Cargando…
Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma
Tacrolimus is the mainstay of immunosuppression in liver transplantation to prevent rejection. However, the clinical use of tacrolimus is complicated by its narrow therapeutic window and significant intra-patient variability (IPV). High tacrolimus IPV is associated with overexposure and adverse effe...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519914/ https://www.ncbi.nlm.nih.gov/pubmed/36171260 http://dx.doi.org/10.1038/s41598-022-20636-3 |
_version_ | 1784799505664704512 |
---|---|
author | Kim, Hyun Jeong Lee, Juhan Lee, Jae Geun Joo, Dong Jin Kim, Myoung Soo |
author_facet | Kim, Hyun Jeong Lee, Juhan Lee, Jae Geun Joo, Dong Jin Kim, Myoung Soo |
author_sort | Kim, Hyun Jeong |
collection | PubMed |
description | Tacrolimus is the mainstay of immunosuppression in liver transplantation to prevent rejection. However, the clinical use of tacrolimus is complicated by its narrow therapeutic window and significant intra-patient variability (IPV). High tacrolimus IPV is associated with overexposure and adverse effects, including malignancy. The effects of tacrolimus IPV in liver transplant recipients with and without hepatocellular carcinoma (HCC) are unknown. We investigated the association between tacrolimus IPV and transplant outcomes in 636 liver transplant patients. Tacrolimus IPV was determined by calculating the coefficient of variance (CV) of outpatient tacrolimus trough levels from 3 to 12 months after transplantation. High tacrolimus IPV was defined as CV > 30%. Patients were grouped according to tacrolimus IPV and HCC status. Among 636 liver transplant patients, 349 had HCC and 287 had no HCC. Overall survival in HCC patients was significantly reduced with high tacrolimus IPV (P < 0.001), whereas survival of non-HCC patients was not associated with tacrolimus IPV. Multivariable analysis confirmed the independent association between high tacrolimus IPV and overall mortality in HCC patients (HR, 3.010; 95% CI, 1.084–4.918). HCC recurred in 59 patients (16.9%) post-transplantation. After adjusting for donor/recipient factors, immunosuppression, and tumor characteristics, high tacrolimus IPV was independently associated with an increased risk of HCC recurrence (HR, 2.196; 95% CI, 1.272–3.791). High tacrolimus IPV was associated with significantly increased risks of overall mortality and HCC recurrence in liver transplant recipients with HCC. |
format | Online Article Text |
id | pubmed-9519914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95199142022-09-30 Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma Kim, Hyun Jeong Lee, Juhan Lee, Jae Geun Joo, Dong Jin Kim, Myoung Soo Sci Rep Article Tacrolimus is the mainstay of immunosuppression in liver transplantation to prevent rejection. However, the clinical use of tacrolimus is complicated by its narrow therapeutic window and significant intra-patient variability (IPV). High tacrolimus IPV is associated with overexposure and adverse effects, including malignancy. The effects of tacrolimus IPV in liver transplant recipients with and without hepatocellular carcinoma (HCC) are unknown. We investigated the association between tacrolimus IPV and transplant outcomes in 636 liver transplant patients. Tacrolimus IPV was determined by calculating the coefficient of variance (CV) of outpatient tacrolimus trough levels from 3 to 12 months after transplantation. High tacrolimus IPV was defined as CV > 30%. Patients were grouped according to tacrolimus IPV and HCC status. Among 636 liver transplant patients, 349 had HCC and 287 had no HCC. Overall survival in HCC patients was significantly reduced with high tacrolimus IPV (P < 0.001), whereas survival of non-HCC patients was not associated with tacrolimus IPV. Multivariable analysis confirmed the independent association between high tacrolimus IPV and overall mortality in HCC patients (HR, 3.010; 95% CI, 1.084–4.918). HCC recurred in 59 patients (16.9%) post-transplantation. After adjusting for donor/recipient factors, immunosuppression, and tumor characteristics, high tacrolimus IPV was independently associated with an increased risk of HCC recurrence (HR, 2.196; 95% CI, 1.272–3.791). High tacrolimus IPV was associated with significantly increased risks of overall mortality and HCC recurrence in liver transplant recipients with HCC. Nature Publishing Group UK 2022-09-28 /pmc/articles/PMC9519914/ /pubmed/36171260 http://dx.doi.org/10.1038/s41598-022-20636-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Kim, Hyun Jeong Lee, Juhan Lee, Jae Geun Joo, Dong Jin Kim, Myoung Soo Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma |
title | Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma |
title_full | Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma |
title_fullStr | Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma |
title_full_unstemmed | Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma |
title_short | Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma |
title_sort | clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519914/ https://www.ncbi.nlm.nih.gov/pubmed/36171260 http://dx.doi.org/10.1038/s41598-022-20636-3 |
work_keys_str_mv | AT kimhyunjeong clinicalassociationbetweentacrolimusintrapatientvariabilityandlivertransplantationoutcomesinpatientswithandwithouthepatocellularcarcinoma AT leejuhan clinicalassociationbetweentacrolimusintrapatientvariabilityandlivertransplantationoutcomesinpatientswithandwithouthepatocellularcarcinoma AT leejaegeun clinicalassociationbetweentacrolimusintrapatientvariabilityandlivertransplantationoutcomesinpatientswithandwithouthepatocellularcarcinoma AT joodongjin clinicalassociationbetweentacrolimusintrapatientvariabilityandlivertransplantationoutcomesinpatientswithandwithouthepatocellularcarcinoma AT kimmyoungsoo clinicalassociationbetweentacrolimusintrapatientvariabilityandlivertransplantationoutcomesinpatientswithandwithouthepatocellularcarcinoma |