of five databases, Medline, Embase, ProQuest, Scopus and Google Scholar, as well as article reference lists, was performed. Eligible studies that focused on adult liver and renal transplant recipients without pretransplantation hyperglycaemia or diabetes were included. Other eligibility criteria included quantitative studies which reported magnesium concentrations, studies with at least 6 months of follow-up, and studies published in English. The Newcastle-Ottawa Assessment Tool was used for the quality assessment. RESULTS In total, 12 studies were included in the final analysis. Eleven focused on renal transplantation and one on liver transplantation. All studies were medium to high quality with eight out of 12 achieving the highest rating of nine. Eight studies found a negative association between either pretransplant or early post-transplant serum magnesium concentration and the risk of PTDM, three studies found no association between these two variables, and one study found a positive association between the magnesium concentration at 8 weeks after transplantation and glycosylated haemoglobin A1C. CONCLUSIONS Further large-scale prospective studies with at least 6 months of follow-up are needed to confirm these findings, particularly in liver transplantation, to further clarify and explore the relationship between hypomagnesaemia and PTDM.
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Affiliation(s)
- Shujie Chen
- Sydney Nursing School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, Australia
| | - David Geoffrey Bowen
- Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Helen Vidot
- Department of Nutrition & Dietetics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
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Caturano A, di Martino A, Albanese G, Coppola C, Russo V, Koudelková K, Galiero R, Rinaldi L, Sardu C, Marrone A, Monda M, Marfella R, Gojda J, Sasso FC, Salvatore T. The impact of new onset diabetes on cardiovascular risks in orthotopic liver transplant recipients: findings from the COLT study. Acta Diabetol 2024:10.1007/s00592-024-02406-x. [PMID: 39527295 DOI: 10.1007/s00592-024-02406-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT). METHODS We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development. RESULTS Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0-62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59-17.72, p = 0.006) and Kaplan-Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44-22.92, p = 0.013 and OR 7.29; 95% CI 1.46-36.41, p = 0.015, respectively). CONCLUSIONS Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose.
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Affiliation(s)
- Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy.
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy.
- Department of Internal Medicine, Third Faculty of Medicine, Charles University and Královské Vinohrady University Hospital, Prague, Czech Republic.
| | - Anna di Martino
- Unit of Hepatology and Interventional Ultrasonography, Department of Internal Medicine, OORR Area Stabiese, Gragnano, 80054, Italy
| | - Gaetana Albanese
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy
| | - Carmine Coppola
- Unit of Hepatology and Interventional Ultrasonography, Department of Internal Medicine, OORR Area Stabiese, Gragnano, 80054, Italy
| | - Vincenzo Russo
- Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA
- Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Kateřina Koudelková
- Department of Internal Medicine, Third Faculty of Medicine, Charles University and Královské Vinohrady University Hospital, Prague, Czech Republic
- Team MetaDiab, Institute of Metabolic and Cardiovascular Diseases, INSERM/Paul Sabatier University UMR1297, Toulouse, France
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy
| | - Luca Rinaldi
- Department of Medicine and Health Sciences "Vincenzo Tiberio", Università degli Studi del Molise, Campobasso, 86100, Italy.
| | - Celestino Sardu
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy
| | - Marcellino Monda
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy
| | - Jan Gojda
- Department of Internal Medicine, Third Faculty of Medicine, Charles University and Královské Vinohrady University Hospital, Prague, Czech Republic
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy
| | - Teresa Salvatore
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, I-80138, Italy
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Khan MQ, Watt KD, Teasdale C. Development of posttransplant diabetes mellitus in US recipients of liver transplant is influenced by OPTN region. Liver Transpl 2024:01445473-990000000-00487. [PMID: 39724669 DOI: 10.1097/lvt.0000000000000508] [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: 07/02/2024] [Accepted: 09/24/2024] [Indexed: 12/28/2024]
Abstract
Posttransplant diabetes mellitus (PTDM) is associated with significant morbidity and mortality in liver transplant recipients (LTRs). We used the Organ Procurement and Transplantation Network (OPTN) database to compare the incidence of developing PTDM across the United States and develop a risk prediction model for new-onset PTDM using OPTN region as well as donor-related, recipient-related, and transplant-related factors. All US adult, primary, deceased donor, LTRs between January 1, 2007, and December 31, 2016, with no prior history of diabetes noted, were identified. Kaplan-Meier estimators were used to calculate the cumulative incidence of PTDM, stratified by OPTN region. Multivariable Cox proportional hazards models were fitted to estimate hazards of PTDM in each OPTN region and build a risk prediction model, through backward selection. Cumulative incidence of PTDM at 1 year, 3 years, and 5 years after transplant was 12.0%, 16.1%, and 18.9%, respectively. Region 3, followed by regions 8, 2, and 9, had the highest adjusted hazards of developing PTDM. Inclusion of OPTN region in a risk prediction model for PTDM in LTRs (including recipient age, sex, race, education, insurance coverage, body mass index, primary liver disease, cold ischemia time, and donor history of diabetes) modestly improved performance (C-statistic = 0.60). In patients without pre-existing, confirmed diabetes mellitus, the incidence of PTDM in LTRs varied across OPTN regions, with the highest hazards in region 3, followed by regions 8, 2, and 9. The performance of a novel risk prediction model for PTDM in LTRs has improved performance with the inclusion of the OPTN region. Vigilance is recommended to centers in high-risk regions to identify PTDM and mitigate its development.
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Affiliation(s)
- Mohammad Qasim Khan
- Division of Gastroenterology, Department of Medicine, University of Western Ontario, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
| | - Kymberly D Watt
- Division of Gastroenterology & Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Chloe Teasdale
- Department of Epidemiology and Biostatistics, CUNY Graduate School of Public Health and Health Policy, New York, New York, USA
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Yilmaz ZB, Memisoglu F, Akbulut S. Management of cytomegalovirus infection after liver transplantation. World J Transplant 2024; 14:93209. [PMID: 39295968 PMCID: PMC11317856 DOI: 10.5500/wjt.v14.i3.93209] [Citation(s) in RCA: 1] [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: 02/21/2024] [Revised: 05/05/2024] [Accepted: 05/27/2024] [Indexed: 07/31/2024] Open
Abstract
Cytomegalovirus (CMV) infection is one of the primary causes of morbidity and mortality following liver transplantation (LT). Based on current worldwide guidelines, the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment. CMV- IgG serology is the established technique for pretransplant screening of both donors and recipients. The clinical presentation of CMV infection and disease exhibits variability, prompting clinicians to consistently consider this possibility, particularly within the first year post-transplantation or subsequent to heightened immunosuppression. At annual symposia to discuss CMV prevention and how treatment outcomes can be improved, evidence on the incorporation of immune functional tests into clinical practice is presented, and the results of studies with new antiviral treatments are evaluated. Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation, a consensus reflected in the guidelines has not been formed. Determining the most appropriate strategy at the individual level appears to be the key to enhancing outcomes. Although prevention strategies reduce the risk of CMV disease, the disease can still occur in up to 50% of high-risk patients. A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients. The objective of this study was to establish a comprehensive framework for the management of CMV in patients who have had LT.
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Affiliation(s)
- Zeynep Burcin Yilmaz
- Infectious Diseases and Clinical Microbiology, Inonu University Faculty of Medicine, Malatya 44280, Türkiye
| | - Funda Memisoglu
- Infectious Diseases and Clinical Microbiology, Inonu University Faculty of Medicine, Malatya 44280, Türkiye
| | - Sami Akbulut
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Türkiye
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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10
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Bai R, An R, Chen S, Ding W, Xue M, Zhao G, Ma Q, Shen X. Risk factors and prediction score for new-onset diabetes mellitus after liver transplantation. J Diabetes Investig 2024; 15:1105-1114. [PMID: 38641877 PMCID: PMC11292396 DOI: 10.1111/jdi.14204] [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: 08/07/2023] [Revised: 03/14/2024] [Accepted: 03/18/2024] [Indexed: 04/21/2024] Open
Abstract
AIM New-onset diabetes mellitus is a frequent and severe complication arising after liver transplantation (LT). We aimed to identify the risk factors for new-onset diabetes mellitus after liver transplantation (NODALT) and to develop a risk prediction score system for relevant risks. METHODS We collected and analyzed data from all recipients who underwent liver transplantation at the First Affiliated Hospital of Xi'an Jiaotong University. The OR derived from a multiple logistic regression predicting the presence of NODALT was used to calculate the risk prediction score. The performance of the risk prediction score was externally validated in patients who were from the CLTR (China Liver Transplant Registry) database. RESULTS A total of 468 patients met the outlined criteria and finished the follow-up. Overall, NODALT was diagnosed in 115 (24.6%) patients. Age, preoperative impaired fasting glucose (IFG), postoperative fasting plasma glucose (FPG), and the length of hospital stay were significantly associated with the presence of NODALT. The risk prediction score includes age, preoperative IFG, postoperative FPG, and the length of hospital stay. The risk prediction score of the area under the receiver operating curve was 0.785 (95% CI: 0.724-0.846) in the experimental population and 0.782 (95% CI: 0.708-0.856) in the validation population. CONCLUSIONS Age at the time of transplantation, preoperative IFG, postoperative FPG, and length of hospital stay were independent predictive factors of NODALT. The use of a simple risk prediction score can identify the patients who have the highest risk of NODALT and interventions may start early.
