Reticuloendothelial activation and phenotypic alteration of peripheral monocytes with enhanced liver recruitment drive liver injury secondary to yellow phosphorus
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY(2023)
摘要
Background and AimMonocytes and macrophages play a crucial role in the pathogenesis of acute liver failure (ALF). We aimed to study reticuloendothelial activation and its correlation with disease severity in commonly encountered yellow phosphorus (rodenticide)-induced hepatotoxicity patients. We also studied peripheral monocyte phenotype in a subset of patients. MethodsReticuloendothelial activation markers were analyzed and correlated with disease severity score in a prospectively collected database of yellow phosphorus-related hepatoxicity patients between 2018 and 2021. In a prospective cohort of these patients and age-matched healthy controls, peripheral blood monocyte phenotyping was performed. ResultsReticuloendothelial activation markers were analyzed in 67 patients [Age: 23(12-64) years; median (range), men: 25, acute liver injury (ALI): 38, ALF: 29, model for end-stage liver disease (MELD) score: 28 (7-40)] of yellow phosphorus-induced hepatotoxicity. Serum ferritin (927; 10.3-34 807 ng/mL), sCD163 (4.59; 0.11-12.7 mu g/mL), sCD25 (3050; 5.6-17 300 pg/mL) and plasma von Willebrand factor (423.5, 103-1106 IU/dL) were increased and showed significant correlation with liver disease severity assessed by MELD score (rho = 0.29, rho = 0.6, rho = 0.56 and rho = 0.46 respectively).Phenotyping and serum immune markers were performed in seven patients (M: 4; age: 27, 15-37 years; median, range; MELD score: 36, 21-40) and compared with eight healthy controls. Increase in classical monocytes and decrease in patrolling and intermediate monocyte subsets were observed in ALF cohort. HLA-DR(low)CD163(hi) (immune exhaustion), CD64(hi) (immune complex-mediated response), and CCR2(hi) (liver homing) monocyte phenotype was noted. ConclusionAltered peripheral monocyte phenotype with enhanced liver homing and macrophage activation, suggests important role of innate immune activation, and provides a potential therapeutic target, in yellow phosphorus-induced hepatotoxicity.
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关键词
CD163, macrophage activation, VWF, yellow phosphorus hepatotoxicity
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