扶正化瘀片联合恩替卡韦治疗慢性乙型肝炎肝纤维化的效果观察

顾宏图; 桂红莲; 徐列明; 郭清; 谢青; 赵长青

doi:10.3969/j.issn.1001-5256.2021.02.013

扶正化瘀片联合恩替卡韦治疗慢性乙型肝炎肝纤维化的效果观察

DOI: 10.3969/j.issn.1001-5256.2021.02.013

顾宏图^{1, 2, 3},
桂红莲⁴,
徐列明^{1, 2, 3},
郭清⁴,
谢青^4, ,,
赵长青^{1, 2, 3, ,}

1.
上海中医药大学附属曙光医院肝硬化科，上海 201203
2.
上海市中医临床重点实验室，上海 201203
3.
上海中医药大学肝肾疾病病证教育部重点实验室，上海 201203
4.
上海交通大学医学院附属瑞金医院感染科，上海 200025

基金项目:

上海市临床重点专科建设项目 (shslczdzk01103);

国家自然科学基金 (81673780)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突，特此声明。

作者贡献声明：顾宏图、桂红莲、郭清参与收集数据；徐列明、谢青负责课题设计，拟定写作思路，指导撰写文章；赵长青负责资料分析，撰写论文并最后定稿。

详细信息

作者简介:
顾宏图(1970—)，男，副主任医师，主要从事慢性肝病、肝硬化及其并发症的研究

桂红莲(1982—)，女，主治医师，主要从事慢性肝炎及肝硬化的研究

通信作者:
谢青，xieqingrjh@163.com

赵长青，cathy090909@126.com

二者对本文贡献相同，同为第一作者

中图分类号: R512.62;R575.2
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- 被引次数: 0
出版历程
- 收稿日期: 2020-08-28
- 录用日期: 2020-09-30
- 出版日期: 2021-02-20

Clinical effect of Fuzheng Huayu tablets combined with entecavir in the treatment of chronic hepatitis B liver fibrosis

Hongtu GU^{1, 2, 3},
Honglian GUI⁴,
Lieming XU^{1, 2, 3},
Qing GUO⁴,
Qing XIE^{4
, ,},
Changqing ZHAO^{1, 2, 3
, ,}

1.
Department of Liver Cirrhosis, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2.
Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China
3.
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai 201203, China
4.
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

摘要

摘要: 目的观察扶正化瘀片(FZHY)联合恩替卡韦(ETV)治疗慢性乙型肝炎(CHB)肝纤维化的疗效与安全性。方法选取2011年4月—2013年1月在上海交通大学附属瑞金医院和上海中医药大学附属曙光医院2个中心，肝纤维化Ishak分期≥F3的CHB肝纤维化患者52例，分为FZHY联合ETV组(联合组，n=26)和安慰剂联合ETV组(对照组，n=26)，分别治疗48周。治疗前后行两次肝穿刺活检，以两组的肝脏病理纤维化Ishak分期逆转率和肝组织学活动指数(HAI)炎症分级改善率等判断疗效，以心电图等为安全性指标。确定3个分析数据集(全分析集、符合方案集、安全数据集)，计量资料两组间比较采用t检验或Wilcoxon检验；计数资料组间比较采用CMH χ²法、χ²检验或Fisher精确概率法。结果 46例患者完成了治疗前后两次肝穿刺，其中联合组22例，对照组24例。治疗48周时，两组Ishak分期下降≥1级患者比例差异有统计学意义(81.8% vs 54.2%，χ²=5.297，P=0.021)。联合组和对照组HAI分级改善率分别为59.1%、25.0%，差异有统计学意义(χ²=6.822，P=0.009)。两组不良事件发生率、严重不良事件发生率，不良反应发生率、生命体征安全性分析、实验室安全性指标等比较，差异均无统计学意义(P值均＞0.05)。结论在改善肝纤维化和肝脏炎症方面，FZHY联合ETV相较于单用ETV有显著优势，抗病毒联合抗纤维化治疗能够给CHB患者带来更好的肝组织学改善。FZHY联合ETV治疗CHB肝纤维化患者有良好的安全性。
- 乙型肝炎, 慢性 /
- 肝硬化 /
- 恩替卡韦 /
- 扶正化瘀片 /
- 治疗结果
Abstract: Objective To investigate the efficacy and safety of Fuzheng Huayu tablets (FZHY) combined with entecavir (ETV) in the treatment of chronic hepatitis B (CHB) liver fibrosis. Methods A total of 52 patients with CHB liver fibrosis with an Ishak stage of ≥F3 who were treated in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from April 2011 to January 2013 were enrolled and divided into FZHY combined with ETV group (combination group) and placebo combined with ETV group (control group), with 26 patients in each group, and the course of treatment was 48 weeks for both groups. Liver biopsy was performed before and after these treatment; clinical outcome was determined based on the reversal rate of Ishak stage for liver fibrosis and the improvement rate of histological activity index (HAI) for inflammation grade, and safety was evaluated based on electrocardiographic findings. Three datasets (full analysis set, per-protocol set, and safety dataset) were identified for analysis; the t-test or the Wilcoxon test was used for comparison of continuous data between two groups, and the CMH chi-square test, the chi-square test, or the Fisher's exact test was used for comparison of categorical data between groups. Results Of all 52 patients, 46 underwent the two liver biopsies before and after treatment, with 22 in the combination group and 24 in the control group. At week 48 of treatment, there was a significant difference in the proportion of patients with Ishak stage reduced by ≥1 stage between the combination group and the control group (81.8% vs 54.2%, χ²=5.297, P=0.021). There was also a significant difference in the improvement rate of HAI grade between the combination group and the control group were (59.1% vs 25.0%, χ²=6.822, P=0.009). There were no significant differences between the two groups in the incidence rates of adverse events and serious adverse events, the safety analysis of vital signs, and laboratory safety indicators (all P > 0.05). Conclusion FZHY combined with ETV has significant advantages over ETV alone in improving liver fibrosis and inflammation, and antiviral therapy combined with anti-fibrosis therapy can bring better hepatic histological improvement for CHB patients. FZHY combined with ETV has good safety in the treatment of patients with CHB liver fibrosis.
- Hepatitis B, Chronic /
- Liver Cirrhosis /
- Entecavir /
- Fuzheng Huayu Tablet /
- Treatment Outcome