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Affiliation(s)
- Ruiping Bai
- Department of AnesthesiologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Rui An
- Department of AnesthesiologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Siyu Chen
- Department of AnesthesiologyThe First Affiliated Hospital of Xinjiang Medical UniversityUrumqiChina
| | - Wenkang Ding
- Department of AnesthesiologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
| | - Mengwen Xue
- Department of AnesthesiologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Ge Zhao
- Department of AnesthesiologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Qingyong Ma
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
- The Center of Pancreatic Disease Diagnosis and TreatmentThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Xin Shen
- Department of AnesthesiologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
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11
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Russo MW, Wheless W, Vrochides D. Management of long-term complications from immunosuppression. Liver Transpl 2024; 30:647-658. [PMID: 38315054 DOI: 10.1097/lvt.0000000000000341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 01/29/2024] [Indexed: 02/07/2024]
Abstract
This review discusses long-term complications from immunosuppressants after liver transplantation and the management of these complications. Common complications of calcineurin inhibitors include nephrotoxicity and metabolic diseases. Nephrotoxicity can be managed by targeting a lower drug level and/or adding an immunosuppressant of a different class. Metabolic disorders can be managed by treating the underlying condition and targeting a lower drug level. Gastrointestinal adverse effects and myelosuppression are common complications of antimetabolites that are initially managed with dose reduction or discontinuation if adverse events persist. Mammalian targets of rapamycin inhibitors are associated with myelosuppression, proteinuria, impaired wound healing, and stomatitis, which may require dose reduction or discontinuation. Induction agents and agents used for steroid-refractory rejection or antibody-mediated rejection are reviewed. Other rare complications of immunosuppressants are discussed as well.
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Affiliation(s)
- Mark W Russo
- Division of Hepatology, Department of Medicine, Carolinas Medical Center Wake Forest, University School of Medicine, Atrium Health, Charlotte, North Carolina, USA
| | - William Wheless
- Division of Hepatology, Department of Medicine, Carolinas Medical Center Wake Forest, University School of Medicine, Atrium Health, Charlotte, North Carolina, USA
| | - Dionisios Vrochides
- Transplant Surgery, Carolinas Medical Center Wake Forest, University School of Medicine, Atrium Health, Charlotte, North Carolina, USA
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12
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Fernández-Ramírez A, Olivas-Martinez A, Ruiz-Manriquez J, Kauffman-Ortega E, Moctezuma-Velázquez C, Marquez-Guillen E, Contreras AG, Vilatobá M, González-Flores E, Cruz-Martínez R, Flores-García NC, García-Juárez I. Posttransplantation diabetes mellitus after liver transplant and the impact of family history of diabetes in a Mexican cohort. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:249-257. [PMID: 37858455 DOI: 10.1016/j.rgmxen.2023.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 06/08/2023] [Indexed: 10/21/2023]
Abstract
INTRODUCTION AND AIMS Posttransplantation diabetes mellitus (PTDM) is a serious long-term complication that has a negative impact on graft and patient survival. The purpose of the present study was to describe the incidence of PTDM in a Mexican cohort and evaluate its association with a previous family history of diabetes (FHD). METHODS A retrospective single-center cohort study was conducted on patients undergoing liver transplantation (LT). The primary outcome was time from LT to PTDM. The diagnosis of PTDM was established using the ADA criteria. A mediation analysis that used adjusted Cox regression models and considered pretransplant prediabetes a mediator was performed, to determine the total effect and direct effect of FHD on PTDM. RESULTS A total of 152 patients were included, with a median follow-up time of 41 months; 19.2% (n = 29) had pretransplant diabetes. During the follow-up time, 15% of patients developed PTDM (n = 23), with an incidence rate of 4.71 cases/100 person-years. PTDM was significantly higher in patients with FHD, compared with those with no FHD (8.72 cases/100 person-years vs 2.04 cases/100 person-years, respectively; p = 0.001). The adjusted hazard ratio of PTDM for FHD was 4.14 (95% CI 1.60-10.7), p = 0.005) and 3.48 (95% CI 1.35-9.01, p = 0.010), when further controlled for pretransplant prediabetes. CONCLUSION The occurrence of PTDM was similar to that reported in most international studies. As with type 2 diabetes, family history plays an important role in the development of PTDM, even after accounting for pretransplant prediabetes. Patients with FHD should undergo a stricter metabolic program.
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Affiliation(s)
- A Fernández-Ramírez
- Departamento de Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - A Olivas-Martinez
- Departamento de Bioestadística, Universidad de Washington, Seattle, WA, United States
| | - J Ruiz-Manriquez
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - E Kauffman-Ortega
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - C Moctezuma-Velázquez
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - E Marquez-Guillen
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - A G Contreras
- Departamento de Cirugía y Trasplante, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - M Vilatobá
- Departamento de Cirugía y Trasplante, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - E González-Flores
- Centro de Atención Integral del Paciente con Diabetes (CAIPaDi), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - R Cruz-Martínez
- Departamento de Cirugía y Trasplante, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - N C Flores-García
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - I García-Juárez
- Unidad de Hepatología y Trasplante Hepático, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
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13
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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14
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Mac Curtain BM, O'Brien L, El Sherif O, Mc Cormack A, Carolan E, Ryan JD, O'Shea D, Gallagher TK. Biguanides and glucagon like peptide 1 receptor agonists in the amelioration of post liver transplant weight gain; a scoping review of the mechanism of action, safety and efficacy. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2024; 17:17-27. [PMID: 38737926 PMCID: PMC11080689 DOI: 10.22037/ghfbb.v17i1.2899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 12/02/2023] [Indexed: 05/14/2024]
Abstract
Weight gain post-liver transplant can lead to adverse patient outcomes in the post-transplant period. Pharmacotherapy and other measures can be utilised to reduce the burden and occurrence of weight gain in this population. We explored the mechanism of action, safety, and efficacy of these medications, specifically GLP-1 receptor agonists and metformin, focusing on liver transplant patients. This scoping review was conducted in line with the scoping review structure as outlined by the PRISMA guidelines. Metformin and GLP-1 receptor agonists have been observed to be safe and effective in liver transplant patients. Experimental models have found liver-centric weight loss mechanisms in this drug cohort. There is a paucity of evidence about the use of antihyperglycemics in a post-transplant population for weight loss purposes. However, some small studies have shown strong safety and efficacy data. The evidence in relation to using these medications in patients with metabolic syndrome for weight loss warrants further study in a transplant population.
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Affiliation(s)
| | - Luke O'Brien
- Hepatopancreatobiliary Group, St Vincent's University Hospital, Dublin 4, Ireland
| | - Omar El Sherif
- National Liver Transplant Unit, St Vincent's University Hospital, Dublin 4, Ireland
| | - Aidan Mc Cormack
- National Liver Transplant Unit, St Vincent's University Hospital, Dublin 4, Ireland
| | - Emer Carolan
- Department of Hepatology, Beaumont Hospital, Dublin 9, Ireland
| | - John D Ryan
- Department of Hepatology, Beaumont Hospital, Dublin 9, Ireland
| | - Donal O'Shea
- Department of Endocrinology, St Vincent's University Hospital, Dublin 4, Ireland
| | - Tom K Gallagher
- Hepatopancreatobiliary Group, St Vincent's University Hospital, Dublin 4, Ireland
- National Liver Transplant Unit, St Vincent's University Hospital, Dublin 4, Ireland
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15
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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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16
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Todeschini L, Cristin L, Martinino A, Mattia A, Agnes S, Giovinazzo F. The Role of mTOR Inhibitors after Liver Transplantation for Hepatocellular Carcinoma. Curr Oncol 2023; 30:5574-5592. [PMID: 37366904 DOI: 10.3390/curroncol30060421] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 06/28/2023] Open
Abstract
Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in this setting. However, their inhibitory effect on T-cell activity accounts for a higher risk of tumour regrowth. mTOR inhibitors (mTORi) have been introduced as an alternative immunosuppressive approach to conventional CNI-based regimens to address both immunosuppression and cancer control. The PI3K-AKT-mTOR signalling pathway regulates protein translation, cell growth, and metabolism, and the pathway is frequently deregulated in human tumours. Several studies have suggested the role of mTORi in reducing HCC progression after LT, accounting for a lower recurrence rate. Furthermore, mTOR immunosuppression controls the renal damage associated with CNI exposure. Conversion to mTOR inhibitors is associated with stabilizing and recovering renal dysfunction, suggesting an essential renoprotective effect. Limitations in this therapeutic approach are related to their negative impact on lipid and glucose metabolism as well as on proteinuria development and wound healing. This review aims to summarize the roles of mTORi in managing patients with HCC undergoing LT. Strategies to overcome common adverse effects are also proposed.
