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1.
EClinicalMedicine ; 49: 101476, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35747194

RESUMEN

Background: The forecast accuracy of the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) and Asian Pacific Association for the Study of the Liver (APASL) acute-on-chronic liver failure (ACLF) criteria in assessing long-term outcomes after liver transplantation (LT) is still unclear, especially when the staging of the two standards is inconsistent. Methods: A retrospective cohort (NCT05036031) including 565 patients from January 2015 to June 2021 was conducted. The 28 and 90 days, 1- and 3-years overall survival (OS) after LT were compared between different grades. Findings: Total of 162 (28.7%) and 230 (40.7%) patients met the ACLF standards. In the EASL-CLIF criteria, the 3-year OS rates were 83·0%, 80·3%, and 69·8% for ACLF1-3, respectively. In the APASL criteria, the 3-year OS rates were 85·7% for APASL ACLF Research Consortium (AARC)-1, similar to ACLF-1. The 3-year OS rates were 84·5% for AARC-2, which were slightly better than ACLF-2. Regarding AARC-3, the 3-year OS rate was 5·8% higher than ACLF-3. For patients who met neither set of criteria for ACLF, the 3-year OS rates were 89·8%. The multivariate analysis showed that alanine aminotransferase >100 U/L, respiration failure, and cerebral failure were independent risk factors for post-LT death. Interpretation: This study provides the first large-scale long-term follow-up data in Asia. Both criteria showed favorable distinguishing ability for post-LT survival. Patients with ACLF had a higher post-LT mortality risk, and ACLF-3 and AARC-3 correlated with significantly greater mortality. Funding: National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality.

2.
Front Immunol ; 12: 653437, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34349755

RESUMEN

Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.


Asunto(s)
Carcinoma Hepatocelular/terapia , Rechazo de Injerto/epidemiología , Neoplasias Hepáticas/terapia , Trasplante de Hígado/efectos adversos , Terapia Neoadyuvante/métodos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Incidencia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Receptor de Muerte Celular Programada 1/metabolismo , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Tasa de Supervivencia
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