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1
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Pattanaik S, Monchaud C. Pharmacokinetic Boosting of Calcineurin Inhibitors in Transplantation: Pros, Cons, and Perspectives. Ther Drug Monit 2025; 47:118-140. [PMID: 39774591 DOI: 10.1097/ftd.0000000000001288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 09/27/2024] [Indexed: 01/11/2025]
Abstract
ABSTRACT The concept of pharmacokinetic (PK) boosting of calcineurin inhibitors (CNI) emerged after the FDA approval of cyclosporine-A. Several studies followed, and the proof of concept was well established by the late 1990s. This also continued for the next blockbuster immunosuppressant, tacrolimus. The driver for such research was an endeavor to save costs, as both drugs were expensive due to patent protection. Two CYP inhibitors, ketoconazole and diltiazem, have been extensively studied in this context and continue to be prescribed off-label along with the CNI. It has been observed that using ketoconazole reduces the dose requirement of tacrolimus by about 50% and 30% with diltiazem, which is in conformity with their pharmacological actions. Off-label co-prescription of these drugs with CNI is often encountered in low and middle-income countries. The foremost reason cited is economic. This article collates the evidence from the clinical studies that evaluate the PK-boosting effects of CNI and also reviews the gaps in the current evidence base. The current knowledge prevents the transplant community from making meaningful inferences about the risks and benefits of such strategies. Although the PK-boosting strategy can lead to serious adverse events, emerging evidence suggests that it may be advantageous for individuals with high CNI dose requirements. Hence, PK boosting may be an unmet need in the therapeutics of CNI. Nevertheless, there are several unanswered questions surrounding such use, and therefore, this merits testing in well-designed clinical studies. Moreover, drugs with better safer profiles and a history of successful PK boosting may be considered for evaluation with CNI.
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Affiliation(s)
- Smita Pattanaik
- Clinical Pharmacology Unit, Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Caroline Monchaud
- Service de Pharmacologie, Toxicologie et Pharmacovigilance, CHU Limoges, Limoges, France
- INSERM UMR-1248 Pharmacologie et Transplantation, Université Limoges, Limoges, France; and
- FHU SUPORT, Limoges, France
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2
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Karazeybek E. Determining the Relationship Between Perceived Social Support and Immunosuppressive Medication Adherence After Kidney Transplantation: A Descriptive Correlational Study. J Eval Clin Pract 2025; 31:e70021. [PMID: 39930744 PMCID: PMC11811600 DOI: 10.1111/jep.70021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 11/20/2024] [Accepted: 01/19/2025] [Indexed: 02/14/2025]
Abstract
BACKGROUND What is known about how the level of social support, which is among the factors affecting medication adherence, affects medication adherence is limited. OBJECTIVES This study investigated the relationship between perceived social support and immunosuppressive medication adherence among kidney recipients. DESIGN This study was conducted using a descriptive correlational research method. PARTICIPANTS The study conducted research with 168 kidney transplant recipients who agreed to participate between April and June 2021. Participants completed the Immunosuppressive Medication Adherence Scale (IMAS) and the Multidimensional Scale of Perceived Social Support (MSPSS). MEASUREMENTS AND RESULTS Participants had a mean IMAS and MSPSS score of 50.24 ± 3.71 and 57.21 ± 13.96, respectively. Participants' MSPSS total (r = 0.209, p = 0.006) and 'family' (r = 0.248, p = 0.001) and 'friends' (r = 0.226, p = 0.003) subscale scores were weakly and positively correlated with their IMAS total score. CONCLUSION Understanding the effect of perceived social support on immunosuppressive medication adherence is important for designing future interventions to increase immunosuppressive medication adherence.
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Affiliation(s)
- Ebru Karazeybek
- Surgical Nursing Department, Faculty of NursingAkdeniz UniversityAntalyaTurkey
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3
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Lieber SR, Serper M. Mapping out a Medication Adherence Promotion System (MAPS): Can it reduce graft rejection in pediatric liver transplantation? Liver Transpl 2025; 31:7-9. [PMID: 39226388 DOI: 10.1097/lvt.0000000000000479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 08/23/2024] [Indexed: 09/05/2024]
Affiliation(s)
- Sarah R Lieber
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA
| | - Marina Serper
- Department of Medicine, Division of Gastroenterology & Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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Chen H, Liu S, Yu L, Hou X, Zhao R. Factors and interventions affecting tacrolimus intrapatient variability: A systematic review and meta-analysis. Transplant Rev (Orlando) 2024; 38:100878. [PMID: 39260119 DOI: 10.1016/j.trre.2024.100878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/16/2024] [Accepted: 08/17/2024] [Indexed: 09/13/2024]
Abstract
BACKGROUNDS Tacrolimus is a cornerstone of posttransplantation immunosuppressive regimens. Despite routine monitoring, the efficacy of its trough concentrations in reflecting drug concentration fluctuations is limited. Intrapatient variability (IPV) emerges as a novel monitoring marker for predicting clinical outcomes. However, understanding the factors affecting IPV and assessing interventions to address it remain enigmatic, posing a conundrum in clinical management. OBJECTIVES This systematic review aimed to investigate a spectrum of factors affecting IPV and assess the effect of strategic interventions, thereby charting a course for enhanced clinical stewardship. METHODS We electronically searched of PubMed, Embase, and the Cochrane Library databases for studies investigating factors and interventions affecting IPV up to October 2023. Two reviewers independently screened literature, extracted data, and assessed quality, using RevMan 5.4.1 software for meta-analysis. RESULTS A total of 15 randomized controlled trials (RCTs), 34 cohort studies, and 20 self-controlled studies were included. The results indicated that IPV was significantly higher in cytochrome P450 3A5 (CYP3A5) expressers, nonadherent patients, patients taking proton pump inhibitors or statins, and Black or African American recipients, whereas recipients consuming extended-release formulation exhibited lower IPV. Additionally, the participation of pharmacists had a positive effect on improving IPV. CONCLUSIONS Factors affecting IPV encompassed genotype, formulation, adherence, drug combinations, and ethnicity, with each factor exerting varying degrees of effect. Identifying these factors was crucial for developing targeted intervention strategies. While the participation of pharmacists held a promise in improving IPV, further investigation of interventions such as mobile technology, educational measures to enhance adherence, and personalized dosing regimens was warranted.
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Affiliation(s)
- Hongsheng Chen
- Department of Pharmacy, Peking University Third Hospital, Beijing, China; Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
| | - Shuang Liu
- Department of Pharmacy, Peking University Third Hospital, Beijing, China
| | - Lingling Yu
- Department of Pharmacy, Peking University Third Hospital, Beijing, China; Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Xiaofei Hou
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Rongsheng Zhao
- Department of Pharmacy, Peking University Third Hospital, Beijing, China.
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Lattimore S, Chambers A, Angeli-Pahim I, Shrestha A, Eke BO, Pomputius A, Bylund C, Gregory ME, Zarrinpar A. Impact of Intrapatient Immunosuppression Variability in Liver Transplantation Outcomes: A Systematic Review and Meta-analysis. Transplant Direct 2024; 10:e1700. [PMID: 39188531 PMCID: PMC11346865 DOI: 10.1097/txd.0000000000001700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/09/2024] [Accepted: 07/11/2024] [Indexed: 08/28/2024] Open
Abstract
Background To investigate the impact of intrapatient variability (IPV) in the levels of immunosuppressant drugs on health outcomes after liver transplantation. Methods A comprehensive systematic review and meta-analysis were conducted, examining literature from MEDLINE/PubMed, Embase, Web of Science, Cochrane Reviews, and Cochrane CENTRAL. Results The analysis focused on acute rejection, graft survival, acute kidney injury, and cancer risk as health outcomes. Of 2901 articles screened, 10 met the inclusion criteria. The results indicate a 19% reduction in the risk of acute rejection in patients with lower IPV (RR = 0.81; 95% confidence interval, 0.66-0.99), although 6 studies found no significant association between high IPV and acute rejection. Contrasting results were observed for graft survival, with 1 study indicating worse outcomes for high IPV, whereas another reported no significant difference. High IPV was consistently associated with acute kidney injury across 3 studies. One study suggested a link between high IPV and hepatocellular carcinoma, although a meta-analysis for these outcomes was not feasible. Conclusions These findings point to a marginal but statistically significant association between high IPV and an increased risk of acute rejection, highlighting the importance of precise management of immunosuppressive drugs in liver transplant recipients to enhance patient outcomes.
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Affiliation(s)
| | | | | | | | - Benjamin O. Eke
- Department of Surgery, University of Florida, Gainesville, FL
| | - Ariel Pomputius
- Health Sciences Library, University of Florida, Gainesville, FL
| | - Carma Bylund
- Department of Health Outcomes and Biomedical Science, University of Florida, Gainesville, FL
| | - Megan E. Gregory
- Department of Health Outcomes and Biomedical Science, University of Florida, Gainesville, FL
| | - Ali Zarrinpar
- Division of Transplantation and Hepatobiliary Surgery, University of Florida, Gainesville, FL
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Gabrielli F, Biagi F, Avossa A, Falcini M, Nascimbeni F, Andreone P, Gitto S. Frailty after Liver Transplantation: A Complex Unexplored Issue. J Clin Med 2024; 13:4537. [PMID: 39124803 PMCID: PMC11313396 DOI: 10.3390/jcm13154537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/30/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024] Open
Abstract
Frailty is a multidimensional syndrome predominantly studied in the elderly, characterized by reduced resistance to stressors due to diminished physiological reserve and resilience. Advances in surgical techniques and immunosuppressive drugs have improved long-term survival rates in solid organ transplant recipients, yet the 10-year survival is satisfying. However, liver transplant recipients have a noteworthy risk of developing frailty status. After liver transplant, frailty can be favored by socioeconomic, cultural, and health-related factors, leading to increased risks of hospitalization, morbidity, and mortality. Various tools for frailty assessment exist, but none are universally validated for post-transplant patients. The integration of socioeconomic and psychological factors into frailty evaluation could improve quality of life and long-term outcomes for transplant recipients. Multidisciplinary approaches, including psychosocial support, are essential for managing frailty and enhancing the overall care of transplanted patients. This narrative review aims to comprehensively address the principal frailty risk factors associated with liver transplantation.
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Affiliation(s)
- Filippo Gabrielli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy; (F.G.)
- Department of Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Filippo Biagi
- Internal Medicine, University Hospital Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Alessandra Avossa
- Internal Medicine, University Hospital Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Margherita Falcini
- Internal Medicine, University Hospital Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Fabio Nascimbeni
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy; (F.G.)
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy; (F.G.)
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Stefano Gitto
- Internal Medicine, University Hospital Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
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Walters S, Yerkovich S, Hopkins PM, Leisfield T, Winks L, Chambers DC, Divithotawela C. Erratic tacrolimus levels at 6 to 12 months post-lung transplant predicts poor outcomes. JHLT OPEN 2024; 3:100043. [PMID: 40145121 PMCID: PMC11935420 DOI: 10.1016/j.jhlto.2023.100043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
Background It has previously been described that erratic tacrolimus blood levels are associated with graft failure in kidney and liver transplantation. Using a small cohort, we previously described that a higher tacrolimus standard deviation (SD) 6 to 12 months after lung transplantation increased the risk of chronic lung allograft dysfunction (CLAD) and death. We aimed to assess this in a larger cohort using the coefficient of variation (CoV) and identify potential risk factors for higher CoV. Methods We retrospectively reviewed 351 lung transplant recipients who received tacrolimus-based immunosuppression therapy. Cox proportional hazard modeling was used to investigate the effects of mean tacrolimus and CoV levels on survival and CLAD. Results Tacrolimus CoV from 6 to 12 months was independently associated with both CLAD (hazard ratio [HR], 19.99; 95% CI, 7.55-52.91; p < 0.001) and death (HR, 14.57; 95% (confidence interval) CI, 6.08-34.90; p < 0.001). Conversely, the mean trough tacrolimus blood concentration between 6 to 12 months was not associated with an increased risk of CLAD (HR, 0.94; 95% CI, 0.84-1.06; p = 0.34) or death (HR, 0.91; 95% CI, 0.82-1.01; p = 0.07). In a multivariable model, erratic tacrolimus levels were associated with antifungal use (β 0.10 95% CI 0.54-1.51, p < 0.001) and younger age (Î2 -0.0015, 95% CI -0.17 to -0.03, p = 0.005 per 5 years). Conclusions Erratic tacrolimus levels at 6 to 12 months post-lung transplant were associated with poor lung transplant outcomes. Future studies are required to determine whether interventions designed to optimize tacrolimus CoV could improve lung transplant outcomes.
