Abstract:

Objective　To investigate the value of lenvatinib combined with atezolizumab sequential transhepatic arterial chemoembolization (TACE) in the treatment of patients with hepatitis B complicated with advanced liver cancer. Methods　This study was a randomized controlled trial. A total of 96 patients with hepatitis B complicated with advanced liver cancer admitted to Liaocheng People's Hospital from January 10, 2019 to September 10, 2022 were selected for the study, and were divided into an observation group and a control group according to the random number table method. In the control group, there were 25 males and 23 females, aged (54.52±7.13) years; in the observation group, there were 28 males and 20 females, aged (53.74±6.55) years. The control group was given conventional TACE treatment, and the observation group was given lenvatinib combined with atezolizumab sequential TACE treatment. The disease remission rate, disease control rate, liver function indexes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL)], cellular immune function indexes [lymphocytes (CD₃⁺, CD₄⁺, and CD₈⁺) and CD₄⁺/CD₈⁺], and infiltrative metastasis indexes [vascular endothelial growth factor (VEGF) and glypican-3 (GPC-3)] before and after treatment, and occurrence of adverse events were compared between the two groups. t test, χ² test, and Ridit test were used for statistical analysis. Results　The disease remission rate and disease control rate of the observation group were higher than those of the control group [72.92% (35/48) vs. 52.08% (25/48), 85.42% (41/48) vs. 62.50% (30/48)] (χ²=4.444, P=0.035; χ²=6.544, P=0.010). After treatment, the CD₃⁺, CD₄⁺, CD₄⁺/CD₈⁺ in the observation group were (64.28±5.35)%, (33.52±2.81)%, and (1.28±0.23), which were higher than those in the control group [(58.92±5.13)%, (28.75±2.63)%, and (1.03±0.19)]; the AST, ALT, TBIL, VEGF, GPC-3, and CD₈⁺ were (38.73±8.41) U/L, (47.62±10.39) U/L, (17.95±2.35) µmol/L, (312.58±33.45) ng/L, (10.75±1.98) µg/L, and (26.19±2.04)%, which were lower than those in the control group [(55.62±7.85) U/L,(67.88±11.55) U/L,  (22.46±2.71) µmol/L, (338.74±35.76) ng/L, (12.46±2.05) µg/L, and (27.91±2.13)%]; the differences were statistically significant (t=15.010, 8.587, 5.806, 10.172, 9.035, 8.711, 3.701, 4.156, and 4.040; all P<0.001). There was no statistically significant difference in the total incidence of adverse events between the observation group and the control group [31.25% (15/48) vs. 25.00% (12/48)] (P>0.05). Conclusion　Lenvatinib combined with atezolizumab sequential TACE has better clinical effect in the treatment of patients with hepatitis B complicated with advanced liver cancer, which can effectively reduce the immune suppression, improve the liver function, and alleviate the disease.

Key words:

Liver cancer, Hepatitis B, Lenvatinib, Atezolizumab, TACE, Immune function

摘要：

目的　探究仑伐替尼联合阿替利珠单抗序贯经导管动脉化疗栓塞术（TACE）在乙型肝炎合并晚期肝癌患者治疗中的应用价值。方法　本研究为随机对照试验。选取2019年1月10日至2022年9月10日聊城市人民医院收治的96例乙型肝炎合并晚期肝癌患者为研究对象，按随机数字表法分为观察组和对照组，各48例。对照组男25例，女23例，年龄（54.52±7.13）岁，给予常规TACE治疗；观察组男28例，女20例，年龄（53.74±6.55）岁，给予仑伐替尼联合阿替利珠单抗序贯TACE治疗。比较两组疾病缓解率、疾病控制率，治疗前后肝功能指标［天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、总胆红素（TBIL）］、细胞免疫功能指标［淋巴细胞（CD₃⁺、CD₄⁺、CD₈⁺）、CD₄⁺/CD₈⁺］、浸润转移指标［血管内皮生长因子（VEGF）、磷脂酰肌醇蛋白聚糖-3（GPC-3）］，不良事件发生情况。统计学方法采用t检验、χ²检验、Ridit检验。结果　观察组疾病缓解率、疾病控制率均高于对照组［72.92%（35/48）比52.08%（25/48）、85.42%（41/48）比62.50%（30/48）］（χ²=4.444，P=0.035；χ²=6.544，P=0.010）。治疗后，观察组CD₃⁺、CD₄⁺、CD₄⁺/CD₈⁺分别为（64.28±5.35）%、（33.52±2.81）%、（1.28±0.23），均高于对照组的（58.92±5.13）%、（28.75±2.63）%、（1.03±0.19）；AST、ALT、TBIL、VEGF、GPC-3、CD₈⁺分别为（38.73±8.41）U/L、（47.62±10.39）U/L、（17.95±2.35）µmol/L、（312.58±33.45）ng/L、（10.75±1.98）µg/L、（26.19±2.04）%，均低于对照组的（55.62±7.85）U/L、（67.88±11.55）U/L、（22.46±2.71）µmol/L、（338.74±35.76）ng/L、（12.46±2.05）µg/L、（27.91±2.13）%；差异均有统计学意义（t=15.010、8.587、5.806、10.172、9.035、8.711、3.701、4.156、4.040，均P<0.001）。观察组不良事件总发生率与对照组比较差异无统计学意义［31.25%（15/48）比25.00%（12/48）］（P>0.05）。结论　仑伐替尼联合阿替利珠单抗序贯TACE治疗乙型肝炎合并晚期肝癌患者具有较好的疗效，可有效减轻免疫功能抑制，改善肝功能，缓解病情。

关键词:

肝癌, 乙型肝炎, 仑伐替尼, 阿替利珠单抗, 经肝动脉化疗栓塞术, 免疫功能