Xin Yuwei, Xiong Yu, Liu Feifei, Qu Linlin, Li Wenxue, Yang Li, Liu Yiqun, Zhu Jia'an
Department of Ultrasound, Peking University People's Hospital, Beijing, China.
Department of Ultrasound, Binzhou Medical University Hospital, Binzhou, China.
Quant Imaging Med Surg. 2023 Aug 1;13(8):4908-4918. doi: 10.21037/qims-22-1145. Epub 2023 May 22.
Hepatic acute graft-versus-host disease (aGVHD) is a major life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We hypothesized that contrast-enhanced ultrasound (CEUS) could serve as a new imaging biomarker in early diagnosis of hepatic aGVHD by detecting liver microcirculation.
Thirty Wistar rats received allo-HSCT were finally included after excluding 9 rats, and they were randomly divided into 5 groups (1- to 5-week groups, 6 per group). Six rats were used for the control group without any intervention. We observed the clinical scores, serum liver enzyme levels and liver CEUS parameters of rats in each group. Hepatic aGVHD was finally confirmed by histopathologic analysis. The diagnostic performance of CEUS parameters in detecting GVHD was evaluated by comparing the area under the receiver operating curve (AUC) values.
After HSCT, the rats developed ruffling of fur, maculopapular rash, weight loss, accompanied by increased clinical scores. Serum liver enzymes were significantly higher than those in the control group from the third week, especially alkaline phosphatase, while CEUS parameters, peak intensity (PI) and mean transit time (MTT), changed in the second week (P<0.001). Compared with non-aGVHD group, the PI was significantly decreased while time to peak and MTT were prolonged in aGVHD group. CEUS parameters were more strongly correlated with pathological grade than serology. PI was an independent predictor for hepatic aGVHD. The AUC of CEUS parameters for diagnosing hepatic aGVHD was 0.933 (95% CI: 0.779-0.992), which was higher than that of clinical scores (AUC =0.748, 95% CI: 0.557-0.888, P=0.032) and serological markers (AUC =0.902, 95% CI: 0.737-0.980, P=0.694).
CEUS exhibits promising applications as a quantitative method to detect hepatic aGVHD and early liver damage.
肝急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（allo-HSCT）的一种主要的危及生命的并发症。我们推测，对比增强超声（CEUS）通过检测肝脏微循环，可作为肝aGVHD早期诊断的一种新的成像生物标志物。
排除9只大鼠后，最终纳入30只接受allo-HSCT的Wistar大鼠，并将它们随机分为5组（1至5周组，每组6只）。6只大鼠作为未进行任何干预的对照组。我们观察了每组大鼠的临床评分、血清肝酶水平和肝脏CEUS参数。最终通过组织病理学分析确诊肝aGVHD。通过比较受试者操作特征曲线（ROC）下面积（AUC）值，评估CEUS参数检测GVHD的诊断性能。
HSCT后，大鼠出现毛发竖起、斑丘疹、体重减轻，同时临床评分增加。从第三周起，血清肝酶显著高于对照组，尤其是碱性磷酸酶，而CEUS参数，即峰值强度（PI）和平均渡越时间（MTT）在第二周发生变化（P<0.001）。与非aGVHD组相比，aGVHD组的PI显著降低，而达峰时间和MTT延长。CEUS参数与病理学分级的相关性比血清学更强。PI是肝aGVHD的独立预测指标。CEUS参数诊断肝aGVHD的AUC为0.933（95%CI：0.779-0.992），高于临床评分（AUC =0.748，95%CI：0.557-0.888，P=0.032）和血清学标志物（AUC =0.902，95%CI：0.737-0.980，P=0.694）。
CEUS作为检测肝aGVHD和早期肝损伤的定量方法，具有广阔的应用前景。
