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Razzaq R, Nguyen M, Connelly MA, Baral A, Khan H, Garg S, Ang A, Kim A, Roache G, Patidar KR, Yakubu I, Shalaurova I, Bakker SJL, Dullaart RPF, Kumaran V, Bui AT, Patel V, Siddiqui MS. Liver Transplantation and Metabolic Dysfunction Associated Steatotic Liver Disease Is Associated with Markers of Metabolic Risk and Inflammation. Dig Dis Sci 2025:10.1007/s10620-025-09072-1. [PMID: 40274677 DOI: 10.1007/s10620-025-09072-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 04/16/2025] [Indexed: 04/26/2025]
Abstract
BACKGROUND Liver transplant (LT) recipients are at high risk of cardiometabolic disease and mortality. However, routinely employed clinical risk tools have sub-optimal diagnostic performance due to transplant related biological changes. Metabolic vulnerability index (MVX) is a serum-based composite biomarker comprised of nutritional risk [metabolic malnutrition index or MMX] and chronic inflammation [inflammatory vulnerability index or IVX]. MVX is a predictor of cardiovascular risk and all-cause mortality in the general population, however, the effect of LT on MVX is unknown. METHODS To better quantify MVX after transplantation, LT recipients (n = 181) prospectively enrolled in a natural history study were matched with non transplant controls from the MESA study of healthy individuals. All controls were matched 1:1 regarding age and gender. Additionally, lean controls were identified as those with BMI < 25 kg/m2 and BMI-matched controls who were propensity matched for BMI. RESULTS Compared to matched controls, LT recipients had significantly higher MVX (56.9 ± 10.1 vs. 45.8 ± 9.4 vs. 44.8 ± 9.3, p < 0.001), IVX [53.1 ± 12 vs. 39.3 ± 11.2 vs. 40.2 ± 10.9, p < 0.001), and MMX (58.7 ± 8.2 vs. 55.4 ± 6.5 vs. 53.1 ± 6.0, p < 0.001). No significant differences were noted in MVX in LT recipients who developed metabolic dysfunction associated steatotic liver disease (MASLD) after LT. In a multivariate analysis, MVX scores were positively associated with female gender, diabetes, serum AST and BMI, and negatively with dyslipidemia. CONCLUSION LT is associated with a significant increase in MVX and its components, suggesting a heightened risk in LT recipients that is above that of the non-LT population. Future well designed prospective studies are required to calibrate MVX to clinical outcomes in LT patients.
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Affiliation(s)
- Rehan Razzaq
- Department of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA
| | - Madison Nguyen
- Department of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA
| | | | - Alok Baral
- Department of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA
| | - Hiba Khan
- Department of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA
| | - Shreya Garg
- Department of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA
| | - Audrey Ang
- Department of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA
| | - Alexis Kim
- Department of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA
| | - Geneva Roache
- Division of Gastroenterology and Hepatology, VCU, MCV Campus, West Hospital, 1200 E. Broad St, PO Box 980341, Richmond, VA, 23298-0341, USA
| | | | - Idris Yakubu
- Division of Transplant Surgery, VCU, Richmond, VA, USA
| | | | - Stephan J L Bakker
- Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen (UMCG), Groningen, Netherlands
| | - Robin P F Dullaart
- Division of Endocrinology, Department of Internal Medicine, University of Groningen, UMCG, Groningen, Netherlands
| | - Vinay Kumaran
- Division of Transplant Surgery, VCU, Richmond, VA, USA
| | - Anh T Bui
- Department of Statistical Science and Operations Research, VCU, Richmond, USA
| | - Vaishali Patel
- Division of Gastroenterology and Hepatology, VCU, MCV Campus, West Hospital, 1200 E. Broad St, PO Box 980341, Richmond, VA, 23298-0341, USA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology and Hepatology, VCU, MCV Campus, West Hospital, 1200 E. Broad St, PO Box 980341, Richmond, VA, 23298-0341, USA.
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Pagano G, Koshy AN, Chadha R, VanWagner LB, Crespo G. Management of the liver transplant candidate with high cardiac risk: Multidisciplinary best practices and recommendations. Liver Transpl 2024; 30:1304-1315. [PMID: 38727607 DOI: 10.1097/lvt.0000000000000396] [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: 02/10/2024] [Accepted: 05/03/2024] [Indexed: 07/19/2024]
Abstract
In a setting characterized by a growing prevalence of patients with alcohol-associated and metabolic dysfunction-associated steatotic liver diseases, coupled with an aging patient demographic, the incidence of cardiac comorbidities in liver transplant candidates is on the rise. These comorbidities not only pose barriers to transplant eligibility but also impact the intraoperative course and affect posttransplant outcomes. As such, there is a significant need to optimize the clinical management of these cardiac comorbidities. However, there is a scarcity of evidence regarding the best practices for managing cardiac comorbidities such as coronary and valvular heart diseases, arrhythmia, and cardiomyopathy in this population, both before and during transplant surgery. These conditions necessitate a coordinated and multidisciplinary approach to care. In this manuscript, we conduct a comprehensive review of the most recent evidence pertaining to the preoperative and intraoperative management of these cardiac comorbidities in liver transplant candidates. Our aim is to provide recommendations that improve and standardize their clinical care.
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Affiliation(s)
- Giulia Pagano
- Department of Hepatology, Hospital Clínic, Liver Transplant Unit, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Anoop N Koshy
- Department of Cardiology and Victorian Liver Transplant Unit, Austin Health, University of Melbourne, Victoria, Australia
| | - Ryan Chadha
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | - Lisa B VanWagner
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Gonzalo Crespo
- Department of Hepatology, Hospital Clínic, Liver Transplant Unit, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
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3
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Bhati C, Kirkman D, Forsgren MF, Kamal H, Khan H, Boyett S, Leinhard OD, Linge J, Patel V, Patel S, Wolver S, Siddiqui MS. Liver transplant recipients have worse metabolic body phenotype compared with matched non-transplant controls. JGH Open 2024; 8:e70024. [PMID: 39318868 PMCID: PMC11420625 DOI: 10.1002/jgh3.70024] [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: 05/15/2024] [Revised: 07/12/2024] [Accepted: 08/27/2024] [Indexed: 09/26/2024]
Abstract
Background and Aim Quantification of body compartments, particularly the interaction between adipose tissue and skeletal muscle, is emerging as novel a biomarker of metabolic health. The present study evaluated the impact of liver transplant (LT) on body compartments. Methods Totally 66 adult LT recipients were enrolled in whom body compartments including visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), muscle fat infiltration (MFI), fat-free muscle volume (FFMV), and liver fat (LF) were quantified via whole body magnetic resonance imaging (MRI). To provide non-LT comparison, each LT recipient was matched to at least 150 non-LT controls for same sex, age, and body mass index (BMI) from the UK Biobank registry. Results LT recipients (vs matched non-LT controls) had significantly higher subcutaneous (13.82 ± 5.47 vs 12.10 ± 5.10 L, P < 0.001) and visceral fat (7.59 ± 3.75 vs 6.72 ± 3.06 L, P = 0.003) and lower LF (5.88 ± 7.14 vs 8.75 ± 6.50%, P < 0.001) and muscle volume (11.69 ± 2.95 vs 12.12 ± 2.90 L, P = 0.027). In subgroup analysis, patients transplanted for metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis (vs non-MASH cirrhosis) had higher ASAT, VAT, and MFI. A trend toward higher LF content was noted; however, this did not reach statistical significance (6.90 ± 7.35 vs 4.04 ± 6.23%, P = 0.189). Finally, compared with matched non-LT controls, patients transplanted for MASH cirrhosis had higher ASAT and VAT; however, FFMV and MFI were similar. Conclusion Using non-LT controls, the current study established the higher-than-expected adiposity burden among LT recipients, which is even higher among patients transplanted for MASH cirrhosis. These findings provide data needed to design future studies developing radiomics-based risk-stratification strategies in LT recipients.
