Effect of Xiangsha Liujunzi Decoction combined with Entecavir on T cell subsets in patients with decompensation period of hepatitis B cirrhosis
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摘要: 目的 探讨香砂六君子汤加减联合恩替卡韦对乙肝肝硬化失代偿期患者的疗效和对成纤维细胞生长因子(fibroblast growth factor，FGF)-9、FGF-21及细胞免疫状态的影响。方法 选取2020年5月—2022年12月接受治疗的120例乙肝肝硬化失代偿期患者为研究对象，应用随机数字表法分为对照组和研究组。对照组采取恩替卡韦治疗，研究组在对照组的基础上加用香砂六君子汤，比较两组患者的疗效和治疗前后T细胞亚群的变化情况。结果 研究组治疗总有效率高于对照组(P>0.05)。治疗后对照组和研究组患者的各中医症状积分比治疗前均明显减少，且研究组减少幅度比对照组更大(P < 0.05)；治疗后对照组和研究组患者的透明质酸(hyaluronic acid，HA)、层黏蛋白(laminin，LN)、Ⅲ型前胶原(procollagen Ⅲ，PCⅢ)、Ⅳ型胶原(Ⅳ collagen，Ⅳ-C)水平均较治疗前明显减少，前白蛋白(pre-albumin，PA)、白蛋白(albumin，ALB)、血清胆碱酯酶(cholinesterase，CHE)水平明显增加，且研究组上述指标改善程度优于对照组(P < 0.05)；治疗后两组患者的血清FGF-9水平明显降低，FGF-21水平明显升高，且研究组改善程度优于对照组(P < 0.05)；治疗后两组患者的T细胞亚群CD3+、CD4+、CD4+/CD8+均明显升高，CD8+明显降低，且研究组上述指标变化程度高于对照组(P < 0.05)。两组患者治疗过程中均未见严重不良反应，患者可耐受。结论 香砂六君子汤联合恩替卡韦治疗乙肝肝硬化能明显改善患者症状，促进肝功能指标恢复，同时还能显著改善FGF-9、FGF-21水平，延缓疾病进展，提升机体细胞免疫功能，值得临床推广应用。Abstract: Objective To investigate the effects of Xiangsha Liujunzi Decoction combined with Entecavir on fibroblast growth factor(FGF)-9, FGF-21 and cellular immunity in patients with decompensation period of hepatitis B cirrhosis.Methods One hundred and twenty patients with decompensated hepatitis B cirrhosis who received treatment in our hospital from May 2020 to December 2022 were selected for this study. They were divided into control group and study group by random number table method. The control group was treated with Entecavir, and the study group was treated with Xiangsha Liujunzi Decoction on the basis of the control group. The therapeutic effect and T cell subsets before and after treatment were compared.Results The total effective rate of the study group was higher than that of the control group(P>0.05). After treatment, the scores of Traditional Chinese Medicine symptoms in both the control group and the study group were significantly reduced compared with before treatment, and the reduction in the study group was greater than that in the control group(P < 0.05). After treatment, hyaluronic acid(HA), laminin, LN, procollagen Ⅲ(PCⅢ) and Ⅳcollagen(Ⅳ-C) decreased significantly compared with that before treatment, and pre-albumin(PA), albumin(ALB) and serum cholinesterase(CHE) increased significantly. The improvement of these indexes in the study group was higher than those in the control group(P < 0.05). After treatment, the serum FGF-9 level was significantly decreased and FGF-21 level was significantly increased, T cell subsets CD3+, CD4+, CD4+/CD8+were significantly increased in both groups, while CD8+was significantly decreased, and the improvement degree of the study group was better than that of the control group(P < 0.05). No serious adverse reactions were observed in the two groups, which were tolerated by the patients.Conclusion Xiangsha Liujunzi Decoction combined with conventional Entecavir can significantly improve the symptoms of patients with hepatitis B cirrhosis, promote the recovery of liver function indicators, and also significantly improve the levels of FGF-9 and FGF-21, delay the progress of disease, and enhance the cellular immune function of the body, which is worthy of clinical application.