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Affiliation(s)
- Letizia Todeschini
- Faculty of Medicine and Surgery, University of Verona, 37134 Verona, Italy
| | - Luca Cristin
- Faculty of Medicine and Surgery, University of Verona, 37134 Verona, Italy
| | | | - Amelia Mattia
- General Surgery and Liver Transplantation Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Salvatore Agnes
- General Surgery and Liver Transplantation Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Giovinazzo
- General Surgery and Liver Transplantation Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
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17
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Douglas SJ, Remily EA, Sax OC, Pervaiz SS, Mohamed NS, Kelemen MN, Delanois RE, Johnson AJ. Primary total hip arthroplasty complications and costs in liver transplant recipients: a matched analysis using a national database. Hip Int 2023; 33:178-183. [PMID: 34748455 DOI: 10.1177/11207000211037225] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The number of liver transplant recipients (LTR) is worldwide increasing and, as the survival is improving as well, there is an increasing number of patients needing total hip arthroplasty (THA). There might be increased risks for this specific group of patients and due to their comorbidities costs might be higher too. Using a big national database outcome and cost of THA should be compared between liver transplant recipients and the general population. METHODS The study was performed using a collection of Medicare, Medicaid, and private insurance claims. Length of stay (LOS), 30-day readmissions, complications rates up to 5 years, and 90-day total cost of care between liver transplant recipients and matched non-transplant patients should be compared. All primary THAs from 2010 to 2019 were identified. 513 patients with a liver transplant before their THA were matched to 10,759 patients without a history of solid organ transplant at a 1:20 ratio based on age, sex, Charlson Comorbidity Index, obesity, and diabetes status. RESULTS LTR had a longer average LOS (4.2 vs. 3.4 days, p < 0.001). There was no difference in the thirty-day readmissions (5.7% vs. 4.1%, p = 0.117) and 90-day dislocation rates (2.9% vs. 2.4%, p = 0.600). Total costs in the first ninety days after THA were not different between the LTR and controls (p = 0.756). CONCLUSIONS These findings suggest that complications and costs are no major point of concern in patients with liver transplant that are operated with THA.
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Affiliation(s)
- Scott J Douglas
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Ethan A Remily
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Oliver C Sax
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Sahir S Pervaiz
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Nequesha S Mohamed
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Margaret N Kelemen
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Ronald E Delanois
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Aaron J Johnson
- Department of Orthopaedics, University of Maryland Administrative Offices, Baltimore, MD, USA
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18
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Battistella S, D'Arcangelo F, Grasso M, Zanetto A, Gambato M, Germani G, Senzolo M, Russo FP, Burra P. Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management. Clin Mol Hepatol 2023; 29:S286-S301. [PMID: 36577425 PMCID: PMC10029965 DOI: 10.3350/cmh.2022.0392] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 12/22/2022] [Indexed: 12/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the fastest growing indication to liver transplantation (LT) in Western Countries, both for end stage liver disease and hepatocellular carcinoma. NAFLD/non-alcoholic steatohepatitis (NASH) is often expression of a systemic metabolic syndrome; therefore, NAFLD/NASH patients require a multidisciplinary approach for a proper pre-surgical evaluation, which is important to achieve a post-transplant outcome comparable to that of other indications to LT. NAFLD/NASH patients are also at higher risk of post-transplant cardiovascular events, diabetes, dyslipidemia, obesity, renal impairment and recurrent NASH. Lifestyle modifications, included diet and physical activity, are key to improve survival and quality of life after transplantation. A tailored immunosuppressive regimen may be proposed in selected patients. Development of new drugs for the treatment of recurrent NASH is awaited.
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Affiliation(s)
- Sara Battistella
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Francesca D'Arcangelo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Marco Grasso
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Martina Gambato
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Giacomo Germani
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, University of Padua, Padua, Italy
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19
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Belfort-DeAguiar R, Lomonaco R, Cusi K. Approach to the Patient With Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab 2023; 108:483-495. [PMID: 36305273 DOI: 10.1210/clinem/dgac624] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 10/13/2022] [Indexed: 01/20/2023]
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes (T2D), causing substantial burden from hepatic and extrahepatic complications. However, endocrinologists often follow people who are at the highest risk of its more severe form with nonalcoholic steatohepatitis or NASH (i.e., T2D or obesity with cardiometabolic risk factors). Endocrinologists are in a unique position to prevent cirrhosis in this population with early diagnosis and treatment. OBJECTIVE This work aims to offer endocrinologists a practical approach for the management of patients with NAFLD, including diagnosis, fibrosis risk stratification, and referral to hepatologists. PATIENTS (1) An asymptomatic patient with obesity and cardiometabolic risk factors, found to have hepatic steatosis; (2) a patient with T2D and NASH with clinically significant liver fibrosis; and (3) a liver transplant recipient with a history of NASH cirrhosis, with significant weight regain and with recurrent NAFLD on the transplanted organ. CONCLUSION NASH can be reversed with proper management of obesity and of T2D. While no agents are currently approved for the treatment of NASH, treatment should include lifestyle changes and a broader use of structured weight-loss programs, obesity pharmacotherapy, and bariatric surgery. Diabetes medications such as pioglitazone and some glucagon-like peptide 1 receptor agonists may also improve liver histology and cardiometabolic health. Sodium-glucose cotransporter-2 inhibitors and insulin may ameliorate steatosis, but their effect on steatohepatitis remains unclear. Awareness by endocrinologists about, establishing an early diagnosis of fibrosis (ie, FIB-4, liver elastography) in patients at high-risk of cirrhosis, long-term monitoring, and timely referral to the hepatologist are all critical to curve the looming epidemic of cirrhosis from NAFLD.
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Affiliation(s)
- Renata Belfort-DeAguiar
- Internal Medicine Department, Endocrinology Section, Yale University, New Haven, Connecticut 06520, USA
| | - Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610, USA
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20
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Dascal R, Wiebe C, Niazi M, Worobetz L, Bhanji RA, Knowles C, Uhanova J, Peretz D, Faisal N, Minuk GY. Post-transplant diabetes mellitus in Canadian liver and renal transplant recipients. CANADIAN LIVER JOURNAL 2022; 5:466-475. [PMID: 38144402 PMCID: PMC10735196 DOI: 10.3138/canlivj-2022-0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/18/2022] [Indexed: 12/26/2023]
Abstract
BACKGROUND: Post-transplant diabetes mellitus (PTDM) occurs in 10%-40% of liver and renal transplant recipients. Whether the risk factors for PTDM in liver and renal transplant recipients are similar and whether Indigenous Canadians, who have a high underlying prevalence of diabetes mellitus (DM), are at increased risk of developing PTDM have yet to be determined. OBJECTIVE: To describe and compare those variables associated with PTDM in adult Canadian liver and renal transplant recipients. METHODS: A retrospective chart review of adult liver and renal transplant recipients attending four transplant follow-up clinics in three Canadian provinces was undertaken. RESULTS: De novo PTDM was diagnosed in 184/905 (20.3%) liver and 179/390 (45.9%) renal transplant recipients. Older age, higher pre-transplant BMI, underlying immune-mediated liver disease, lower trough tacrolimus levels and longer duration of follow-up were independently associated with PTDM in liver transplant recipients and non-Caucasian race, higher pre-transplant BMI, and incidence of organ rejection in renal transplant recipients. Compared with Caucasians, Indigenous Canadians who had undergone renal transplantation had a significantly increased prevalence of PTDM (56.5% versus 40.0%, p = 0.035). The prevalence of PTDM in liver transplant recipients was similar in Indigenous Canadians and Caucasians (27.9% versus 20.1%, p = 0.215). CONCLUSIONS: The variables associated with PTDM differ in liver and renal transplant recipients. Compared with Caucasians, Indigenous Canadians undergoing renal transplantation are at increased risk of developing PTDM.
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Affiliation(s)
- Roman Dascal
- Division of Hepatology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Chris Wiebe
- Division of Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Mina Niazi
- Division of Gastroenterology and Hepatology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Lawrence Worobetz
- Division of Gastroenterology and Hepatology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Rahima A Bhanji
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Cori Knowles
- Paladin Labs Inc., Medical Department, Saint-Laurent, Quebec, Canada
| | - Julia Uhanova
- Division of Hepatology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - David Peretz
- Division of Hepatology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Nabiha Faisal
- Division of Hepatology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Gerald Y Minuk
- Division of Hepatology, University of Manitoba, Winnipeg, Manitoba, Canada
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21
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Lonardo A, Mantovani A, Petta S, Carraro A, Byrne CD, Targher G. Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation. Nat Rev Endocrinol 2022; 18:638-650. [PMID: 35840803 DOI: 10.1038/s41574-022-00711-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2022] [Indexed: 11/08/2022]
Abstract
The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major health concern worldwide. NAFLD - specifically its more advanced form, non-alcoholic steatohepatitis (NASH)-related cirrhosis - is now the fastest growing indication for liver transplantation in the USA and Europe. Although the short-term and mid-term overall survival rates of patients who receive a liver transplant for NASH-related cirrhosis are essentially similar to those of patients who receive a transplant for other liver indications, recipients with NASH-related cirrhosis have an increased risk of waiting-list mortality and of developing recurrent liver disease and cardiometabolic complications in the longer term after liver transplantation. This Review provides a brief overview of the epidemiology of NAFLD and NASH and the occurrence of NAFLD or NASH in patients after liver transplantation for NASH and other liver indications. It also discusses the putative metabolic mechanisms underlying the emergence of NAFLD or NASH after liver transplantation as well as optimal therapeutic approaches for recipients of liver transplants, including the management of cardiometabolic comorbidities, tailored immunosuppression, lifestyle changes and pharmacotherapy for NAFLD.
