肝硬化原发性肝癌直径<1 cm超声造影表现及其与血清AFU、AFP-L3、GPC3、TSGF、GP73水平相关性研究

摘要 目的：探讨肝硬化原发性肝癌（PHC）直径<1cm超声造影（CEUS）表现及其与血清α-L-岩藻糖苷酶（AFU）、甲胎蛋白异质体-L3（AFP-L3）、磷脂酰肌醇蛋白聚糖-3（GPC3）、肿瘤特异生长因子（TSGF）、高尔基体糖蛋白（GP73）水平相关性。方法：选取2018年1月-2022年8月于湖北省襄阳市中医院收治的肝硬化PHC直径<1 cm患者44例，根据术后病理结果分为高分化组、中分化组和低分化组。所有患者术前均完善CEUS和血清AFU、AFP-L3、GPC3、TSGF、GP73水平检查。比较三组CEUS表现、定量时间-强度曲线（TIC）分析、血清AFU、AFP-L3、GPC3、TSGF、GP73水平。采用Spearman相关性分析肝硬化PHC直径<1 cm患者的CEUS表现与血清AFU、AFP-L3、GPC3、TSGF、GP73水平的相关性。结果：44例肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶，呈圆形或类圆形，病灶边界清晰，周围可见声晕。不同分化程度肝硬化PHC直径<1 cm患者在动脉期、门脉期和延迟期的CEUS表现上差异均无统计学意义（P＞0.05）。高分化组、中分化组和低分化组的达峰时间、廓清时间和峰值加速时间逐渐减少，差异有统计学意义（P＜0.05）。而高分化组、中分化组和低分化组的峰值强度增加率逐渐增加，差异有统计学意义（P＜0.05）。高分化组、中分化组和低分化组的增强时间对比差异无统计学意义（P＞0.05）。高分化组、中分化组和低分化组血清AFU、AFP-L3、GPC3、TSGF、GP73水平逐渐升高，差异有统计学意义（P＜0.05）。Spearman相关性分析显示，达峰时间、廓清时间和峰值加速时间与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈负相关（P＜0.05）；峰值强度增加率与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈正相关（P＜0.05）。结论：肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶，呈圆形或类圆形，病灶边界清晰，周围可见声晕。CEUS表现和血清AFU、AFP-L3、GPC3、TSGF、GP73水平具有相关性，两者可辅助鉴别肝硬化PHC直径<1 cm的不同分化程度。

Contrast-Enhanced Ultrasound Manifestations of Cirrhosis Primary Hepatocellular Carcinoma Diameter <1 cm and its Correlation with AFU, AFP-L3, GPC3, TSGF, GP73 Levels

ABSTRACT Objective: To investigate the contrast-enhanced ultrasound (CEUS) manifestations of cirrhosis primary hepatocellular carcinoma (PHC) diameter <1 cm and its correlation with alpha-L-fucosidase (AFU), alpha-fetoprotein-L3 (AFP-L3), glypican-3 (GPC3), tumor specific growth factor (TSGF) and golgi protein 73 (GP73) levels. Methods: 44 patients with cirrhosis PHC diameter <1 cm treated at Xiangyang Hospital of traditional Chinese medicine, Hubei Province, from January 2018 to August 2022 were selected, According to the postoperative pathological results, they were divided into high differentiation group, middle differentiation group and low differentiation group. CEUS and serum erum AFU, AFP-L3, GPC3, TSGF and GP73 levels were tested in all patients before operation. CEUS manifestations, quantitative time-intensity curve(TIC) analysis, and serum AFU, AFP-L3, GPC3, TSGF and GP73 levels were compared among the three groups. Spearman correlation was used to analyze the correlation between CEUS manifestations of cirrhosis PHC diameter <1cm and serum AFU, AFP-L3, GPC3, TSGF and GP73 levels. Results: The CEUS manifestations of the 44 patients with cirrhosis PHC diameter <1 cm were all single intrahepatic lesions, which were round or ceroid in shape with a clear lesion border and a visible acoustic halo around them. There was no significant difference in CEUS manifestations in arterial phase, portal phase and delayed phase in patients with different differentiation degrees of cirrhosis PHC diameter <1 cm(P>0.05). In terms of peak time, clearance time and peak acceleration time for high differentiation group, middle differentiation group and low differentiation group gradually decreased, and the differences were statistically significant(P<0.05). However, The rate of increase peak intensity of high differentiation group, middle differentiation group and low differentiation group gradually increased, and the differences were statistically significant (P<0.05). There was no significant difference in the enhancement time compared among the high differentiation group, middle differentiation group and low differentiation group(P>0.05). Serum AFU, AFP-L3, GPC3, TSGF and GP73 leves in the high differentiation group, middle differentiation group and low differentiation group were gradually increased, and the differences were statistically significant(P<0.05). Spearman correlation analysis showed that the peak time, clearance time and peak acceleration time were negatively correlated with serum AFU, AFP-L3, GPC3, TSGF, and GP73 levels(P<0.05), and the rate of increase peak intensity was positively correlated with serum AFU, AFP-L3, GPC3, TSGF, and GP73 levels (P<0.05). Conclusion: The CEUS manifestations of cirrhosis PHC diameter <1 cm were all single intrahepatic lesions, which were round or ceroid in shape with a clear lesion border and a visible acoustic halo around them. The CEUS manifestations are correlated with serum AFU, AFP-L3, GPC3, TSGF and GP73 levels, which can assist identify the different differentiation degrees of cirrhosis PHC diameter <1 cm.