Abstract: Background Portal vein tumor thrombosis（PVTT） is a common complication of hepatocellular carcinoma（HCC）. The presence of PVTT（HCC-PVTT） at diagnosis often signifies advanced liver cancer，worsened liver function，increased risk of intrahepatic dissemination，systemic metastasis，and complications related to portal hypertension. Currently，the diagnosis of PVTT primarily depends on imaging techniques，with a notable lack of simple and cost-effective diagnostic markers to complement and enhance the prediction of PVTT occurrence. Objective To investigate the impact of serum high-density lipoprotein-cholesterol（HDL-C） levels on the development of PVTT in patients with non-B，non-C hepatocellular carcinoma（NBNC-HCC），we aimed to explore the predictive value of HDL-C levels for PVTT occurrence. Methods A total of 119 patients diagnosed with NBNC-HCC admitted to the Third Hospital of Hebei Medical University from January 2015 to December 2020（including 26 patients with PVTT） were selected，and 102 patients with HBV and HCVassociated hepatocellular carcinoma（BC-HCC） hospitalized during the same period（including 34 patients with PVTT） were selected. Baseline data were collected through the electronic inpatient record system，and patients with NBNC-HCC were followed up until December 31，2022 to record their overall survival. Patients with PVTT in NBNC-HCC and BC-HCC were categorized into the NBNC-PVTT group（n=26） and BC-PVTT group（n=34），respectively，and their baseline characteristics were compared. Additionally，NBNC-HCC patients were divided into the PVTT group（n=26） and the non-PVTT group（n=93）based on the presence or absence of PVTT，and comparisons were made regarding clinical baseline characteristics and survival outcomes between the two groups. Multivariate Logistic regression analysis was performed to identify independent factors influencing PVTT in NBNC-HCC. The predictive performance of HDL-C levels for PVTT in NBNC-HCC was evaluated using receiver operating characteristic（ROC）curves. Kaplan-Meier survival curves were plotted to assess the prognosis of NBNCHCC patients with PVTT at different HDL-C levels. Furthermore，restricted cubic spline plots were utilized to analyze the nonlinear relationship between HDL-C levels and the risk of mortality in NBNC-HCC patients. Results Compared to the BC PVTT group，the NBNC-PVTT group exhibited higher levels of age，total bilirubin（TBIL），direct bilirubin（DBIL），total cholesterol（TC），and low-density lipoprotein cholesterol（LDL-C），while the proportion of males and the HDL-C levels were lower（P<0.05）. Multivariate Logistic regression analysis revealed that serum HDL-C level was an independent factor influencing PVTT in NBNC-HCC patients（OR=0.170，95%CI=0.054-0.533，P=0.002）. ROC curve analysis showed that the area under the curve（AUC）for HDL-C in predicting PVTT in NBNC-HCC patients was 0.702（95%CI=0.5877-0.817），with sensitivity and specificity values of 84.6% and 51.6%，respectively，and an optimal cut-off value of 0.675 mmol/L. NBNC-HCC patients were divided into a low HDL-C group（≤ 0.675 mmol/L，n=67）and a high HDL-C group（>0.675 mmol/L，n=52）.Survival curve analysis indicated that patients in the high HDL-C group had better survival outcomes than those in the low HDL-C group（χ2 =6.383，P<0.000 1）. After adjusting for age and sex，a nonlinear association between HDL-C levels and the risk of death in NBNC-HCC patients was observed（Nonlinear P=0.003 2）. Conclusion Serum HDL-C level serves as a predictive marker for the risk of progression of PVTT in NBNC-HCC patients，it also has a significant impact on the prognosis of NBNC PVTT patients，offering valuable insights for risk classification management and prognosis enhancement.

Key words: Hepatocellular carcinoma；Non-viral hepatocellular carcinoma；Non-B, non-C hepatocellular carcinoma；Portal vein tumor thrombosis；HDL-C

摘要： 背景 门静脉癌栓（PVTT）是肝细胞癌（HCC）常见的并发症之一，HCC患者在诊断时并发 PVTT（HCC-PVTT）常提示肝癌晚期，肝功能恶化加剧，肝内癌细胞播散、全身转移以及门静脉高压并发症的风险增加。目前 PVTT 的诊断主要依靠影像学，仍然缺乏简易、价格低廉的诊断指标。目的 探讨血清高密度脂蛋白胆固醇（HDL-C）预测乙型肝炎病毒和丙型肝炎病毒阴性肝细胞癌（NBNC-HCC）患者发生PVTT的价值。方法 选取2015—2020年河北医科大学第三医院收治的NBNC-HCC患者119例（其中合并PVTT患者26例），并选取同期住院治疗的102例HBV、HCV相关肝细胞癌（BC-HCC）患者102例（其中合并PVTT患者34例），通过电子住院病历系统收集患者的基线资料，并对NBNC-HCC患者进行随访，随访截止时间为2022-12-31，记录患者的总生存期。将NBNC-HC和BC-HCC中合并PVTT的患者分别作为NBNC-PVTT组（n=26）和BC-PVTT组（n=34），比较两组患者的基线资料；同时，依据是否合并PVTT，将NBNC-HCC患者分为合并PVTT组（n=26）和无PVTT组（n=93），比较两组的临床基线资料和生存预后结局。采用多因素Logistic回归分析探究NBNC-HCC发生PVTT的独立影响因素。绘制血清HDL-C水平预测NBNC-HCC发生PVTT的受试者工作特征（ROC）曲线。采用Kaplan-Meier法绘制不同HDL-C水平的NBNC-HCC合并PVTT患者的生存曲线。采用限制性立方样条图分析HDL-C与NBNC-HCC患者死亡风险之间的非线性关系。结果 与BC-PVTT组相比，NBNC-PVTT组患者年龄、总胆红素（TBIL）、直接胆红素（DBIL）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）水平均升高，男性所占比例、HDL-C水平均降低（P <0.05）。多因素Logistic回归分析结果显示，血清HDL-C水平是NBNC-HCC患者发生PVTT的独立影响因素（OR=0.170，95%CI=0.054~0.533，P=0.002）。ROC曲线结果显示，HDL-C预测NBNC-HCC患者发生PVTT的ROC曲线下面积（AUC）为0.702（95%CI=0.587~0.817），灵敏度和特异度分别为84.6%和51.6%，最佳截断值为0.675mmol/L。将NBNC-HCC患者分为低HDL-C组（≤0.675mmol/L，n=67）和高HDL-C组（ >0.675mmol/L，n=52），生存曲线结果显示，高HDL-C组患者的生存情况优于低HDL-C组（χ2=6.383，P <0.0001）。调整年龄、性别因素后，HDL-C与NBNCHCC患者死亡风险之间存在非线性相关关系（NonlinearP=0.0032）。结论 入院血清HDL-C水平对NBNC-HCC患者发生PVTT的风险具有重要预测价值，并且对NBNC-HCC合并PVTT患者的预后生存有显著影响，为风险分级管理和改善预后提供参考。

关键词: 肝细胞癌, 非病毒性肝细胞癌, 乙型肝炎病毒和丙型肝炎病毒阴性肝细胞癌, 门静脉癌栓, 高密度脂蛋白胆固醇