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Affiliation(s)
- Chandra Bhati
- Division of Transplant Surgery University of Maryland Baltimore Maryland USA
| | - Danielle Kirkman
- Department of Kinesiology and Health Sciences Virginia Commonwealth University (VCU) Richmond Virginia USA
| | - Mikael F Forsgren
- AMRA Medical AB Linköping Sweden
- Center for Medical Image Science and Visualization and Department of Health, Medicine and Caring Sciences Linkoping University Linköping Sweden
| | - Hiba Kamal
- Division of Gastroenterology and Hepatology VCU Richmond Virginia USA
- Virginia Commonwealth University Richmond Virginia USA
| | - Hiba Khan
- Department of Internal Medicine VCU Richmond Virginia USA
| | - Sherry Boyett
- Division of Gastroenterology and Hepatology VCU Richmond Virginia USA
- Virginia Commonwealth University Richmond Virginia USA
| | - Olof Dahlqvist Leinhard
- AMRA Medical AB Linköping Sweden
- Center for Medical Image Science and Visualization and Department of Health, Medicine and Caring Sciences Linkoping University Linköping Sweden
| | | | - Vaishali Patel
- Division of Gastroenterology and Hepatology VCU Richmond Virginia USA
- Department of Internal Medicine VCU Richmond Virginia USA
| | - Samarth Patel
- University of Pennsylvania Philadelphia Pennsylvania USA
| | - Susan Wolver
- Department of Internal Medicine VCU Richmond Virginia USA
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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. [Not Available]. 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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5
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Lim WH, Ng CH, Tan DJH, Xiao J, Fu CE, Ong C, Koh B, Chung C, Tan SN, Wong ZY, Mitchell K, Joseph AA, Tseng M, Syn N, Mak LY, Fung J, Huang DQ, Muthiah M, Tan EXX, Siddiqui MS. Donor Diabetes and Steatosis Affects Recipient Survival Following Liver Transplantation Based on Etiology of Liver Cirrhosis. Transplantation 2024; 108:473-482. [PMID: 37439778 DOI: 10.1097/tp.0000000000004718] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
BACKGROUND Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT. METHODS This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis. RESULTS Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P < 0.001) but not other etiologies of cirrhosis. CONCLUSIONS Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients.
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Affiliation(s)
- Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng Han Ng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Clarissa Elysia Fu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Christen Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Benjamin Koh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Charlotte Chung
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Shi Ni Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Zhen Yu Wong
- School of Medicine, International Medical University, Kuala Lumpur, Malaysia
| | - Kimberly Mitchell
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA
| | | | - Michael Tseng
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Lung Yi Mak
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Eunice X X Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
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6
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Sampaio Rodrigues T, Koshy AN, Gow PJ, Weinberg L, Cailes B, Testro A, Smith G, Lim HS, Teh AW, Lim RP, Farouque O. Atherosclerosis on CT coronary angiography and the risk of long-term cardiovascular events after liver transplantation. Liver Transpl 2024; 30:182-191. [PMID: 37432891 DOI: 10.1097/lvt.0000000000000215] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 06/28/2023] [Indexed: 07/13/2023]
Abstract
Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5-13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2-4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3-6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6-20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24-0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.
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Affiliation(s)
- Thalys Sampaio Rodrigues
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia
| | - Anoop N Koshy
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia
| | - Paul J Gow
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Laurence Weinberg
- Department of Anesthesiology, Austin Health, Melbourne, Victoria, Australia
| | - Benjamin Cailes
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
| | - Adam Testro
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Gerard Smith
- Department of Radiology, Austin Health, Melbourne, Victoria, Australia
| | - Han S Lim
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia
| | - Andrew W Teh
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia
| | - Ruth P Lim
- Department of Radiology, Austin Health, Melbourne, Victoria, Australia
| | - Omar Farouque
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia
- Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia
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7
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Hassouneh R, Flynn S, Shen S, Tseng M, Bui AT, Pham J, Park D, Matherly S, Bruno D, Lee S, Kumaran V, Patel V, Muthiah M, Sharma A, Siddiqui MS. Impact of Liver Transplantation on Adipose Tissue Compartments and Its Association With Metabolic Sequela. Transplantation 2024; 108:235-241. [PMID: 37439776 DOI: 10.1097/tp.0000000000004704] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
BACKGROUND Loss of skeletal muscle can be accompanied by an increase in adipose tissue leading to sarcopenic obesity. There are limited data on how liver transplantation (LT) might impact adipose tissue compartments, particularly among patients with metabolically active disease, such as nonalcoholic steatohepatitis (NASH) and subsequent metabolic sequela. METHODS Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured using cross-sectional imaging performed in 190 patients pre-LT, 6 mo post-LT and 12 mo post-LT. Changes in adipose tissue and their impact on metabolic diseases were determined in patients transplanted for NASH versus non-NASH. RESULTS Skeletal muscle, VAT, and SAT were similar in patients with NASH and non-NASH pre-LT despite a higher burden of metabolic diseases in patients with NASH. Following LT, no significant differences between skeletal muscle and SAT were observed in the entire cohort and among patients with NASH (versus non-NASH). LT recipients with the highest muscle mass pre-LT were at the greatest risk for muscle loss post-LT. A time-dependent increase in VAT was noted post-LT, which was more robust among patients with a history of NASH cirrhosis. In adjusted multivariate analysis, NASH versus non-NASH was a strong predictor of post-LT increase in VAT (β-coefficient 3.00, P = 0.04). Pre-LT VAT was an independent predictor of post-LT serum triglycerides (β-coefficient 5.49 ± 2.78, P = 0.05) and low-density lipoprotein cholesterol (β-coefficient 1.80 ± 0.75, P = 0.02). A trend between pre-LT VAT and diabetes was noted but did not reach statistical significance. CONCLUSIONS VAT but not SAT increases rapidly after LT, especially among patients transplanted for NASH cirrhosis and predicts future metabolic burden.
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Affiliation(s)
- Ramzi Hassouneh
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
- Department of Gastroenterology, Indiana University, Indianapolis, IN
| | - Sean Flynn
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
| | - Steve Shen
- Virginia Commonwealth University School of Medicine, Richmond, VA
| | - Michael Tseng
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
| | - Anh Tuan Bui
- Department of Statistical Sciences and Operations Research, Virginia Commonwealth University, Richmond, VA
| | - Jay Pham
- Department of Radiology, Virginia Commonwealth University, Richmond, VA
| | - Dan Park
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
| | - Scott Matherly
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA
| | - David Bruno
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA
| | - Seung Lee
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA
| | - Vinay Kumaran
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA
| | - Vaishali Patel
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA
| | - Mark Muthiah
- Department of Gastroenterology and Heptology, National University Hospital, Singapore
| | - Amit Sharma
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA
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8
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Siddiqui MS, Muthiah M, Satapathy SK, Patidar KR, Bhat M, Brandman D, Watt KD, Rinella M. Defining an approach for therapeutic strategies in metabolic dysfunction-associated steatotic liver disease after liver transplantation. Hepatology 2023:01515467-990000000-00683. [PMID: 38088872 DOI: 10.1097/hep.0000000000000720] [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: 10/02/2023] [Accepted: 11/24/2023] [Indexed: 03/13/2024]
Abstract
Occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) is common following liver transplantation (LT). MASLD can be classified as a recurrent disease when it occurs in patients receiving LT for metabolic dysfunction-associated steatohepatitis (MASH) or as de novo when it occurs in patients undergoing transplantation for non-metabolic dysfunction-associated steatohepatitis etiologies of liver disease. Fibrosis progression in patients with MASLD is accelerated, with progression to cirrhosis occurring more rapidly compared with the general (ie, non-LT) population. Moreover, the metabolic burden in LT recipients with MASLD is high and synergizes with liver disease to negatively affect the clinical course. Despite the oversized clinical burden of MASLD among LT recipients, there is currently a lack of regulatory approach and pathway for therapeutics development in this patient population. The present document, thus, provides guidance for therapeutics development that incorporates nuances of transplant care in patients with post-LT MASLD to facilitate drug development.
