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摘要：
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摘要：目的 探讨同期肝癌射频消融（radiofrequency ablation，RFA）联合Hassab手术对肝细
胞癌（hepatocellular carcinoma，HCC）合并门静脉高压患者细胞免疫功能的影响。方法 选
择2018年1月至2019年6月就诊于首都医科大学附属北京地坛医院的47例HCC合并肝硬化门
静脉高压的患者为研究对象。按照不同手术方式分为试验组（28例）和对照组（19例），
试验组采用肝癌RFA联合Hassab术，对照组采用肝癌切除联合Hassab术。分别留取患者术
前、术后3 d、术后4周外周血。采用流式细胞术检测外周血T细胞亚群（CD4+
、CD8+
、
CD4+
/CD8+
），采用酶联免疫吸附实验测定外周血Th1细胞因子和Th2细胞因子，Th1细胞
因子包括干扰素γ（interferon γ，IFN γ）、白细胞介素（interleukin，IL）-2、肿瘤坏死因子
α（tumor necrosis factor-α，TNF-α），Th2细胞因子包括IL-4和IL-8。比较不同手术方式对患
者细胞免疫功能的影响。结果 试验组和对照组患者术前CD4+
T细胞（中位数：29.80% vs
29.50%）、CD8+
T细胞（中位数：23.60% vs 24.30%）及CD4+
/CD8+
T细胞（中位数：1.30%
vs 1.23%）比例差异均无统计学意义（P ＞ 0.05）；术后3 d和术后4周，试验组患者CD4+
T细
胞（术后3 d中位数：26.55% vs 21.80%；术后4周中位数：34.95% vs 33.30%）和CD4+
/CD8+
T
细胞（术后3 d中位数：1.22% vs 0.87%；术后4周中位数：1.46% vs 1.23%）比例均显著高于
对照组，CD8+
T细胞比例（术后3 d中位数：22.25% vs 25.50%；术后4周中位数：24.20% vs
26.50%）显著低于对照组，差异均有统计学意义（P均＜ 0.05）。与术前相比，试验组患
者CD4+
T细胞、CD8+
T细胞比例于术后3 d显著下降，术后4周外周血CD4+
T细胞、CD8+
T细
胞及CD4+
/CD8+
T细胞比例显著升高（P均＜ 0.05）；而对照组术后3 d CD4+
T细胞及CD4+
/
CD8+
T细胞比例同样先下降，然后于术后4周显著升高（P均＜ 0.05）。对照组CD8+
T细
胞术后无下降，呈持续升高（中位数：24.30% vs 25.50% vs 26.50%）。同对照组比较，试
验组患者各指标于术后3 d及术后4周皆有显著差异（P均＜ 0.05）。试验组和对照组患者
术前Th1细胞因子即IFN-γ（中位数：138.85 pg/ml vs 140.91 pg/ml）、IL-2（中位数：36.57 pg/ml vs
36.17 pg/ml）和TNF-α（中位数：367.74 pg/ml vs 352.08 pg/ml）水平差异无统计学意义（P
均＞ 0.05），术后4周，试验组患者IFN-γ和IL-2水平均显著高于对照组（P均＜ 0.05），
TNF-α水平差异无统计学意义（z = -0.607，P = 0.544）；两组患者术后4周IL-2水平均较术
前显著升高，但IFN-γ仅试验组显著升高（P均＜ 0.05），两组患者手术前后TNF-α水平差
异均无统计学意义（P均＞ 0.05）。两组患者术前Th2细胞因子即IL-4（中位数：91.31 pg/ml
vs 90.75 pg/ml）和IL-8（中位数：193.71 pg/ml vs 231.65 pg/ml）差异无统计学意义（P均＞
0.05），术后4周试验组均显著低于对照组（IL-4中位数：40.01 pg/ml vs 46.64 pg/ml，IL-8中
位数：200.67 pg/ml vs 209.73 pg/ml；P均＜ 0.05）。与术前相比，术后4周两组患者IL-4水平
均显著降低，试验组IL-8水平显著升高，对照组显著降低（P均＜ 0.05）。结论 与肝切除联
合Hassab手术相比，肝癌RFA联合Hassab手术对HCC合并肝硬化门脉高压患者术后细胞免
疫功能影响更小，理论上减少了术后肿瘤复发转移的风险。该术式于术后4周可见机体细
胞免疫功能显著上调。该术式为患者提供了一种创伤小、恢复快的治疗方式，且为将来联
合免疫相关的肿瘤预防和治疗提供了理论基础。
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Abstract: Objective To investigate the effects of radiofrequency ablation (RFA) combined with
Hassab operation on cellular immune function of patients with hepatocellular carcinoma (HCC)
and portal hypertension. Methods Total of 47 patients with hepatocellular carcinoma (HCC) and
portal hypertension in Beijing Ditan Hospital, Capital Medical University from January 2018 to
June 2019 were selected. The patients were divided into experimental group (28 cases) and control
group (19 cases) according to different methods of surgery. Patients in experimental group were
given RFA combined with Hassab operation and patients in control group were given liver cancer
resection combined with Hassab operation. The peripheral blood were collected before surgery,
3 d and 4 weeks after surgery, respectively. Peripheral T cell subsets (CD4+
, CD8+
, CD4+
/CD8+
)
was detected by flow cytometry, Th1 cytokines and Th2 cytokines were detected by enzymelinked immunosorbent assay. Th1 cytokines included interferon γ (IFN γ), interleukin (IL)-2 and
tumor necrosis factor-α (TNF-α), and Th2 cytokines included IL-4 and IL-8. The effects of different
surgical methods on cellular immunity of the patient were compared. Results There were no
significant differences of CD4+
T cells (median: 29.80% vs 29.50%), CD8+
T cells (median: 23.60%
vs 24.30%) and CD4+
/CD8+
T cells (median: 1.30% vs 1.23%) between patients in experimental
group and control group before surgery (all P ＞ 0.05). Three days and 4 weeks after operation,
