Min-De Zeng

Prediction of significant fibrosis in HBeAg‐positive patients with chronic hepatitis B by a noninvasive model

A model was constructed consisting of clinical and serum variables to discriminate between hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients with and without significant fibrosis (stages 2‐4 vs. stages 0‐1). Consecutive treatment‐naive CHB patients who underwent liver biopsy were divided into 2 sequential groups: a training group (n = 200) and a validation group (n = 172). Multivariate analysis identified α2‐macroglobulin, age, gamma glutamyl transpeptidase, and hyaluronic acid as independent predictors of fibrosis. The area under the receiver operating characteristic curve was 0.84 for the training group and 0.77 for the validation group. Using a cutoff score of <3.0, the presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (86.1% negative predictive value [NPV], 70.1% positive predictive value [PPV], and 94.8% sensitivity) in 43 (21.5%) of 200 patients in the training group, and with the same certainty (90.9% NPV, 64.7% PPV, and 98.0% sensitivity) in 22 (12.8%) of 172 patients in the validation group. Similarly, applying a cutoff score of >8.7, the presence of significant fibrosis could be correctly identified with high accuracy (91.1% PPV, 51.6% NPV, and 95.2% specificity) in 41 (20.5%) of 200 patients in the training group, and with the same certainty (84.8% PPV, 52.4% NPV, and 90.4% specificity) in 39 (22.7%) of 172 patients of the validation group. In conclusion, a predictive model with a combination of easily accessible variables identified HBeAg‐positive CHB patients with and without significant fibrosis with a high degree of accuracy. Application of this model may decrease the need for liver biopsy in staging of 35.5% CHB. (HEPATOLOGY 2005;42:1437–1445.)

A double‐blind randomized trial of adefovir dipivoxil in Chinese subjects with HBeAg‐positive chronic hepatitis B

Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)–positive chronic hepatitis B (CHB) were enrolled in a multicenter, double‐blind, randomized, placebo‐controlled study of adefovir dipivoxil (ADV) 10 mg once daily. There was a significant difference in reduction of serum hepatitis B virus (HBV) DNA after 12 weeks between subjects who received ADV and those who received the placebo (3.4 and 0.1 log10 copies/mL, respectively, P < .001). Further reductions in serum HBV DNA and increases in the proportion of subjects with an HBV DNA level of at most 10 5 copies/mL, with HBV DNA undetectable, and with ALT normalization were observed in ADV‐treated subjects at week 52 (median HBV DNA reduction of 4.5 log10 copies/mL, 67% with HBV DNA ≤ 10 5 copies/mL, 28% with HBV DNA undetectable, and 79% with ALT normalization). Subjects who initially received ADV lost some treatment benefit after being rerandomized to the placebo in week 40. Subjects with YMDD mutant HBV at baseline had virological, biochemical, and serological responses to treatment that were similar to those of subjects with wild‐type HBV. The incidence of clinically adverse events was similar in nature and severity between the treatment groups, and there was no evidence of renal toxicity. No adefovir‐related HBV mutations were identified. In conclusion, treatment with ADV 10 mg daily over 52 weeks was safe and effective in Chinese subjects with HBeAg‐positive CHB and did not lead to the emergence of drug resistance. The study is continuing for an additional 4 years with all subjects on open‐label ADV 10 mg daily. (HEPATOLOGY 2006;44:108–116.)

Preliminary study on therapeutic effect of oxymatrine in treating patients with chronic hepatitis C

OBJECTIVE To evaluate the efficacy of oxymatrine in treating chronic hepatitis C and its mechanism. METHODS Forty-three patient were divided randomly into the treated group (20 cases) and the control group (23 cases). The treated group was given oxymatrine 600 mg per day intramuscularly, and the control group was given the general liver protective agents such as vitamins. The therapeutic course of both groups was 3 months. RESULTS HCVRNA of 8 in 17 cases (47.1%) of the treated group converted to negative, while in 18 cases of the control group, the negative conversion only took place in 1 patient (5.6%), the negative conversion rate was significantly higher in the treated group than that in the control group (P < 0.05). The normalization rates of serum alanine transaminase (ALT) of the treated group after 1 month and 2 months treatment was higher than that of the control group, but after 3 months treatment, the normalization rates of the two groups were not different significantly. Plasma level of soluble interleukin-2 receptor and serum level of collagen type IV in the treated group were lowered significantly after treatment, but in the control group, there were no significant change, the difference between the two groups was significant (P < 0.01, P < 0.05). CONCLUSION Oxymatrine is effective in inhibiting proliferation of HCV, antagonisting liver fibrosis and regulating immune reaction of the host, so it could be a safe, effective drug in treating chronic hepatitis C.

Preliminary study on efficacy of oxymatrine in treatment of patients with chronic hepatitis C

Objective: To evaluate the efficacy of oxymatrine in the treatment of chronic hepatitis C and to discuss its mechanism.Methods: Forty-three patients with chronic HCV infection were randomly divided into the treated group (20 cases) and the control group (23 cases). The treated group was given oxymatrine 600 mg per day intramuscularly for three months, and the control group was given the general liver protective agents such as vitamins. Serum HCV-RNA, alanine aminotransferase (ALT), soluble interleukin-2 receptor and collagen type IV (IV-C) were determined before and after treatment.Results: Eight out of 17 HCV-RNA-positive (47.1%) in the treated group converted to HCV-RNA-negative cases, while in 18 cases of the control group, the negative convertion only took place in 1 patient (5.6%), the negative conversion rate was significantly higher in the treated group than that in the control group (P < 0.05). The normalization rates of serum ALT of the treated group at the end of the first and second month treatment were higher than those of the control group, but after three months treatment, the normalization rates of the two groups were not different significantly. Both serum levels of IV-C and plasma levels of soluble interleukin-2 receptor were significantly reduced after oxymatrine treatment for three months (P < 0.05).Conclusion: Oxymatrine is effective on eliminating HCV-RNA and reducing fibrosis activity, so it could be a safe, effective drug in the treatment of chronic hepatitis C.