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Affiliation(s)
- Amedeo Lonardo
- Metabolic Syndrome Unit, University of Modena, Modena, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Amedeo Carraro
- Liver Transplant Unit, University of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
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22
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Engelmann C, Aehling NF, Schob S, Nonnenmacher I, Handmann L, Macnaughtan J, Herber A, Surov A, Kaiser T, Denecke T, Jalan R, Seehofer D, Moche M, Berg T. Body fat composition determines outcomes before and after liver transplantation in patients with cirrhosis. Hepatol Commun 2022; 6:2198-2209. [PMID: 35420246 PMCID: PMC9315113 DOI: 10.1002/hep4.1946] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 01/24/2022] [Accepted: 02/17/2022] [Indexed: 11/25/2022] Open
Abstract
Cachexia occurs in late stages of liver cirrhosis, and a low-fat mass is potentially associated with poor outcome. This study compared different computed tomography (CT)-derived fat parameters with respect to its prognostic impact on the development of complications and death before and after liver transplantation. Between 2001 and 2014, 612 patients with liver cirrhosis without hepatocellular carcinoma listed for liver transplantation met the inclusion criteria, including abdominal CT scan (±200 days to listing). A total of 109 patients without cirrhosis served as controls. The subcutaneous fat index (SCFI), the paraspinal muscle fat index, and the visceral fat index were assessed at L3/L4 level and normalized to the height (cm2 /m2 ). Data were collected and analyzed retrospectively. Low SCFI was associated with a higher rate of ascites and increased C-reactive protein levels (p < 0.001). In addition, multivariate Cox regression analysis adjusting for sex, age, body mass index (BMI), and Model for End-Stage Liver Disease showed that decreasing SCFI was also associated with an increased risk of cirrhosis-related complications (p = 0.003) and death on the transplant wait list (p = 0.013). Increased paraspinal and visceral fat were not only positively correlated with creatinine levels (p < 0.001), BMI, and metabolic comorbidities (all p < 0.001) before transplantation, but also predictive for 1-year mortality after transplantation. Conclusion: The distribution of body fat is a major determinant for complications and outcome in cirrhosis before and after liver transplantation.
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Affiliation(s)
- Cornelius Engelmann
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany.,Liver Failure GroupInstitute for Liver and Digestive HealthUniversity College LondonRoyal Free CampusLondonUK.,Department of Hepatology and GastroenterologyCampus Virchow-KlinikumCharité-Universitaetsmedizin BerlinBerlinGermany.,522475Berlin Institute of HealthBerlinGermany
| | - Niklas F Aehling
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Stefan Schob
- Department for NeuroradiologyUniversity Hospital LeipzigLeipzigGermany
| | - Ines Nonnenmacher
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Luise Handmann
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Jane Macnaughtan
- Liver Failure GroupInstitute for Liver and Digestive HealthUniversity College LondonRoyal Free CampusLondonUK
| | - Adam Herber
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Alexey Surov
- Department of Diagnostic and Interventional RadiologyUniversity Hospital LeipzigLeipzigGermany
| | - Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular DiagnosticsUniversity Hospital LeipzigLeipzigGermany
| | - Timm Denecke
- Department of Diagnostic and Interventional RadiologyUniversity Hospital LeipzigLeipzigGermany
| | - Rajiv Jalan
- Liver Failure GroupInstitute for Liver and Digestive HealthUniversity College LondonRoyal Free CampusLondonUK
| | - Daniel Seehofer
- Department of VisceralVascularThoracic and Transplant SurgeryUniversity Hospital LeipzigLeipzigGermany
| | - Michael Moche
- Department of Diagnostic and Interventional RadiologyUniversity Hospital LeipzigLeipzigGermany.,Diagnostic and Interventional RadiologyPark Hospital LeipzigLeipzigGermany
| | - Thomas Berg
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
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23
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Richardson B, Khan MQ, Brown SA, Watt KD, Izzy M. Personalizing Diabetes Management in Liver Transplant Recipients: The New Era for Optimizing Risk Management. Hepatol Commun 2022; 6:1250-1261. [PMID: 34921530 PMCID: PMC9134800 DOI: 10.1002/hep4.1876] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 11/18/2021] [Accepted: 11/18/2021] [Indexed: 12/12/2022] Open
Abstract
Post-transplant diabetes mellitus (PTDM) is a significant contributor to morbidity and mortality in liver transplant recipients (LTRs). With concurrent comorbidities and use of various immunosuppression medications, identifying a safe and personalized regimen for management of PTDM is needed. There are many comorbidities associated with the post-transplant course including chronic kidney disease, cardiovascular disease, allograft steatosis, obesity, and de novo malignancy. Emerging data suggest that available diabetes medications may carry beneficial or, in some cases, harmful effects in the setting of these co-existing conditions. Sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have shown the most promising beneficial results. Although there is a deficiency of LTR-specific data, they appear to be generally safe. Effects of other medications are varied. Metformin may reduce the risk of malignancy. Pioglitazone may be harmful in patients combatting obesity or heart failure. Insulin may exacerbate obesity and increase the risk of developing malignancy. This review thoroughly discusses the roles of these extra-glycemic effects and safety considerations in LTRs. Through weighing the risks and benefits, we conclude that alternatives to insulin should be strongly considered, when feasible, for personalized long-term management based on risk factors and co-morbidities.
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Affiliation(s)
- Brooks Richardson
- Department of Internal MedicineVanderbilt University Medical CenterNashvilleTNUSA
| | | | - Sara A Brown
- Division of Gastroenterology, Hepatology and NutritionVanderbilt University Medical CenterNashvilleTNUSA
| | - Kymberly D Watt
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Manhal Izzy
- Division of Gastroenterology, Hepatology and NutritionVanderbilt University Medical CenterNashvilleTNUSA
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24
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Newell BJ, Melton BL, Burkhardt CD, Ruisinger JF. Semaglutide Initiation in a Type 2 Diabetes Mellitus, Post-Liver Transplant Patient. Sr Care Pharm 2022; 37:221-226. [PMID: 35610766 DOI: 10.4140/tcp.n.2022.221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Objective To describe the process of initiation of semaglutide for complex management of type 2 diabetes mellitus (T2DM) in a patient after liver transplantation. Setting Family medicine clinic. Practice Description A family medicine clinic comprising six physicians with an ambulatory care pharmacist. The pharmacist has direct interaction with patients and providers within the clinic assisting in the management of chronic disease states under a collaborative practice agreement. Practice Innovation A 63-year-old White male with a history of liver transplantation in the context of T2DM, treated with basal-bolus insulin therapy, was referred by his family medicine provider to the ambulatory care pharmacist for diabetes management because of a hemoglobin A1c (HbA1c) level greater than 10%. Semaglutide was initiated and titrated to improve blood glucose control in combination with basal-bolus insulin adjustments taking disease states, cost, and health literacy into consideration. Results The addition of semaglutide, over an eight-month period, assisted with glycemic control to an HbA1c of less than 7%. Conclusion Semaglutide, in addition to basal-bolus insulin therapy, allowed for overall improved glycemic control; however, further studies are needed to evaluate efficacy because of the complexity of diabetes management in this patient population. Throughout the course of treatment of patients with T2DM and organ transplantation, dual monitoring of antidiabetic therapy and antirejection medications is essential to reduce the risk of organ rejection.