the proportion of CD4+
T cells (3 d after operation, median: 26.55% vs 21.80%; 4 weeks after
operation, median: 34.95% vs 33.30%) and CD4+
/CD8+
T cells (3 d after operation, median: 1.22%
vs 0.87%; 4 weeks after operation, median: 1.46% vs 1.23%) were significantly higher than those of
control group, CD8+
T cell (3 d after operation, median: 22.25% vs 25.50%; 4 weeks after operation,
median: 24.20% vs 26.50%) was significantly lower than that of control group, the differences were
all statistically significant (all P ＜ 0.05). Compared with those before operation, the proportion
of CD4+
T cells and CD8+
T cells of patients in experimental group decreased significantly 3 days
after surgery, and the proportion of peripheral blood CD4+
T cells, CD8+
T cells and CD4+
/CD8+
T cells
increased significantly 4 weeks after surgery (all P ＜ 0.05). The proportion of CD4+
T cells and
CD4+
/CD8+
T cells of patients in control group also decreased 3 days after surgery, and increased
significantly 4 weeks after surgery (all P ＜ 0.05). In control group, CD8+
T cells did not decrease
after surgery and remained continuously elevated. Compared with those in control group, the above
indexes of patients in experimental group were significantly different 3 days and 4 weeks after
operation (all P ＜ 0.05). There were no significant differences of Th1 cytokines including IFN- γ
(median: 138.85 pg/ml vs 140.91 pg/ml), IL-2 (median: 36.57 pg/ml vs 36.17 pg/ml) and TNF- α
(median: 367.74 pg/ml vs 352.08 pg/ml) between patients in experimental group and control group
before surgery (all P ＞ 0.05). At 4 weeks after surgery, both IFN- γ and IL-2 levels of patients in
experimental group were significantly higher than those in control group (both P ＜ 0.05), and there
was no significant difference in TNF- α level (z = -0.607, P = 0.544). Compared with those before
operation, the level of IL-2 increased significantly 4 weeks after surgery in both groups and IFN- γ
increased only in experimental group (all P ＜ 0.05). There was no significant difference in TNF- α
level of patients in both groups before and after surgery, respectively (all P ＞ 0.05). There were
no significant differences of Th2 cytokines including IL-4 (median: 91.31 pg/ml vs 90.75 pg/ml)
and IL-8 (median: 193.71 pg/ml vs 231.65 pg/ml) between patients in experimental group and
control group before surgery (all P ＞ 0.05). The above indexes of patients in experimental group
were significantly lower those in control group (IL-4 median : 40.01 pg/ml vs 46.64 pg/ml; IL-8
median: 200.67 pg/ml vs 209.73 pg/ml; all P ＜ 0.05). Compared with those before operation, IL-4
level reduced significantly in both groups at 4 weeks after surgery, IL-8 level increased significantly
in experimental group and decreased significantly in control group (all P ＜ 0.05). Conclusions RFA
combined with Hassab operation can cause less impairment to the cellular immunity of patients with HCC
and portal hypertension than hepatectomy combined with Hassab operation,which can theoretically reduce
the risk of tumor recurrence and metastasis. It can increase cellular immunity and enhance the anti-tumor
ability 4 weeks after surgery. The surgery provides a new treatment with minimally invasive and healing
faster for HCC patients with portal hypertension and it provides a theoretical basis for the prevention and
treatment of tumors with immunotherapy in the future.
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