Multicenter clinical study on Fuzhenghuayu capsule against liver fibrosis due to chronic hepatitis B

AIM: To study the efficacy and safety of Fuzhenghuayu capsule (FZHY capsule, a capsule for strengthening body resistance to remove blood stasis) against liver fibrosis due to chronic hepatitis B. METHODS: Multicenter, randomized, double blinded and parallel control experiment was conducted in patients (aged from 18 to 65 years) with liver fibrosis due to chronic hepatitis B. Hepatic histologic changes and HBV markers were examined at wk 0 and 24 during treatment. Serologic parameters (HA, LM, P-Ⅲ-P, Ⅳ-C) were determined and B ultrasound examination of the spleen and liver was performed at wk 0, 12 and 24. Liver function (liver function and serologic parameters for liver fibrosis) was observedat wk 0, 6, 12, 18 and 24. Blood and urine routine test, renal function and ECG were examined before and after treatment. RESULTS: There was no significant difference between experimental group (110 cases) and control group (106 cases) in demographic features, vital signs, course of illness, history for drug anaphylaxis and previous therapy, liver function, serologic parameters for liver fibrosis, liver histologic examination (99 cases in experimental group, 96 cases in control group), HBV markers, and renal function. According to the criteria for liver fibrosis staging, meanscore of fibrotic stage(s) in experimental group after treatment (1.80) decreased significantly compared to the previous treatment (2.33, P＜0.05), but there was no significant difference in mean score of fibrotic stage(s) (2.11 and 2.14 respectively). There was a significant difference in reverse rate between experimental group (52%) and control group (23.3%) in liver biopsy. With marked effect on decreasing the mean value of inflammatory activity and score of inflammation (P＜0.05), Fuzhenghuayu capsule had rather good effects on inhibiting inflammatory activity and was superior to that of Heluoshugan capsule. Compared to that of pretreatment, there was a significant decrease in HA, LM, P-Ⅲ-P and Ⅳ-C content in experimental group after 12 and 24 wk of treatment. The difference in HA, LM, P-Ⅲ-P and Ⅳ-C content between 12 and 24 wk of treatment and pretreatment in experimental group was significantly greater than that in control group (P＜0.01-0.05). The effect, defined as two of four parameters lowering more than 30% of the baseline, was 72.7% in experimental group and 27.4% in control group (P＜0.01). Obvious improvement in serum Alb, ALT, AST and GGT was seen in two groups. Compared to that of control group, marked improvement in GGT and Alb was seen in experimental group (P＜0.05). The effective rate of improvement in serum ALT was 72.7% in experimental group and 59.4% in control group. No significant difference was seen in blood and urine routine and ECG before and after treatment. There was also no significant difference in stable rate in ALT and serologic parameters for liver fibrosis between experimental group and control group after 12 wk of withdrawal. CONCLUSION: Fuzhenghuayu capsule has good therapeutic effects on alleviating liver fibrosis due to chronic hepatitis B without any adverse effect and is superior to that of Heluoshugan capsule.

Oxymatrine therapy for chronic hepatitis B:A randomized doubleblind and placebo-controlled multi-center trial

AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B.METHODS: A randomised double-blind and placebocontrolled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo.After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed.RESULTS: Among the 216 patients, six were dropped off,and 11 inconsistent with the standard were excluded.Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47 % became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33 % became normal in ALT level,43.33 % and 39.29 % became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00 % became normal in ALT level, 7.46 % and 6.45 % became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84 % in the capsule treated patients, and 33.33 % and 50.00 % in the injection treated patients, and 2.99 % and 41.79 % in the placebo treated patients, respectively.There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule,injection and placebo were 7.77 %, 6.67 % and 8.82 %,respectively. There was no statistically significant difference among them.CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis:A randomized,double blind,placebo-controlled,multicenter clinical study

AIM: To evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a randomized, double blind, placebocontrolled, multicenter clinical study. One hundred and fortyfour patients were divided into oxymatrine capsule group (group A) and placebo group (group B). The course was 52wk. Patients were visited once every 12wk and the last visit was at 12wk after cessation of the treatment. All patients had liver biopsy before treatment, part of them had a second biopsy at the end of therapy. Clinical symptoms, liver function test, serum markers of hepatic fibrosis were tested. Ultrasound evaluation was performed before, during and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled in the study. Of them 132 patients completed the study according to the protocol, 49 patients had liver biopsy twice (25 patients in group A and 24 in group 13). At the end of therapy, significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system (SSS) were achieved in group A. The total effective rate of the treatment was 48.00%, much higher than that of 4.17% in group B (P<0.05). Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid (HA) and type Ⅲ procollagenic peptide (PⅢ P) in group A was seen (P<0.05). The total effective rate of serum markers at the end of therapy in group A was 68.19%, much higher than that of 34.85% in group B (P<0.05). The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%, much higher than that of 30.30% in group B (P<0.05). The rate of adverse events was similar in two groups. CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.

