受体酪氨酸激酶Axl及其剪切产物可溶性Axl（sAxl）的表达在肝纤维化、肝硬化和肝细胞癌（HCC）中增加。在这项多中心研究中，我们评估了Axl的高亲和力配体Gas6在慢性肝病患者中的诊断价值。分析了经活检证实的肝纤维化、晚期肝病、HCC和健康对照的血清样本中的sAxl和Gas6水平以及它们与白蛋白（Alb）的比率，并与Fibrosis-4（FIB-4）指数、增强肝纤维化（ELF™）试验、Child-Pugh评分（CPS）、终末期肝病模型评分（MELD）评分、肝静脉压梯度和α-胎蛋白进行比较。共分析了1111名患者（中位年龄57.8岁，67.3%为男性）。Gas6/Alb显示出对显著（≥F2：AUC 0.805）至进展期肝纤维化（≥F3：AUC 0.818）的检测具有高的诊断准确性，并且对于肝硬化（F4：AUC 0.897 vs. 0.878）的检测优于Fib-4。此外，Gas6/Alb对肝病严重程度具有很高的预测能力（CPS B/C、MELD≥15和临床意义的门静脉高压的Odds比分别为16.534，10.258和12.115），并且与无移植的存活率相关（危险比1.031）。虽然与无肝硬化的慢性肝病患者相比，Gas6和Gas6/Alb对HCC的诊断准确性较高（AUC 0.852，0.868），但它们无法区分肝硬化中的HCC和仅有肝硬化的情况。总之，Gas6/Alb对显著到进展期肝纤维化和肝硬化的诊断具有高准确性，并预测肝病严重程度，包括临床意义的门静脉高压。© 2023. 作者（们）

The expression of the receptor tyrosine kinase Axl and its cleavage product soluble Axl (sAxl) is increased in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this multicenter study, we evaluated the diagnostic value of Gas6, the high-affinity ligand of Axl, in patients with chronic liver disease. Levels of sAxl and Gas6, and their albumin (alb) ratios were analyzed in serum samples of patients with biopsy-proven liver fibrosis, end-stage liver disease, HCC, and healthy controls, and were compared to Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF™) test, Child-Pugh score (CPS), model of end-stage liver disease (MELD) score, hepatic venous pressure gradient, and α-fetoprotein, respectively. A total of 1111 patients (median age 57.8 y, 67.3% male) was analyzed. Gas6/alb showed high diagnostic accuracy for the detection of significant (≥F2: AUC 0.805) to advanced fibrosis (≥F3: AUC 0.818), and was superior to Fib-4 for the detection of cirrhosis (F4: AUC 0.897 vs. 0.878). In addition, Gas6/alb was highly predictive of liver disease severity (Odds ratios for CPS B/C, MELD ≥ 15, and clinically significant portal hypertension (CSPH) were 16.534, 10.258, and 12.115), and was associated with transplant-free survival (Hazard ratio 1.031). Although Gas6 and Gas6/alb showed high diagnostic accuracy for the detection of HCC in comparison to chronic liver disease patients without cirrhosis (AUC 0.852, 0.868), they failed to discriminate between HCC in cirrhosis versus cirrhosis only. In conclusion, Gas6/alb shows a high accuracy to detect significant to advanced fibrosis and cirrhosis, and predicts severity of liver disease including CSPH.© 2023. The Author(s).