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Affiliation(s)
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Wang L, Zhang Y, Yu H, Song J, Wang Y. Sequential transplantation of the liver-kidney-heart from different donors: a case report. Eur Heart J Case Rep 2023; 7:ytad472. [PMID: 37854104 PMCID: PMC10580372 DOI: 10.1093/ehjcr/ytad472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 08/08/2023] [Accepted: 09/25/2023] [Indexed: 10/20/2023]
Abstract
Background Multi-organ transplantation has emerged as a viable treatment strategy for patients afflicted with multiple organ failure or significant organ dysfunctions. Despite the promising therapeutic outcomes, this approach also amplifies the risk of organ rejection, infection, or neoplastic growth. We present a unique case of a patient who sequentially underwent liver, kidney, and heart transplantation, all sourced from different donors. This case brings forth intriguing possibilities about the interplay between cardiovascular diseases and complications arising post-transplantation, thereby enriching our understanding of comprehensive transplant immunomodulation and cardiovascular disease prevention. Case summary A 59-year-old male with chronic alcohol misuse developed liver cirrhosis in 2012 and subsequent kidney failure in 2018 due to alcoholic liver disease, type II diabetes, hyperlipidaemia, and severe hypertension. Subsequently, an incident of extensive transmural myocardial infarction (Killip III) warranted a heart transplant in 2022. Post-transplant, the patient was maintained on a standard immunosuppression regimen with regular post-operative follow-ups. No signs of rejection were noted 1-year post-final transplantation under standard immunosuppression. Discussion The presented case exemplifies the potential and feasibility of sequential multi-organ transplantation. The multifaceted interplay between the transplanted organs and the immunosuppressive pharmaceuticals likely exert distinct influences on transplantation immune regulation, possibly diverging from the dynamics observed in single-organ transplantation. A comprehensive exploration of the mechanisms governing immune responses in the context of multi-organ transplantation could yield valuable insights for mitigating graft dysfunction. Furthermore, the rapid progression of atherosclerosis observed after liver and kidney transplantation necessitates further scrutiny to elucidate potential correlations with the post-transplantation state.
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Affiliation(s)
- Liaoran Wang
- Department of Organ Transplantation, The Second Affiliated Hospital of Hainan Medical University, 368 Yehai Ave., Haikou, Hainan 570311, China
| | - Yu Zhang
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 North Lishi Road, Xicheng District, Beijing 100037, China
- The Cardiomyopathy Research Group at Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fengcunxili, Yongding Town, Mentougou District, Beijing 102308, China
| | - Hang Yu
- Department of Cardiovascular and Vascular Surgery Intensive Care Unit, The Second Affiliated Hospital of Hainan Medical University, 368 Yehai Ave., Haikou, Hainan 570311, China
| | - Jiangping Song
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 North Lishi Road, Xicheng District, Beijing 100037, China
- The Cardiomyopathy Research Group at Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fengcunxili, Yongding Town, Mentougou District, Beijing 102308, China
| | - Yi Wang
- Department of Organ Transplantation, The Second Affiliated Hospital of Hainan Medical University, 368 Yehai Ave., Haikou, Hainan 570311, China
- The Transplantation Institute of Hainan, 368 Yehai Ave., Haikou, Hainan 570311, China
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Siddiqui MS, Parmar D, Shaikh F, Forsgren M, Patel S, Bui AT, Boyett S, Patel V, Sanyal AJ. Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients. Liver Transpl 2023; 29:979-986. [PMID: 36847136 DOI: 10.1097/lvt.0000000000000110] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 01/23/2023] [Indexed: 03/01/2023]
Abstract
NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor α/γ agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter ≥264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3±10.5% at baseline to 8.1±7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.
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Affiliation(s)
| | | | | | - Mikael Forsgren
- AMRA Medical AB, Centre for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Samarth Patel
- Leigh Valley Health Network, Allentown, Pennsylvania, USA
| | - Anh Tuan Bui
- Department of Statistical Sciences and Operations Research, VCU, Richmond, Virginia, USA
| | - Sherry Boyett
- Division of Gastroenterology, Hepatology and Nutrition, VCU, Richmond, Virginia, USA
| | - Vaishali Patel
- Division of Gastroenterology, Hepatology and Nutrition, VCU, Richmond, Virginia, USA
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, VCU, Richmond, Virginia, USA
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Tseng M, Connelly MA, Vanier D, Arshad T, Kirkman D, Siddiqui MS, Liver Transplant Biomarker Group. Interplay Between Dyslipidemia, Atherogenic Lipoproteins, and Residual Atherogenic Risk in Liver Transplant Recipients. Clin Gastroenterol Hepatol 2023; 21:1660-1662.e1. [PMID: 35533996 PMCID: PMC9637233 DOI: 10.1016/j.cgh.2022.04.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/07/2022] [Accepted: 04/12/2022] [Indexed: 02/07/2023]
Affiliation(s)
- Michael Tseng
- Department of Internal Medicine, Virginia Commonwealth University Health Systems, Richmond, Virginia
| | | | - Dylan Vanier
- Department of Internal Medicine, Virginia Commonwealth University Health Systems, Richmond, Virginia
| | - Tamoore Arshad
- Department of Internal Medicine, Virginia Commonwealth University Health Systems, Richmond, Virginia
| | - Danielle Kirkman
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Section of Hepatology, Virginia Commonwealth University Health Systems, Richmond, Virginia
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12
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Lim WH, Tan C, Xiao J, Tan DJH, Ng CH, Yong JN, Fu C, Chan KE, Zeng RW, Ren YP, Goh XL, Chew N, Tseng M, Syn N, Mak LY, Fung J, Muthiah M, Siddiqui MS, Tan EXX. De novo metabolic syndrome after liver transplantation: a meta-analysis on cumulative incidence, risk factors, and outcomes. Liver Transpl 2023; 29:413-421. [PMID: 36724882 DOI: 10.1097/lvt.0000000000000004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 10/14/2022] [Indexed: 02/03/2023]
Abstract
Post-transplant metabolic syndrome (PTMS) has been associated with increased cardiovascular risk which significantly impacts the morbidity and mortality rates of liver transplant (LT) recipients. This study sought to conduct a meta-analysis and systematic review on the cumulative incidence, risk factors, and cardiovascular outcomes associated with de novo PTMS.Medline and Embase were searched for articles describing the incidence, risk factors, and cardiovascular outcomes of de novo PTMS. Meta-analysis of proportions was conducted to calculate incidence. Conventional pairwise analysis using random effects model was used to tabulate OR and hazard ratio for risk factors and cardiovascular outcomes, respectively. Fifteen studies involving 2683 LT recipients were included. Overall rate of de novo PTMS was 24.7% (CI: 18.0%-32.9%) over a mean follow-up period of 15.3 months and was highest in patients with NAFLD (60.0%, CI: 52.0%-67.5%) compared with other liver diseases. Older age (OR: 1.05, CI: 1.01-1.09, p = 0.02) and pre-LT type II diabetes mellitus (OR: 5.00, CI: 4.17-5.99, p < 0.01) were predictive factors of de novo PTMS. Patients with de novo PTMS had significantly higher likelihood of cardiovascular disease events compared with those who did not (hazard ratio: 2.42, CI: 1.54-3.81, p < 0.01). De novo PTMS is a common complication and is significantly associated with increased cardiovascular disease morbidity. High-risk patients such as elderly recipients, those with pre-LT type II diabetes mellitus, or NASH-related cirrhosis should undergo routine screening to allow timely intervention.