Relationship between clinical and pathologic findings in patients with chronic liver diseases

AIM: To explore the relationship between clinical findings of patients with chronic liver diseases and the pathologic grading and staging of liver tissues.METHODS: The inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients were determined according to the diagnosis criteria of chronic hepatitis in China established in 1995. A comparative analysis was carried out for 200 patients with chronic liver diseases by comparing their clinical manifestations, serum biochemical markers with the grading and staging of liver tissues.RESULTS: It was revealed that age, index of clinical symptoms and physical signs were obviously relevant to the pathologic grading and staging of liver tissues (P＜0.05). Blood platelet, red blood cells, aspartate aminotransferase (AST),N-terminal procollagen Ⅲ (PⅢ NP) were apparently correlated with the degree of inflammation. PGA (prothrombin time,GGT, apoprotein A1) index, PGAA (PGA+△2-macroglobublin)index, albumin and albumin/globulin were relevant to both inflammation and fibrosis. Hyaluronic acid (HA) was an accurate variable for the severity of hepatic inflammation and fibrosis. The combination of serum markers for fibrosis could increase the diagnostic accuracy. It was notable that viral replication markers were not relevant to the degree of inflammation and fibrosis.CONCLUSION: There is a good correlation between clinical findings and the pathologic grading and staging of liver tissues, which may give aid to the noninvasive diagnosis of liver fibrosis.

Grading and staging of hepatic fibrosis,and its relationship with noninvasive diagnostic parameters

AIM: To explore the grade and stage of pathology and the relationship between grading and staging of hepatic fibrosis and noninvasive diagnostic parameters.METHODS: Inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients with chronic liver disease were determined according to the Diagnostic Criteria of Chronic Hepatitis in China, 1995. A comparative analysis was made in these patients comparing serum markers,Doppler ultrasonography, CT and/or MR imaging with the findings of liver biopsy.RESULTS: With increase of inflammatory activity, the degree of fibrosis also rose. There was a close correlation between liver fibrosis and inflammatory activity. AST, GGT, albumin,albumin/globulin, ALP, AFP, hyaluronic acid, N-terminal procollagen Ⅲ(P Ⅲ NP), collagen type Ⅳ(Col Ⅳ), tissue inhibitors of metalloproteinases-1(TIMP-1), alpha-2-macroglobulin, natural killer cells(NK), some parameters of Doppler ultrasonography, CT and/or MR imaging were all related to the degree of inflammatory activity. GGT, albumin,albumin/globulin, ALP, AFP, hyaluronic acid, Col Ⅳ, TIMP1, alpha-2- macroglobulin, transforming growth factor-beta 1(TGFβ1), NK, some parameters of Doppler ultrasonography,CT and/or MR imaging were all related to the staging of fibrosis. By regression analysis, the parameters used in combination to differentiate the presence or absence of fibrosis were age, GGT, the parameter of blood flow of portal vein per minute, the maximum oblique diameter of right liver by B ultrasound, the wavy hepatic surface contour by CT and/or MR. The sensitivity, specificity and accuracy of the above parameters were 80.36 %, 86.67 %, and 81.10 %,respectively.CONCLUSION: There is close correlation between liver fibrosis and inflammatory activity. The grading and staging of liver fibrosis are related to serum markers, Doppler ultrasonography, CT and/or MR imaging. The combinationof the above mentioned noninvasive parameters are quite sensitive and specific in the diagnosis of hepatic fibrosis.

Frequency of apoptosisin cardiac myocytes of patients with myocarditisand dilated cardiomyopathy

Background Programmed cell death has previously been observed in animal models of viral myocarditis and in patients with end stage dilated cardio myopathy (DCM). The purpose of the present study was to investigate if apoptosis is also detectable in endomyocardial biopsies of patients with clinical and immuno histological signs of myocarditis. Methods Right ventricular myocardial biopsies were obtained from 53 patients with clinically suspected myocarditis (left ventricular ejection fraction 30±14%). Cardiac tissues from 4 patients with end stage heart failure were obtained during heart transplantation. Diagnosis of myocarditis and DCM was based on clinical presentation and on histological and immunohistological findings. The presence of apoptosis was investigated in paraffin embedded tissue sections by in situ end labeling of nuclear DNA strand breaks. Results By histological and immunohistological analysis 19 patients (36%) were diagnosed as myocarditis and 34 patients (64%) as DCM. Apoptosis was detected in 9 out of 19 patients with myocarditis, in 12 out of 34 patients with DCM (47% versus 35%, p=NS), and in all patients with end stage heart failure. Conclusions A high frequency of apoptosis was detectable in endomyocardial biopsies of patients with immunohistologically documented myocarditis. The rate of apoptosis in patients with myocarditis, however, was not different to patients with DCM. These findings suggest that apoptosis may be one common pathway in the pathogenesis of cardiac contractile dysfunction in patients with myocarditis and DCM.