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Affiliation(s)
| | - Stephanie Yerkovich
- Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia
| | - Peter M Hopkins
- University of Queensland, Brisbane, Australia
- Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia
| | - Trish Leisfield
- Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia
| | - Lesleigh Winks
- Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia
| | - Daniel C Chambers
- University of Queensland, Brisbane, Australia
- Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia
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Day J, Hames A, Earl M, Simpson A, Joshi D, Pissas E, Samyn M. Self-management skills in a UK sample of young people with chronic liver disease. Pediatr Transplant 2023; 27:e14614. [PMID: 37807641 DOI: 10.1111/petr.14614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 08/26/2023] [Accepted: 09/01/2023] [Indexed: 10/10/2023]
Abstract
BACKGROUND We aimed to assess self-management skills and adherence behaviors in young people post-liver transplant and compare these with those of young people with autoimmune liver disease and other forms of chronic liver disease. METHOD As part of our specialist multidisciplinary clinic, n = 156 young people (aged 16-25 years) completed the Liver Self-Management Questionnaire (an adaptation of the Developmentally Based Skills Checklist for adolescents post-liver transplant and modified for us across liver disease type and within the United Kingdom). Those taking medication (n = 128) also completed a service-designed questionnaire regarding adherence. The statistical significance of group differences was assessed with non-parametric analyses. RESULTS Young people post-liver transplant were less likely to report managing their condition independently than those with autoimmune liver disease or those with other forms of chronic liver disease. They also reported higher adherence (93%) compared to those with autoimmune liver disease (77%) and those with other forms of chronic liver disease (85%). However, the vast majority of self-management and adherence behaviors were comparable between young people post-transplant and those with autoimmune liver disease/other forms of chronic liver disease. CONCLUSION Our data are in line with existing data from US samples and also extend these findings to include those with other forms of chronic liver disease. These data highlight the importance of individualized care for young adults, regardless of condition type or healthcare setting, and of clinicians managing their expectations regarding what is considered appropriate condition management in early adulthood.
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Affiliation(s)
- Jemma Day
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Anna Hames
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Megan Earl
- Paediatric Liver, Gastroenterology & Nutrition Centre, King's College Hospital, London, UK
| | - Anna Simpson
- Institute of Psychiatry, Psychology & Neuroscience, King's College Hospital, London, UK
| | - Deepak Joshi
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Eleanna Pissas
- Paediatric Liver, Gastroenterology & Nutrition Centre, King's College Hospital, London, UK
| | - Marianne Samyn
- Paediatric Liver, Gastroenterology & Nutrition Centre, King's College Hospital, London, UK
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9
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Jibai N, Koch A, Ulmer TF, Erdmann P, Koeck JA, Eisert A. Pharmaceutical Interventions for Inpatients with Liver Cirrhosis and Liver Transplantation: A Systematic Review of Experimental Studies. J Clin Med 2023; 12:7030. [PMID: 38002644 PMCID: PMC10671912 DOI: 10.3390/jcm12227030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 10/29/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
Liver cirrhosis, which is considered one of the leading causes of death in the world, can lead to severe complications, and is often followed by a liver transplantation. These patients take an average of nine medications daily. If not managed adequately, it can be accompanied by serious drug-related problems. To reduce this risk, a clinical pharmacist may be included as part of the healthcare team to optimize medication therapy in this population. This study aimed to systematically identify the pharmaceutical interventions which reduced drug-related problems and improved medication therapy for adult hospitalized liver cirrhotic and liver transplant patients when compared to standard care. Three databases (PubMed, Embase, and CENTRAL) were systematically searched from the inception of each database to 25 October 2023, and interventional studies in the English language were included. The risk of bias was assessed according to RoB-I for the UBA study and RoB2 for the identified RCT. The detected interventions to reduce drug-related problems in liver cirrhotic and liver transplant patients were extracted and classified according to a "Hierarchy of Controls" model. Two studies from Germany and the USA met our inclusion criteria, respectively. In these studies, we identified two interventions that included education, expert consultation, and the monitoring of the immunosuppressive medications serum level. The main objective of the two included studies was improving patients' compliance through adherence. These pharmaceutical interventions identified were classified as administrative controls, which is one of the lowest levels in the "Hierarchy of Controls" with which to address a potential risk. Pharmaceutical interventions to optimize medication therapy were found to be rare in the examined population, and were limited to "administrative controls". These interventions were limited to transplant patients' education and the monitoring of the immunosuppressive medication serum levels. No interventional studies were found to have investigated pharmaceutical interventions in patients with liver cirrhosis. Especially regarding this patient group, future studies to reduce DRPs using pharmaceutical interventions are needed. This study received no external funding and its PROSPERO registration number is CRD42022309122.
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Affiliation(s)
- Nagham Jibai
- Hospital Pharmacy, RWTH Aachen University Hospital, 52074 Aachen, Germany; (N.J.); (P.E.)
| | - Alexander Koch
- Department of Internal Medicine III, RWTH Aachen University Hospital, 52074 Aachen, Germany;
| | - Tom Florian Ulmer
- Department of General, Visceral and Transplantation Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany;
| | - Pia Erdmann
- Hospital Pharmacy, RWTH Aachen University Hospital, 52074 Aachen, Germany; (N.J.); (P.E.)
| | | | - Albrecht Eisert
- Hospital Pharmacy, RWTH Aachen University Hospital, 52074 Aachen, Germany; (N.J.); (P.E.)
- Institute of Clinical Pharmacology, RWTH Aachen University Hospital, 52074 Aachen, Germany
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10
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Serper M, Burdzy A, Schaubel DE, Mason R, Banerjee A, Goldberg DS, Martin EF, Mehta SJ, Russell LB, Cheung AC, Ladner DP, Yoshino Benavente J, Wolf MS. Patient randomised controlled trial of technology enabled strategies to promote treatment adherence in liver transplantation: rationale and design of the TEST trial. BMJ Open 2023; 13:e075172. [PMID: 37723108 PMCID: PMC10510935 DOI: 10.1136/bmjopen-2023-075172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 08/25/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND AND AIMS Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes. METHODS AND ANALYSIS This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated. ETHICS AND DISSEMINATION The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders. TRIAL REGISTRATION NUMBER NCT05260268.
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Affiliation(s)
- Marina Serper
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Alexander Burdzy
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Douglas E Schaubel
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Richard Mason
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Arpita Banerjee
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - David S Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Eric F Martin
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Shivan J Mehta
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Louise B Russell
- Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Amanda C Cheung
- Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Daniela P Ladner
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Julia Yoshino Benavente
- Center for Applied Health Research on Aging, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Michael S Wolf
- Center for Applied Health Research on Aging, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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11
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Morais MC, Soares ME, Costa G, Guerra L, Vaz N, Codes L, Bittencourt PL. Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation. World J Transplant 2023; 13:254-263. [PMID: 37746041 PMCID: PMC10514747 DOI: 10.5500/wjt.v13.i5.254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/31/2023] [Accepted: 08/11/2023] [Indexed: 09/15/2023] Open
Abstract
Tacrolimus (Tac) is currently the most common calcineurin-inhibitor employed in solid organ transplantation. High intra-patient variability (IPV) of Tac (Tac IPV) has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation. Few data are available concerning the impact of high Tac IPV in non-kidney transplants. However, even in kidney transplantation, there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival. This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature. Little is also known about the influence of high Tac IPV in the development of other untoward adverse events, update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney, liver, heart, lung, and pancreas tran splantation to better evaluate its use in clinical practice.
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Affiliation(s)
- Maria Clara Morais
- School of Medicine, Bahiana School of Medicine and Public Health, Salvador 40290-000, Bahia, Brazil
| | - Maria Eduarda Soares
- School of Medicine, Federal University of Bahia, Salvador 40110-100, Bahia, Brazil
| | - Gabriela Costa
- School of Medicine, Bahiana School of Medicine and Public Health, Salvador 40290-000, Bahia, Brazil
| | - Laura Guerra
- School of Medicine, Bahiana School of Medicine and Public Health, Salvador 40290-000, Bahia, Brazil
| | - Nayana Vaz
- School of Medicine, Bahiana School of Medicine and Public Health, Salvador 40290-000, Bahia, Brazil
- Unit of Gastroenterology and Hepatology, Portuguese Hospital, Salvador 40130-030, Bahia, Brazil
| | - Liana Codes
- School of Medicine, Bahiana School of Medicine and Public Health, Salvador 40290-000, Bahia, Brazil
- Unit of Gastroenterology and Hepatology, Portuguese Hospital, Salvador 40130-030, Bahia, Brazil
| | - Paulo Lisboa Bittencourt
- School of Medicine, Bahiana School of Medicine and Public Health, Salvador 40290-000, Bahia, Brazil
- Unit of Gastroenterology and Hepatology, Portuguese Hospital, Salvador 40130-030, Bahia, Brazil
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12
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Sgrò A, Cambridge WA, McLean KA, Drake TM, Camilleri-Brennan J, Knight SR, Pius R, Wu DA, Wigmore SJ, Harrison EM. Is socioeconomic deprivation associated with worse quality of life, anxiety and depression in liver transplant recipients? A cross-sectional study in a national transplantation programme. BMJ Open 2023; 13:e070422. [PMID: 37558450 PMCID: PMC10414121 DOI: 10.1136/bmjopen-2022-070422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 06/02/2023] [Indexed: 08/11/2023] Open
Abstract
OBJECTIVE To identify whether socioeconomic deprivation is associated with worse health-related quality of life (HR-QoL), anxiety and depression following liver transplantation. DESIGN Cross-sectional study. SETTING AND PARTICIPANTS Liver transplant recipients within a national transplantation programme. METHODS Participants completed the condition-specific 'Short Form of Liver Disease Quality of Life' Questionnaire, the Generalised Anxiety Disorder-7 (GAD-7) Questionnaire and the Patient Health Questionnaire-9 (PHQ-9). The aggregate HR-QoL Score (range 0-100) was derived, and multivariable linear regression was performed based on sociodemographic and clinical variables to estimate its independent association with Scottish Index of Multiple Deprivation (SIMD) quintiles. The GAD-7 Questionnaire and PHQ-9 were used to screen respondents for anxiety and depression, and multivariable logistic regression was performed to estimate their independent association with SIMD quintiles. RESULTS Some 331 patients completed the questionnaires. Quintiles were equally distributed in the cohort, with no significant differences observed in underlying patient characteristics. Following multivariable adjustment, greater socioeconomic deprivation was associated with lower post-transplantation HR-QoL scores, with a difference of 9.7 points (95% CI: 4.6 to 14.9, p<0.001) between the most and least deprived quintiles. Recipients living in areas of least deprivation were less likely to suffer from anxiety (OR 0.05, 95% CI: 0.00 to 0.28, p=0.003) or depression (OR 0.13, 95% CI: 0.02 to 0.56, p=0.009). CONCLUSION Despite the highly selected nature of liver transplant recipients, those living in the most deprived areas have a significantly lower HR-QoL and are more likely to suffer from anxiety and depression.
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Affiliation(s)
- Alessandro Sgrò
- Centre for Medical Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - William A Cambridge
- Centre for Medical Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Kenneth A McLean
- Centre for Medical Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Thomas M Drake
- Centre for Medical Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | | | - Stephen R Knight
- Centre for Medical Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Riinu Pius
- Centre for Medical Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
| | - Diana A Wu
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Stephen J Wigmore
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Ewen M Harrison
- Centre for Medical Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
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13
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Deng LX, Sharma A, Gedallovich SM, Tandon P, Hansen L, Lai JC. Caregiver Burden in Adult Solid Organ Transplantation. Transplantation 2023; 107:1482-1491. [PMID: 36584379 PMCID: PMC10993866 DOI: 10.1097/tp.0000000000004477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The informal caregiver plays a critical role in supporting patients with various end-stage diseases throughout the solid organ transplantation journey. Caregiver responsibilities include assistance with activities of daily living, medication management, implementation of highly specialized treatments, transportation to appointments and treatments, and health care coordination and navigation. The demanding nature of these tasks has profound impacts across multiple domains of the caregiver's life: physical, psychological, financial, logistical, and social. Few interventions targeting caregiver burden have been empirically evaluated, with the majority focused on education or mindfulness-based stress reduction techniques. Further research is urgently needed to develop and evaluate interventions to improve caregiver burden and outcomes for the patient-caregiver dyad.
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Affiliation(s)
- Lisa X. Deng
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Arjun Sharma
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Seren M. Gedallovich
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, CA
| | - Puneeta Tandon
- Division of Gastroenterology, Liver Unit, University of Alberta, Edmonton, AB, Canada
| | - Lissi Hansen
- School of Nursing, Oregon Health and Science University, Portland, OR
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA
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14
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Kaplan A, Korenjak M, Brown RS. Post-liver transplantation patient experience. J Hepatol 2023; 78:1234-1244. [PMID: 37208108 DOI: 10.1016/j.jhep.2023.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 01/02/2023] [Accepted: 01/12/2023] [Indexed: 05/21/2023]
Abstract
Given improvements in post-transplant patient and graft survival, there is a growing need to focus on patient experience and health-related quality of life (HRQOL). Though liver transplantation can be life-saving, it can also be associated with significant morbidity and complications. Patient HRQOL improves after transplantation, but it may not improve to that of age-matched cohorts. Understanding patient experience and the factors that contribute to it, including physical and psychological health, immunosuppression and medication adherence, return to employment or school, financial burden, and expectations, helps when thinking creatively about potential interventions to improve HRQOL.
