营养指标和炎症指标对信迪利单抗联合贝伐珠单抗治疗晚期肝细胞癌患者总生存期的影响

摘要/Abstract

摘要： 目的: 探讨营养指标和炎症指标预测信迪利单抗联合贝伐珠单抗治疗晚期肝细胞癌（hepatocellular carcinoma, HCC）患者预后的价值。
方法: 本研究为回顾性研究,选择2021年1月至2021年12月永州市中心医院收治的85例HCC患者。根据营养指标[预后营养指数（prognostic nutritional index, PNI）和血红蛋白-白蛋白-淋巴细胞-血小板（hemoglobin-albumin-lymphocyte-platelet, HALP）评分]和炎症指标[单核细胞/高密度脂蛋白比值（monocyte to high-density lipoprotein ratio, MHR）、C反应蛋白/前白蛋白比值（C-reactive protein to prealbumin ratio, CPR）和C反应蛋白/淋巴细胞计数比值（C-reactive protein to lymphocyte ratio, CLR）]最佳临界值,将患者分为高PNI组与低PNI组、高HALP评分组与低HALP评分组、高MHR组与低MHR组、高CPR组与低CPR组及高CLR组与低CLR组。采用Kaplan-Meier法对不同营养状态或炎症水平的晚期HCC患者进行生存分析,并采用log-rank检验进行比较。采用单因素和多因素Cox回归模型筛选信迪利单抗联合贝伐珠单抗治疗后晚期HCC患者总生存期的危险因素。绘制受试者操作特征（receiver operator characteristic, ROC）曲线以评价营养指标和炎症指标对信迪利单抗联合贝伐珠单抗治疗后晚期HCC患者死亡的预测价值。
结果: 高PNI组、高HALP评分组、低MHR组、低CPR组、低CLR组疾病控制率（disease control ratio, DCR）均高于低PNI组、低HALP评分组、高MHR组、高CPR组、高CLR组（84.0%比65.7%,χ²=19.961,P<0.001;84.8%比66.7%,χ²=6.467,P=0.011;87.0%比64.1%,χ²=6.127,P=0.013;92.0%比65.7%,χ²=4.947,P=0.026;84.5%比63.6%,χ²=4.938,P=0.016)。高PNI组、高HALP评分组、低MHR组、低CPR组、低CLR组患者总生存期均长于低PNI组、低HALP评分组、高MHR组、高CPR组、高CLR组患者（P均<0.05）。ROC曲线显示,PNI、HALP评分、MHR、CPR和CLR预测晚期HCC患者死亡的曲线下面积（area under the curve, AUC）分别为0.797[95%置信区间（95% confidence interval, 95%CI）：0.738~0.855]、0.773（95%CI：0.713~0.833）、0.606（95%CI：0.528~0.683）、0.726（95%CI：0.665~0.788）、0.759（95%CI：0.701~0.818）。多因素Cox回归模型分析结果表明,PNI和HALP评分是影响信迪利单抗联合贝伐珠单抗治疗后晚期HCC患者预后的独立保护因素,MHR、CPR和CLR是影响信迪利单抗联合贝伐珠单抗治疗后晚期HCC患者预后的独立危险因素。
结论: 营养指标和炎症指标是信迪利单抗联合贝伐珠单抗治疗晚期HCC患者预后的有效预测指标。

关键词: 晚期肝细胞癌, 营养, 炎症, 信迪利单抗联合贝伐珠单抗, 预后

Abstract: Objective: To explore the value of nutritional and inflammatory indicators in predicting the prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with combination therapy of Sintilimab and Bevacizumab.
Method: This study is a retrospective study. Totally 85 HCC patients admitted to Yongzhou Central Hospital from January 2021 to December 2021 were selected. According to the optimal critical values of nutritional indicators (prognostic nutritional index [PNI] and hemoglobin albumin lymphocyte platelet [HALP] scores) and inflammatory indicators (monocyte to high-density lipoprotein ratio [MHR], C-reactive protein to prealbumin ratio [CPR], and C-reactive protein to lymphocyte count ratio [CLR]), patients were divided into high PNI group and low PNI group, high HALP score group and low HALP score group, high MHR group and low MHR group, high CPR group and low CPR group, and high CLR group and low CLR group. Kaplan Meier method was used to analyze the survival of advanced HCC patients with different nutritional status or inflammation levels, and log rank test was used for comparison. Single factor and multiple factor Cox regression models were used to screen risk factors for overall survival in advanced HCC patients treated with combination therapy of Sintilimab and Bevacizumab. Draw receiver operator characteristic (ROC) curves to evaluate the predictive value of nutritional and inflammatory indicators for mortality in advanced HCC patients after treatment with Sintilimab combined with Bevacizumab.
Result: The disease control ratio (DCR) of the high PNI group, high HALP score group, low MHR group, low CPR group, and low CLR group were all higher than those of the low PNI group, low HALP score group, high MHR group, high CPR group, and high CLR group (84.0% vs. 65.7%, χ²=19.961, P<0.001; 84.8% vs. 66.7%, χ²=6.467, P=0.011; 87.0% vs. 64.1%, χ²=6.127, P=0.013; 92.0% vs. 65.7%, χ²=4.947, P=0.026; 84.5% vs. 63.6%, χ²=4.938, P=0.016). The overall survival of patients in the high PNI group, high HALP score group, low MHR group, low CPR group, and low CLR group was longer than that of patients in the low PNI group, low HALP score group, high MHR group, high CPR group, and high CLR group (all P<0.05). The ROC curve shows that the area under the curve (AUC) for predicting death in advanced HCC patients using PNI, HALP score, MHR, CPR, and CLR is 0.797 (95% confidence interval [95%CI]: 0.738-0.855), 0.773 (95%CI: 0.713-0.833), 0.606 (95%CI: 0.528-0.683), 0.726 (95%CI: 0.665-0.788), and 0.759 (95%CI: 0.701-0.818), respectively. The results of the multivariate Cox regression model analysis showed that PNI and HALP scores were independent protective factors affecting the prognosis of advanced HCC patients treated with combination therapy of Sintilimab and Bevacizumab, while MHR, CPR, and CLR were independent risk factors affecting the prognosis of advanced HCC patients treated with combination therapy of Sintilimab and Bevacizumab.

Key words: Advanced hepatocellular carcinoma, Nutrition, Inflammation, Sindilimab combined with Bevacizumab, Prognosis

何华日, 夏旺宁, 唐彪, 刘鑫涛, 李来. 营养指标和炎症指标对信迪利单抗联合贝伐珠单抗治疗晚期肝细胞癌患者总生存期的影响[J]. 肝癌电子杂志, 2025, 12(1): 39-45.

He Huari, Xia Wangning, Tang Biao, Liu Xintao, Li Lai. The value of nutritional and inflammatory indicators in predicting the prognosis of patients with advanced hepatocellular carcinoma treated with Sintilimab combined with Bevacizumab[J]. Electronic Journal of Liver Tumor, 2025, 12(1): 39-45.

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