Angelini Giulia, Panunzi Simona, Pompili Maurizio, Riccardi Laura, Garcovich Matteo, Verrastro Ornella, Russo Sara, Mare Tracey, Luxton James, le Roux Carel W, Raffaelli Marco, Mingrone Geltrude, Vincent Royce P
Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
CNR-IASI, Consiglio Nazionale delle Ricerche, Istituto di Analisi dei Sistemi ed Informatica, Laboratorio di Biomatematica, Rome, Italy.
Clin Chem. 2025 Mar 3;71(3):406-417. doi: 10.1093/clinchem/hvae208.
Noninvasive tests (NITs) to monitor metabolic dysfunction-associated steatohepatitis (MASH) progression and response to interventions are needed because of the risks of liver biopsy. A monocytes-based diagnostic test using perilipin-2 (PLIN2) and Ras-related protein-14 (RAB14) predict the severity of MASH and fibrosis. Here we compared the performances of PLIN2 and RAB14 with cytokeratin-18 (CK18) assessed by Ella™ or M65 ELISA in predicting MASH and fibrosis resolution following bariatric surgery in a longitudinal and histologically characterized cohort of individuals with obesity.
Participants in the BRAVES randomized controlled trial underwent ultrasound-guided needle liver biopsy at baseline and 1 year after surgery. We evaluated NITs' performance using area under the receiver operating characteristic and calculated accuracy, sensitivity, and specificity based on the Youden threshold. Univariable and multivariable logistic models were used to assess the role of recorded covariates in predicting MASH and fibrosis severity, as well as resolution or improvement.
After surgery, patients who experienced MASH improvement or resolution showed a significant decrease in PLIN2 expression as compared to those who did not, while patients with fibrosis improvement displayed an increase in RAB14. No differences were found for CK18. The diagnostic accuracy of PLIN2 and RAB14 for the prediction of MASH resolution or fibrosis improvement was superior to CK18 assessed by either Ella or M65 ELISA.
PLIN2 and RAB14, but not CK18, are markers for monitoring improvements in MASH and fibrosis after interventions such as bariatric surgery. This may reduce or eliminate the need for frequent liver biopsies. ClinicalTrials.gov Registration Number: NCT03524365.
由于肝活检存在风险,因此需要非侵入性检测(NITs)来监测代谢功能障碍相关脂肪性肝炎(MASH)的进展以及对干预措施的反应。一种基于单核细胞的诊断测试,使用脂滴包被蛋白2(PLIN2)和Ras相关蛋白14(RAB14),可以预测MASH和纤维化的严重程度。在此,我们在一个具有纵向和组织学特征的肥胖个体队列中,比较了PLIN2和RAB14与通过Ella™或M65 ELISA评估的细胞角蛋白18(CK18)在预测减肥手术后MASH和纤维化消退方面的性能。
BRAVES随机对照试验的参与者在基线和手术后1年接受了超声引导下的经皮肝穿刺活检。我们使用受试者操作特征曲线下面积评估了NITs的性能,并根据约登指数计算了准确性、敏感性和特异性。使用单变量和多变量逻辑模型评估记录的协变量在预测MASH和纤维化严重程度以及消退或改善方面的作用。
手术后,与未经历MASH改善或消退的患者相比,经历MASH改善或消退的患者PLIN2表达显著降低,而纤维化改善的患者RAB14增加。CK18未发现差异。PLIN2和RAB14预测MASH消退或纤维化改善的诊断准确性优于通过Ella或M65 ELISA评估的CK18。
PLIN2和RAB14而非CK18是监测减肥手术等干预措施后MASH和纤维化改善情况的标志物。这可能减少或消除频繁进行肝活检的必要性。ClinicalTrials.gov注册号:NCT03524365。