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Affiliation(s)
- Alyson Kaplan
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell School of Medicine, New York Presbyterian, New York, NY, USA
| | | | - Robert S Brown
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell School of Medicine, New York Presbyterian, New York, NY, USA.
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15
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Ozdemir Koken Z, Sezer Ceren RE, Karahan S, Abbasoglu O. Factors Affecting Immunosuppressive Medication Adherence in Liver Transplant Recipients with Poor Adherence: A Qualitative Study. Patient Prefer Adherence 2023; 17:983-993. [PMID: 37056399 PMCID: PMC10088901 DOI: 10.2147/ppa.s398770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 03/30/2023] [Indexed: 04/15/2023] Open
Abstract
PURPOSE Preserving graft functions and preventing rejection is closely related to immunosuppressive medication adherence in liver transplant recipients. Therefore, it is essential to determine factors affecting immunosuppressive medication use positively or negatively in liver transplant recipients. This study aimed to explore the use of immunosuppressive medication experience in liver transplant recipients with poor adherence and reveal the factors affecting the medication adherence. MATERIAL AND METHODS The study was conducted as a qualitative study with phenomenological approach. Seven adult liver transplant recipients were included in this study, who had poor adherence to immunosuppressive medication. Data was collected via in-depth personal interviews. Data analysis was conducted through inductive content analysis with three steps of preparation, organization, and reporting phases. RESULTS Content analysis revealed four main categories, nine categories and 31 sub-categories. Four main categories emerged from the interview data: medication adherence perception, types of medication non-adherence, factors affecting medication adherence negatively and factors affecting medication adherence positively. CONCLUSION This study explored that there are several factors affecting immunosuppressive medication adherence among liver transplant recipients, both positively and negatively. In order to achieve liver transplant recipients' total adherence to immunosuppressive medication, the factors affecting medication adherence positively and negatively should be understood. The study results are expected to contribute developing strategies to improve immunosuppressive medication adherence in liver transplant recipients.
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Affiliation(s)
- Zeliha Ozdemir Koken
- Surgical Nursing Department, Hacettepe University Faculty of Nursing, Ankara, Turkiye
| | | | - Sabri Karahan
- Surgical Nursing Department, Harran University, Faculty of Health Science, Sanliurfa, Turkiye
| | - Osman Abbasoglu
- General Surgery Department, Hacettepe University Faculty of Medicine, Ankara, Turkiye
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16
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Sakhuja S, Himes R, Carreker C, Guffey D, Beer S, Amin M, Hiremath G, Mysore K. Impact of psychosocial factors on medication level variability index and outcomes in pediatric liver transplant recipients. Pediatr Transplant 2023; 27:e14425. [PMID: 36325588 DOI: 10.1111/petr.14425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 09/20/2022] [Accepted: 10/16/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Caregivers play an important role in maintaining a functioning graft after pediatric liver transplantation. Therefore, the psychosocial factors of both patients and caregivers can have a critical impact on transplant outcomes. Appropriate assessment and recognition of these factors pre-transplantation may allow transplant teams to better define the needs of pediatric organ recipients and develop specific countermeasures, which may then contribute toward improving transplant outcomes. METHODS We studied 136 pediatric LT recipients followed at Texas Children's Hospital. Licensed social workers conducted comprehensive pre-transplant assessments on each patient, consisting of 22 psychosocial variables that were thought to impact adherence, which were reviewed during our study period. Non-adherence was determined using the MLVI for up to 4 years after transplantation. Biopsy-confirmed rejection episodes were assessed in the first 3 years after liver transplantation. RESULTS Factors significantly associated with non-adherence (defined as MLVI >2) included parental age and parental education level at assessment, type of insurance, and household income. The number of ACR episodes trended higher in patients with non-adherence, and these patients had a higher number of moderate to severe rejection episodes but this trend was not statistically significant. CONCLUSIONS Psychosocial characteristics such as parental age, education level, insurance, and household income may contribute significantly to suboptimal adherence to medications after transplantation. Identification of these psychosocial factors and early intervention is essential to the success and equitable care of our pediatric LT recipients.
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Affiliation(s)
- Shruti Sakhuja
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
| | - Ryan Himes
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.,Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Ochsner Health, New Orleans, Louisiana, USA
| | - Colleen Carreker
- Department of Patient and Family Services, Texas Children's Hospital, Houston, Texas, USA
| | - Danielle Guffey
- Institution for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA
| | - Stacey Beer
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
| | - Mansi Amin
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.,Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Duke University, Durham, North Carolina, USA
| | - Girish Hiremath
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.,Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Vanderbilt Children's, Nashville, Tennessee, USA
| | - Krupa Mysore
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
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17
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Song X, Liu F, Gao H, Yan M, Zhang F, Zhao J, Qin Y, Li Y, Zhang Y. Compare the performance of multiple machine learning models in predicting tacrolimus concentration for infant patients with living donor liver transplantation. Pediatr Transplant 2023; 27:e14379. [PMID: 36039686 DOI: 10.1111/petr.14379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 07/20/2022] [Accepted: 08/02/2022] [Indexed: 01/24/2023]
Abstract
BACKGROUND This study aims to establish multiple ML models and compare their performance in predicting tacrolimus concentration for infant patients who received LDLT within 3 months after transplantation. METHODS Retrospectively collected basic information and relevant biochemical indicators of included infant patients. CMIA was used to determine tacrolimus C0 . PCR was used to determine the donors' and recipients' CYP3A5 genotypes. Multivariate stepwise regression analysis and stepwise elimination covariates were used for covariates selection. Thirteen machine learning algorithms were applied for the development of prediction models. APE, the ratio of the APE ≤3 ng ml-1 and ideal rate (the proportion of the predicted value with a relative error of 30% or less) were used to evaluate the predictive performance of the model. RESULTS A total of 163 infant patients were included in this study. In the case of the optimal combination of covariates, the Ridge model had the lowest APE, 2.01 (0.85, 3.35 ng ml-1 ). The highest ratio of the APE ≤3 ng ml-1 was the LAR model (71.77%). And the Ridge model showed the highest ideal rate (55.05%). For the Ridge model, GRWR was the most important predictor. CONCLUSIONS Compared with other ML models, the Ridge model had good predictive performance and potential clinical application.
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Affiliation(s)
- XueWu Song
- First Central Clinical College of Tianjin Medical University, Tianjin, China
| | - FangHao Liu
- College of Computer Science, Tianjin Key Laboratory of Network and Data Security Technology, Nankai University, Tianjin, China
| | - HuiEr Gao
- Department of Pharmacy, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - MeiLing Yan
- Department of Pharmacy, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - FeiYu Zhang
- First Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Jia Zhao
- First Central Clinical College of Tianjin Medical University, Tianjin, China
| | - YinPeng Qin
- Department of Pharmacy, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Yue Li
- College of Computer Science, KLMDASR, Key Laboratory for Medical Data Analysis and Statistical Research, Nankai University, Tianjin, China
| | - Yi Zhang
- Department of Pharmacy, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
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18
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Panchani N, Aryan M, Dabke I, Ousley R, Reif M, Hegazy Y, Wilcox C, Shoreibah M. Marijuana use and post-transplant complications and non-compliance in liver transplant patients. Am J Med Sci 2023; 365:115-120. [PMID: 36202161 DOI: 10.1016/j.amjms.2022.09.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 09/16/2022] [Accepted: 09/29/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND Liver transplant (LT) is a lifesaving treatment for patients with end stage liver disease. Historically, institutions across the United States have deemed active marijuana use as an exclusion criterion for listing. This study aims to investigate LT outcomes in patients with history of marijuana use prior to LT. METHODS We performed a retrospective review of 111 patients who tested positive for marijuana on urine drug screen during initial LT evaluation between February 2016 and January 2021. 100 non-marijuana users who underwent LT were cross matched for control. Patient demographics, substance use history, and transplant decisions were recorded. Post-LT variables were also collected up to 1 year post surgery including postoperative infections, issues with non-compliance, and continued substance use. Chi-square analysis was used to assess the association between pre-transplant marijuana use and post-transplant complications. Logistics regression was implemented to measure associations amongst the entire cohort. RESULTS From 111 marijuana users, 32 (29%) received a transplant. There was no statistical difference in post-LT outcomes between marijuana and non-marijuana users, including incidence of cardiac, respiratory, renal, psychiatric, or neurological complications, as well as readmission rates post-surgery. There were no statistically significant associations between marijuana use with post-transplant bacterial or fungal infections, medication non-compliance, or continued substance use (all p>0.05). Marijuana use was associated with pre-LT tobacco use (p = 0.020). CONCLUSIONS Our data indicates that marijuana is not associated with increased risk of postoperative noncompliance, other organ complications, infections, or death. As a single factor, marijuana may not need to be a contraindication for LT.
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Affiliation(s)
- Nishah Panchani
- Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Mahmoud Aryan
- Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Isha Dabke
- Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Robert Ousley
- Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Meagan Reif
- Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Yassmin Hegazy
- Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Charles Wilcox
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Mohamed Shoreibah
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, United States.
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19
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Improved Medication Adherence with the Use of Extended-Release Tacrolimus in Liver Transplant Recipients: A Pilot Randomized Controlled Trial. J Transplant 2023; 2023:7915781. [PMID: 36642992 PMCID: PMC9833930 DOI: 10.1155/2023/7915781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 12/17/2022] [Accepted: 12/19/2022] [Indexed: 01/06/2023] Open
Abstract
Background Nonadherence to immunosuppression in liver transplant recipients (LTRs) leads to deterioration in health outcomes. Once-dailyextended-release tacrolimus (TAC-ER) may improve adherence when compared to twice-dailyimmediate-release tacrolimus (TAC-IR). Methods We conducted a randomized controlled study to evaluate medication adherence, clinical efficacy, and safety of TAC-ER in stable LTR. All patients >18 years who underwent liver transplantation before 6 months were eligible. Patients were randomized 1 : 1 to continued TAC-IR or conversion to TAC-ER. The primary outcome was change in medication adherence from baseline to 9 months, assessed using BAASIS. Secondary outcomes were tacrolimus trough levels, safety, and quality of life. Results Thirty-one patients were consented and randomized to either of the two groups: conversion to TAC-ER (n = 15) or continued TAC-IR (n = 16). Six patients in the TAC-ER group withdrew after randomization due to apprehension about switching medication (n = 2), unwillingness to travel (n = 2), and increased liver tests after conversion (n = 2, both were acute rejections despite therapeutic tacrolimus levels and were considered unrelated to TAC-ER). We compared the results of nine patients in the TAC-ER group that completed the study with those of sixteen in the TAC-IR group. At baseline, there was no difference in tacrolimus trough levels between groups. Improved adherence was observed in the TAC-ER group as 100% of patients reported at least one period of full adherence during the study period (100% vs. 62.6%, p = 0.035). Tacrolimus trough levels and liver tests were comparable between groups throughout the study. There were no differences in eGFR, HbA1c, or QoL between the groups. Conclusion TAC-ER improved medication adherence while maintaining comparable trough levels, liver function, and QoL as TAC-IR in LTR.
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20
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Toti L, Manzia TM, Blasi F, Lenci I, Baiocchi L, Toschi N, Tisone G. Renal Function, Adherence and Quality of Life Improvement After Conversion From Immediate to Prolonged-Release Tacrolimus in Liver Transplantation: Prospective Ten-Year Follow-Up Study. Transpl Int 2022; 35:10384. [PMID: 36601628 PMCID: PMC9806113 DOI: 10.3389/ti.2022.10384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 11/24/2022] [Indexed: 12/23/2022]
Abstract
Immunosuppression non-adherence is a major cause of graft failure after liver transplantation. The aim of this study was to evaluate practice surrounding conversion from immediate-release to prolonged-release Tacrolimus formulation and to assess patient adherence and quality of life (QoL). One hundred and seven adult liver transplant recipients, receiving immediate-release Tacrolimus for a minimum of 6 months, were converted to prolonged-release formulation, based on a dose ratio of one (1:1). The median follow-up was 120 [IQR, 120-123] months. Tacrolimus dosage and blood level, liver and renal function, lipid and glucose profiles were recorded. In addition, questionnaires were submitted to evaluate adherence and QoL following conversion. No rejection was recorded. The median serum Tacrolimus blood level decreased over 1 month (5.80, [IQR, 2.0-10.8] vs. 3.8 [IQR, 1.4-8.7]; p < 0.0005). Significant improvement in renal function was noted (median GFR was 81.7 [IQR, 43.4-128.6] vs. 73.9 [IQR, 27.1-130.2]; p = 0.0002). At the end of the follow-up, conversion resulted in an overall decrease in non-adherence of 53.3% (p = 0.0001) and an improvement in QoL was reported by 76.2% of patients. Thus, 1:1 conversion from immediate to prolonged-release Tacrolimus is safe, feasible and efficient, avoiding under-therapeutic and toxic peak concentrations, improving renal function, adherence to immunosuppression and overall patient QoL.
