[Cpd 861对慢性乙型肝炎相关纤维化和早期肝硬化的影响：一项随机、双盲、安慰剂对照临床试验]

[The effect of Cpd 861 on chronic hepatitis B related fibrosis and early cirrhosis: a randomized, double blind, placebo controlled clinical trial].

作者信息

Yin Shan-shan, Wang Bao-en, Wang Tai-ling, Jia Ji-dong, Qian Lin-xue

机构信息

Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 100050, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2004 Aug;12(8):467-70.

PMID:15329205

Abstract

OBJECTIVES

To further assess the clinical antifibrotic efficacy of Cpd 861 on chronic hepatitis B related fibrosis and early cirrhosis using a randomized, double blind, and placebo controlled clinical trial.

METHODS

Total 136 patients with HBV-related fibrosis and early cirrhosis were allocated randomly into Cpd 861 treatment group and placebo group for 24 weeks treatment. Serum fibrosis markers including hyaluronic acid (HA), IV collagen (IV-C), amino terminal propeptide of type III procollagen (PIIIP), and laminin (LN) and serum MMP1, 2, 9, TIMP1, 2 level were determined before and after 24 weeks treatment. Liver biopsies before and after 24 weeks of treatment were assessed according to modified Scheuer and Chevallier's scoring system.

RESULTS

Total 52 patients in Cpd 861 treatment group and 50 patients in placebo-controlled group completed the 6 months. ALT level decreased from 68.2 U/L+/-68.6 U/L to 45.9 U/L+/-26.1 U/L, AST level decreased from 60.4 U/L+/-62.6 U/L to 46.7 U/L+/-39.0 U/L (P < 0.05) after 24 weeks treatment, whereas there was no significant change in placebo group (ALT: 65.3 U/L+/-48.3 U/L to 85.4 U/L+/-115.5 U/L; AST: 60.4 U/L+/-44.6 U/L to 77.6 U/L+/-89.6 U/L, P > 0.05). Serum fibrosis markers, including HA, IV-C, PIIIP, and LN were decreased after treatment, but there is no statistically significant compared with placebo group. Compared with placebo group, serum TIMP1 and MMP9 level decreased significantly (TIMP1 172.0 ng/ml+/-79.6 ng/ml vs 133.5 ng/ml+/-66.8 ng/ml; MMP9 116.1 ng/ml+/-88.2 ng/ml vs 80.4 ng/ml+/-79.0 ng/ml), and the ratio of TIMP1/MMP1 (48.3+/-96.3 vs 19.9+/-28.0) were also decreased after 861 treatment. In patients treated with Cpd 861, hepatic inflammatory score (from 14.0+/-6.0 to 10.2+/-6.1), fibrosis score (from 11.9+/-6.5 to 8.2+/-4.5), and relative content of collagen (from 18.9%+/-9.5% to 14.9%+/-8.4%) decreased significantly. In contrast, there was no significant change in placebo group. The reversal (fibrosis score decrease > or = 2) rate of fibrosis in Cpd 861 group was 38.9% in S2, 53.3% in S3 (precirrhotic) and 78.6% in S4 (cirrhosis), significantly higher than those in placebo group (14.3%, 25.0%, and 41.7%, respectively). The overall reversal rate was 52.0% in Cpd 861 group, and 20.0% in placebo group (P < 0.05). No serious adverse effects were observed during Cpd 861 treatment.

CONCLUSION

Liver fibrosis and early cirrhosis due to HBV infection in man could be definitely reversed by herbal remedy Cpd 861.

摘要

目的

采用随机、双盲、安慰剂对照临床试验，进一步评估化合物861对慢性乙型肝炎相关纤维化和早期肝硬化的临床抗纤维化疗效。

方法

将136例乙肝相关纤维化和早期肝硬化患者随机分为化合物861治疗组和安慰剂组，进行24周治疗。在治疗24周前后测定血清纤维化标志物，包括透明质酸（HA）、IV型胶原（IV-C）、III型前胶原氨基端前肽（PIIIP）和层粘连蛋白（LN）以及血清MMP1、2、9、TIMP1、2水平。根据改良的Scheuer和Chevallier评分系统对治疗24周前后的肝活检进行评估。

结果

化合物861治疗组52例患者和安慰剂对照组50例患者完成了6个月的治疗。治疗24周后，ALT水平从68.2 U/L±68.6 U/L降至45.9 U/L±26.1 U/L，AST水平从60.4 U/L±62.6 U/L降至46.7 U/L±39.0 U/L（P<0.05），而安慰剂组无显著变化（ALT：65.3 U/L±48.3 U/L至85.4 U/L±115.5 U/L；AST：60.4 U/L±44.6 U/L至77.6 U/L±89.6 U/L，P>0.05）。治疗后血清纤维化标志物，包括HA、IV-C、PIIIP和LN均下降，但与安慰剂组相比无统计学意义。与安慰剂组相比，血清TIMP1和MMP9水平显著下降（TIMP1 172.0 ng/ml±79.6 ng/ml对133.5 ng/ml±66.8 ng/ml；MMP9 116.1 ng/ml±88.2 ng/ml对80.4 ng/ml±79.0 ng/ml），化合物861治疗后TIMP1/MMP1比值（48.3±96.3对19.9±28.0）也下降。在接受化合物861治疗的患者中，肝脏炎症评分（从14.0±6.0降至10.2±6.1）、纤维化评分（从11.9±6.5降至8.2±4.5）和胶原相对含量（从18.9%±9.5%降至14.9%±8.4%）显著下降。相比之下，安慰剂组无显著变化。化合物861组纤维化逆转（纤维化评分下降≥2）率在S2期为38.9%，S3期（肝硬化前期）为53.3%，S4期（肝硬化）为78.6%，显著高于安慰剂组（分别为14.3%、25.0%和41.7%）。化合物861组总体逆转率为52.0%，安慰剂组为20.0%（P<0.05）。在化合物861治疗期间未观察到严重不良反应。