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Affiliation(s)
- Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Caitlyn Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Clarissa Fu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | - Yi Ping Ren
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Xin Lei Goh
- Department of Internal Medicine, Tan Tock Seng Hospital, Singapore
| | - Nicholas Chew
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Michael Tseng
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Biostatistics & Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Lung Yi Mak
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Hospital, Singapore
| | - Mohammad Shadab Siddiqui
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Eunice X X Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Hospital, Singapore
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Cheng XS, VanWagner LB, Costa SP, Axelrod DA, Bangalore S, Norman SP, Herzog C, Lentine KL. Emerging Evidence on Coronary Heart Disease Screening in Kidney and Liver Transplantation Candidates: A Scientific Statement From the American Heart Association: Endorsed by the American Society of Transplantation. Circulation 2022; 146:e299-e324. [PMID: 36252095 PMCID: PMC10124159 DOI: 10.1161/cir.0000000000001104] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Coronary heart disease is an important source of mortality and morbidity among kidney transplantation and liver transplantation candidates and recipients and is driven by traditional and nontraditional risk factors related to end-stage organ disease. In this scientific statement, we review evidence from the past decade related to coronary heart disease screening and management for kidney and liver transplantation candidates. Coronary heart disease screening in asymptomatic kidney and liver transplantation candidates has not been demonstrated to improve outcomes but is common in practice. Risk stratification algorithms based on the presence or absence of clinical risk factors and physical performance have been proposed, but a high proportion of candidates still meet criteria for screening tests. We suggest new approaches to pretransplantation evaluation grounded on the presence or absence of known coronary heart disease and cardiac symptoms and emphasize multidisciplinary engagement, including involvement of a dedicated cardiologist. Noninvasive functional screening methods such as stress echocardiography and myocardial perfusion scintigraphy have limited accuracy, and newer noninvasive modalities, especially cardiac computed tomography-based tests, are promising alternatives. Emerging evidence such as results of the 2020 International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease trial emphasizes the vital importance of guideline-directed medical therapy in managing diagnosed coronary heart disease and further questions the value of revascularization among asymptomatic kidney transplantation candidates. Optimizing strategies to disseminate and implement best practices for medical management in the broader end-stage organ disease population should be prioritized to improve cardiovascular outcomes in these populations.
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Affiliation(s)
| | | | | | | | | | | | - Charles Herzog
- Hennepin Healthcare/University of Minnesota, Minneapolis, MN
| | - Krista L. Lentine
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO
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14
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Eucommia ulmoides Oliver's Multitarget Mechanism for Treatment of Ankylosing Spondylitis: A Study Based on Network Pharmacology and Molecular Docking. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3699146. [PMID: 36267087 PMCID: PMC9578855 DOI: 10.1155/2022/3699146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/06/2022] [Indexed: 11/17/2022]
Abstract
Background Eucommia ulmoides Oliver (EU) is a plant used in Chinese medicine as a medicinal herb to treat autoimmune and inflammatory conditions. We used network pharmacology to examine the active ingredients and estimate the main targets and pathways affected by EU when it is used to treat ankylosing spondylitis (AS). Materials and Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to search for active ingredients in EU and their target proteins. The GeneCards Database was used to find AS-related targets. The targets from the EU and AS searches that coincided were selected by constructing a Venn diagram. Then, a STRING network platform and Cytoscape software were used to analyse the protein-protein interaction (PPI) network and key targets. The strong affinity between EU and its targets was confirmed using molecular docking techniques. The Gene Ontology and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis of overlapping targets was performed using the database for annotation, visualization, and integrated discovery online tool. Results The number of active ingredients against AS in EU was discovered to be 28. Major targets against AS in the PPI network and core targets analyses were identified as IL-1B, PTGS2, IL-8, nMMP-9, CCL2, MYC, and IL-2. Furthermore, molecular docking studies showed the strong affinity between EU's bioactive molecules and their AS targets. Enrichment analysis revealed that active ingredients from EU were involved in a variety of biological processes, including the response to molecules derived from bacteria, extracellular stimuli, nutrient levels, and the regulation of reactive oxygen species, all of which are mediated by interleukin-17, TNF-α, and other signalling pathways. Conclusion The therapy for AS using EU involves a multitarget, multipathway, and multiselection mechanism that includes anti-inflammatory and analgesic effects. This study provides a theoretical basis for future research into targeted molecular therapies for AS.
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Hassouneh R, Patel S, Shen S, Bui A, Syed T, Flynn S, Patel V, Muthiah MD, Sharma A, Bhati C, Siddiqui MS. Glomerular filtration rate early after liver transplantation independently predicts atherosclerotic events. Liver Transpl 2022; 28:1186-1195. [PMID: 35124881 DOI: 10.1002/lt.26425] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 01/10/2022] [Accepted: 01/28/2022] [Indexed: 02/07/2023]
Abstract
Cardiovascular disease (CVD) is an important cause of mortality among liver transplantation (LT) recipients; however, the data on CVD risk stratification following LT are limited. Thus, the primary aim of this study was to evaluate the association between decline in renal function early after LT and atherosclerotic events. This retrospective study included all patients receiving LT between 2007 and 2019. Early renal function was quantified as estimated glomerular filtration rate (GFR) 6 months after LT. The primary endpoint for the study was a composite atherosclerotic cardiovascular event of three-point major adverse cardiovascular events (MACEs), which includes nonfatal myocardial infarction (MI), nonfatal stroke, or death from CVD. A total of 553 LT recipients met entry criteria. After a median follow-up of 74 months (interquartile range 46-111), 94 (17%) LT recipients died and CVD-associated death occurred in 20 patients. MACE-3 occurred in 66 (12%) patients, with nonfatal MI being the most common event (n = 30). A strong inverse relationship between early GFR and MACE-3 was noted in unadjusted analysis with hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.95-0.98; p = 0.0001) and remained significant even after accounting for age, sex, coronary artery disease, diabetes mellitus, hypertension, calcineurin inhibitor use, and Framingham Risk Score (FRS; HR 0.96, 95% CI 0.95-0.97; p = 0.0001 per unit increase in GFR). Furthermore, an independent interaction between GFR, FRS, and likelihood of developing an MACE-3 was noted. GFR 6 months following LT is a strong predictor of developing atherosclerotic events. This relationship is independent of traditional CVD risk stratification models (e.g. FRS) and thus has the potential to be incorporated into CVD risk assessment after LT but requires further validation.