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表 1 两组患者主要基线资料比较

项目	联合组(n=25)	对照组(n=26)	统计值	P值
年龄(岁)	44.48±10.31	42.46±11.39	t=0.663	0.511
男性[例(%)]	15(60.0)	19(73.1)	χ²=0.981	0.322
身高(cm)	165.44±7.81	168.27±7.70	t=1.302	0.199
体质量(kg)	65.26±11.15	64.94±9.51	t=0.110	0.913
诊断			χ²=0.024	0.877
乙型肝炎[例(%)]	11(44.0)	12(46.2)
乙型肝炎肝硬化[例(%)]	14(56.0)	14(53.8)
病程
乙型肝炎病程(年)	11.00(4.75~14.25)	15.50(10.34~21.13)	χ²=3.896	0.048
肝硬化病程(月)	22.20(3.36~63.88)	6.45(1.03~29.69)	χ²=1.218	0.270
实验室检查指标
HBV DNA (log拷贝/ml)	5.94±0.92	5.87±1.23	t=0.222	0.826
HBeAg阳性[例(%)]	15(60.0)	14(53.8)	χ²=0.197	0.662
HBeAg阴性[例(%)]	10(40.0)	12(46.2)
ALT(U/L)	42.24±22.23	43.35±24.93	t=0.167	0.868
AST(U/L)	34.60±16.32	36.88±16.17	t=0.502	0.618
TBil(μmol/L)	18.12±5.18	16.15±5.46	t=1.320	0.193
ALP(U/L)	72.24±24.19	67.96±15.29	t=0.752	0.457
白蛋白(g/L)	44.30±2.99	44.12±3.72	t=0.187	0.853
球蛋白(g/L)	30.62±3.68	31.38±3.62	t=0.740	0.463
PT(s)	13.19±1.40	13.71±1.23	t=1.062	0.298
肝脏炎症HAI分级[例(%)]			χ²=0.008	0.928
1级	2(8.0)	0
2级	11(44.0)	17(65.4)
3级	11(44.0)	7(26.9)
4级	1(4.0)	2(7.7)
肝纤维化Ishak分期[例(%)]			χ²=0.034	0.854
3期	8(32.0)	5(19.2)
4期	4(16.0)	9(34.6)
5期	6(24.0)	8(30.8)
6期	7(28.0)	4(15.4)
LSM(kPa)	13.80±8.94	16.24±13.11	t=0.774	0.442

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表 2 治疗前后肝纤维化Ishak分期和肝脏炎症HAI分级改变情况

项目	联合组 (n=22)	对照组 (n=24)	χ²值	P值
Ishak分期改变[例(%)]			5.297	0.021
增加≥1期	0	4(16.7)
不变	4(18.2)	7(29.2)
下降≥1期	18(81.8)	13(54.2)
HAI分级改变[例(%)]			6.822	0.009
增加≥1级	0	3(12.5)
不变	9(40.9)	15(62.5)
下降≥1级	13(59.1)	6(25.0)

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参考文献(12)

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