ABSTRACT
BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.
ABSTRACT
Whole-tissue transcriptomic analyses have been helpful to characterize molecular subtypes of hepatocellular carcinoma (HCC). Metabolic subtypes of human HCC have been defined, yet whether these different metabolic classes are clinically relevant or derive in actionable cancer vulnerabilities is still an unanswered question. Publicly available gene sets or gene signatures have been used to infer functional changes through gene set enrichment methods. However, metabolism-related gene signatures are poorly co-expressed when applied to a biological context. Here, we apply a simple method to infer highly consistent signatures using graph-based statistics. Using the Cancer Genome Atlas Liver Hepatocellular cohort (LIHC), we describe the main metabolic clusters and their relationship with commonly used molecular classes, and with the presence of TP53 or CTNNB1 driver mutations. We find similar results in our validation cohort, the LIRI-JP cohort. We describe how previously described metabolic subtypes could not have therapeutic relevance due to their overall downregulation when compared to non-tumoral liver, and identify N-glycan, mevalonate and sphingolipid biosynthetic pathways as the hallmark of the oncogenic shift of the use of acetyl-coenzyme A in HCC metabolism. Finally, using DepMap data, we demonstrate metabolic vulnerabilities in HCC cell lines.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Transcriptome , Humans , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Transcriptome/genetics , Gene Expression Regulation, Neoplastic , Gene Expression Profiling , Metabolic Networks and Pathways/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Cell Line, Tumor , beta Catenin/metabolism , beta Catenin/genetics , MutationABSTRACT
BACKGROUND/AIMS: New prognostic markers are needed to identify patients with hepatocellular carcinoma (HCC) who carry a worse prognosis. Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess both circulating tumor DNA (ctDNA) fraction and large structural genomic alterations. Here, we studied the performance of ULP-WGS of plasma cfDNA to infer prognosis in patients with HCC. METHODS: Plasma samples were obtained from patients with HCC prior to surgery, locoregional or systemic therapy, and were analyzed by ULP-WGS of cfDNA to an average genome-wide fold coverage of 0.3x. ctDNA and copy number alterations (CNA) were estimated using the software package ichorCNA. RESULTS: Samples were obtained from 73 HCC patients at different BCLC stages (BCLC 0/A: n=37, 50.7%; BCLC B/C: n=36, 49.3%). ctDNA was detected in 18 out of 31 patients who received systemic treatment. Patients with detectable ctDNA showed significantly worse overall survival (median, 13.96 months vs not reached). ctDNA remained an independent predictor of prognosis after adjustment by clinical-pathologic features and type of systemic treatment (hazard ratio 7.69; 95%, CI 2.09-28.27). Among ctDNA-positive patients under systemic treatments, the loss of large genomic regions in 5q and 16q arms was associated with worse prognosis after multivariate analysis. CONCLUSION: ULP-WGS of cfDNA provides clinically relevant information about the tumor biology. The presence of ctDNA and the loss of 5q and 16q arms in ctDNA-positive patients are independent predictors of worse prognosis in patients with advanced HCC receiving systemic therapy.
Subject(s)
Carcinoma, Hepatocellular , Cell-Free Nucleic Acids , Circulating Tumor DNA , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Circulating Tumor DNA/genetics , Prognosis , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Mutation , Biomarkers, TumorSubject(s)
COVID-19 , Vitamin D Deficiency , Humans , Pandemics , Vitamin D , Vitamin D Deficiency/epidemiology , PrevalenceSubject(s)
Humans , Male , Middle Aged , Cutaneous Fistula , Echinococcosis, Hepatic , Reference Values , Liver , Cysts/diagnostic imagingABSTRACT
ABSTRACT: Contrast-enhancing renal masses are likely to be malignant in over 90% of cases due to the high diagnostic accuracy of abdominal imaging. In this situation, tumor biopsy is unnecessary and should be managed as a renal cell carcinoma. Resection remains the only potentially curative treatment. However, as in the case herein presented, comorbidities can prevent surgical resection. Radioembolization with 90 Y microspheres is an intra-arterial procedure capable of delivering high doses of radiation to tumors. The present case demonstrates the concept of partial radiation nephrectomy in treating renal tumors with malignant characteristics in patients not amenable to surgery.