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Affiliation(s)
- Ramzi Hassouneh
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Samarth Patel
- Division of Gastroenterology, Hunter Holmes McGuire, Richmond, Virginia, USA
| | - Steve Shen
- Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Anh Bui
- Department of Statistical Sciences and Operations Research, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Taseen Syed
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Sean Flynn
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Vaishali Patel
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Mark D Muthiah
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore
| | - Amit Sharma
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Chandra Bhati
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Mohammad Shadab Siddiqui
- Department of Statistical Sciences and Operations Research, Virginia Commonwealth University, Richmond, Virginia, USA
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Is Liver Transplant Curative in Homozygous Familial Hypercholesterolemia? A Review of Nine Global Cases. Adv Ther 2022; 39:3042-3057. [PMID: 35471728 PMCID: PMC9122866 DOI: 10.1007/s12325-022-02131-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/15/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening, inherited condition characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C). Patients are at high risk of atherosclerotic cardiovascular disease, adverse cardiovascular events, and associated early mortality. Liver transplant is sometimes used with curative intent. The objective of the current case series was to evaluate the follow-up of a range of patients who have undergone liver transplant for the treatment of HoFH. METHODS Patients with clinical and/or genetic diagnoses of HoFH were treated according to local practices in four units in Europe and the Middle East. All patients underwent liver transplantation. Baseline and long-term follow-up data were collected, including LDL-C levels, DNA mutations, lipid-lowering medications, and complications due to surgery and immunosuppressive therapy. RESULTS Nine patients were included with up to 22 years' follow-up (mean ± SD 11.7 ± 11.7 years; range 0.5-28 years). Three of the patients died as a result of complications of transplant surgery (mortality rate 33%). Among the surviving six patients, four required continued lipid-lowering therapy (LLT) to maintain LDL-C levels and two patients show signs of increasing LDL-C levels that require management. One case (11%) required two consecutive transplants to achieve a viable graft and is awaiting a third transplant because of graft failure. CONCLUSIONS Liver transplant did not enable attainment of recommended LDL-C targets in most patients with HoFH, and the majority of patients still required post-transplant LLT. Liver transplant was not curative in most of the patients with HoFH followed. Guidelines suggest that transplant is a treatment of last resort if contemporary treatments are not available or possible.
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Koshy AN, Nerlekar N, Gow PJ, Lim R, Smith G, Galea M, Rodriques TS, Lim HS, Teh A, Farouque O. A prospective natural history study of coronary atherosclerosis following liver transplantation. Atherosclerosis 2022; 344:40-48. [DOI: 10.1016/j.atherosclerosis.2022.01.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 01/22/2022] [Accepted: 01/25/2022] [Indexed: 11/24/2022]
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Syed T, Siddiqui MS. Atherogenic Dyslipidemia After Liver Transplantation: Mechanisms and Clinical Implications. Liver Transpl 2021; 27:1326-1333. [PMID: 33837670 DOI: 10.1002/lt.26069] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 03/17/2021] [Accepted: 04/01/2021] [Indexed: 12/21/2022]
Abstract
Cardiovascular disease (CVD), particularly atherosclerosis-associated CVD, is a major cause of long-term mortality after liver transplantation (LT). The liver is central in lipid homeostasis, and changes associated with insulin resistance, weight gain, adipose tissue inflammation, and development of nonalcoholic fatty liver disease (NAFLD) after LT promote atherogenesis. These factors synergistically alter lipid homeostasis, thereby leading to the production of proatherogenic lipoproteins, which contribute to the heighted risk of CVD-associated events observed in LT recipients. Although the exact mechanism promoting this shift of a proatherogenic lipoprotein profile is currently not known, the choice of immunosuppression and preexisting metabolic risk factors (ie, NAFLD) are likely contributors. This shift in proatherogenic lipoprotein subparticles presents clinical challenges as the traditional lipid profile employed in clinical practice may not fully capture this atherogenic risk. This review focuses on lipoprotein metabolism and atherogenesis in LT recipients.
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Affiliation(s)
- Taseen Syed
- Department of Gastroenterology, Nutrition and Transplant Hepatology, Virginia Commonwealth University, Richmond, VA.,Department of Gastroenterology, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA
| | - Mohammad S Siddiqui
- Department of Gastroenterology, Nutrition and Transplant Hepatology, Virginia Commonwealth University, Richmond, VA.,Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA
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The Relationship Between Hypoadiponectinemia and Cardiovascular Events in Liver Transplant Recipients. Transplantation 2020; 103:2323-2328. [PMID: 30946215 DOI: 10.1097/tp.0000000000002714] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND Cardiovascular disease (CVD) is an important cause of morbidity and mortality after liver transplantation (LT). Serum adiponectin levels inversely correlate with CVD-related outcomes, but the relationship between hypoadiponectinemia and CVD after LT is unknown. Thus, the aim of the present study was to prospectively evaluate this relationship in LT recipients (LTR). METHODS LTR were prospectively enrolled (N = 130) between January 1, 2012, and January 1, 2014. Baseline adiponectin levels were drawn at enrollment and patients were followed for CVD events. Hypoadiponectinemia was defined as serum adiponectin <10 µg/mL. The primary endpoint was a composite CVD outcome consisting of myocardial infarction, angina, need for coronary revascularization, stroke, or cardiac death. RESULTS The mean age was 58 ± 11 years and prevalence of obesity, diabetes, and dyslipidemia was 40%, 35%, and 40%, respectively. A total of 20 CVD events were noted, after median follow up of 45 months. Hypoadiponectinemia was significantly associated with future risk of CVD events (hazard ratio, 3.519; 95% confidence interval, 1.180-10.499, P = 0.024). This association was independent of traditional CVD risk factors including age, gender, obesity, hypertension, diabetes, and choice of immunosuppression. CONCLUSIONS Hypoadiponectinemia is a strong independent predictor of future cardiovascular events in LTR, which can be incorporated in clinical practice to assess CVD risk assessment after LT.
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Risk factors for the metabolic syndrome components of hypertension, diabetes mellitus, and dyslipidemia after living donor liver transplantation. HPB (Oxford) 2020; 22:511-520. [PMID: 31561946 DOI: 10.1016/j.hpb.2019.08.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 08/11/2019] [Accepted: 08/12/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Metabolic syndrome (MS) is the most common long-term complication after liver transplantation, and it has been increasing in incidence. The aim of this study was to clarify the risk factors for each MS component -hypertension, diabetes mellitus, and dyslipidemia-after living-donor liver transplantation (LDLT), including characteristics of living-donors. METHODS Data related to clinicopathological parameters including MS components in 461 consecutive patients who underwent LDLT were analyzed retrospectively. RESULTS Prevalence of all MS components (hypertension, diabetes mellitus, and dyslipidemia) increased from 9.3%, 16.5%, and 7.2% before LDLT to 44.9%, 45.3%, and 50.8% after LDLT, respectively. By multivariate logistic regression analysis, the three factors, cyclosporine use (OR 2.086, P = 0.001), recipient age (OR 1.036, P = 0.001), and BMI (OR 1.072, P = 0.026) were independent predictors for post-LDLT hypertension. Next, the three factors, male recipient (OR 2.471, P < 0.001), recipient age (OR 1.039, P = 0.002), and donor BMI (OR 1.124, P = 0.012) were independent for post-LDLT diabetes mellitus. The four factors, cyclosporine use (OR 2.015, P = 0.001), prolonged prednisolone use (OR 1.928, P = 0.002), recipient age (OR 1.019, P = 0.037), and GRWR (OR 0.316, P = 0.037) were independent for post-LDLT dyslipidemia as well. CONCLUSIONS Not only recipient-related factors but also donor-related factors were independently associated with each targeted post-LDLT MS component.