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表 1 两组患者的临床资料比较
例，X±S 组别 例数 性别 年龄/岁 病程/年 HBV DNA/
(log10 coppies/mL)ALT/
(U/L)ALB/
(g/L)TBIL/
(μmol/L)Child-Pugh
分级(B/C)男 女 对照组 60 47 13 50.23±12.44 2.59±0.57 6.40±0.78 208.06±25.04 92.13±23.18 24.09±3.22 33/27 研究组 60 45 15 50.53±11.75 2.64±0.49 6.37±0.74 204.11±55.40 95.46±25.47 24.32±2.67 36/24 χ2/t 0.186 0.136 0.515 0.216 0.503 0.749 0.426 0.307 P 0.666 0.892 0.607 0.829 0.616 0.455 0.671 0.580 注：ALT：谷丙转氨酶；ALB：血清白蛋白；TBIL：总胆红素。 
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表 2 研究组和对照组的治疗效果比较
例(%) 组别 例数 显效 有效 无效 总有效 研究组 60 32(53.33) 18(30.00) 10(16.67) 50(83.33) 对照组 60 22(36.67) 17(28.33) 21(35.00) 39(65.00) χ2 5.263 P 0.022
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表 3 研究组和对照组治疗前后的中医症状积分比较
分，X±S 组别 例数 纳差 倦怠乏力 胁肋刺痛 脘腹痞闷 肋下痞块 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 研究组 60 2.28±0.53 0.33± 0.091) 2.04±0.22 0.21± 0.071) 2.46±0.32 0.32± 0.101) 2.27±0.45 0.30± 0.091) 2.40±0.29 0.34± 0.111) 对照组 60 2.39±0.50 0.98± 0.201) 1.98±0.26 0.88± 0.171) 2.41±0.33 0.96± 0.241) 2.31±0.39 0.89± 0.241) 2.43±0.32 0.91± 0.171) t 1.169 2.957 1.365 28.229 0.843 19.067 0.520 17.830 0.539 21.805 P 0.245 < 0.001 0.175 < 0.001 0.401 < 0.001 0.604 < 0.001 0.592 < 0.001 与治疗前比较，1)P < 0.05。
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表 4 研究组和对照组治疗前后肝脏硬度值、肝功能指标及肝纤维化指标比较
X±S 组别 例数 肝脏硬度值/kPa ALB/(g/L) PA/(mg/L) CHE/(U/L) 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 研究组 60 20.39±3.19 13.29± 2.121) 23.51±5.17 36.40± 5.531) 79.12±22.02 106.05± 28.721) 1 547.19±465.90 3 478.15± 983.521) 对照组 60 20.47±3.02 16.74± 3.301) 21.94±6.11 32.09± 6.241) 81.39±24.63 91.05± 21.661) 1 528.60±487.79 2 782.31± 836.941) t 0.141 6.813 1.519 4.004 0.532 3.230 0.213 4.174 P 0.888 < 0.001 0.131 < 0.001 0.596 0.002 0.831 < 0.001 组别 例数 HA/(μg/L) LN/(μg/L) PCⅢ/(μg/L) Ⅳ-C/(μg/L) 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 研究组 60 180.59±55.73 126.43± 31.721) 202.35±56.54 142.45± 32.181) 203.37±59.56 112.39± 19.521) 175.38±50.37 92.74± 30.091) 对照组 60 182.06±57.50 163.26± 35.951) 201.48±58.15 183.57± 45.691) 201.98±60.60 143.25± 29.741) 177.13±56.16 123.05± 33.471) t 0.142 5.950 0.083 5.699 0.127 6.720 0.180 5.217 P 0.887 < 0.001 0.934 < 0.001 0.899 < 0.001 0.858 < 0.001 与治疗前比较，1)P < 0.05。
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表 5 研究组和对照组治疗前后血清FGF-9、FGF-21水平比较
ng/L，X±S 组别 例数 FGF-21 FGF-9 治疗前 治疗后 治疗前 治疗后 研究组 60 90.47±9.91 137.53±12.911) 426.72±59.44 352.34±53.071) 对照组 60 91.62±11.03 166.39±15.801) 423.97±60.15 304.16±50.841) t 0.601 10.956 0.252 5.078 P 0.549 < 0.001 0.802 < 0.001 与治疗前比较，1)P < 0.05。
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表 6 研究组和对照组治疗前后T细胞亚群比较
X±S 组别 例数 CD3+/% CD4+/% CD8+/% CD4+/CD8+ 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 研究组 60 52.57±6.49 70.06± 5.631) 30.07±2.92 39.36± 3.181) 37.35±4.41 28.04± 3.021) 1.05±0.22 1.51± 0.17 对照组 60 53.14±6.75 60.04± 5.821) 30.37±2.64 33.09± 2.601) 37.81±4.39 32.06± 2.891) 1.09±0.24 1.34± 0.15 t 0.472 9.585 0.590 11.824 0.573 7.449 0.952 5.808 P 0.638 < 0.001 0.556 < 0.001 0.568 < 0.001 0.343 < 0.001 与治疗前比较，1)P < 0.05。
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