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


CONCLUSIONS
Liver fibrosis and early cirrhosis due to HBV infection in man could be definitely reversed by herbal remedy Cpd 861.
Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 100050, China.
Shan-shan
SS
Yin
Bao-en
BE
Wang
Tai-ling
TL
Wang
Ji-dong
JD
Jia
Lin-xue
LX
Qian
D000293:Adolescent; D000328:Adult; D000368:Aged; D024141:Collagen Type IV / Q000097:blood; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy
D024141:Collagen Type IV; D004365:Drugs, Chinese Herbal; C476499:herbal compound 861; D006820:Hyaluronic Acid