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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: 5] [Impact Index Per Article: 1.0] [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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22
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Siddiqui MB, Siddiqui MS. Reply. Hepatology 2020; 71:401-402. [PMID: 31556129 DOI: 10.1002/hep.30971] [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: 12/07/2022]
Affiliation(s)
- Mohammad Bilal Siddiqui
- Divisions of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
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23
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Cotter TG, Charlton M. Nonalcoholic Steatohepatitis After Liver Transplantation. Liver Transpl 2020; 26:141-159. [PMID: 31610081 DOI: 10.1002/lt.25657] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/07/2019] [Indexed: 02/07/2023]
Abstract
Currently, nonalcoholic steatohepatitis (NASH) is the second leading indication for liver transplantation (LT), behind alcohol-related liver disease. After transplant, both recurrent and de novo nonalcoholic fatty liver disease are common; however, recurrence rates of NASH and advanced fibrosis are low. Identification of high-risk groups and optimizing treatment of metabolic comorbidities both before and after LT is paramount to maintaining a healthy allograft, especially with the additional consequences of longterm immunosuppression. In addition, NASH LT recipients are at an increased risk of cardiovascular events and malignancy, and their condition warrants a tailored approach to management. The optimal approach to NASH LT recipients including metabolic comorbidities management, tailored immunosuppression, the role of bariatric surgery, and nutritional and pharmacotherapy of NASH are discussed in this review. Overall, aggressive management of metabolic syndrome after LT via medical and surgical modalities and a minimalist approach to immunosuppression is advised.
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Affiliation(s)
- Thomas G Cotter
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL
| | - Michael Charlton
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL
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24
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Patel SS, Rodriguez VA, Siddiqui MB, Faridnia M, Lin FP, Chandrakumaran A, Laurenzano J, Clinton J, Kowlgi GN, Kirkman D, Sima AP, Liptrap E, Bhati C, Siddiqui MS. The Impact of Coronary Artery Disease and Statins on Survival After Liver Transplantation. Liver Transpl 2019; 25:1514-1523. [PMID: 31344758 PMCID: PMC6754286 DOI: 10.1002/lt.25613] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 07/03/2019] [Indexed: 12/12/2022]
Abstract
Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n = 495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50 years were evaluated via coronary angiography. The impact of pre-LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new-onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3 ± 9.3 years at the time of LT, and median follow-up was 4.5 years. CAD was noted in 129 (26.1%) patients during the pre-LT evaluation. The presence or severity of pre-LT CAD did not impact post-LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new-onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new-onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5 years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12-0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre-LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre-LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.
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Affiliation(s)
- Samarth S. Patel
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University (VCU)
| | | | - Mohammad B Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University (VCU)
| | | | - Fe-Pi Lin
- School of medicine, Virginia Commonwealth University
| | | | | | | | | | | | | | - Erika Liptrap
- School of medicine, Virginia Commonwealth University
| | - Chandra Bhati
- Division of Transplant Surgery, Department of Surgery, VCU
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University (VCU)
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25
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Siddiqui MB, Arshad T, Patel S, Lee E, Albhaisi S, Sanyal AJ, Stravitz RT, Driscoll C, Sterling RK, Reichman T, Bhati C, Siddiqui MS. Small Dense Low-Density Lipoprotein Cholesterol Predicts Cardiovascular Events in Liver Transplant Recipients. Hepatology 2019; 70:98-107. [PMID: 30672598 PMCID: PMC7018439 DOI: 10.1002/hep.30518] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 01/03/2019] [Indexed: 12/11/2022]
Abstract
Cardiovascular disease (CVD) is an important cause of morbidity and mortality after liver transplantation (LT). Although LT is associated with dyslipidemia, particularly atherogenic lipoprotein subparticles, the impact of these subparticles on CVD-related events is unknown. Therefore, the aim of the current study was to evaluate the impact of small dense (sdLDL-C) low-density lipoprotein (LDL) cholesterol (LDL-C) on CVD events. Prospectively enrolled patients (N = 130) had detailed lipid profile consisting of traditional lipid parameters and sdLDL-C and were followed for CVD events. The primary endpoint was a CVD composite consisting of myocardial infarction (MI), angina, need for coronary revascularization, and cardiac death. Mean age of the cohort was 58 ± 11 years, and the most common etiology of liver disease (LD) was hepatitis C virus (N = 48) and nonalcoholic steatohepatitis (N = 23). A total of 20 CVD events were noted after median follow-up of 45 months. The baseline traditional profile was similar in patients with and without CVD events. A serum LDL-C cutoff of 100 mg/dL was unable to identify individuals at risk of a CVD event (P = 0.86). In contrast, serum concentration of atherogenic sdLDL-C >25 mg/dL was predictive of CVD events with a hazard ratio of 6.376 (95% confidence interval, 2.65, 15.34; P < 0.001). This relationship was independent of diabetes, hypertension, sex, ethnicity, LD, obesity, and statin use. Conclusion: sdLDL-C independently predicted CVD events whereas LDL-C did not. Thus, sdLDL-C may provide a useful clinical tool in risk stratifying and managing patients after LT.
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Affiliation(s)
- Mohammad Bilal Siddiqui
- Divisions of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
| | - Tamoore Arshad
- Department of Medicine and Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA
| | - Samarth Patel
- Divisions of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
| | - Emily Lee
- Divisions of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
| | | | - Arun J. Sanyal
- Divisions of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
| | - R. Todd Stravitz
- Divisions of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
| | - Carolyn Driscoll
- Divisions of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
| | - Richard K. Sterling
- Divisions of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
| | - Trevor Reichman
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA
| | - Chandra Bhati
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA
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Germani G, Laryea M, Rubbia-Brandt L, Egawa H, Burra P, OʼGrady J, Watt KD. Management of Recurrent and De Novo NAFLD/NASH After Liver Transplantation. Transplantation 2019; 103:57-67. [PMID: 30335694 DOI: 10.1097/tp.0000000000002485] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) is a growing indication for liver transplant whether the primary or secondary cause of liver disease, and it is expected to be the leading indication in the years to come. Nonalcoholic steatohepatitis recurs after transplant but the impact of the recurrence on allograft and patient outcomes is unclear. A group of multidisciplinary transplant practice providers convened at the International Liver Transplantation Society NASH consensus conference with the purpose of determining the current knowledge and future directions for understanding the recurrence rates, risk and management of NASH in the transplant allograft. Specific questions relating to posttransplant NASH were proposed and reviewed in detail with recommendations on future actions to fill the knowledge gaps.
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Affiliation(s)
- Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marie Laryea
- University of Rochester Medical Center, Rochester NY
| | | | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - John OʼGrady
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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27
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Linhares LMC, Oliveira CP, Alvares-da-Silva MR, Stefano JT, Barbeiro HV, Barbeiro DF, Terrabuio DRB, Abdala E, Soriano FG, Carrilho FJ, Farias AQ, Siddiqui MS, D'Albuquerque LAC. Evolution of Biomarkers of Atherogenic Risk in Liver Transplantation Recipients. Transplant Proc 2018; 50:3650-3655. [PMID: 30586839 DOI: 10.1016/j.transproceed.2018.04.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 04/12/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.