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25
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Wong HJ, Lim WH, Ng CH, Tan DJH, Bonney GK, Kow AWC, Huang DQ, Siddiqui MS, Noureddin M, Syn N, Muthiah MD. Predictive and Prognostic Roles of Gut Microbial Variation in Liver Transplant. Front Med (Lausanne) 2022; 9:873523. [PMID: 35620719 PMCID: PMC9127379 DOI: 10.3389/fmed.2022.873523] [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: 02/10/2022] [Accepted: 04/06/2022] [Indexed: 11/16/2022] Open
Abstract
Patients undergoing liver transplant (LTX) typically confront a challenging postoperative journey. A dysbiotic gut microbiome is associated with the development of complications, including post-LTX allograft rejection, metabolic diseases and de novo or recurrent cancer. A major explanation of this are the bipartite interactions between the gut microbiota and host immunity, which modulates the alloimmune response towards the liver allograft. Furthermore, bacterial translocation from dysbiosis causes pathogenic changes in the concentrations of microbial metabolites like lipopolysaccharides, short-chain fatty acids (SCFAs) and Trimethylamine-N-Oxide, with links to cardiovascular disease development and diabetes mellitus. Gut dysbiosis also disrupts bile acid metabolism, with implications for various post-LTX metabolic diseases. Certain taxonomy of microbiota such as lactobacilli, F.prausnitzii and Bacteroides appear to be associated with these undesired outcomes. As such, an interesting but as yet unproven hypothesis exists as to whether induction of a “beneficial” composition of gut microbiota may improve prognosis in LTX patients. Additionally, there are roles of the microbiome as predictive and prognostic indicators for clinicians in improving patient care. Hence, the gut microbiome represents an exceptionally exciting avenue for developing novel prognostic, predictive and therapeutic applications.
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Affiliation(s)
- Hon Jen Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Glenn K Bonney
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Hospital Singapore, Singapore, Singapore
| | - Alfred W C Kow
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Hospital Singapore, Singapore, Singapore
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Centre, Cedars-Sinai Medical Centre, Los Angeles, CA, United States
| | - Nicholas Syn
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mark D Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
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26
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Congly SE. Is diabetes a risk factor for malignancy post-transplant in liver transplant recipients? Ann Hepatol 2022; 27:100703. [PMID: 35338011 DOI: 10.1016/j.aohep.2022.100703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 03/16/2022] [Indexed: 02/04/2023]
Affiliation(s)
- Stephen E Congly
- Divisions of Gastroenterology and Hepatology and Transplant Medicine, Department of Medicine, Cumming School of Medicine, O'Brien Institute of Public Health, University of Calgary, 6th Floor, Teaching Research and Wellness Building, 3280 Hospital Drive NW, Calgary AB T2N 4N1 Canada.
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27
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A Comprehensive Review on the Risk of Metabolic Syndrome and Cardiovascular Disease after Liver Transplantation. LIVERS 2022. [DOI: 10.3390/livers2020006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Survival rates after liver transplantation have increased dramatically over the past 20 years. Cardiovascular disease is the most common extra-hepatic cause of mortality in the long-term post liver transplant. This is intimately linked with both the higher pre-existing rates of metabolic syndrome in these patients as well as increased propensity to develop de novo metabolic syndrome post-transplant. This unfavorable metabolic profile that contributes to cardiovascular disease is multifactorial and largely preventable. This review explores metabolic syndrome and cardiovascular disease and their contributory factors post liver transplantation to highlight areas for potential intervention and thus reduce the significant morbidity and mortality of patients due to metabolic syndrome and cardiovascular disease.
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28
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Campos MB, Riguetto CM, de Fátima Santana Ferreira Boin I, Moura A. Risk factors associated with diabetes after liver transplant. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2022; 66:182-190. [PMID: 35315984 PMCID: PMC9832889 DOI: 10.20945/2359-3997000000447] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Objective Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after liver transplant that negatively affects a recipient's survival and graft function. This study aims to identify risk factors associated with diabetes after liver transplant. Methods This is a cross-sectional study conducted from September to November 2019. Data collection was performed by chart review, and patients were divided into 3 groups: patients without diabetes mellitus (DM), patients with pre-transplant diabetes mellitus, and patients with PTDM. Results Two hundred and forty-seven patients' medical charts were screened, and 207 patients were included: 107 without DM, 42 with pre-transplant DM, and 58 with PTDM. The leading cause for liver transplant was hepatitis C, followed by hepatocellular carcinoma secondary to alcohol. There was a higher exposure to tacrolimus in patients without DM (P = 0.02) and to ciclosporin in patients with pre-transplant DM, compared to others (P = 0.005). Microscopic interface inflammatory activity was more severe in patients without DM as well as those with PTDM (P = 0.032). There was a higher prevalence of steatosis in recipients with pre-transplant DM than there was in others (P < 0.001). Multivariate logistic regression identified the following independent risk factors for DM: cirrhosis due to alcohol, hepatitis C, and triglycerides. For PTDM, these independent risk factors were cirrhosis due to alcohol, hepatitis C, and prednisone exposure. Conclusion Alcoholic cirrhosis is a risk factor for PTDM in liver recipients. Liver transplant recipients with a pre-transplant history of cirrhosis due to alcohol, hepatitis C, and prednisone exposure deserve more caution during PTDM screening.
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Affiliation(s)
- Mariana Baldini Campos
- Disciplina de Endocrinologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade de Campinas, Campinas, SP, Brasil
| | - Cínthia Minatel Riguetto
- Disciplina de Endocrinologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade de Campinas, Campinas, SP, Brasil
| | | | - Arnaldo Moura
- Disciplina de Endocrinologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade de Campinas, Campinas, SP, Brasil,
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Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes. Nat Med 2022; 28:999-1005. [PMID: 35393535 DOI: 10.1038/s41591-022-01758-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 02/24/2022] [Indexed: 12/13/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n = 1,581) and their donors (n = 1,555), and kidney recipients (n = 2,062) and their donors (n = 533). Recipient T2D PRS was associated with pre-transplant T2D and the development of PTDM. T2D PRS in liver donors, but not in kidney donors, was an independent risk factor for PTDM development. The inclusion of a combined liver donor and recipient T2D PRS significantly improved PTDM prediction compared with a model that included only clinical characteristics: the area under the curve (AUC) was 67.6% (95% confidence interval (CI) 64.1-71.1%) for the combined T2D PRS versus 62.3% (95% CI 58.8-65.8%) for the clinical characteristics model (P = 0.0001). Liver recipients in the highest quintile of combined donor and recipient T2D PRS had the greatest risk of PTDM, with an odds ratio of 3.22 (95% CI 2.07-5.00) (P = 1.92 × 10-7) compared with those in the lowest quintile. In conclusion, T2D PRS identifies transplant candidates with high risk of PTDM for which pre-emptive diabetes management and donor selection may be warranted.
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Doumouras AG, Lovrics O, Paterson JM, Sutradhar R, Paszat L, Sivapathasundaram B, Tarride JE, Anvari M. Bariatric Surgery and Breast Cancer Incidence: a Population-Based, Matched Cohort Study. Obes Surg 2022; 32:1261-1269. [PMID: 35212909 DOI: 10.1007/s11695-022-05946-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/25/2022] [Accepted: 02/03/2022] [Indexed: 10/19/2022]
Abstract
PURPOSE Obesity is associated with increased breast cancer risk in women. Bariatric surgery induces substantial weight loss. However, the effects of such weight loss on subsequent breast cancer risk in women with obesity are poorly understood. To examine breast cancer incidence and related outcomes in women with obesity undergoing bariatric surgery. MATERIALS AND METHODS This was a population-based matched cohort study of breast surgery outcomes utilizing linked clinical databases in Ontario, Canada. Women with obesity who underwent bariatric surgery were 1:1 matched using a propensity score to non-surgical controls for age and breast cancer screening history. The main outcomes were incidence of breast cancer after lag periods of 1, 2, and 5 years. Additional outcomes included tumor hormone receptor status, cancer stage, and treatments undertaken. Time-varying Cox proportional hazard models accounting for screening during follow-up were used to model cancer incidence. RESULTS A total of 12,724 women per group were included, average age 45.09. After a 1-year lag, breast cancer incidence occurred in 1.09% and 0.79% of the control and surgery groups, respectively (adjusted hazard ratio, 0.81 [95%CI 0.69-0.95]; p = 0.01). This association was maintained after lag periods of 2 and 5 years. Women in the surgical cohort diagnosed with breast cancer were more likely to have low-grade tumors and less likely to have high-grade tumors (overall p < 0.01). No association was found for tumor hormone receptor status, although the surgical group was more likely to have her2neu-negative tumors (p = 0.01). CONCLUSION Bariatric surgery was associated with a lower incidence of breast cancer and lower tumor grade in women with obesity. Further evaluation of outcomes, including mortality, is required.
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Affiliation(s)
- Aristithes G Doumouras
- Division of General Surgery, McMaster University, Hamilton, ON, L8V 1C3, Canada
- ICES, Toronto, ON, M4N 3M5, Canada
- Department of Health Research Methods, Evidence, and Impact (HEI), Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Division of General Surgery, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6, Canada
| | - Olivia Lovrics
- Division of General Surgery, McMaster University, Hamilton, ON, L8V 1C3, Canada
| | - J Michael Paterson
- ICES, Toronto, ON, M4N 3M5, Canada
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, M5T 3M6, Canada
- Department of Family Medicine, McMaster University, Hamilton, ON, L8P 1H6, Canada
| | - Rinku Sutradhar
- ICES, Toronto, ON, M4N 3M5, Canada
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, M5T 3M6, Canada
| | - Lawrence Paszat
- ICES, Toronto, ON, M4N 3M5, Canada
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, M5T 3M6, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON, M5T 1P5, Canada
| | | | - Jean-Eric Tarride
- Department of Health Research Methods, Evidence, and Impact (HEI), Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Center for Health Economics and Policy Analysis (CHEPA), McMaster University, Hamilton, ON, L8S 4L8, Canada
- Programs for Assessment of Technology in Health (PATH), The Research Institute of St. Joe's Hamilton, St. Joseph's Healthcare Hamilton, Hamilton, ON, L8N 4A6, Canada
| | - Mehran Anvari
- Division of General Surgery, McMaster University, Hamilton, ON, L8V 1C3, Canada.
