柴胡疏肝散配方颗粒与饮片治疗慢性乙肝疗效比较

Comparative efficacy of Chaihu Shugan San formula granules and traditional decoction pieces in treating chronic hepatitis B: a randomized controlled trial

摘要

目的: 评价柴胡疏肝散配方颗粒与传统饮片治疗慢性乙型肝炎(chronic hepatitis B,CHB)免疫清除期肝郁气滞证的临床疗效与安全性的一致性,为临床剂型选择提供循证依据。方法: 采用多中心、随机、单盲、阳性对照临床试验设计,纳入133例CHB免疫清除期肝郁气滞证患者,按随机数字表法分为受试组(配方颗粒)和对照组(传统饮片)。两组均饭前口服,tid,14 d为1个疗程,疗程间隔1 d,连续治疗2个疗程。以治疗应答率、乙型肝炎病毒脱氧核糖核酸(hepatitis B virus DNA,HBV-DNA)定量、肝功能指标[谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)]、中医证候评分及不良反应为评价指标,采用一致性检验方法分析两组疗效与安全性的一致性。结果: 两组治疗应答率一致性较强(κ=0.645),受试组完全应答率(8.0%)高于对照组;两组肝功能AST、ALT改善情况一致性均较强[相关系数(ICC)=0.689、0.791],且受试组治疗后AST、ALT均值均低于对照组;两组中医证候评分改善一致性较强(ICC=0.637),受试组治疗后证候评分低于对照组;两组HBV-DNA转阴率一致性一般(κ=0.332),受试组转阴率(42.7%)高于对照组(30.0%);受试组不良反应发生率为5.0%,对照组无不良反应发生。结论: 柴胡疏肝散配方颗粒与传统饮片在整体应答率及肝功能改善方面一致性较强;配方颗粒在中医证候改善、HBV-DNA转阴率及完全应答率方面优于传统饮片,但轻度不良反应发生率较高,提示临床选方配药时应考虑安全风险。

Abstract

Objective: To evaluate the consistency of clinical efficacy and safety between Chaihu Shugan San formula granules and traditional decoction pieces in the treatment of chronic hepatitis B (CHB) in the immune clearance phase with liver depression and qi stagnation syndrome, and to provide an evidence-based basis for clinical dosage form selection. Methods: A multicenter, randomized, single-blind, positive-controlled clinical trial design was adopted. A total of 133 patients with CHB in the immune clearance phase with liver depression and qi stagnation syndrome were enrolled and randomly divided into a test group (formula granules) and a control group (traditional decoction pieces) using a random number table. Both groups received oral administration before meals, three times a day, with 14 days as one course of treatment, an interval of 1 day between courses, and a total of 2 consecutive courses. The treatment response rate, hepatitis B virus DNA (HBV-DNA) quantification, liver function indexes [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], TCM syndrome score and adverse reactions were used as evaluation indicators, and a consistency test was employed to analyze the consistency of efficacy and safety between the two groups. Results: The consistency of treatment response rate between the two groups was strong (κ=0.645); the complete response rate in the test group (8.0%) was higher than that in the control group. The consistency of improvement of AST and ALT between the two groups was strong [intraclass correlation coefficient (ICC)=0.689, 0.791], and the mean AST and ALT after treatment in the test group were lower than those in the control group. The consistency of the improvement in TCM syndrome scores between the two groups was strong (ICC=0.637), and the post treatment syndrome score in the test group was lower than that in the control group. The consistency of HBV-DNA negative conversion rate between the two groups was moderate (κ=0.332), and the negative conversion rate in the test group (42.7%) was higher than that in the control group (30.0%). The incidence of adverse reactions in the test group was 5.0%, and no adverse reactions occurred in the control group. Conclusion: Chaihu Shugan San formula granules and traditional decoction pieces show strong consistency in overall response rate and liver function improvement. Formula granules demonstrate advantages in TCM syndrome improvement, HBV-DNA negative conversion rate, and complete response rate; however, they are associated with a higher incidence of adverse reactions. Therefore, the benefits and risks should be carefully weighed when selecting the dosage form in clinical practice.

关键词

柴胡疏肝散 / 中药配方颗粒 / 慢性乙型肝炎 / 免疫清除期 / 肝郁气滞证 / 疗效一致性

Key words

Chaihu Shugan Powder / traditional Chinese medicine formula granules / chronic hepatitis B / immune clearance phase / liver depression and qi stagnation syndrome / efficacy consistency

[1] 张伟, 孙叶芬, 金传山, 等. 中药配方颗粒研究现状与展望[J]. 中草药, 2022, 53(22): 7221-7233.
[2] 白娟, 刘燕, 王丹妮, 等. 柴胡疏肝散在肝郁证中的作用机制[J]. 中国实验方剂学杂志, 2020, 26(3): 199-204.
[3] 张金付. 柴胡疏肝散联合富马酸替诺福韦二吡呋酯治疗肝郁气滞型慢性乙型肝炎临床观察[J]. 中国中医药现代远程教育, 2021, 19(24): 121-123.
[4] 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎诊断标准(2015年版)[J]. 中西医结合肝病杂志, 2015, 25(6): 384, 后插1, 后插2.
[5] 国家中医药管理局. 中医病证诊断疗效标准[J]. 南京: 南京大学出版社, 1995: 121-123.
[6] 原凌燕, 胡开进, 张婷, 等. 柴胡舒肝散治疗常见病毒性肝炎的疗效及安全性[J]. 基因组学与应用生物学, 2019, 38(4): 1776-1785.
[7] 薛运浩. 比较中药配方颗粒与传统中药饮片汤剂治疗胃溃疡患者的效果及安全性研讨[J]. 内蒙古中医药, 2025, 44(8): 157-158, 168.
[8] 李佳怡, 郭媛媛, 郑长辉, 等. 《中药配方颗粒临床使用指南》解读[J]. 中国现代中药, 2025, 27(8): 1417-1422.
[9] 党玉霞. 中药配方颗粒和中药汤剂等效性研究进展[J]. 内蒙古中医药, 2025, 44(5): 151-153.
[10] 李雅雄, 王扶桑, 张梅, 等. 基于全面触发工具对住院患者使用中药配方颗粒及饮片不良事件的回顾性分析[J]. 中国药房, 2025, 36(5): 606-611.
[11] 郭卓琳, 郭新邓, 张智恒, 等. 连翘配方颗粒与传统汤剂的抗炎和保肝效果的比较研究[J/OL]. 中药药理与临床, 1-20[2026-01-28].https://doi.org/10.13412/j.cnki.zyyl.20251011.004.

基金资助

四川省中医药发展专项资金资助项目(T000011947436)