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Affiliation(s)
- L M C Linhares
- Department of Gastroenterology (LIM-07/LIM-37), University of São Paulo School of Medicine, São Paulo, Brazil
| | - C P Oliveira
- Department of Gastroenterology (LIM-07/LIM-37), University of São Paulo School of Medicine, São Paulo, Brazil.
| | - M R Alvares-da-Silva
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - J T Stefano
- Department of Gastroenterology (LIM-07/LIM-37), University of São Paulo School of Medicine, São Paulo, Brazil
| | - H V Barbeiro
- Division of Emergency Medicine (LIM-51), University of São Paulo School of Medicine, São Paulo, Brazil
| | - D F Barbeiro
- Division of Emergency Medicine (LIM-51), University of São Paulo School of Medicine, São Paulo, Brazil
| | - D R B Terrabuio
- Department of Gastroenterology (LIM-07/LIM-37), University of São Paulo School of Medicine, São Paulo, Brazil
| | - E Abdala
- Department of Gastroenterology (LIM-07/LIM-37), University of São Paulo School of Medicine, São Paulo, Brazil
| | - F G Soriano
- Division of Emergency Medicine (LIM-51), University of São Paulo School of Medicine, São Paulo, Brazil
| | - F J Carrilho
- Department of Gastroenterology (LIM-07/LIM-37), University of São Paulo School of Medicine, São Paulo, Brazil
| | - A Q Farias
- Department of Gastroenterology (LIM-07/LIM-37), University of São Paulo School of Medicine, São Paulo, Brazil
| | - M S Siddiqui
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA
| | - L A C D'Albuquerque
- Department of Gastroenterology (LIM-07/LIM-37), University of São Paulo School of Medicine, São Paulo, Brazil
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Impact of Allograft Steatosis on Cardiovascular Outcomes. CURRENT TRANSPLANTATION REPORTS 2018. [DOI: 10.1007/s40472-018-0205-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Kogiso T, Tokushige K. Key roles of hepatologists in successful liver transplantation. Hepatol Res 2018; 48:608-621. [PMID: 29722107 DOI: 10.1111/hepr.13183] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 04/18/2018] [Accepted: 04/21/2018] [Indexed: 12/14/2022]
Abstract
Liver transplantation (LT) has been carried out for acute liver failure, end-stage liver disease, and congenital metabolic disease in more than 7000 cases in Japan. Liver transplantation has been established as a treatment option, and survival rates have improved. In 2016, a new registration/allocation policy and a new scoring system for deceased donor LT were established. The management of perioperative patients and preoperative therapy for liver failure, nutrition, and preventing infection were upgraded. Moreover, methods for preventing disease recurrence, and treating hepatitis C and B have been developed and are particularly crucial for good outcomes in LT. Treatment of the complications of obesity, lifestyle-related diseases, and malignancy is also required post-LT. Managing patients after LT contributes to better survival and quality of life. The role of hepatologists is becoming broader and more important.
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Affiliation(s)
- Tomomi Kogiso
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Katsutoshi Tokushige
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan
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30
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Van Laecke S, Malfait T, Schepers E, Van Biesen W. Cardiovascular disease after transplantation: an emerging role of the immune system. Transpl Int 2018; 31:689-699. [PMID: 29611220 DOI: 10.1111/tri.13160] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2017] [Revised: 02/12/2018] [Accepted: 03/22/2018] [Indexed: 02/06/2023]
Abstract
Cardiovascular disease (CVD) after transplantation remains a major concern. Little is known about what drives the increased cardiovascular risk in transplant recipients apart from traditional risk factors. The immune system is involved in the pathogenesis of hypertension, atherosclerosis, and coronary artery disease in the general population. Recently, inhibition of interleukin 1 - β by canakinumab versus placebo decreased the incidence of cardiovascular events. Emerging evidence points to a role of adaptive cellular immunity in the development of CVD. Especially, expansion of pro-inflammatory and antiapoptotic cytotoxic CD4+ CD28null T cells is closely associated with incident CVD in various study populations including transplant recipients. The association of cytomegalovirus exposure with increased cardiovascular mortality might be explained by its capacity to upregulate these cytotoxic cells. Also, humoral immunity seems to be relevant for cardiovascular outcome in transplant recipients. Panel-reactive antibodies at baseline and donor-specific antibodies are independently associated with poor cardiovascular outcome after kidney transplantation. Cardiovascular effects of immunosuppressive drugs and statins do not only imply indirect positive or negative effects on traditional cardiovascular risk factors but also intrinsic immunological effects. How immunosuppressive drugs modify atherosclerosis largely remains elusive.
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Affiliation(s)
| | - Thomas Malfait
- Renal Division, Ghent University Hospital, Ghent, Belgium
| | - Eva Schepers
- Renal Division, Ghent University Hospital, Ghent, Belgium
| | - Wim Van Biesen
- Renal Division, Ghent University Hospital, Ghent, Belgium
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31
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Bhanji RA, Watt KD. Fatty allograft and cardiovascular outcomes after liver transplantation. Liver Transpl 2017; 23:S76-S80. [PMID: 28815935 DOI: 10.1002/lt.24843] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 08/07/2017] [Accepted: 08/11/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Rahima A Bhanji
- Division of Gastroenterology and Hepatology, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN
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Long-term Outcomes in Patients Undergoing Liver Transplantation for Nonalcoholic Steatohepatitis-Related Cirrhosis. Transplantation 2017; 101:1867-1874. [PMID: 28296807 DOI: 10.1097/tp.0000000000001709] [Citation(s) in RCA: 114] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Nonalcoholic steatohepatitis (NASH), a clinically aggressive variant of nonalcoholic fatty liver disease (NAFLD), is becoming an increasingly common indication for liver transplantation (LT); however, relatively little is known regarding its clinical course post-LT. The aim of the current study is to describe disease recurrence and clinical course after LT. METHODS All surviving patients transplanted for NASH at the authors' institution had transient elastography (TE) to evaluate hepatic steatosis and fibrosis. The charts of deceased patients were reviewed for liver biopsy to evaluate for disease recurrence. Finally, causes of mortality in these patients were evaluated. RESULTS Of the 103 patients who met criteria, 56 had TE, whereas 34 had a liver biopsy. Steatosis was detected in 49 (87.5%) of the patients who had a TE and were defined to have recurrent NAFLD. Most patients had liver stiffness measurements consistent with no fibrosis (42.9%) or F1-F2 fibrosis (30.4%). Advanced fibrosis was noted in 26.8%, whereas 5.4% had cirrhosis but were clinically compensated. In patients with liver biopsy, 88.2% had recurrent NAFLD, whereas 41.2% had recurrent NASH. Bridging fibrosis was noted in 20.6% of patients but no patients had cirrhosis. Within the cohort, 32 patients died with the leading cause of mortality cancer (25%), infectious complications (25%), and cardiovascular disease (21.9%). Only 9% of deaths were attributable to graft cirrhosis. CONCLUSIONS Recurrent NAFLD is common post-LT occurring in nearly 88% of all patients, whereas nearly a quarter of patients were noted to have advanced fibrosis.
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Abstract
OPINION STATEMENT The long-term survival in liver transplant recipients (LTRs) is currently at an historical high level stemming from improvement in perioperative care, infection control, and immunosuppression medications. However, compared to the general population, LTRs have decreased survival. Metabolic diseases like hypertension, dyslipidemia, type 2 diabetes, and obesity are key determinants of long-term mortality in LTRs. The incidence and prevalence of these metabolic comorbidities is considerably higher in LTRs and likely results from a combination of factors including exposure to chronic immunosuppression, weight gain, and recurrence of chronic liver disease after liver transplantation (LT). Although there is currently little guidance in managing these metabolic conditions post-LT, recommendations are often extrapolated from non-transplant cohorts. In the current review, we explore the relationship between metabolic syndrome and its comorbidities in LTRs.
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Affiliation(s)
- Maaike Kockx
- aANZAC Research Institute bDepartment of Cardiology, Concord Repatriation General Hospital; University of Sydney, Sydney, New South Wales, Australia
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35
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Nemes K, Åberg F, Gylling H, Isoniemi H. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications. World J Hepatol 2016; 8:924-932. [PMID: 27574546 PMCID: PMC4976211 DOI: 10.4254/wjh.v8.i22.924] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 06/07/2016] [Accepted: 07/13/2016] [Indexed: 02/06/2023] Open
Abstract
The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.