- ICES, Toronto, ON, M4N 3M5, Canada.
- Division of General Surgery, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6, Canada.
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Puri P, Kotwal N. An Approach to the Management of Diabetes Mellitus in Cirrhosis: A Primer for the Hepatologist. J Clin Exp Hepatol 2022; 12:560-574. [PMID: 35535116 PMCID: PMC9077234 DOI: 10.1016/j.jceh.2021.09.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 09/07/2021] [Indexed: 12/12/2022] Open
Abstract
The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar values are low and glycosylated hemoglobin may not be a reliable marker. The challenges in the management of diabetes in cirrhosis include the likelihood of cognitive impairment, risk of hypoglycemia, altered drug metabolism, frequent renal dysfunction, risk of lactic acidosis, and associated malnutrition and sarcopenia. Moreover, calorie restriction and an attempt to lose weight in obese diabetics may be associated with a worsening of sarcopenia. Many commonly used antidiabetic drugs may be unsafe or be associated with a high risk of hypoglycemia in cirrhotics. Post-transplant diabetes is common and may be contributed by immunosuppressive medication. There is inadequate clinical data on the use of antidiabetic drugs in cirrhosis, and the management of diabetes in cirrhosis is hampered by the lack of guidelines focusing on this issue. The current review aims at addressing the practical management of diabetes by a hepatologist.
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Key Words
- ADA, American Diabetes Association
- AGI, Alfa Glucosidase inhibitors
- BMI, Body mass index
- CLD, Chronic liver disease
- CYP-450, Cytochrome P-450
- Dipeptidyl-peptidase 4, DPP-4
- GLP-1, Glucagon-like peptide-1
- HCC, Hepatocellular carcinoma
- HCV, Hepatitis C virus
- HbA1c, Hemoglobin A1c
- IGF, Insulin-like growth factor
- MALA, Metformin-associated lactic acidosis
- NASH, Nonalcoholic steatohepatitis
- NPL, Neutral protamine lispro
- OGTT, Oral glucose tolerance test
- SMBG, Self-monitoring of blood glucose
- Sodium-glucose cotransporter 2, SGLT2
- VEGF, Vascular endothelial growth factor
- antidiabetic agents
- antihyperglycemic drugs
- chronic liver disease
- cirrhosis
- diabetes mellitus
- eGFR, estimated glomerular filtration rates
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, New Delhi, 110025, India
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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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Schwarzenbach M, Bernhard FE, Czerlau C, Sidler D. Chances and risks of sodium-glucose cotransporter 2 inhibitors in solid organ transplantation: A review of literatures. World J Transplant 2021; 11:254-262. [PMID: 34316450 PMCID: PMC8290999 DOI: 10.5500/wjt.v11.i7.254] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 05/17/2021] [Accepted: 05/26/2021] [Indexed: 02/06/2023] Open
Abstract
Solid organ transplantation offers life-saving treatment for patients with end-organ dysfunction. Patient survival and quality of life have improved over the past few decades as a result of pharmacological development, expansion of the donor pool, technological advances and standardization of practices related to transplantation. Still, transplantation is associated with cardiovascular complications, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus, but also from specific post-transplant risk factors such as metabolic side effects of immunosuppressive drugs, post-transplant viral infections and hypomagnesemia. Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients. However, the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited. The favourable risk/benefit ratio, which is suggested by large-scale and long-term studies on new glucose-lowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, makes studies warranted to assess the potential role of these agents in the management of PTDM.
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Affiliation(s)
- Marlene Schwarzenbach
- Department of Nephrology and Hypertension, University Hospital Insel Bern, Bern 3010, Switzerland
| | - Flavia Elena Bernhard
- Department of Nephrology and Hypertension, University Hospital Insel Bern, Bern 3010, Switzerland
| | - Cecilia Czerlau
- Department of Nephrology and Hypertension, University Hospital Insel Bern, Bern 3010, Switzerland
| | - Daniel Sidler
- Department of Nephrology and Hypertension, University Hospital Insel Bern, Bern 3010, Switzerland
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Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study. Transplant Direct 2021; 7:e722. [PMID: 34263020 PMCID: PMC8274734 DOI: 10.1097/txd.0000000000001166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 03/08/2021] [Accepted: 03/09/2021] [Indexed: 01/27/2023] Open
Abstract
Background Immunosuppression with calcineurin inhibitors (CNIs) is reportedly associated with risk of renal impairment in liver transplant recipients. It is believed that this can be mitigated by decreasing initial exposure to CNIs or delaying CNI introduction until 3-4 d posttransplantation. The ADVAGRAF studied in combination with mycophenolate mofetil and basiliximab in liver transplantation (DIAMOND) trial evaluated different administration strategies for prolonged-release tacrolimus (PR-T). Methods DIAMOND was a 24-wk, open-label, phase 3b trial in de novo liver transplant recipients randomized to: PR-T 0.2 mg/kg/d (Arm 1); PR-T 0.15-0.175 mg/kg/d plus basiliximab (Arm 2); or PR-T 0.2 mg/kg/d delayed until day 5 posttransplant plus basiliximab (Arm 3). In a 5-y follow-up, patients were maintained on an immunosuppressive regimen according to standard clinical practice (NCT02057484). Primary endpoint: graft survival (Kaplan-Meier analysis). Results Follow-up study included 856 patients. Overall graft survival was 84.6% and 73.5% at 1 and 5 y post transplant, respectively. Five-year rates for Arms 1, 2, and 3 were 74.7%, 71.5%, and 74.5%, respectively. At 5 y, death-censored graft survival in the entire cohort was 74.7%. Overall graft survival in patients remaining on PR-T for ≥30 d was 79.1%. Graft survival in patients who remained on PR-T at 5 y was 87.3%. Patient survival was 86.6% at 1 y and 76.3% at 5 y, with survival rates similar in the 3 treatment arms at 5 y. Estimated glomerular filtration rate at the end of the 24-wk initial study and 5 y posttransplant was 62.1 and 61.5 mL/min/1.73 m2, respectively, and was similar between the 3 treatment arms at 5 y. Overall, 18 (2.9%) patients had ≥1 adverse drug reaction, considered possibly related to PR-T in 6 patients. Conclusions In the DIAMOND study patient cohort, renal function, graft survival, and patient survival were similar between treatment arms at 5 y posttransplant.
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35
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Grottenthaler JM, Füger JK, Mahling M, Königsrainer A, Malek NP, Birkenfeld AL, Nadalin S, Berg CP, Heyne N, Guthoff M. Dynamics of glucose metabolism after liver transplantation: Prediabetes as a window of opportunity for patient survival and long-term kidney function. Transpl Int 2021; 34:1959-1970. [PMID: 34214208 DOI: 10.1111/tri.13967] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/30/2021] [Accepted: 06/28/2021] [Indexed: 12/01/2022]
Abstract
Posttransplantation diabetes mellitus (PTDM) is a relevant complication following liver transplantation with profound impact on morbidity and mortality. To date, little is known about the evolution and dynamics of glucose metabolism and the impact of prediabetes in long-term follow-up. To address this issue, all consecutive adult liver transplant recipients (n=429) from a European university hospital transplant center between 2007 and 2017 were analyzed retrospectively. In patients without pre-existing diabetes (n=327), we conducted a longitudinal characterization of glucose metabolism. Median follow-up was 37 [9-64, IQR] months. Median prevalence of prediabetes was 39 [37-39]% and of PTDM 21 [17-22]%. Throughout follow-up, intra-individual glucose regulation of patients was highly variable, continuously fluctuating between different states of glucose metabolism (normal glucose tolerance, prediabetes, PTDM). Whereas overall survival and long-term kidney function of patients with PTDM were significantly lower than that of patients with normal glucose metabolism, prediabetes was not associated with adverse outcome. This study provides new insight into the dynamics and impact of glucose metabolism after liver transplantation. Unlike PTDM, prediabetes is not associated with adverse outcome, providing a window of opportunity for targeted intervention. The results underline the need for constant screening and intervention in post-transplant care of liver allograft recipients.