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Affiliation(s)
- Luca Toti
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Tommaso Maria Manzia
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Francesca Blasi
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Ilaria Lenci
- Hepatology and Liver Transplant Unit, University of Rome Tor Vergata, Rome, Italy
| | - Leonardo Baiocchi
- Hepatology and Liver Transplant Unit, University of Rome Tor Vergata, Rome, Italy
| | - Nicola Toschi
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Roma, Italy
- Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, MA, United States
| | - Giuseppe Tisone
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
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21
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Cai XJ, Li RD, Li JH, Tao YF, Zhang QB, Shen CH, Zhang XF, Wang ZX, Jiao Z. Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: A comparison of Michaelis-Menten and theory-based pharmacokinetic models. Front Pharmacol 2022; 13:1031969. [DOI: 10.3389/fphar.2022.1031969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 10/17/2022] [Indexed: 11/11/2022] Open
Abstract
Background and Objective: Tacrolimus, a calcineurin inhibitor widely used as a potent immunosuppressant to prevent graft rejection, exhibits nonlinear kinetics in patients with kidney transplantation and nephrotic syndrome. However, whether nonlinear drug metabolism occurs in adult patients undergoing liver transplantation remains unclear, as do the main underlying mechanisms. Therefore, here we aimed to further confirm the characteristics of nonlinearity through a large sample size, and determine the potential influence of nonlinearity and its possible mechanisms.Methods: In total, 906 trough concentrations from 176 adult patients (150 men/26 women; average age: 50.68 ± 9.71 years, average weight: 64.54 ± 11.85 kg after first liver transplantation) were included in this study. Population pharmacokinetic analysis was performed using NONMEM®. Two modeling strategies, theory-based linear compartmental and nonlinear Michaelis–Menten (MM) models, were evaluated and compared. Potential covariates were screened using a stepwise approach. Bootstrap, prediction-, and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine model stability and predictive performance. Finally, Monte Carlo simulations based on the superior model were conducted to design dosing regimens.Results: Postoperative days (POD), Aspartate aminotransferase (AST), daily tacrolimus dose, triazole antifungal agent (TAF) co-therapy, and recipient CYP3A5*3 genotype constituted the main factors in the theory-based compartmental final model, whereas POD, Total serum bilirubin (TBIL), Haematocrit (HCT), TAF co-therapy, and recipient CYP3A5*3 genotype were important in the nonlinear MM model. The theory-based final model exhibited 234 L h−1 apparent plasma clearance and 11,000 L plasma distribution volume. The maximum dose rate (Vmax) of the nonlinear MM model was 6.62 mg day−1; the average concentration at steady state at half-Vmax (Km) was 6.46 ng ml−1. The nonlinear MM final model was superior to the theory-based final model and used to propose dosing regimens based on simulations.Conclusion: Our findings demonstrate that saturated tacrolimus concentration-dependent binding to erythrocytes and the influence of daily tacrolimus dose on metabolism may partly contribute to nonlinearity. Further investigation is needed is need to explore the causes of nonlinear pharmacokinetic of tacrolimus. The nonlinear MM model can provide reliable support for tacrolimus dosing optimization and adjustment in adult patients undergoing liver transplantation.
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22
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Kniepeiss D, Rosenkranz AR, Fickert P, Schemmer P. [Update: Immunosuppression in organ transplantation]. Dtsch Med Wochenschr 2022; 147:1199-1212. [PMID: 36070738 DOI: 10.1055/a-1716-8031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Immunosuppression is an essential prerequisite for successful transplantation. In order to reduce the sometimes-considerable side effects, combination therapies with different agents are used. This article aims to provide an up-to-date overview of immunosuppression after liver and kidney transplantation.
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23
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Lieber SR, Kim HP, Baldelli L, Nash R, Teal R, Magee G, Desai CS, Loiselle MM, Lee SC, Singal AG, Marrero JA, Barritt AS, Evon DM. Early Survivorship After Liver Transplantation: A Qualitative Study Identifying Challenges in Recovery From the Patient and Caregiver Perspective. Liver Transpl 2022; 28:422-436. [PMID: 34529886 PMCID: PMC10548343 DOI: 10.1002/lt.26303] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/06/2021] [Accepted: 09/11/2021] [Indexed: 02/04/2023]
Abstract
Survivorship after liver transplantation (LT) is a novel concept providing a holistic view of the arduous recovery experienced after transplantation. We explored components of early survivorship including physical, emotional, and psychological challenges to identify intervention targets for improving the recovery process of LT recipients and caregivers. A total of 20 in-person interviews were conducted among adults 3 to 6 months after LT. Trained qualitative research experts conducted interviews, coded, and analyzed transcripts to identify relevant themes and representative quotes. Early survivorship comprises overcoming (1) physical challenges, with the most challenging experiences involving mobility, driving, dietary modifications, and medication adherence, and (2) emotional and psychological challenges, including new health concerns, financial worries, body image/identity struggles, social isolation, dependency issues, and concerns about never returning to normal. Etiology of liver disease informed survivorship experiences including some patients with hepatocellular carcinoma expressing decisional regret or uncertainty in light of their post-LT experiences. Important topics were identified that framed LT recovery including setting expectations about waitlist experiences, hospital recovery, and ongoing medication requirements. Early survivorship after LT within the first 6 months involves a wide array of physical, emotional, and psychological challenges. Patients and caregivers identified what they wish they had known prior to LT and strategies for recovery, which can inform targeted LT survivorship interventions.
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Affiliation(s)
- Sarah R. Lieber
- Division of Digestive and Liver Diseases, Department of Medicine, University of Texas Southwestern, Dallas, TX
| | - Hannah P. Kim
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Luke Baldelli
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Rebekah Nash
- Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Randall Teal
- Connected Health Applications and Interventions, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Gabrielle Magee
- Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Chirag S. Desai
- Division of Transplantation, Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Marci M. Loiselle
- Division of Behavioral Medicine, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC
| | - Simon C. Lee
- Department of Population and Data Sciences, University of Texas Southwestern Medical, Dallas, TX
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, Department of Medicine, University of Texas Southwestern, Dallas, TX
| | - Jorge A. Marrero
- Division of Digestive and Liver Diseases, Department of Medicine, University of Texas Southwestern, Dallas, TX
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Donna M. Evon
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
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The Role of Intra-Patient Variability of Tacrolimus Drug Concentrations in Solid Organ Transplantation: A Focus on Liver, Heart, Lung and Pancreas. Pharmaceutics 2022; 14:pharmaceutics14020379. [PMID: 35214111 PMCID: PMC8878862 DOI: 10.3390/pharmaceutics14020379] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/02/2022] [Accepted: 02/05/2022] [Indexed: 11/17/2022] Open
Abstract
Tacrolimus, the keystone immunosuppressive drug administered after solid organ transplantation, presents a narrow therapeutic index and wide inter- and intra-patient pharmacokinetic variability (IPV). The latter has been fairly studied in kidney transplantation, where it could impact outcomes. However, literature about other transplanted organ recipients remains inconclusive. This review aimed at summarizing the evidence about the IPV of tacrolimus concentrations outside of the scope of kidney transplantation. First, factors influencing IPV will be presented. Then, the potential of IPV as a biomarker predictive of graft outcomes will be discussed in liver, heart, lung and pancreas transplantation. Lastly, strategies to reduce IPV will be reviewed, with the ultimate objective being ready-to-implement solutions in clinical practice by transplantation professionals.
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Serper M, Asrani S, VanWagner L, Reese PP, Kim M, Wolf MS. Redefining Success After Liver Transplantation: From Mortality Toward Function and Fulfillment. Liver Transpl 2022; 28:304-313. [PMID: 34608746 PMCID: PMC10236315 DOI: 10.1002/lt.26325] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/31/2021] [Accepted: 09/29/2021] [Indexed: 01/13/2023]
Abstract
Liver transplantation (LT), the only cure for end-stage liver disease, is a lifesaving, costly, and limited resource. LT recipients (LTRs) are aging with an increasing burden of medical comorbidities. Patient and graft survival rates exceed 70% at 5 years; however, patient-centered health outcomes beyond survival have received relatively little attention. LTRs must have strong self-management skills to navigate health systems, adhere to clinical monitoring, and take complex, multidrug regimens. All of these tasks require formidable cognitive abilities for active learning and problem solving. Yet, LTRs are at higher risk for impaired cognition as a result of the high prevalence of pretransplant hepatic encephalopathy, multiple chronic conditions, alcohol use, physical frailty, sarcopenia, and older age. Cognitive impairment after transplant may persist and has been causally linked to poor self-management skills, worse physical function, and inferior health outcomes in other health care settings, yet its impact after LT is largely unknown. There is a need to study potentially modifiable, posttransplant targets including caregiver support, physical activity, sleep, and treatment adherence to inform future health system responses to promote the long-term health and well-being of LTRs. Prospective, longitudinal data collection that encompasses key sociodemographic, cognitive-behavioral, psychosocial, and medical factors is needed to improve risk prediction and better inform patient and caregiver expectations. Interventions with proactive monitoring, reducing medical complexity, and improved care coordination can be tailored to optimize posttransplant care. We propose a research agenda focused on understudied, potentially modifiable risk factors to improve the long-term health of LTRs. Our conceptual model accounts for cognitive function, caregiver and patient self-management skills, health behaviors, and patient-centered outcomes beyond mortality. We propose actionable health-system, patient, and caregiver-directed interventions to fill knowledge gaps and improve outcomes.
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Affiliation(s)
- Marina Serper
- 14640Division of Gastroenterology and HepatologyUniversity of PennsylvaniaPerelman School of MedicinePhiladelphiaPA
- Leonard Davis Institute of Health EconomicsUniversity of PennsylvaniaPhiladelphiaPA
| | | | - Lisa VanWagner
- 3270Division of Gastroenterology & HepatologyDepartment of MedicineNorthwestern University Feinberg School of MedicineChicagoIL
- 3270Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoIL
- 3270Comprehensive Transplant CenterNorthwestern University Feinberg School of MedicineChicagoIL
| | - Peter P Reese
- Leonard Davis Institute of Health EconomicsUniversity of PennsylvaniaPhiladelphiaPA
- Department of Biostatistics, Epidemiology and InformaticsUniversity of PennsylvaniaPhiladelphiaPA
- Division of Renal Electrolyte and HypertensionDepartment of MedicinePerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA
| | - Minjee Kim
- 3270Department of NeurologyNorthwestern University Feinberg School of MedicineChicagoIL
- 3270Center for Circadian and Sleep MedicineNorthwestern University Feinberg School of MedicineChicagoIL
- 3270Northwestern University Transplant Outcomes Research Collaborative, Comprehensive Transplant CenterNorthwestern University Feinberg School of MedicineChicagoIL
| | - Michael S Wolf
- 3270Division of General Internal Medicine & GeriatricsNorthwestern University Feinberg School of MedicineChicagoIL
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Maurer MM, Ibach M, Plewe J, Winter A, Ritschl P, Globke B, Öllinger R, Lurje G, Schöning W, Pratschke J, Eurich D. Reducing the Pill Burden: Immunosuppressant Adherence and Safety after Conversion from a Twice-Daily (IR-Tac) to a Novel Once-Daily (LCP-Tac) Tacrolimus Formulation in 161 Liver Transplant Patients. Biomedicines 2022; 10:biomedicines10020272. [PMID: 35203481 PMCID: PMC8869578 DOI: 10.3390/biomedicines10020272] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 01/02/2022] [Accepted: 01/03/2022] [Indexed: 01/12/2023] Open
Abstract
Non-adherence to immunosuppressant therapy reduces long-term graft and patient survival after solid organ transplantation. The objective of this 24-month prospective study was to determine adherence, efficacy and safety after conversion of stable liver transplant (LT) recipients from a standard twice-daily immediate release Tacrolimus (IR-Tac) to a novel once-daily life cycle pharma Tacrolimus (LCP-Tac) formulation. We converted a total of 161 LT patients at baseline, collecting Tacrolimus trough levels, laboratories, physical examination data and the BAASIS© questionnaire for self-reported adherence to immunosuppression at regular intervals. With 134 participants completing the study period (17% dropouts), the overall adherence to the BAASIS© increased by 57% until month 24 compared to baseline (51% vs. 80%). Patients who required only a morning dose of their concomitant medications reported the largest improvement in adherence after conversion. The intra-patient variability (IPV) of consecutive Tacrolimus trough levels after conversion did not change significantly compared to pre-conversion levels. Despite reducing the daily dose by 30% at baseline as recommended by the manufacturer, Tac-trough levels remained stable, reflected by an increase in the concentration-dose (C/D) ratio. No episodes of graft rejection or loss occurred. Our data suggest that the use of LCP-Tac in liver transplant patients is safe and can increase adherence to immunosuppression compared to conventional IR-Tac.
