Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
PECEM, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Liver Int. 2022 Oct;42(10):2260-2273. doi: 10.1111/liv.15326. Epub 2022 Jun 12.
BACKGROUND & AIMS: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a β-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications.
We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections.
Increased galectin-3 levels were found in advanced cirrhosis. Galectin-3 significantly correlated with disease severity parameters and inflammatory markers. Galectin-3 had significant discriminating power for compensated and advanced cirrhosis (AUC = 0.78/0.84, circulating/liver galectin-3; p < .01), and was even higher to discriminate severe AH (AUC = 0.95, p < .0001). Cox Proportional-hazard model showed that galectin-3, MELD-Na and the presence of SIRS predict the development of post-transplant infectious complications. Patients with circulating galectin-3 (>16.58 ng/ml) were at 2.19-fold 95% CI (1.12-4.29) increased risk, but when combined with MELD-Na > 20.0 and SIRS, the risk to develop post-transplant infectious complications, increased to 4.60, 95% CI (2.38-8.90).
Galectin-3 is a novel biological marker of active inflammation and disease severity that could be clinically useful alone or in combination with other scores to discriminate advanced cirrhosis and predict post-transplant infectious complications.
晚期肝硬化患者常伴有免疫功能障碍，更容易发生感染。半乳糖凝集素-3 是一种β-半乳糖苷结合凝集素，参与炎症、免疫调节和肝纤维化。本研究旨在探讨晚期肝硬化患者中半乳糖凝集素-3 的表达及其预测肝移植后感染并发症的能力。
我们收集了 129 例肝硬化患者肝移植时的血清和肝组织样本，以及来自另一个包含 37 例酒精性肝病患者的外部队列（包括酒精性肝炎患者）的诊断时的血清样本。通过 ELISA、实时 PCR、免疫组化和 RNA 测序检测半乳糖凝集素-3。通过受试者工作特征曲线和 Cox 比例风险回归分析评估半乳糖凝集素-3 对疾病严重程度和肝移植后感染的预测能力。
晚期肝硬化患者的半乳糖凝集素-3 水平升高。半乳糖凝集素-3 与疾病严重程度参数和炎症标志物显著相关。循环和肝组织中的半乳糖凝集素-3 对半代偿期和晚期肝硬化的区分能力具有显著差异（AUC = 0.78/0.84，p <.01），对半乳糖凝集素-3 对严重酒精性肝炎的区分能力甚至更高（AUC = 0.95，p <.0001）。Cox 比例风险模型显示，半乳糖凝集素-3、MELD-Na 和 SIRS 的存在预测肝移植后感染并发症的发生。循环半乳糖凝集素-3 水平>16.58 ng/ml 的患者发生肝移植后感染并发症的风险增加 2.19 倍（95%CI，1.12-4.29），但当与 MELD-Na > 20.0 和 SIRS 联合时，发生肝移植后感染并发症的风险增加至 4.60（95%CI，2.38-8.90）。
半乳糖凝集素-3 是一种新型的炎症活跃和疾病严重程度的生物学标志物，单独或与其他评分联合使用可用于区分晚期肝硬化和预测肝移植后感染并发症。