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Affiliation(s)
- Julia M Grottenthaler
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Judith K Füger
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
| | - Moritz Mahling
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Alfred Königsrainer
- Department of General-, Visceral- and Transplant Surgery, University of Tuebingen, Tuebingen, Germany
| | - Nisar P Malek
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Andreas L Birkenfeld
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Silvio Nadalin
- Department of General-, Visceral- and Transplant Surgery, University of Tuebingen, Tuebingen, Germany
| | - Christoph P Berg
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Nils Heyne
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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36
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Bhadada SK, Pal R. Post-liver transplantation diabetes mellitus — a clinical challenge for diabetologists? Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00955-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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37
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Khan MQ, Watt KD. Scientific Relief: When Science and Technology Agree and Lead. Liver Transpl 2021; 27:484-485. [PMID: 37160032 DOI: 10.1002/lt.25998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 12/17/2020] [Indexed: 01/13/2023]
Affiliation(s)
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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38
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Chin YH, Tan HQM, Ng CH, Tan DJH, Lin SY, Huang DQ, Khoo CM, Muthiah MD. A Time-Based Meta-Analysis on the Incidence of New Onset Diabetes after Liver Transplantation. J Clin Med 2021; 10:jcm10051045. [PMID: 33802465 PMCID: PMC7959476 DOI: 10.3390/jcm10051045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/08/2021] [Accepted: 02/24/2021] [Indexed: 12/29/2022] Open
Abstract
NODAT (new-onset diabetes after transplantation) is an important complication after liver transplant, however, there is variation in the reported incidence of NODAT. Therefore, a meta-analysis was performed to estimate the incidence of NODAT in liver transplant. Electronic databases were searched for articles regarding NODAT incidence after liver transplantation. Incidence of NODAT were analyzed at six different timepoints. Summary statistics were calculated using a generalized linear mixed model in random effects. 28 articles were included and out of a pooled population of 71,257 patients, overall incidence of NODAT was found to be 15.51%, 16.09%, 18.30%, 20.86%, 18.08%, 25.05% for three-months, six-months, one-year, three-year, five-year, and ten-year timepoints respectively. After a sensitivity analysis which only included articles with clear definitions of NODAT, the incidence of NODAT was found to be higher at three-year (21.79%), five-year (25.82%), and ten-year (44.95%) timepoints. Subgroup analysis according to ethnicity found no significant differences for all timepoints. However, studies with predominantly Asian participants generally had a higher incidence of NODAT. In conclusion, this meta-analysis provides a pooled estimate of the incidence of NODAT following liver transplantation. Further studies are required to provide a more comprehensive understanding on how ethnicity can affect the incidence of NODAT.
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Affiliation(s)
- Yip Han Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Hon Qin Marcus Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Correspondence: or (C.H.N.); (M.D.M.)
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
- National University Centre for Organ Transplantation, National University Hospital, Singapore 119074, Singapore
| | - Chin Meng Khoo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
| | - Mark Dhinesh Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (Y.H.C.); (H.Q.M.T.); (D.J.H.T.); (S.Y.L.); (D.Q.H.); (C.M.K.)
- Department of Medicine, National University Hospital, Singapore 119074, Singapore
- National University Centre for Organ Transplantation, National University Hospital, Singapore 119074, Singapore
- Correspondence: or (C.H.N.); (M.D.M.)
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39
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De-novo nonalcoholic fatty liver disease at 5 years after liver transplantation: prevalence and predictive factors. Eur J Gastroenterol Hepatol 2021; 33:399-406. [PMID: 32317584 DOI: 10.1097/meg.0000000000001736] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is a long-term complication after liver transplantation. Our aims were to determine de-novo-NAFLD at 5-year post-liver transplantation and identify predictive risk factors. METHODS This was a retrospective analysis of de-novo-NAFLD at 5-year post-liver transplantation. NAFLD was defined as the radiological evidence of steatosis. Data from transplanted patients between November 2001 and May 2014 were collected. Noninvasive fibrosis scores were calculated. Predictors of de-novo NAFLD and survival were assessed by multivariate analyses and Kaplan-Meier method. RESULTS A total of 252 liver transplantations were evaluated after applying exclusion criteria, (78.6% men) with 54.9 years old (SD ± 9.5). Prevalence of de-novo NAFLD at 5-year post-liver transplantation was 36.1%. Cardiovascular events were presented in 19.88% and 23.08% of non-NAFLD and NAFLD patients, (P = 0.58). On multivariate analysis, male sex (OR, 5.40; P = 0.001), obesity (OR, 3.72; P = 0.017), metabolic syndrome (OR, 4.69; P < 0.001) and de-novo diabetes (OR, 2.79; P = 0.018), were predictive. Significant fibrosis (≥F2) was presented in 58-86%. The mean survival in NAFLD and control group was 166.3 and 173.6 months, respectively (P = 0 0.50). CONCLUSION De-novo NAFLD at fifth-year post-liver transplantation is frequently and associated with cardiovascular comorbidity. Male sex, obesity, de-novo diabetes and metabolic syndrome were factors associated with de-novo NAFLD. A significant proportion of patients had advanced fibrosis. This group trends toward worse patients' survival.
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Subramaniyan V, Chakravarthi S, Jegasothy R, Seng WY, Fuloria NK, Fuloria S, Hazarika I, Das A. Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy. Toxicol Rep 2021; 8:376-385. [PMID: 33680863 PMCID: PMC7910406 DOI: 10.1016/j.toxrep.2021.02.010] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 02/11/2021] [Accepted: 02/12/2021] [Indexed: 12/13/2022] Open
Abstract
One of the global burdens of health care is an alcohol-associated liver disease (ALD) and liver-related death which is caused due to acute or chronic consumption of alcohol. Chronic consumption of alcohol damage the normal defense mechanism of the liver and likely to disturb the gut barrier system, mucosal immune cells, which leads to decreased nutrient absorption. Therapy of ALD depends upon the spectrum of liver injury that causes fatty liver, hepatitis, and cirrhosis. The foundation of therapy starts with abstinence from alcohol. Corticosteroids are used for the treatment of ALD but due to poor acceptance, continuing mortality, and identification of tumor necrosis factor-alpha as an integral component in pathogenesis, recent studies focus on pentoxifylline and, antitumor necrosis factor antibody to neutralize cytokines in the therapy of severe alcoholic hepatitis. Antioxidants also play a significant role in the treatment but till today there is no universally accepted therapy available for any stage of ALD. The treatment aspects need to restore the gut functions and require nutrient-based treatments to regulate the functions of the gut system and prevent liver injury. The vital action of saturated fatty acids greatly controls the gut barrier. Overall, this review mainly focuses on the mechanism of alcohol-induced metabolic dysfunction, contribution to liver pathogenesis, the effect of pregnancy, and targeted therapy of ALD.
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Key Words
- ALD, alcohol associated liver disease
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Alcohol
- CD14, cluster of differentiation14
- CHD, congenital heart disease
- ECM, extracellualr matrix
- FASD, fetal alcohol spectrum disorders
- FDA, food and drug administration
- GGTP, gamma-glutamyl transpeptidase
- GSH, Glutathione
- H2O2, hydrogen peroxide
- HCV, chronic hepatitis C
- HSC, hepatic stellate cells
- IGR, intrauterine growth retardation
- IL, interleukin
- Immune modulation
- JECH, Japan Environment and Children's Study
- Liver pathogenesis
- MDF, maddrey’s discriminant function
- NA, nutritional assessment
- NAC, N-acetylcysteine
- NADPH, Nicotinamide adenine dinucleotide phosphate
- OLT, Orthotopic liver transplantation
- Pregnancy
- ROS, reactive oxygen species
- TLR4, toll-like receptor 4
- TNF, Tumor necrosis factor
- Targeted therapy
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Affiliation(s)
- Vetriselvan Subramaniyan
- Department of Pharmacology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia
| | - Srikumar Chakravarthi
- Department of Pathology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia
| | - Ravindran Jegasothy
- Department of Obstetrics and Gynecology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia
| | - Wu Yuan Seng
- Department of Biochemistry, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia
| | - Neeraj Kumar Fuloria
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy AIMST University, Jalan Bedong-Semeling, 08100, Malaysia
| | - Shivkanya Fuloria
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy AIMST University, Jalan Bedong-Semeling, 08100, Malaysia
| | - Iswar Hazarika
- Department of Pharmacology, Girijananda Chowdhury Institute of Pharmaceutical Sciences, Guwahati, 781017, India
| | - Anju Das
- Department of Pharmacology, Royal School of Pharmacy, Royal Global University, Guwahati, 781035, India
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Association between Liver Cirrhosis and Diabetes Mellitus: A Review on Hepatic Outcomes. J Clin Med 2021; 10:jcm10020262. [PMID: 33445629 PMCID: PMC7827383 DOI: 10.3390/jcm10020262] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 01/07/2021] [Accepted: 01/11/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Liver cirrhosis (LC) is largely associated with diabetes mellitus (DM). More than 80% of patients with LC manifest glucose intolerance and about 30% have type 2 DM. A particular and yet unrecognized entity is hepatogenous diabetes (HD), defined as impaired glucose regulation caused by altered liver function following LC. Numerous studies have shown that DM could negatively influence liver-related outcomes. AIM We aimed to investigate whether patients with LC and DM are at higher risk for hepatic encephalopathy (HE), variceal hemorrhage (VH), infections and hepatocellular carcinoma (HCC). The impact of DM on liver transplant (LT) outcomes was also addressed. METHODS Literature search was performed in PubMed, Ovid, and Elsevier databases. Population-based observational studies reporting liver outcomes in patients with LC were included. RESULTS Diabetics are at higher risk for HE, including post-transjugular intrahepatic portosystemic shunt HE. DM also increases the risk of VH and contributes to elevated portal pressure and variceal re-bleeding, while uncontrolled DM is associated with increased risk of bacterial infections. DM also increases the risk of HCC and contributes to adverse LT outcomes. CONCLUSIONS Patients with DM and LC may benefit from close follow-up in order to reduce readmissions and mortality. Due to the heterogeneity of available research, prospective multicenter clinical trials are needed to further validate these findings.
