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摘要：
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摘要：目的 探讨恩替卡韦联合奥沙利铂、卡培他滨治疗对乙型肝炎病毒（hepatitis B virus，HBV）相
关晚期肝细胞癌（hepatocellular carcinama，HCC）患者外周血淋巴细胞亚群的影响。方法 回顾性分
析2016年5月至2017年5月聊城市传染病医院收治的154例HBV相关晚期HCC患者的临床资料，根据使
用药物不同分为研究组（77例）和对照组（77例），对照组采用恩替卡韦治疗（0.5 mg，1次/d），
研究组在对照组的基础上应用奥沙利铂（50 mg，1次/d）和卡培他滨（1.0 g/次，2次/d，连服14 d）
进行化学治疗，化学治疗21 d为1个疗程，共治疗2个疗程。比较两组患者治疗前和治疗后1个月血清
CD3、CD4、CD8、CD19、CD56 + 、天门冬氨酸氨基转移酶（aspartate aminotransferase，AST）、
丙氨酸氨基转移酶（alanine aminotransferase，ALT）、总胆红素（total bilirubin，TBil）和甲胎蛋白
（alpha-fetoprotein，AFP）水平。记录两组患者不良反应发生情况。采用Spearman相关性分析CD3、
CD4、CD8、CD19、CD56 + 与AFP的相关性。结果 研究组和对照组患者治疗前CD3 [（55.9 ± 11.2）%
vs（54.2 ± 10.3）%]、CD4 [（32.1 ± 8.3）% vs（32.2 ± 8.1）%]、CD8 [（11.4 ± 4.7）% vs（11.5 ±
1.5）%]、CD19 [（8.3 ± 2.7）% vs（8.2 ± 2.2）%]及CD56 + [（8.3 ± 2.2）% vs（8.2 ± 2.2）%]水平差
异无统计学意义（P均＞ 0.05），治疗后研究组CD3 [（76.2 ± 8.2）% vs（60.1 ± 6.4）%]、CD4 [（50.6 ±
10.2）% vs（38.2 ± 9.2）%]、CD19 [（11.0 ± 3.1）% vs（8.2 ± 2.2）%]及CD56 + [（17.3 ± 4.3）% vs
（13.1 ± 5.1）%]水平均显著高于对照组，CD8水平[（4.8 ± 0.4）% vs（9.6 ± 1.2）%]显著低于对照
组，差异均有统计学意义（P均＜ 0.05）。研究组和对照组患者治疗前TBil [（17.8 ± 7.1）μmoI/L vs
（18.5 ± 6.4）μmoI/L]、ALT [（38.4 ± 8.1）U/L vs（38.5 ± 8.2）U/L]及AST [（32.5 ± 8.2）U/L vs（32.1 ±
6.5）U/L]水平差异无统计学意义（P均＞ 0.05），治疗后1个月研究组患者TBil [（16.5 ± 4.4）μmoI/L vs
（18.2 ± 5.2）μmoI/L]、ALT [（40.1 ± 7.2）U/L vs（42.9 ± 9.3）U/L]及AST [（28.1 ± 5.3）U/L vs（32.7 ±
8.4）U/L]均显著低于对照组（P均＜ 0.05）。研究组和对照组患者治疗前AFP [（132.32 ± 34.5）μg/L vs
（135.51 ± 29.2）μg/L]差异无统计学意义（t = 1.088，P = 0.062）；治疗后1个月研究组AFP显著低
于对照组[（56.11 ± 26.3）μg/L vs（125.7 ± 35.1）μg/L；t = 11.366，P = 0.033]。研究组并发症发生
率为23.4%（18/77），对照组为6.5%（5/77），差异有统计学意义（χ 2 = 5.369，P = 0.034）。CD3、
CD4、CD19和CD56 + 与AFP呈负相关（r值分别为-0.655、-0.366、-0.965、-0.431，P值分别为0.046、
0.042、0.035、0.026），CD8与AFP呈正相关（r = 0.693，P = 0.026）。结论 对于HBV相关晚期HCC
患者，采用恩替卡韦联合奥沙利铂和卡培他滨化学治疗有助于改善外周血淋巴细胞计数。
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Abstract: Objective To investigate the effects of entecavir combined with oxaliplatin and capecitabine
chemotherapy on peripheral blood lymphocyte subsets of patients with hepatitis B virus (HBV) related
advanced hepatocellular carcinoma (HCC). Methods The clinical data of 154 cases with HBV related
advanced HCC in Liaocheng Infectious Disease Hospital from May 2016 to May 2017 were retrospectively
analyzed. They were divided into research group (77 cases) and control group (77 cases) according to the
use of different drugs. Patients in control group were treated with entecavir (0.5 mg, 1 time/d), patients in
research group were treated with oxaliplatin (50 mg, 1 time/d) and capecitabine (1.0 g/time, 2 times/d, for 14