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Affiliation(s)
- Max M. Maurer
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
- Correspondence: ; Tel.: +49-(0)-30-450-652-418
| | - Marius Ibach
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
| | - Julius Plewe
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
| | - Axel Winter
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
| | - Paul Ritschl
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
- BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), 13353 Berlin, Germany
| | - Brigitta Globke
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
- BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), 13353 Berlin, Germany
| | - Robert Öllinger
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
| | - Georg Lurje
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
| | - Wenzel Schöning
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
| | - Johann Pratschke
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
| | - Dennis Eurich
- Department of Surgery, Experimental Surgery, Campus Charité Mitte, | Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; (M.I.); (J.P.); (A.W.); (P.R.); (B.G.); (R.Ö.); (G.L.); (W.S.); (J.P.); (D.E.)
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Maciel NB, Schwambach KH, Blatt CR. LIVER TRANSPLANTATION: TACROLIMUS BLOOD LEVELS VARIATION AND SURVIVAL, REJECTION AND DEATH OUTCOMES. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:370-376. [PMID: 34705973 DOI: 10.1590/s0004-2803.202100000-62] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 04/12/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Immunosuppressive drugs have important role in transplant of solid grafts, it aim avoid episodes of acute and chronic rejection and improving graft survival and patient survival. In Brazil, in 2016, liver transplantation was the third most frequent, with 1,880 transplants performed, of which 150 in Rio Grande do Sul. Several studies evaluated the association between variability in blood levels of immunosuppressive tacrolimus and late acute cellular graft rejection. OBJECTIVE To investigate the association of tacrolimus blood levels with clinical outcomes late acute cellular rejection, death, patient survival and graft survival in patients undergoing liver transplantation. METHODS This is a retrospective longitudinal study including patients submitted to adult liver transplantation by the Liver Transplantation Group in the Santa Casa de Misericórdia Hospital of Porto Alegre, from January 2006 to January 2013, and who used tacrolimus as immunosuppressive therapy. RESULTS Of the 127 patients included in the study, the majority were male (70.1%), 52-60 years old (33.9%) at the transplant. The most frequent causes of liver transplantation in this series were hepatitis C virus and hepatocellular carcinoma (24.4%) and alcohol (15.7%). Thirteen patients had late acute cellular rejection (10.2%); of these, three had two episodes. Regarding severity classification, seven patients had mild late acute cellular rejection. The mean time of rejection after liver transplantation was 14 months (ranging from 8 to 33 months). Overall survival was 8.98 years. Regarding tacrolimus blood levels, 52 patients with a variation ≥2 standard deviations were identified. Of these patients, eight had rejection; however, the association was not significant (P=0.146). A significant association was found between variation ≥2 standard deviations in tacrolimus blood levels and death (P=0.023) and survival (P=0.019). Regarding 5-year follow-up of graft survival, being two standard deviations above increases by 2.26 times the risk of transplanted graft loss, and for each unit of increase of standard deviation of tacrolimus blood levels there is a two-fold increase in the risk of graft loss in 5 years. CONCLUSION Increased risk of graft loss associated with increased standard deviations of tacrolimus blood levels may indicate the need for more rigorous and prospective monitoring of tacrolimus blood levels.
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Affiliation(s)
- Nicole Bianchin Maciel
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Hepatologia, Porto Alegre, RS, Brasil
| | - Karin Hepp Schwambach
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Hepatologia, Porto Alegre, RS, Brasil
| | - Carine Raquel Blatt
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Hepatologia, Porto Alegre, RS, Brasil
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28
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Shemesh E. Using Medication Level Variability to Predict Posttransplant Risk. Liver Transpl 2021; 27:936-937. [PMID: 33576115 DOI: 10.1002/lt.26012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 01/25/2021] [Indexed: 01/13/2023]
Affiliation(s)
- Eyal Shemesh
- Division of Behavioral and Developmental Health, Department of Pediatrics and Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, NY
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Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl 2021; 27:900-912. [PMID: 33492795 DOI: 10.1002/lt.25996] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 11/30/2020] [Accepted: 01/13/2021] [Indexed: 12/11/2022]
Abstract
Liver transplantation (LT) is a life-saving therapy; therefore, equitable distribution of this scarce resource is of paramount importance. We searched contemporary literature on racial, gender, and socioeconomic disparities across the LT care cascade in referral, waitlist practices, allocation, and post-LT care. We subsequently identified gaps in the literature and future research priorities. Studies found that racial and ethnic minorities (Black and Hispanic patients) have lower rates of LT referral, more advanced liver disease and hepatocellular carcinoma at diagnosis, and are less likely to undergo living donor LT (LDLT). Gender-based disparities were observed in waitlist mortality and LT allocation. Women have lower LT rates after waitlisting, with size mismatch accounting for much of the disparity. Medicaid insurance has been associated with higher rates of chronic liver disease and poor waitlist outcomes. After LT, some studies found lower overall survival among Black compared with White recipients. Studies have also shown lower literacy and limited educational attainment were associated with increased posttransplant complications and lower use of digital technology. However, there are notable gaps in the literature on disparities in LT. Detailed population-based estimates of the advanced liver disease burden and LT referral and evaluation practices, including for LDLT, are lacking. Similarly, little is known about LT disparities worldwide. Evidence-based strategies to improve access to care and reduce disparities have not been comprehensively identified. Prospective registries and alternative "real-world" databases can provide more detailed information on disease burden and clinical practices. Modeling and simulation studies can identify ways to reduce gender disparities attributed to size or inaccurate estimation of renal function. Mixed-methods studies and clinical trials should be conducted to reduce care disparities across the transplant continuum.
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Affiliation(s)
- Lauren D Nephew
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
| | - Marina Serper
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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Holderried M, Hoeper A, Holderried F, Heyne N, Nadalin S, Unger O, Ernst C, Guthoff M. Attitude and potential benefits of modern information and communication technology use and telemedicine in cross-sectoral solid organ transplant care. Sci Rep 2021; 11:9037. [PMID: 33907269 PMCID: PMC8079672 DOI: 10.1038/s41598-021-88447-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 04/06/2021] [Indexed: 12/20/2022] Open
Abstract
Situations like the COVID-19 pandemic urgently require the implementation of eHealth for vulnerable patient populations. Here we quantitatively evaluate use and potential of modern information and communication technology (ICT) in solid organ transplant (SOT) recipients. We conducted a structured, questionnaire-based, cross-sectional study that was addressed to patients after kidney, liver, pancreas, or combined transplantation. We focused on: sociodemographic data, present use of digital technologies in daily life and for health reasons, patients' eHealth literacy, and their overall attitude towards eHealth. A total of 234 patients completed the questionnaire. Most of the patients (90%) have a web-enabled computer, 78.2% have a smartphone, and 71.8% regularly search the internet for health-related information. Sixty-eight percent would like to receive discharge summaries online, and 54% would like to chat online with their physicians. Even though ICT use in daily life was age-related, no significant difference could be shown for health reasons or the type of transplanted organ. Modern ICT use is predominantly accepted for health reasons by SOT recipients. Regardless of the transplanted organ, a deeper integration of eHealth has potential for improving cross-sectoral care. To successfully implement eHealth technologies in cross-sectoral care future research should include online physician-patient communication, data security, data safety, and the aspects of quality and safety of care.
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Affiliation(s)
- Martin Holderried
- eHealth Research-Group, Department of Strategic Medical Development and Quality Management, University of Tuebingen, Hoppe-Seyler-Str. 6, 72076, Tuebingen, Germany
- Institute for Healthcare and Public Management, University of Hohenheim, Hohenheim, Stuttgart, Germany
| | - Ansgar Hoeper
- eHealth Research-Group, Department of Strategic Medical Development and Quality Management, University of Tuebingen, Hoppe-Seyler-Str. 6, 72076, Tuebingen, Germany
| | - Friederike Holderried
- eHealth Research-Group, Department of Strategic Medical Development and Quality Management, University of Tuebingen, Hoppe-Seyler-Str. 6, 72076, Tuebingen, Germany.
| | - Nils Heyne
- Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tuebingen, Tuebingen, Germany
| | - Silvio Nadalin
- Department of General-, Visceral- and Transplant Surgery, University of Tuebingen, Tuebingen, Germany
| | - Oliver Unger
- Faculty of Business Management and Economics, Julius-Maximilians-University, Wuerzburg, Germany
| | - Christian Ernst
- Institute for Healthcare and Public Management, University of Hohenheim, Hohenheim, Stuttgart, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tuebingen, Tuebingen, Germany
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Likhitsup A, Saeed N, Winder GS, Hassan A, Sonnenday CJ, Fontana RJ. Marijuana use among adult liver transplant candidates and recipients. Clin Transplant 2021; 35:e14312. [PMID: 33829569 DOI: 10.1111/ctr.14312] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 03/22/2021] [Accepted: 04/02/2021] [Indexed: 01/25/2023]
Abstract
BACKGROUND Data regarding marijuana (MJ) use among liver transplant (LT) candidates are limited. We set out to determine the incidence and pre- and post-LT outcomes of adult LT candidates with a self-reported history of MJ use. METHODS Baseline clinical characteristics, waitlist, and post-LT outcomes of adult LT candidates from January 2010 to March 2017 were compared. RESULTS Among 2690 LT candidates, 630(23%) and 298(11%) reported a history of MJ use and use within the past 12 months, respectively. Although the proportion of MJ users increased over time(β = .76, p = .03), the proportion listed and transplanted did not change. Listing for LT increased with male (OR 1.24, 95% CI 11.01-1.52), MELD score (OR 1.08, 95% CI 1.01-1.15), HCC (OR 1.83, 95% CI 1.39-2.41) but decreased among MJ users (OR 0.67, 95% CI 0.50-0.91, p = .01). The median time to listing was longer among MJ users compared to non-users (115 vs. 87 days, p < .0005). Post-LT survival was similar in 83 MJ users and 306 non-users. CONCLUSION The proportion of MJ users among LT candidates is increasing. MJ users have a greater burden of psychosocial issues which may contribute to longer evaluations and lower rate of LT listing. Post-LT survival was not impacted by self-reported MJ use history.
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Affiliation(s)
- Alisa Likhitsup
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Naba Saeed
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Gerald Scott Winder
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.,Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Ammar Hassan
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | | | - Robert J Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
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Bzeizi KI, Albenmousa A, Shawkat AM, Ahmed Z, Alabbad S, Al-hamoudi W, Troisi R, Broering D. Efficacy and safety of once daily tacrolimus compared to twice daily tacrolimus after liver transplantation. World J Hepatol 2021; 13:375-383. [PMID: 33815679 PMCID: PMC8006077 DOI: 10.4254/wjh.v13.i3.375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 01/04/2021] [Accepted: 02/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability, safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients. AIM To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients. METHODS MEDLINE, EMBASE, CENTRAL databases were searched for clinical trials until December 2020. Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection, Serum creatinine, graft loss, or death. Two reviewers independently selected studies, collected data and assessed risk of bias. The results are reported as risk ratio with 95% confidence interval (CI) for dichotomous data. RESULTS Seven studies included with 965 patients. All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool. Biopsy-proven acute rejection was reported in four studies, and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups (risk ratio: 1.06, 95%CI: 0.84-1.34, n = 758, I2 = 0%) and also we found no significant difference between both groups for renal outcome (serum creatinine; mean difference, 0.001 mg/dL, 95%CI: -0.042 to 0.043, n = 846, I2 = 18.6%). Similarly, there was similar number of adverse events such as hypertension, headache, back pain, blood related disorders, infections and nausea observed in both groups. CONCLUSION The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.
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Affiliation(s)
- Khalid Ibrahim Bzeizi
- Department of Liver Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia.
| | - Ali Albenmousa
- Department of Liver Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia
| | | | - Zidan Ahmed
- Department of Liver and Small Bowel Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia
| | - Saleh Alabbad
- Department of Liver and Small Bowel Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia
| | - Waleed Al-hamoudi
- Department of Liver and Small Bowel Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia
| | - Roberto Troisi
- Department of Liver and Small Bowel Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia
| | - Deiter Broering
- Organ Transplant Center, King Faisal Specialist Hosp and Res Ctr, Riyadh 11211, Saudi Arabia
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Hammond C, Hussaini T, Yoshida EM. Medical adherence and liver transplantation: a brief review. CANADIAN LIVER JOURNAL 2021; 4:8-15. [PMID: 35991471 PMCID: PMC9203162 DOI: 10.3138/canlivj-2020-0016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 06/16/2020] [Indexed: 11/13/2023]
Abstract
Liver transplantation remains the only feasible long-term treatment option for patients with end-stage liver disease. Despite significant medical and surgical advances over the decades, liver transplantation remains a complex undertaking with the need for indefinite immunosuppression and avoidance of patient behaviours that may jeopardize the allograft. Adherence (formerly called "compliance") to medical recommendations in terms of anti-rejection medications and-in the case of alcoholic liver disease, abstinence-is considered a key cornerstone to long-term allograft and patient survival. Not surprisingly, a history of habitual non-adherence is considered a contraindication to liver transplantation, especially re-transplantation. It is often assumed that non-adherence policies are "self-evidential" based on "common sense" and "expert opinion." In fact, non-adherence and its negative effects have been well studied in medicine, including in solid organ transplantation. In this review, we present the evidence that non-adherence to medical advice is clearly associated with worse medical outcomes, supporting the concept that efforts to support patient adherence post-transplant need to be optimized at all times.