Subject(s)
Brachytherapy , Carcinoma, Renal Cell , Kidney Neoplasms , Liver Neoplasms , Humans , Microspheres , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Nephrectomy/methods , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/radiotherapy , Carcinoma, Renal Cell/surgery , Liver Neoplasms/surgerySubject(s)
Humans , Female , Aged , Bronchiectasis/diagnosis , Bronchiectasis/etiology , Prototheca , Infections/diagnosisABSTRACT
INTRODUCTION: Cases of acute myocarditis have been after administration of the BNT162b2 and Ad26.COV2.S vaccine. OBJECTIVE: Describe another possible mechanism of myocarditis after COVID-19 vaccination. CASE PRESENTATION: We describe the clinical case of a 72-year-old female with pleuritic chest pain one week after the third of the BNT162b2 mRNA vaccine. Serological tests for cardiotropic pathogens were negative, and autoimmunity screening was positive with anti-nuclear antibody (ANA) in 1:160 dilution, Anti-double-stranded DNA (anti-dsDNA), and anti-histone antibodies. 18F-fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) showed a focal myocardial and pericardial inflammatory process in the cardiac apex. RESULTS AND DISCUSSION: Systemic lupus erythematosus (SLE) diagnosis was made with myocardial affection. As far as we know, this is the first report of a case of lupus myocarditis after the COVID-19 vaccine. CONCLUSION: Given the pathogenic rationales, the association between SLE and myocarditis should be considered.
Subject(s)
COVID-19 Vaccines , COVID-19 , Lupus Erythematosus, Systemic , Myocarditis , Aged , Female , Humans , Ad26COVS1 , Antibodies, Antinuclear , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Lupus Erythematosus, Systemic/diagnosis , Myocarditis/diagnosis , Myocarditis/etiology , Positron Emission Tomography Computed Tomography , VaccinationABSTRACT
Introduction: Cases of acute myocarditis have been after administration of the BNT162b2 and Ad26.COV2.S vaccine. Objective: Describe another possible mechanism of myocarditis after COVID-19 vaccination. Case presentation: We describe the clinical case of a 72-year-old female with pleuritic chest pain one week after the third of the BNT162b2 mRNA vaccine. Serological tests for cardiotropic pathogens were negative, and autoimmunity screening was positive with anti-nuclear antibody (ANA) in 1:160 dilution, Anti-double-stranded DNA (anti-dsDNA), and anti-histone antibodies. 18F-fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) showed a focal myocardial and pericardial inflammatory process in the cardiac apex. Results and discussion: Systemic lupus erythematosus (SLE) diagnosis was made with myocardial affection. As far as we know, this is the first report of a case of lupus myocarditis after the COVID-19 vaccine. Conclusion: Given the pathogenic rationales, the association between SLE and myocarditis should be considered.(AU)
Introducción: Se han presentado casos de miocarditis aguda tras la administración de las vacunas BNT162b2 y Ad26.COV2.S. Objetivo: Describir otro posible mecanismo de miocarditis posterior a la vacunación contra el COVID-19. Presentación del caso: Describimos el caso clínico de una mujer de 72 años con dolor torácico pleurítico una semana después de la tercera vacuna de ARNm BNT162b2. Las pruebas serológicas para patógenos cardiotrópos fueron negativas y el cribado de autoinmunidad fue positivo con anticuerpos antinucleares (ANA) en dilución 1:160, anticuerpos anti-ADN de doble cadena (anti-dsADN) y antihistonas. La tomografía por emisión de positrones/tomografía computarizada (PET/TC) con 18F-fluorodesoxiglucosa (FDG) mostró un proceso inflamatorio miocárdico y pericárdico focal en el ápex cardíaco. Resultados y discusión: Se realizó el diagnóstico de lupus eritematoso sistémico (LES) con afectación miocárdica. Hasta donde sabemos, este es el primer reporte de un caso de miocarditis lúpica después de la vacuna contra el COVID-19. Conclusión: Dadas las justificaciones patogénicas, se debe considerar la asociación entre lupus eritematoso sistémico (LES) y miocarditis.(AU)