days) for chemotherapy on the basis of control group. A course of chemotherapy was 21 d and 2 courses of
treatment were performed. Serum CD3, CD4, CD8, CD19, CD56 + , aspartate aminotransferase (AST), alanine
aminotransferase (ALT), total bilirubin (TBil) and alpha-fetoprotein (AFP) of patients before and 1 month
after treatment were compared. The occurrence of adverse reactions were recorded. Spearman correlation
analysis was used to analyze the relationship of CD3, CD4, CD8, CD19, CD56 + and AFP. Results There were
no significant differences in CD3 [(55.9 ± 11.2)% vs (54.2 ± 10.3)%], CD4 [(32.1 ± 8.3)% vs (32.2 ± 8.1)%],
CD8 [(11.4 ± 4.7)% vs (11.5 ± 1.5)%], CD19 [(8.3 ± 2.7)% vs (8.2 ± 2.2)%] and CD56 + [(8.3 ± 2.2)% vs (8.2 ± 2.2)%]
levels of patients between research group and control group before treatment (all P ＞ 0.05). After treatment
for 1 month, the levels of CD3 [(76.2 ± 8.2)% vs (60.1 ± 6.4)%], CD4 [(50.6 ± 10.2)% vs (38.2 ± 9.2)%],
CD19 [(11.0 ± 3.1)% vs (8.2 ± 2.2)%] and CD56 [(17.3 ± 4.3)% vs (13.1 ± 5.1)%] were significantly higher
than those of control group, CD8 level [（4.8 ± 0.4）% vs（9.6 ± 1.2）%] was significantly lower than that
of control group, the differences were statistically significant (all P ＜ 0.05). There were no significant differences
in TBil [(17.8 ± 7.1) μmoI/L vs (18.5 ± 6.4) μmoI/L], ALT [(38.4 ± 8.1) U/L vs (38.5 ± 8.2) U/L] and AST [(32.5 ±
8.2) U/L vs (32.1 ± 6.5) U/L] levels of patients between research group and control group before treatment (all
P ＞ 0.05). After treatment for 1 month, the levels of TBil [(16.5 ± 4.4) μmoI/L vs (18.2 ± 5.2) μmoI/L],
ALT [(40.1 ± 7.2) U/L vs (42.9 ± 9.3) U/L] and AST [(28.1 ± 5.3) U/L vs (32.7 ± 8.4) U/L] were significantly
lower than those of control group (all P ＜ 0.05). There were no significant differences in the level of
AFP [(132.32 ± 34.5) μg/L vs (135.51 ± 29.2) μg/L] in patients between research group and control group
before treatment. After treatment for 1 month, the level of AFP was significantly lower than that of control
group [(56.11 ± 26.3) μg/L vs (125.7 ± 35.1) μg/L; t = 11.366, P = 0.033]. The incidence of complications
was 23.4% (18/77) in the research group and 6.5% (5/77) in the control group, The difference was statistically
significant (χ 2 = 5.369, P = 0.034). CD3, CD4, CD19 and CD56 were negatively correlated with AFP (r =
-0.655, -0.366, -0.965, -0.431; P = 0.046, 0.042, 0.035, 0.026) and CD8 was positively correlated with AFP
(r = 0.693, P = 0.026). Conclusions Entecavir combined with oxaliplatin and capecitabine chemotherapy for
patients with HBV associated advanced HCC could improve the peripheral blood lymphocyte counts.
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