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Affiliation(s)
- Carl Hammond
- Department of Gastroenterology, University Hospital Coventry & Warwickshire, United Kingdom
| | - Trana Hussaini
- Department of Pharmacy, Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, the University of British Columbia, Vancouver, British Columbia, Canada
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Schumacher L, Leino AD, Park JM. Tacrolimus intrapatient variability in solid organ transplantation: A multiorgan perspective. Pharmacotherapy 2020; 41:103-118. [PMID: 33131078 DOI: 10.1002/phar.2480] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/21/2020] [Accepted: 09/26/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Tacrolimus therapy in solid organ transplant (SOT) recipients is challenging due to its narrow therapeutic window and pharmacokinetic variability both between patients and within a single patient. Intrapatient variability (IPV) of tacrolimus trough concentrations has become a novel marker of interest for predicting transplant outcomes. The purpose of this review is to evaluate the association of tacrolimus IPV with graft and patient outcomes and identify interventions to improve IPV in SOT recipients. METHODS A systematic review of the literature was performed using PubMed and Embase from database inception to September 20, 2020. Studies were eligible only if they evaluated an association between tacrolimus IPV and transplant outcomes. Both pediatric and adult studies were included. Measures of variability were limited to standard deviation, coefficient of variation, and time in therapeutic range. RESULTS Forty-four studies met the inclusion criteria. Studies were published between 2008 and 2020 and were observational in nature. Majority of data were published in adult kidney transplant recipients and identified an association with rejection, de novo donor specific antibody (dnDSA) formation, graft loss, and patient survival. Evaluation of IPV-directed interventions was limited to small preliminary studies. CONCLUSIONS High tacrolimus IPV has been associated with poor outcomes including acute rejection, dnDSA formation, graft loss, and patient mortality in SOT recipients. Future research should prospectively explore IPV-directed interventions to improve transplant outcomes.
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Affiliation(s)
| | - Abbie D Leino
- Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA
| | - Jeong M Park
- Department of Pharmacy, Michigan Medicine, Ann Arbor, MI, USA.,Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA
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Jones LS, Serper M. Medication non-adherence among liver transplant recipients. CURRENT HEPATOLOGY REPORTS 2020; 19:327-336. [PMID: 33816051 PMCID: PMC8011544 DOI: 10.1007/s11901-020-00545-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/07/2020] [Indexed: 01/30/2023]
Abstract
PURPOSE OF REVIEW We provide an overview of the recent evidence on the prevalence, risk factors, and consequences of medication non-adherence (NA) in liver transplant (LT) recipients. RECENT FINDINGS NA in LT is associated with socio-demographic and medication-related factors, low social support, and poor health literacy. Patient-reported adherence is one of the most common methods to measure NA using validated assessments; immunosuppression (IS) drug levels and electronic monitoring may also be used. Simplification of IS regimens such as the conversion from twice daily to once daily has been shown to be safe, effective, and improves adherence. Relatively few studies have prospectively investigated NA predictors or interventions to reduce NA in LT. SUMMARY Medication non-adherence is a multi-faceted issue that is common among LT recipients and associated with adverse outcomes. NA in LT recipients warrants further study as only a few interventions have been published focused on reducing NA in LT.
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Affiliation(s)
- Lauren S. Jones
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine
- Philadelphia College of Osteopathic Medicine, Philadelphia, PA
| | - Marina Serper
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine
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Herzer K, Sterneck M, Welker MW, Nadalin S, Kirchner G, Braun F, Malessa C, Herber A, Pratschke J, Weiss KH, Jaeckel E, Tacke F. Current Challenges in the Post-Transplant Care of Liver Transplant Recipients in Germany. J Clin Med 2020; 9:jcm9113570. [PMID: 33167567 PMCID: PMC7694452 DOI: 10.3390/jcm9113570] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 10/25/2020] [Accepted: 11/04/2020] [Indexed: 02/07/2023] Open
Abstract
Improving long-term patient and graft survival after liver transplantation (LT) remains a major challenge. Compared to the early phase after LT, long-term morbidity and mortality of the recipients not only depends on complications immediately related to the graft function, infections, or rejection, but also on medical factors such as de novo malignancies, metabolic disorders (e.g., new-onset diabetes, osteoporosis), psychiatric conditions (e.g., anxiety, depression), renal failure, and cardiovascular diseases. While a comprehensive post-transplant care at the LT center and the connected regional networks may improve outcome, there is currently no generally accepted standard to the post-transplant management of LT recipients in Germany. We therefore described the structure and standards of post-LT care by conducting a survey at 12 German LT centers including transplant hepatologists and surgeons. Aftercare structures and form of cost reimbursement considerably varied between LT centers across Germany. Further discussions and studies are required to define optimal structure and content of post-LT care systems, aiming at improving the long-term outcomes of LT recipients.
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Affiliation(s)
- Kerstin Herzer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany;
- Knappschafts-Klinik Bad Neuenahr, 53474 Bad Neuenahr-Ahrweiler, Germany
| | - Martina Sterneck
- Department of Medicine, University Medical Center Hamburg Eppendorf, 20251 Hamburg, Germany;
| | - Martin-Walter Welker
- Department of Internal Medicine I, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany;
| | - Silvio Nadalin
- Department for General, Visceral and Transplant Surgery, University Hospital Tuebingen, 72016 Tuebingen, Germany;
| | - Gabriele Kirchner
- Department of Surgery, University Hospital of Regensburg, 93053 Regensburg, Germany;
- Innere Medizin I, Caritaskrankenhaus St. Josef, 93053 Regensburg, Germany
| | - Felix Braun
- Department for Transplantation Surgery, University Hospital Kiel, 24105 Kiel, Germany;
| | - Christina Malessa
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, 07747 Jena, Germany;
| | - Adam Herber
- Department of Gastroenterology and Rheumatology, University Hospital Leipzig, 04103 Leipzig, Germany;
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité University Medicine Berlin, 13353 Berlin, Germany;
- Berlin Institute of Health, 13353 Berlin, Germany
| | - Karl Heinz Weiss
- Department of Internal Medicine, University of Heidelberg, 69120 Heidelberg, Germany;
- Department of Internal Medicine, Salem Medical Center, 69120 Heidelberg, Germany
| | - Elmar Jaeckel
- Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, 30625 Hannover, Germany;
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Campus Charité Mitte/Campus Virchow-Klinikum, Charité University Medicine Berlin, 13353 Berlin, Germany
- Correspondence:
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Kniepeiss D, Rosenkranz AR, Fickert P, Schemmer P. Update: Immunsuppression bei Organtransplantationen. TRANSFUSIONSMEDIZIN 2020. [DOI: 10.1055/a-1238-3285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
ZusammenfassungDie Immunsuppression ist eine wesentliche Grundvoraussetzung für eine erfolgreiche Transplantation. Zur Reduktion der teils beträchtlichen Nebenwirkungen werden Kombinationstherapien mit unterschiedlichen Wirkstoffen durchgeführt. Dieser Beitrag soll einen aktuellen Überblick zur Immunsuppression nach Leber- und Nierentransplantation geben.
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38
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Ross LF. Ethical Issues Raised by the Media Portrayal of Adolescent Transplant Refusals. Pediatrics 2020; 146:S33-S41. [PMID: 32737230 DOI: 10.1542/peds.2020-0818h] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/18/2020] [Indexed: 11/24/2022] Open
Abstract
Cases of adolescents in organ failure who refuse solid organ transplant are not common, but several have been discussed in the media in the United States and the United Kingdom. Using the framework developed by Buchanan and Brock for surrogate decision-making, I examine what role the adolescent should morally play when deciding about therapy for life-threatening conditions. I argue that the greater the efficacy of treatment, the less voice the adolescent (and the parent) should have. I then consider how refusals of highly effective transplant cases are similar to and different from refusals of other lifesaving therapies (eg, chemotherapy for leukemia), which is more commonly discussed in the media and medical literature. I examine whether organ scarcity and the need for lifelong immunosuppression justify differences in whether the state intervenes when an adolescent and his or her parents refuse a transplant. I argue that the state, as parens patriae, has an obligation to provide the social supports needed for a successful transplant and follow-up treatment plan, although family refusals may be permissible when the transplant is experimental or of low efficacy because of comorbidities or other factors. I conclude by discussing the need to limit media coverage of pediatric treatment refusals.
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Affiliation(s)
- Lainie Friedman Ross
- Departments of Pediatrics, Medicine, and Surgery, University of Chicago, Chicago, Illinois
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Wadhwani SI, Beck AF, Bucuvalas J, Gottlieb L, Kotagal U, Lai JC. Neighborhood socioeconomic deprivation is associated with worse patient and graft survival following pediatric liver transplantation. Am J Transplant 2020; 20:1597-1605. [PMID: 31958208 PMCID: PMC7261648 DOI: 10.1111/ajt.15786] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 12/10/2019] [Accepted: 01/08/2020] [Indexed: 01/25/2023]
Abstract
Long-term outcomes remain suboptimal following pediatric liver transplantation; only one third of children have normal biochemical liver function without immunosuppressant comorbidities 10 years posttransplant. We examined the association between an index of neighborhood socioeconomic deprivation with graft and patient survival using the Scientific Registry of Transplant Recipients. We included children <19 years who underwent liver transplantation between January 1, 2008 to December 31, 2013 (n = 2868). Primary exposure was a neighborhood socioeconomic deprivation index-linked via patient home ZIP code-with a range of 0-1 (values nearing 1 indicate neighborhoods with greater socioeconomic deprivation). Primary outcome measures were graft failure and death, censored at 10 years posttransplant. We modeled survival using Cox proportional hazards. In univariable analysis, each 0.1 increase in the deprivation index was associated with a 14.3% (95% confidence interval [CI]): 3.8%-25.8%) increased hazard of graft failure and a 12.5% (95% CI: 2.5%-23.6%) increased hazard of death. In multivariable analysis adjusted for race, each 0.1 increase in the deprivation index was associated with a 11.5% (95% CI: 1.6%-23.9%) increased hazard of graft failure and a 9.6% (95% CI: -0.04% to 20.7%) increased hazard of death. Children from high deprivation neighborhoods have diminished graft and patient survival following liver transplantation. Greater attention to neighborhood context may result in improved outcomes for children following liver transplantation.
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Affiliation(s)
| | - Andrew F. Beck
- Cincinnati Children’s Hospital Medical Center, Cincinnati, OH,University of Cincinnati College of Medicine, Cincinnati, OH
| | - John Bucuvalas
- Icahn School of Medicine at Mount Sinai, New York, NY,Mount Sinai Kravis Children’s Hospital, New York, NY
| | - Laura Gottlieb
- University of California San Francisco, San Francisco, CA
| | - Uma Kotagal
- Cincinnati Children’s Hospital Medical Center, Cincinnati, OH,University of Cincinnati College of Medicine, Cincinnati, OH
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40
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Thompson FM, Ferguson JW, Kelly DA, Hirschfield GM. Liver disease in the young adult: the challenges and rewards. Lancet Gastroenterol Hepatol 2020; 4:248-254. [PMID: 30739664 DOI: 10.1016/s2468-1253(18)30244-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 07/18/2018] [Accepted: 07/23/2018] [Indexed: 01/08/2023]
Abstract
Increasing numbers of children are surviving into adulthood with a diagnosis of liver disease or having undergone liver transplantation. This population presents some challenges for the adult hepatologist, and a formal transition service clearly improves outcomes for patients in this group. Evidence of ongoing neurological development in young people up to the age of 25 years exists, and understanding these physiological processes is important in overcoming some of the challenges that caring for this population presents. A well designed transition service is key to maximising potential for these patients, and should enable young people to take control of their illness and achieve their life goals.
