Supplementary Material for: Contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) in hepatocellular carcinoma ≤ 5cm: biological characteristics and patient outcomes

Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection. Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67 and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI- RADS categories were further analyzed. Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01), and that poor differentiation (32.7% in LR-M, 12% in LR-5 and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5 and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection. Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.

引言：本研究旨在评估肝细胞癌（hepatocellular carcinoma, HCC）的生物学特性对高危患者超声造影（contrast-enhanced ultrasound, CEUS）的2017版肝脏影像报告与数据系统（Liver Imaging Reporting and Data System, LI-RADS）分类的影响，并对比根治性切除术后不同分类患者的预后结局。方法：2017年6月至2020年12月期间，前瞻性收集了中国多家中心的肝脏结节标准化CEUS数据。本研究对经病理确诊、直径不超过5cm的HCC患者的前瞻性收集数据进行回顾性分析。在全面评估CEUS特征后对病灶进行LI-RADS分类。随后，对比不同分化程度、Ki-67表达水平及微血管侵犯（microvascular invasion, MVI）状态下的CEUS LI-RADS分类及主要特征，并进一步分析不同LI-RADS分类患者的无复发生存期（recurrence-free survival, RFS）差异。结果：本研究共纳入293例患者的293个HCC结节。研究发现，不同分化程度（p<0.001）及Ki-67表达水平（p=0.01）的HCC病灶其CEUS LI-RADS分类存在显著差异：低分化病灶更常被归为LR-M类（占比32.7%），其次为LR-5类（12%）与LR-4类（6.2%）（p<0.001）；高Ki-67表达水平（中位值30%）的病灶也更多被归类为LR-M类。而高分化病灶更常被归为LR-4类（占比37.5%），其次为LR-5类（15.1%）与LR-M类（11.5%）；低Ki-67表达水平（中位值11%）的病灶同样更多被归类为LR-4类。微血管侵犯状态与CEUS LI-RADS分类之间未发现显著差异（p>0.05）。中位随访时长为23个月，不同CEUS LI-RADS分类的HCC患者在根治性切除术后的无复发生存期未表现出显著差异。结论：本研究表明，肝细胞癌的生物学特性（包括分化程度与Ki-67表达水平）可影响CEUS的主要特征，并对CEUS LI-RADS分类产生影响。不同CEUS LI-RADS分类的HCC患者在根治性切除术后的无复发生存期无显著差异。