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36
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Siddiqui MS, Charlton M. Liver Transplantation for Alcoholic and Nonalcoholic Fatty Liver Disease: Pretransplant Selection and Posttransplant Management. Gastroenterology 2016; 150:1849-62. [PMID: 26971826 DOI: 10.1053/j.gastro.2016.02.077] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 02/12/2016] [Accepted: 02/16/2016] [Indexed: 02/07/2023]
Abstract
Alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease throughout the world. Although they have similar histologic features, a diagnosis of NAFLD requires the absence of significant alcohol use. ALD is seen commonly in patients with a long-standing history of excessive alcohol use, whereas NAFLD is encountered commonly in patients who have developed complications of obesity, such as insulin resistance, hypertension, and dyslipidemia. Lifestyle contributes to the development and progression of both diseases. Although alcohol abstinence can cause regression of ALD, and weight loss can cause regression of NAFLD, many patients with these diseases develop cirrhosis. ALD and NAFLD account for nearly 30% of liver transplants performed in the United States. Patients receiving liver transplants for ALD or NAFLD have similar survival times as patients receiving transplants for other liver disorders. Although ALD and NAFLD recur frequently after liver transplantation, graft loss from disease recurrence after transplantation is uncommon. Cardiovascular disease and de novo malignancy are leading causes of long-term mortality in liver transplant recipients with ALD or NAFLD.
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Affiliation(s)
- M Shadab Siddiqui
- Division of Gastroenterology & Hepatology, Virginia Commonwealth University, Richmond, Virginia
| | - Michael Charlton
- Division of Transplant Hepatology, Intermountain Medical Center, Murry, Utah
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Zimmermann A, Zobeley C, Weber MM, Lang H, Galle PR, Zimmermann T. Changes in lipid and carbohydrate metabolism under mTOR- and calcineurin-based immunosuppressive regimen in adult patients after liver transplantation. Eur J Intern Med 2016; 29:104-9. [PMID: 26775180 DOI: 10.1016/j.ejim.2015.12.022] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Revised: 12/02/2015] [Accepted: 12/28/2015] [Indexed: 12/16/2022]
Abstract
BACKGROUND Cardiovascular disease is a leading cause of long-term mortality after liver transplantation (LT). Life long immunosuppression harbors the risk of metabolic alterations. We aimed to analyze the impact of calcineurin (CNI)-only containing regimen (group A) compared to mTOR-containing regimen (group B) on lipid and carbohydrate metabolism. PATIENTS/METHODS 92 adult patients after LT, University of Mainz (group A-78 patients, group B-14 patients; 65 M/27 F; mean age 59+/-10.2years; mean time from LT 5.8+/-5years). Clinical data, comorbidities, and medication were assessed. Fasting lipid profile including small dense LDLs (sdLDL) and oral glucose tolerance tests were performed. RESULTS Group B had significantly higher levels of total cholesterol (TC), LDL-cholesterol (LDL-C), triglycerides (TG) and sdLDL, with persistence of higher TC, TG, sdLDLs (mg/dl) after exclusion of patients under lipid lowering medication. Concentrations above the upper limits of normal were found: for LDL-C in 9% of group A/35.7% of group B (p=0.016); for TG: in 32.1% of group A/92.9% in group B (p=0.0001). A positive correlation between time since LT (years) and sdLDL (mg/dl) was found in group B (p=0.018). In patients without previously known diabetes, NODAT and impaired glucose tolerance developed in 27.9% of group A/44.4% of group B (n.s.). CONCLUSION Patients under mTOR-containing regimen are at higher risk to develop dyslipidemia with increased atherogenic sdLDLs compared to patients under CNI-only-containing regimen and display more frequently a dysglycemic status, with uncertain relevance for long-term cardiovascular risk. A careful monitoring after LT is needed to identify early metabolic risk and manage this appropriately.
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Affiliation(s)
- Anca Zimmermann
- Dept. of Endocrinology and Metabolic Diseases, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany.
| | - Christina Zobeley
- Dept. of Gastroenterology and Hepatology, Transplant Hepatology, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany
| | - M M Weber
- Dept. of Endocrinology and Metabolic Diseases, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany
| | - H Lang
- Dept. for General, Visceral and Transplantation Surgery, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany
| | - Peter R Galle
- Dept. of Gastroenterology and Hepatology, Transplant Hepatology, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany
| | - Tim Zimmermann
- Dept. of Gastroenterology and Hepatology, Transplant Hepatology, 1st Medical Clinic, University Medical Center, Langenbeckstr. 1, 55131 Mainz, Germany
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Agarwal A, Prasad GVR. Post-transplant dyslipidemia: Mechanisms, diagnosis and management. World J Transplant 2016; 6:125-134. [PMID: 27011910 PMCID: PMC4801788 DOI: 10.5500/wjt.v6.i1.125] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 11/26/2015] [Accepted: 02/17/2016] [Indexed: 02/05/2023] Open
Abstract
Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to consider with post-transplant therapies for dyslipidemia are preserving or improving allograft function, and reducing cardiovascular risk. Although there are other cardiovascular risk factors such as graft dysfunction, hypertension, and diabetes, attention to dyslipidemia is warranted because interventions for dyslipidemia have an impact on reducing cardiac events in clinical trials specific to the transplant population. Dyslipidemia is not synonymous with hyperlipidemia. Numerous mechanisms exist for the occurrence of post-transplant dyslipidemia, including those mediated by immunosuppressive drug therapy. Statin therapy has received the most attention in all solid organ transplant recipient populations, although the effect of proper dietary advice and adjuvant pharmacological and non-pharmacological agents should not be dismissed. At all stages of treatment appropriate monitoring strategies for side effects should be implemented so that the benefits from these therapies can be achieved. Clinicians have a choice when there is a conflict between various transplant society and lipid society guidelines for therapy and targets.
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Idowu MO, Chhatrala R, Siddiqui MB, Driscoll C, Stravitz RT, Sanyal AJ, Bhati C, Sargeant C, Luketic VA, Sterling RK, Contos M, Matherly S, Puri P, Siddiqui MS. De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients. Liver Transpl 2015; 21:1395-402. [PMID: 26228654 DOI: 10.1002/lt.24223] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Revised: 07/05/2015] [Accepted: 07/16/2015] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P < 0.001), sdLDL-C to low-density lipoprotein cholesterol ratio (32.6 ± 11.6 versus 24.6 ± 10.2; P < 0.01), small-dense low-density lipoprotein particle concentration (sdLDL-P; 770 ± 440 versus 486 ± 402 nmol/L; P < 0.01), very low density lipoprotein particle concentration (VLDL-P; 7.90 ± 7.91 versus 3.86 ± 3.18 nmol/L; P < 0.01), and very low density lipoprotein size (VLDL-size; 51.9 ± 6.4 versus 48.7 ± 6.3 nm; P = 0.06). LTRs with hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P < 0.01) but similar fasting glucose and hemoglobin A1c. Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors.
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Affiliation(s)
| | | | - M Bilal Siddiqui
- Department of Internal Medicine, University of Texas Medical School, Houston, TX
| | | | | | | | - Chandra Bhati
- Transplant Surgery, Virginia Commonwealth University, Richmond, VA
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Abstract
Improvements in overall survival early after liver transplantation result in a growing number of patients with the potential for long-term survival. Data available on long-term survival, to date, reflect the situation of patients who received their liver transplant during a very different health-care era. Translating these data into the current medical era of liver transplantation is an important task, as a better understanding of aspects associated with morbidity and mortality is fundamental in improving the long-term outcome of liver transplant recipients. Malignancy screening, optimal treatment of recurrent disease and adequate management of metabolic disease are crucial contributions to advance patient care. In this Review, data specific to the liver transplant recipient will be evaluated and, in the absence of sufficient evidence at this time, recommendations and guidelines for the general population on management of long-term concerns will be assessed for their applicability after liver transplantation. In addition, other preventive strategies relating to pregnancy, contraception and vaccination are reviewed in detail.
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