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Affiliation(s)
- Fiona M Thompson
- Centre for Rare Diseases, Institute for Translational Medicine, University Hospitals Birmingham, Birmingham, UK.
| | - James W Ferguson
- Centre for Rare Diseases, Institute for Translational Medicine, University Hospitals Birmingham, Birmingham, UK
| | - Deirdre A Kelly
- The Liver Unit, Birmingham Women's and Children's Hospital, Birmingham, UK
| | - Gideon M Hirschfield
- Centre for Rare Diseases, Institute for Translational Medicine, University Hospitals Birmingham, Birmingham, UK; National Institute for Health Research Birmingham Biomedical Research Centre, Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, ON, Canada
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41
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Zarrinpar A, Kim UB, Boominathan V. Phenotypic Response and Personalized Medicine in Liver Cancer and Transplantation: Approaches to Complex Systems. ADVANCED THERAPEUTICS 2020. [DOI: 10.1002/adtp.201900167] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Ali Zarrinpar
- Department of Surgery, College of MedicineUniversity of Florida Gainesville FL 32610 USA
- Department of Biochemistry and Molecular Biology, College of MedicineUniversity of Florida Gainesville FL 32610 USA
- Department of Bioengineering, Herbert Wertheim College of EngineeringUniversity of Florida Gainesville FL 32610 USA
| | - Un Bi Kim
- Department of Surgery, College of MedicineUniversity of Florida Gainesville FL 32610 USA
| | - Vijay Boominathan
- Department of Surgery, College of MedicineUniversity of Florida Gainesville FL 32610 USA
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A Novel, Dose-Adjusted Tacrolimus Trough-Concentration Model for Predicting and Estimating Variance After Kidney Transplantation. Drugs R D 2019; 19:201-212. [PMID: 31073875 PMCID: PMC6544741 DOI: 10.1007/s40268-019-0271-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background and Objective Given that a high intrapatient variability (IPV) of tacrolimus whole blood concentration increases the risk for a poor kidney transplant outcome, some experts advocate routine IPV monitoring for detection of high-risk patients. However, attempts to estimate the variance of tacrolimus trough concentrations (TTC) are limited by the need for patients to receive a fixed dose over time and/or the use of linear statistical models. A goal of this study is to overcome the current limitations through the novel application of statistical methodology generalizing the relationship between TTC and dose through the use of nonparametric functional regression modeling. Methods With TTC as a response and dose as a covariate, the model employs an unknown bivariate function, allowing for the potentially complex, nonlinear relationship between the two parameters. A dose-adjusted variance of TTC is then derived based on standard functional principal component analysis (FPCA). To assess the model, it was compared against an FPCA-based model and linear mixed-effects models using prediction error, bias, and coverage probabilities for simulated data as well as phase III data from the Astellas new drug application studies for extended-release tacrolimus. Results Our numerical investigation indicates that the new model better predicts dose-adjusted TTCs compared with the prediction of linear mixed effects models. Estimated coverage probabilities also indicate that the new model accurately accounts for the variance of TTC during the periods of large fluctuation in dose, whereas the linear mixed effects model consistently underestimates the coverage probabilities because of the inaccurate characterization of TTC fluctuation. Conclusion This is the first known application of a functional regression model to assess complex relationships between TTC and dose in a real clinical setting. This new method has applicability in future clinical trials including real-world data sets due to flexibility of the nonparametric modeling approach. Electronic supplementary material The online version of this article (10.1007/s40268-019-0271-2) contains supplementary material, which is available to authorized users.
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Kwiatkowska E, Kwiatkowski S, Wahler F, Gryczman M, Domańki L, Marchelk-Myśliwiec M, Ciechanowski K, Drozd-Dabrowska M. C/D Ratio in Long-Term Renal Function. Transplant Proc 2019; 51:3265-3270. [PMID: 31732210 DOI: 10.1016/j.transproceed.2019.08.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 07/22/2019] [Accepted: 08/17/2019] [Indexed: 11/24/2022]
Abstract
BACKGROUND/AIMS Tacrolimus is an immunosuppressive drug. Its C0 concentration, commonly used for monitoring, does not always correspond to its pharmacologic effect. Thölking et al developed an indicator, the C/D ratio, that describes the drug's metabolism rate. Our purpose was to determine whether the points dividing the patients into fast, intermediate, and slow metabolizers that were assumed by those authors would be similar for long-term follow-up after renal transplantation (RTx). METHODS We examined the C/D ratio in 571 patients at their most recent appointments-1 year and more after renal transplantation. The mean time after RTx was 84 months. We studied kidney function both at the most recent appointment and early after RTx. RESULTS The median C/D ratio for our group was 1.68. Our observations revealed a negative correlation between the C/D ratio and creatinine concentration and a positive correlation between the C/D ratio and eGFR concentration long term after RTx. We formulated a C/D ratio cutoff point between an eGFR < and ≥ 60 mL/min/1.73 m2 and came up with the value of 1.53. It was found that between the < 1.53 and ≥ 1.53 groups, there were significant differences in creatinine and eGFR concentrations at the most recent appointment, as well as differences in how creatinine and eGFR levels varied over time between RTx and the most recent observation. CONCLUSIONS The C/D ratio is useful for assessing the effect of the tacrolimus metabolism rate on long-term renal function. We propose the C/D ratio value of 1.53 as the cutoff point below which the ratio provides a negative prognosis for long-term renal function.
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Affiliation(s)
- Ewa Kwiatkowska
- Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
| | - Sebastian Kwiatkowski
- Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland
| | - Fabienne Wahler
- Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland
| | - Marta Gryczman
- Department of Nephrology, Independent Public State Integrated Hospital, Szczecin, Poland
| | - Leszek Domańki
- Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland
| | - Małgorzata Marchelk-Myśliwiec
- Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland
| | - Kazimierz Ciechanowski
- Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland
| | - Marzena Drozd-Dabrowska
- Department of Epidemiology and Management, Faculty of Health Sciences, Pomeranian Medical Univeristy, Szczecin, Poland
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Jain M, Venkataraman J, Reddy MS, Rela M. Determinants of Medication Adherence in Liver Transplant Recipients. J Clin Exp Hepatol 2019; 9:676-683. [PMID: 31889747 PMCID: PMC6926177 DOI: 10.1016/j.jceh.2019.03.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 03/07/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of this study was to study the determinants of nonadherence to immunosuppressant drugs in liver transplant (LT) recipients using personalised interview and questionnaire methods. METHODS The study was conducted on adult LT recipients (deceased donor liver transplant [DDLT] and living donor liver transplant [LDLT]) from the Indian subcontinent, at post-LT clinic visit between July and December 2016. Recipient details included baseline demography, comorbidity, psychological status, details of addiction, indication and type of transplant. Details on financial support for transplantation, admissions for rejection, infection and posttransplant complications were obtained from the hospital records. An adherence questionnaire was completed by direct interview and using a questionnaire. RESULTS Sixty-seven LT recipients (56 males, median age 48.17 years) constituted the study group. Overall, 11 patients (16.47%) were nonadherent to treatment. LDLT recipients were more adherent than DDLT recipients. Nonadherent recipients were believers in alternative systems of medicine. Medication-related factors such as improper dosing, meagre drug knowledge difficulty in remembering drug dose and timings and economic constraints in continuing medical treatment were statistically significant in nonadherent recipients. Although variation in the tacrolimus levels were significantly more common in the nonadherent group, acute cellular rejection and infection were not statistically different. CONCLUSIONS The prevalence of nonadherence was 16.5%. Determinants of nonadherence were DDLT, belief in alternative medications, high regimen complexity, poor knowledge about medications and cost issues with long-term medications.
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Affiliation(s)
- Mayank Jain
- Institute of Liver Disease and Transplantation, Gleneagles Global Health City, Chennai 100, India
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Adam R, Karam V, Cailliez V, Trunečka P, Samuel D, Tisone G, Němec P, Soubrane O, Schneeberger S, Gridelli B, Bechstein WO, Risaliti A, Line PD, Vivarelli M, Rossi M, Pirenne J, Klempnauer JL, Rummo A, Di Benedetto F, Zieniewicz K, Troisi R, Paul A, Vali T, Kollmar O, Boudjema K, Hoti E, Colledan M, Pratschke J, Lang H, Popescu I, Ericzon BG, Strupas K, De Simone P, Kochs E, Heyd B, Gugenheim J, Pinna AD, Bennet W, Kazimi M, Bachellier P, Wigmore SJ, Rasmussen A, Clavien PA, Hidalgo E, O'Grady JG, Zamboni F, Kilic M, Duvoux C. Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study. Transplantation 2019; 103:1844-1862. [PMID: 31343568 DOI: 10.1097/tp.0000000000002700] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study. METHODS Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T. Overall, 13 088 patients were included from 44 European centers; propensity score-matched analyses comprised 3006 patients (PR-T: n = 1002; IR-T: n = 2004). RESULTS In multivariate analyses, IR-T-based immunosuppression was associated with reduced graft survival (risk ratio, 1.49; P = 0.0038) and patient survival (risk ratio, 1.40; P = 0.0215). There was improvement with PR-T versus IR-T in graft survival (83% versus 77% at 4 y, respectively; P = 0.005) and patient survival (85% versus 80%; P = 0.017). Patients converted from IR-T to PR-T after 1 month had a higher graft survival rate than patients receiving IR-T at last follow-up (P < 0.001), or started and maintained on PR-T (P = 0.019). One graft loss in 4 years was avoided for every 14.3 patients treated with PR-T versus IR-T. CONCLUSIONS PR-T-based immunosuppression might improve long-term outcomes in liver transplant recipients than IR-T-based immunosuppression.
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Affiliation(s)
- René Adam
- Hepato-Biliary Center, AP-HP Paul Brousse Hospital, University of Paris-Sud, INSERM U935, Villejuif, France
| | - Vincent Karam
- Hepato-Biliary Center, AP-HP Paul Brousse Hospital, University of Paris-Sud, INSERM U935, Villejuif, France
| | - Valérie Cailliez
- Hepato-Biliary Center, AP-HP Paul Brousse Hospital, University of Paris-Sud, INSERM U935, Villejuif, France
| | - Pavel Trunečka
- Transplant Center, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
| | - Didier Samuel
- Hepato-Biliary Center, AP-HP Paul Brousse Hospital, University of Paris-Sud, INSERM U935, Villejuif, France
| | - Giuseppe Tisone
- Liver Transplant Unit, Tor Vergata Polyclinic, University of Rome Tor Vergata, Rome, Italy
| | - Petr Němec
- Center of Cardiovascular Surgery and Transplantation, Brno, Czech Republic
| | - Olivier Soubrane
- Department of Digestive Surgery, AP-HP Beaujon Hospital, Clichy, France
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria
| | - Bruno Gridelli
- Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Palermo, Sicily, Italy
| | - Wolf O Bechstein
- Department of General and Visceral Surgery, Goethe University Hospital and Clinics, Frankfurt, Germany
| | - Andrea Risaliti
- Department of Surgery, Liver Transplant Unit, University Hospital Udine, Udine, Italy
| | - Pal-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Marco Vivarelli
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Massimo Rossi
- Department of General Surgery, Organ Transplant Unit "Paride Stefanini", Umberto 1 Policlinico of Rome, Rome, Italy
| | - Jacques Pirenne
- Abdominal Transplant Surgery, University Hospital Leuven, Leuven, Belgium
| | - Jurgen L Klempnauer
- Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Aleh Rummo
- Republican Scientific and Practical Center (RSPC) for Organ and Tissue Transplantation, Minsk, Belarus
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Roberto Troisi
- Department of General Hepato-Biliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, Belgium
| | - Andreas Paul
- Department of General and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Toomas Vali
- Surgery Clinic, Tartu University Hospital, Tartu, Estonia
| | - Otto Kollmar
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany
| | - Karim Boudjema
- Department of Visceral Surgery, University Hospital Rennes, Pontchaillou Hospital, Rennes, France
| | - Emir Hoti
- Liver Unit, St. Vincent's Hospital, Dublin, Ireland
| | | | - Johan Pratschke
- Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum (CVK), Berlin, Germany
| | - Hauke Lang
- General, Visceral and Transplantation Surgery Clinic, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Irinel Popescu
- Department of Surgery and Liver Transplantation, Fundeni Clinical Institute, University of Medicine "Carol Davila", Bucharest, Romania
| | - Bo-Goran Ericzon
- Department of Transplantation Surgery, Karolinska University Hospital, Huddinge, Sweden
| | - Kestutis Strupas
- Department for Gastroentrology, Nephrology and Surgery, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, Pisa, Italy
| | - Eberhard Kochs
- Surgical Clinic and Polyclinic, University Hospital Klinikum rechts der Isar Munich, Munich, Germany
| | - Bruno Heyd
- Department of Visceral Surgery, University Hospital Besançon, University of Franche-Comté, Besançon, France
| | - Jean Gugenheim
- Department of Digestive Surgery, Archet 2 Hospital, Nice, France
| | - Antonio D Pinna
- University of Bologna, Transplant and HPB Institute, Bologna, Italy
| | - William Bennet
- Surgery Department, Transplantation and Liver Surgery Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Mirjalal Kazimi
- Surgery and Organ Transplantation Center, Central Hospital of Oil Workers, Baku, Azerbaijan
| | - Philippe Bachellier
- Department of Surgery, Hospital Hautepierre, University Hospitals of Strasbourg, Strasbourg, France
| | - Stephen J Wigmore
- Liver Transplantation Unit, University of Edinburgh Royal Infirmary, Edinburgh, United Kingdom
| | - Allan Rasmussen
- Department for Surgery and Transplantation, University Hospital Copenhagen, Copenhagen, Denmark
| | - Pierre-Alain Clavien
- Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Ernest Hidalgo
- St James and Seacroft University Hospital, Leeds, United Kingdom
| | - John G O'Grady
- Liver Unit, King's College Hospital, London, United Kingdom
| | - Frausto Zamboni
- Department of General Surgery and Transplantation, Hospital G. Brotzu, Cagliari, Italy
| | | | - Christophe Duvoux
- Department of Hepatology and Gastroenterology, University Hospital of Henri-Mondor, Creteil, France
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Dumortier J, Duvoux C, Dubel L, Bazin F, Houssel-Debry P. A Multicenter, Prospective, Observational Study of Conversion from Twice-Daily Immediate-Release to Once-Daily Prolonged-Release Tacrolimus in Liver Transplant Recipients in France: The COBALT Study. Ann Transplant 2019; 24:506-516. [PMID: 31451681 PMCID: PMC6728630 DOI: 10.12659/aot.916041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Background In adult liver transplant patients, the use of prolonged-release tacrolimus may have treatment adherence benefits over the immediate-release formulation. The aim of this study was to characterise real-world practice data on conversion of liver transplant recipients from immediate- to prolonged-release tacrolimus in France. Material/Methods A prospective, observational study (NCT02143479) was conducted in 18 transplant centers in France between June 2014 and March 2016. Liver transplant recipients (n=398) included patients who changed from immediate-release to prolonged-release tacrolimus within the first three months (early conversion group) (n=205) or between three and 12 months after transplantation (late conversion group) (n=184). Clinical data were collected at an initial baseline outpatient visit and six-month and 12-month follow-up visits. Endpoints included the dose conversion ratio from immediate-release to prolonged-release tacrolimus, number of and reasons for additional visits due to conversion, safety, and tolerability. Results Baseline clinical and demographic characteristics were similar between the two cohorts. The mean ±SD ratio of conversion of tacrolimus dose was 1.04±0.28; 1.01±0.28 (early) and 1.08±0.28 (late) (p=0.0247). The mean ±SD time from conversion to the first tacrolimus trough blood concentration was 30.8±42.8 days; 24.8±45.4 days (early) and 37.5±38.7 days (late). Only one patient required an additional visit due to conversion. Reasons for conversion included the physician’s preference (56.3%), center practice (38.6%), and the dosing frequency (36.0%). Conversion was associated with a low rate of graft rejection, and no new safety issues were reported. Conclusions Conversion of liver transplant recipients from immediate-release to prolonged-release tacrolimus within three to 12 months of transplantation was easy to manage and associated with favorable clinical outcomes and safety profiles.
