Life sciences · 2026
Liver sinusoidal endothelial cells phenotypes as early predictors of sepsis-associated liver dysfunction.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
García-Concejo Adrián, Vega-Harwood Alicia Wendy, Prieto-Utrera Rosa Dolores, Bardají-Carrillo Miguel, Cobo-Zubia Rosa, Rebollo-Mato Irina, Matesanz-Isabel Jessica, Álvarez-Bardón María, Tamayo-Velasco Álvaro, Aller Rocío, Adamove Peter, Lorenzo-López Mario, Muñoz Felipe, Calaveras Rosario, Tomillo-Cebrian Fe, Gonzalo-Benito Hugo, Bilotta Federico, Santamaria Eduardo, Sanz-Muñoz Iván, Eiros José M, Bernardo David, Poves-Álvarez Rodrigo, Tamayo Eduardo, Gómez-Sánchez Esther, López-Herrero Rocío
Аннотация
AIMS: Sepsis-associated liver dysfunction (SALD) is a common and prognostically relevant complication of critical illness, but its early detection remains challenging. We investigated whether circulating endothelial phenotyping could identify patients at risk of early SALD.
MATERIALS AND METHODS: In this prospective, multicenter observational study, 214 adult postsurgical patients admitted to intensive care units at three Spanish hospitals were classified as critical controls (n = 77), sepsis (n = 61), or septic shock (n = 76) according to Sepsis-3 criteria. During the first 7 days after sepsis diagnosis, 42 patients developed SALD, defined by total serum bilirubin >2 mg/dL and international normalized ratio > 1.5. Peripheral blood mononuclear cells were analysed using high-dimensional spectral flow cytometry. Endothelial cells were defined as CD45-/CD31+, and eight phenotypes were characterized within the CD32b+ compartment according to CD36, PV1, and HLA-DR expression. LASSO-Cox regression identified two populations, differing only in HLA-DR expression, and their ratio was subsequently evaluated as an endothelial marker.
KEY FINDINGS: Total endothelial cell counts did not differ significantly according to subsequent SALD development. A higher HLA-DR ratio was associated with increased SALD incidence (log-rank p = 0.00045) and remained independently associated after adjustment for age and baseline bilirubin. The HLA-DR ratio showed good discrimination for early SALD (AUC 0.802), compared with bilirubin alone (AUC 0.730).
SIGNIFICANCE: Circulating endothelial phenotyping identifies a specific endothelial phenotype associated with subsequent SALD beyond total endothelial cell abundance and conventional bilirubin measurements. The HLA-DR ratio may provide complementary information for early risk stratification of SALD.
IMPACT AND IMPLICATIONS: This study provides biological and clinical support for liver sinusoidal endothelial cells subset phenotyping as an early indicator of sepsis-associated liver dysfunction, addressing the limited sensitivity of conventional biochemical markers. The findings are particularly relevant for hepatologists and intensivists, as they identify an activated HLA-DR+ liver sinusoidal endothelial cells subset associated with subsequent liver dysfunction in critically ill patients. While further validation and methodological simplification are required, endothelial phenotyping could complement existing diagnostic approaches to improve early risk stratification in sepsis-related liver injury.
MATERIALS AND METHODS: In this prospective, multicenter observational study, 214 adult postsurgical patients admitted to intensive care units at three Spanish hospitals were classified as critical controls (n = 77), sepsis (n = 61), or septic shock (n = 76) according to Sepsis-3 criteria. During the first 7 days after sepsis diagnosis, 42 patients developed SALD, defined by total serum bilirubin >2 mg/dL and international normalized ratio > 1.5. Peripheral blood mononuclear cells were analysed using high-dimensional spectral flow cytometry. Endothelial cells were defined as CD45-/CD31+, and eight phenotypes were characterized within the CD32b+ compartment according to CD36, PV1, and HLA-DR expression. LASSO-Cox regression identified two populations, differing only in HLA-DR expression, and their ratio was subsequently evaluated as an endothelial marker.
KEY FINDINGS: Total endothelial cell counts did not differ significantly according to subsequent SALD development. A higher HLA-DR ratio was associated with increased SALD incidence (log-rank p = 0.00045) and remained independently associated after adjustment for age and baseline bilirubin. The HLA-DR ratio showed good discrimination for early SALD (AUC 0.802), compared with bilirubin alone (AUC 0.730).
SIGNIFICANCE: Circulating endothelial phenotyping identifies a specific endothelial phenotype associated with subsequent SALD beyond total endothelial cell abundance and conventional bilirubin measurements. The HLA-DR ratio may provide complementary information for early risk stratification of SALD.
IMPACT AND IMPLICATIONS: This study provides biological and clinical support for liver sinusoidal endothelial cells subset phenotyping as an early indicator of sepsis-associated liver dysfunction, addressing the limited sensitivity of conventional biochemical markers. The findings are particularly relevant for hepatologists and intensivists, as they identify an activated HLA-DR+ liver sinusoidal endothelial cells subset associated with subsequent liver dysfunction in critically ill patients. While further validation and methodological simplification are required, endothelial phenotyping could complement existing diagnostic approaches to improve early risk stratification in sepsis-related liver injury.