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摘要：
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摘要：目的 探讨经导管肝动脉化疗栓塞术（transcatheter arterial chemoembolization，TACE）联合经皮
射频消融术（radiofrequency ablation，RFA）治疗早、中期肝细胞癌（hepatocellular carcinoma，HCC）
的疗效及预后影响因素。方法 选取解放军总医院第五医学中心2016年9月至2018年3月明确诊断的120
例早、中期HCC患者为研究对象，依照患者意愿分为TACE组（60例）和TACE + RFA组（60例），记
录患者肝脏基础疾病、Child-Pugh分级及肿瘤BCLC分期等一般资料。并于术前、术后1个月和3个月检
测血甲胎蛋白（alpha-fetoprotein，AFP）、癌胚抗原（carcinoembryonic antigen，CEA）、糖类抗原199
（carbohydrate antigen199，CA-199）、糖类抗原-125（carbohydrate antigen125，CA-125）、γ-谷氨酰转
移酶（gamma-glutamyltranspeptidase，GGT）、白细胞介素（interlukin，IL）-2、IL-4、IL-6、IL-10、
γ-干扰素（interferon-γ，INF-γ）及肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）等指标。随访
截至2019年3月，采用Kaplan-Meier法计算累计中位总生存期（orerall survival，OS）和无进展生存期
（progression free survival，PFS），采用Cox回归模型分析患者OS及PFS的影响因素。结果 术后1个月，
TACE + RFA组及TACE组AFP（中位数：8.07 μg/L vs 9.59 μg/L）、IL-6（中位数：7.61 ng/L vs
15.96 ng/L）及IL-4（中位数：3.87 ng/L vs 5.39 ng/L）差异有统计学意义（P均＜ 0.05）。术后3个月，
TACE + RFA组及TACE组AFP（中位数：6.67 μg/L vs 8.94 μg/L）、IFN-γ（中位数：19.08 ng/L vs
21.28 ng/L）、IL-6（中位数：8.37 ng/L vs 18.53 ng/L）及IL-4（中位数：4.06 ng/L vs 5.69 ng/L）差异有
统计学意义（P均＜ 0.05）。至随访结束，失访6例，病死16例，TACE + RFA组和TACE组总生存率分
别为94.8%（55/58）、76.8%（43/56），均未出现致命性的严重并发症。TACE + RFA组OS（17.9个月
vs 13.6个月）和PFS（17.3个月vs 7.9个月）均显著长于TACE组（χ 2 = 23.037、35.930，P均＜ 0.001）。
术后3个月及1年疗效评估，TACE + RFA组客观缓解率（术后3个月：91.67% vs 55.00%，术后1年：
63.33% vs 35.00%）和疾病控制率（术后3个月：93.34% vs 65.00%，术后1年：78.33% vs 51.77%）均
显著高于TACE组（P均＜ 0.05）。Log-Rank单因素分析表明，患者的Child-Pugh分级（B级）、肿瘤
BCLC分期（B期）、肿瘤最大直径（≥ 5 cm）、肿瘤数量（≥ 3个）及术前AFP水平（≥ 200 μg/L）等
对TACE + RFA术后疗效及预后均有显著影响（P均＜ 0.05）。Cox多因素分析表明，治疗方法的选择是
影响早、中期HCC患者预后的独立因素（P = 0.014）。结论 治疗方案的选择是影响早、中期HCC患者
术后疗效及预后的影响因素，TACE联合RFA治疗可显著改善早、中期HCC患者疗效，延长OS及PFS。
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Abstract: Objective To investigate the efficacy and influencing factors of transcatheter arterial
chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treatment of early metaphase
hepatocellular carcinoma (HCC). Methods A total of 120 patients with early metaphase HCC in the Fifth
Medical Center of the PLA General Hospital from September 2016 to March 2018 were selected and
divided into TACE group (60 cases) and TACE + RFA group (60 cases) according to their wishes. Clinical
characteristics of all patients were recorded, including basic liver diseases, Child-Pugh grades and BCLC
stages and so on. The levels of serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate
antigen 199 (CA-199), carbohydrate antigen 125 (CA-125), gamma-glutamyltranspeptidase (GGT), interlukin
(IL)-2, IL-4, IL-6, IL-10, interferon-γ (INF-γ) and tumor necrosis factor-α (TNF-α) were detected before
treatment, 1 month and 3 months after treatment. The deadline of followed-up was March 2019, Kaplan-Meier
was used to calculate the overall survival time (OS) and progression free survival (PFS). Cox regression model
was used to analyze the influencing factors of OS and PFS. Results After treatment for 1 month, the differences
of AFP (median: 8.07 μg/L vs 9.59 μg/L), IL-6 (median: 7.61 ng/L vs 15.96 ng/L) and IL-4 (median: 3.87 ng/L
vs 5.39 ng/L) levels of patients in TACE + RFA group and TACE group were statistically significant (all P ＜ 0.05).
After treatment for 3 months, the differences of AFP (median: 6.67 μg/L vs 8.94 μg/L), IFN-γ (median: 19.08 ng/L
vs 21.28 ng/L), IL-6 (median: 8.37 ng/L vs 18.53 ng/L) and IL-4 (median: 4.06 ng/L vs 5.69 ng/L) levels of patients
in TACE + RFA group and TACE group were statistically significant (all P ＜ 0.05). At the end of follow-
up, 6 cases were lost and 16 cases died. The survival rates of patients in TACE + RFA group and TACE group
were 94.8% (55/58) and 76.8% (43/56), respectively. There were no fatal serious complications. The OS
(17.9 months vs 13.6 months) and PFS (17.3 months vs 7.9 months) of patients in TACE + RFA group were
significantly longer than those of TACE group (χ 2 = 23.037, 35.930; all P ＜ 0.001). Three months and 1 year
after treatment, the objective response rate (3 months: 91.67% vs 55.00%, 1 year: 63.33% vs 35.00%) and the
disease control rate (3 months: 93.34% vs 65.00%, 1 year: 78.33% vs 51.77%) were significantly higher than
those of TACE group (all P ＜ 0.05). Log-Rank single factor analysis showed that Child-Pugh grade (grade B),
BCLC stage (B), maximum diameter (＞ 5 cm), number of tumors (＞ 3) and level of AFP (＞ 200 μg/L) all
have significant effects on the curative effect and prognosis of TACE + RFA (all P ＜ 0.05). Cox multivariate
analysis showed that treatment method was the independent factor that affected the prognosis of early and
intermediate-stage HCC (P = 0.014). Conclusions Treatment method is an independent influencing factor on
the curative effect and prognosis of patients with early metaphase HCC. TACE + RFA can significantly improve the
efficacy and prolong OS and PFS of patients with early and intermediate-stage HCC.
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