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Affiliation(s)
- Jérôme Dumortier
- Departement of Hepatology, Edouard Herriot Hospital, Lyon, France
| | - Christophe Duvoux
- Department of Hepatology, Henri Mondor Hospital APHP, Paris Est University UPEC, Créteil, France
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47
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Miserachs M, Parmar A, Bakula A, Hierro L, D'Antiga L, Goldschmidt I, Debray D, A McLin V, Casotti V, Pawłowska J, Camarena C, R Otley A, Baumann U, L Ng V. Health-related quality of life in pre-adolescent liver transplant recipients with biliary atresia: A cross-sectional study. Clin Res Hepatol Gastroenterol 2019; 43:427-435. [PMID: 30528863 DOI: 10.1016/j.clinre.2018.10.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 10/09/2018] [Accepted: 10/25/2018] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Pediatric recipients of liver transplantation (LT) often report lower Health-Related Quality of Life (HRQOL) than healthy controls when assessed on generic HRQOL measurement tools. The recent addition of the Pediatric Liver Transplant Quality of Life (PeLTQL), a novel disease-specific HRQOL instrument for pediatric LT recipients, into the clinical armamentarium of tools now routinely available to clinical care teams, provides the unique opportunity to identify disease-related challenges in children who have undergone this life-saving intervention. This study assesses HRQOL in pre-adolescent aged patients with a primary diagnosis of biliary atresia (BA) who underwent LT as an infant, using both generic and disease-specific HRQOL instruments validated for children. We also examined modifiable factors associated with HRQOL after pediatric LT. METHODS HRQOL was the primary outcome of this study assessed using the disease-specific PeLTQL and the generic Pediatric Quality of Life Inventory 4.0 (PedsQL). Exposure variables of interest included medication status (e.g., monotherapy, dual therapy) and participation in sports. RESULTS A total of 70 (56% female, mean age 9.89 ± 1.25 years) pediatric LT recipients (mean interval since LT was 9.0 ± 1.26 years) comprised the study cohort. LT recipients reported significantly lower PedsQL Scores relative to the general population. Immunosuppression monotherapy was associated with higher patient-reported PeLTQL Scores, and sports participation was associated with higher parent-reported PedsQL Scores. CONCLUSIONS Pre-adolescents who underwent LT as an infant with BA, self-report low HRQOL on both disease-specific and generic HRQOL tools. Further research targeting sports participation and simplifying immunosuppression may further optimize quality of life years restored by life-saving LT.
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Affiliation(s)
- Mar Miserachs
- Transplant and regenerative medicine centre, division of pediatric gastroenterology, hepatology and nutrition, the hospital for sick children, university of Toronto, Toronto, Ontario, Canada; Universitat Autònoma de Barcelona, Bellatera, Spain
| | - Arpita Parmar
- Transplant and regenerative medicine centre, division of pediatric gastroenterology, hepatology and nutrition, the hospital for sick children, university of Toronto, Toronto, Ontario, Canada
| | | | - Loreto Hierro
- Service of pediatric hepatology and transplantation, hospital universitario La Paz, Madrid, Spain
| | | | | | - Dominique Debray
- Pediatric hepatology unit, AP-HP, hôpital Necker-Enfants Malades, université Paris Descartes, Paris, France
| | | | | | | | - Carmen Camarena
- Service of pediatric hepatology and transplantation, hospital universitario La Paz, Madrid, Spain
| | - Anthony R Otley
- Division of gastroenterology and nutrition, department of pediatrics, IWK Health Centre, Halifax, Nova Scotia, Canada; Department of pediatrics, faculty of medicine, Dalhousie university, Halifax, Nova Scotia, Canada
| | | | - Vicky L Ng
- Transplant and regenerative medicine centre, division of pediatric gastroenterology, hepatology and nutrition, the hospital for sick children, university of Toronto, Toronto, Ontario, Canada.
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48
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Ko D, Bratzke LC, Muehrer RJ, Brown RL. Self-management in liver transplantation. Appl Nurs Res 2018; 45:30-38. [PMID: 30683248 DOI: 10.1016/j.apnr.2018.11.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 10/15/2018] [Accepted: 11/05/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Self-management is crucial for liver transplant (LT) recipients to maintain transplants and optimize health outcomes. However, previous literature has been primarily limited to examining medication adherence; there is a knowledge gap regarding self-management in the LT population. AIM The aims of this study were to 1) comprehensively describe self-management behaviors and activities in LT recipients, 2) explore levels of overall self-management, and 3) explore the relationships of self-efficacy, cognition, and health information seeking behavior with self-management. METHODS Adult LT recipients (n = 113) who had a functioning transplant for at least 6 months participated in this cross-sectional, descriptive study. Participants were asked to identify self-management behaviors and rate their performance of those behaviors, including symptom management and medication adherence. They also completed a cognitive assessment and questionnaires measuring self-efficacy and health information seeking behavior. Descriptive statistics, latent profile analysis, and probit model for path analysis were used for the data analysis. RESULTS LT recipients acknowledged engaging in various self-management behaviors including symptom management, physical activity, maintenance of positive attitudes, and communication with healthcare providers. Three levels of self-management (i.e., low, medium, and high) were found; a high level of self-management was related to self-efficacy and health information seeking behavior. CONCLUSIONS The findings indicate that self-management may be improved with interventions aimed at increasing self-efficacy and health information seeking behavior. Findings from this study will inform future interventions, to improve self-management and subsequent health outcomes in this population. Future longitudinal studies are necessary to confirm the causality of the identified relationships.
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Affiliation(s)
- Dami Ko
- School of Nursing, University of Wisconsin-Madison, 701 Highland Ave., Madison, WI 53705, United States of America.
| | - Lisa C Bratzke
- School of Nursing, University of Wisconsin-Madison, 701 Highland Ave., Room 5127, Madison, WI 53705, United States of America.
| | - Rebecca J Muehrer
- School of Nursing, University of Wisconsin-Madison, 701 Highland Ave., Madison, WI 53705, United States of America
| | - Roger L Brown
- School of Nursing, University of Wisconsin-Madison, 701 Highland Ave., Room 4187, Madison, WI 53705, United States of America.
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49
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Lee EC, Kim SH, Park SJ. Safety and Efficacy of Once-Daily Prolonged-Release Tacrolimus in Living Donor Liver Transplantation: An Open-Label, Prospective, Single-Arm, Phase 4 Study. Ann Transplant 2018; 23:713-720. [PMID: 30310047 PMCID: PMC6248274 DOI: 10.12659/aot.910618] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND After liver transplantation (LT), nonadherence to immunosuppressants due to the complex regimen can lead to graft rejection and loss. This study assessed the efficacy and safety of conversion from twice-daily tacrolimus (Bid-Tac) to once-daily prolonged-release tacrolimus (OD-Tac) in living donor LT (LDLT) recipients. MATERIAL AND METHODS Among patients who underwent LDLT between November 2015 and October 2016, those who agreed to participate in this study were screened, and those with good general condition and stable liver functions were enrolled. Participants underwent a conversion from Bid-Tac to OD-Tac with a dose ratio of 1: 1 at about 10-14 weeks after LDLT and were followed-up for 24 weeks. RESULTS Thirty-one patients were enrolled. The median number of conversion days after LDLT was 12.3 weeks (range, 10.3-13.8). Adherence was evaluated during the outpatient visits at weeks 2, 4, 8, 16, and 24 after Tac conversion, and 100% adherence was observed at all time points. There were no cases of acute rejection, graft loss, or patient death after Tac conversion. Nineteen cases of adverse events occurred in 11 patients (35.5%), none of which were severe. Alopecia was the most common, affecting 3 (9.7%) patients, followed by pruritus (n=2, 6.45%). There were no changes in renal function or in liver function test, serum glucose level, and lipid profile. CONCLUSIONS Early Tac conversion from Bid-Tac to OD-Tac is safe and feasible. However, further studies are needed to elucidate its long-term effects.
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Affiliation(s)
- Eung Chang Lee
- Center for Liver Cancer, National Cancer Center, Goyang, Gyeonggi, South Korea
| | - Seong Hoon Kim
- Center for Liver Cancer, National Cancer Center, Goyang, Gyeonggi, South Korea
| | - Sang-Jae Park
- Center for Liver Cancer, National Cancer Center, Goyang, Gyeonggi, South Korea
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50
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Shin MH, Song GW, Lee SG, Hwang S, Kim KH, Ahn CS, Moon DB, Ha TY, Jung DH, Park GC, Yun YI, Kim WJ, Kang WH, Kim SH, Jiang H, Lee S, Tak EY. Once-daily, prolonged-release tacrolimus vs twice-daily, immediate-release tacrolimus in de novo living-donor liver transplantation: A Phase 4, randomized, open-label, comparative, single-center study. Clin Transplant 2018; 32:e13376. [PMID: 30098071 DOI: 10.1111/ctr.13376] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 07/15/2018] [Accepted: 07/28/2018] [Indexed: 11/27/2022]
Abstract
Randomized, open-label, comparative, single-center, Phase 4, 24-week study comparing pharmacokinetics (PK), safety, and efficacy of once-daily, prolonged-release tacrolimus (PR-T) with twice-daily, immediate-release tacrolimus (IR-T) in adult de novo living-donor liver transplant (LDLT) recipients in Korea. All patients received intravenous tacrolimus from Day 0 (transplantation) for 4 days and were randomized (1:1) to receive oral PR-T or IR-T from Day 5. PK profiles were taken on Days 6 and 21. Primary endpoint: area under the concentration-time curve over 24 hour (AUC0-24 ). Predefined similarity interval for confidence intervals of ratios: 80%-125%. Secondary endpoints included: tacrolimus concentration at 24 hour (C24 ), patient/graft survival, biopsy-confirmed acute rejection (BCAR), treatment-emergent adverse events (TEAEs). One-hundred patients were included (PR-T, n = 50; IR-T, n = 50). Compared with IR-T, 40% and 66% higher mean PR-T daily doses resulted in similar AUC0-24 between formulations on Day 6 (PR-T:IR-T ratio of means 96.8%), and numerically higher AUC0-24 with PR-T on Day 21 (128.8%), respectively. Linear relationship was similar between AUC0-24 and C24 , and formulations. No graft loss/deaths, incidence of BCAR and TEAEs similar between formulations. Higher PR-T vs IR-T doses were required to achieve comparable systemic exposure in Korean de novo LDLT recipients. PR-T was efficacious; no new safety signals were detected.
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Affiliation(s)
- Min-Ho Shin
- Division of Hepatobiliary Pancreatic Surgery and Transplantation, Department of Surgery, Chosun University College of Medicine, Gwangju, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-In Yun
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Wan-Jun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seok-Hwan Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hongsi Jiang
- Medical Affairs Asia Oceania, Astellas Pharma, Inc., Singapore City, Singapore
| | - Sungmin Lee
- Medical Affairs, Astellas Pharma Korea, Inc., Seoul, Korea
| | - Eun-Young Tak
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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