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Willuweit K, Frey A, Hörster A, Saner F, Herzer K. Real-World Administration of Once-Daily MeltDose ® Prolonged-Release Tacrolimus (LCPT) Allows for Dose Reduction of Tacrolimus and Stabilizes Graft Function Following Liver Transplantation. J Clin Med 2020; 10:jcm10010124. [PMID: 33396492 PMCID: PMC7795274 DOI: 10.3390/jcm10010124] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/28/2020] [Accepted: 12/28/2020] [Indexed: 01/16/2023] Open
Abstract
The calcineurin inhibitor tacrolimus is included in most immunosuppressive protocols after liver transplantation. This retrospective, observational 24-month study investigated the tolerability of once-daily MeltDose® prolonged-release tacrolimus (LCPT) after switching from twice-daily immediate-release tacrolimus (IR-Tac) in a real-world cohort of 150 patients with previous liver transplantation. No graft rejection or new safety signals were observed. Only 7.3% of patients discontinued LCPT due to side effects. In the overall patient population, median liver transaminases, total cholesterol, triglycerides, glucose, and HbA1c remained constant after switching to LCPT. Total cholesterol significantly decreased (p ≤ 0.002) in patients with initially elevated levels (>200 mg/dL). A total of 71.8% of 96 patients maintained a glomerular filtration rate > 60 mL/min/1.73 m2 throughout the study, while 44.7% of patients were classified as fast metabolizers and 55.3% as slow metabolizers. Median daily tacrolimus dose could be reduced by 50% in fast metabolizers and by 30% in slow metabolizers, while trough levels were maintained in the target range (4–6 ng/mL). In conclusion, our observational study confirmed previous evidence of good overall tolerability and a favorable outcome for the patients after switching from IR-Tac to LCPT after liver transplantation.
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Affiliation(s)
- Katharina Willuweit
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; (A.F.); (A.H.)
- Correspondence: (K.W.); (K.H.); Tel.: +49-2641-860 (K.H.)
| | - Alexandra Frey
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; (A.F.); (A.H.)
| | - Anne Hörster
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; (A.F.); (A.H.)
| | - Fuat Saner
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany;
| | - Kerstin Herzer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; (A.F.); (A.H.)
- Knappschaftsklinik Bad Neuenahr, Georg-Kreuzberg-Straße 2-6, 53474 Bad Neuenahr, Germany
- Correspondence: (K.W.); (K.H.); Tel.: +49-2641-860 (K.H.)
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Lee Y, Tian C, Lovrics O, Soon MS, Doumouras AG, Anvari M, Hong D. Bariatric surgery before, during, and after liver transplantation: a systematic review and meta-analysis. Surg Obes Relat Dis 2020; 16:1336-1347. [DOI: 10.1016/j.soard.2020.05.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 05/09/2020] [Accepted: 05/13/2020] [Indexed: 12/18/2022]
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Cigrovski Berkovic M, Virovic-Jukic L, Bilic-Curcic I, Mrzljak A. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management. World J Gastroenterol 2020; 26:2740-2757. [PMID: 32550751 PMCID: PMC7284186 DOI: 10.3748/wjg.v26.i21.2740] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/24/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Dubrava, Zagreb 10000, Croatia
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
| | - Lucija Virovic-Jukic
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
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Elbahr O, Saleh AA, Bakery LH. PNPLA3 L148M (rs738409) polymorphism as a risk for new onset diabetes mellitus and obesity in non-NASH/cryptogenic living related donor liver transplant recipients. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100607] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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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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Becchetti C, Dirchwolf M, Banz V, Dufour JF. Medical management of metabolic and cardiovascular complications after liver transplantation. World J Gastroenterol 2020; 26:2138-2154. [PMID: 32476781 PMCID: PMC7235200 DOI: 10.3748/wjg.v26.i18.2138] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/26/2020] [Accepted: 04/28/2020] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation represents the only curative option for patients with end-stage liver disease, fulminant hepatitis and advanced hepatocellular carcinoma. Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period, long-term survival is hampered by the lack of improvement in survival in the late post transplantation period (over 5 years after transplantation). The main etiologies for late mortality are malignancies and cardiovascular complications. The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components (arterial hypertension, dyslipidemia, obesity, renal injury, etc.). These comorbidities result from a combination of pre-liver transplant features, immunosuppressive agent side-effects, changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle. In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation, as well as proposing management strategies.
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Affiliation(s)
- Chiara Becchetti
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
| | - Melisa Dirchwolf
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
- Hepatology, Hepatobiliary Surgery and Liver Transplant Unit, Hospital Privado de Rosario, Rosario S2000GAP, Santa Fe, Argentina
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Clinical Research, University of Bern, Bern CH-3008, Switzerland
| | - Jean-François Dufour
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
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Chandrakumaran A, Siddiqui MS. Implications of Nonalcoholic Steatohepatitis as the Cause of End-Stage Liver Disease Before and After Liver Transplant. Gastroenterol Clin North Am 2020; 49:165-178. [PMID: 32033762 PMCID: PMC7008719 DOI: 10.1016/j.gtc.2019.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Nonalcoholic steatohepatitis (NASH) is the clinically aggressive variant of NAFLD and has a propensity for fibrosis progression and cirrhosis. The prevalence of NAFLD and NASH is projected to increase rapidly in the near future and dramatically add to the already substantial health care burden. Cirrhosis and end-stage liver disease resulting from NASH is now the fastest growing indication for liver transplant (LT) in the United States. Patients with NASH cirrhosis have higher prevalence of cardiometabolic diseases. Following LT, recurrence of NAFLD and NASH is common.
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Affiliation(s)
| | - Mohammad Shadab Siddiqui
- Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA 23298-0341, USA.
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Understanding and managing cardiovascular outcomes in liver transplant recipients. Curr Opin Organ Transplant 2020; 24:148-155. [PMID: 30676402 DOI: 10.1097/mot.0000000000000614] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Cardiovascular disease (CVD) is a common cause of mortality after liver transplantation. The transplant community is focused on improving long-term survival. Understanding the prevalence of CVD in liver transplant recipients, precipitating factors as well as prevention and management strategies is essential to achieving this goal. RECENT FINDINGS CVD is the leading cause of death within the first year after transplant. Arrhythmia and heart failure are the most often cardiovascular morbidities in the first year after transplant which could be related to pretransplant diastolic dysfunction. Pretransplant diastolic dysfunction is reflective of presence of cirrhotic cardiomyopathy which is not as harmless as it was thought. Multiple cardiovascular risk prediction models have become available to aid management in liver transplant recipients. SUMMARY A comprehensive prevention and treatment strategy is critical to minimize cardiovascular morbidity and mortality after liver transplant. Weight management and metabolic syndrome control are cornerstones to any prevention and management strategy. Bariatric surgery is an underutilized tool in liver transplant recipients. Awareness of 'metabolic-friendly' immunosuppressive regimens should be sought. Strict adherence to the cardiology and endocrine society guidelines with regard to managing metabolic derangements post liver transplantation is instrumental for CVD prevention until transplant specific recommendations can be made.
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Samji NS, Heda R, Satapathy SK. Peri-transplant management of nonalcoholic fatty liver disease in liver transplant candidates . Transl Gastroenterol Hepatol 2020; 5:10. [PMID: 32190778 DOI: 10.21037/tgh.2019.09.09] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 09/23/2019] [Indexed: 12/12/2022] Open
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly growing, affecting 25% of the world population. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD and affects 1.5% to 6.5% of the world population. Its rising incidence will make end-stage liver disease (ESLD) due to NASH the number one indication for liver transplantation (LT) in the next 10 to 20 years, overtaking Hepatitis C. Patients with NASH also have a high prevalence of associated comorbidities such as type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, and chronic kidney disease (CKD), which must be adequately managed during the peritransplant period for optimal post-transplant outcomes. The focus of this review article is to provide a comprehensive overview of the unique challenges these patients present in the peritransplant period, which comprises the pre-transplant, intraoperative, and immediate postoperative periods.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, USA
| | - Rajiv Heda
- University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA
| | - Sanjaya K Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
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