Systematic Review Of Adefovir Effects On Treating Chronic Virus Hepatitis B

Objective:To evaluate the ADV efficacy and safety in treating CHB.Based on searching results of ADV randomized clinical trials(RCTs)in treating CHB,we used system review and Meta analysis to assess the evidence-based medicine results of ADV clinical effects and apply it to clinical practice.Methods:Search strategy,MEDLINE,EMBASE,CBMdisc,VIP,WANGFANG, CNKI databases were chosen for primary document search.The Cochrane Library(2006,tissue 3):The Cochrane Central Register of Controlled Trials (CENTRAL),The National Research Register,Health technology assessment database(HTA)were chosen for secondary document search.Published or unpublished Chinese articles in relative journals,conference proceedings and thesis were manually searched and some other articles were searched with Google.The references were investigated,the data and full text were traced with E-mail.The search was last to December,2006.Two reviewers assessed the documents quality separately,they select documents back to back and cross check them.Discussion or the third reviewer was invited when the discrepancy happened.The outcome indexes were histological improvement,serum HBV-DNA disappear or decrease,HBeAg decrease or negative,serum ALT/AST decrease or normal,complications or drug side effects.The statistical analysis were done with Revman4.2 software(offered by Cochrane net).Results:1220 CHB patients in 5 RCTs were investigated,in which 2 trials were composed of 1 report in different treating periods.The intervention in all trials was placebo.2 RCTs were multicentre double-blind placebo control trials in more than 30 countries.The treating time,outcome indexes were not all the same in trials,so the Meta analysis was used in 2 similar trials and found that 48 weeks after 10mg/d ADV administration,the efficacy in treating group was significantly higher than the control group(RR2.05 95%CI 1.62,2.61);one trial of which reported that the efficacy in 48 weeks of 30 mg/d ADV administration group was significantly higher than control group(RR2.33 95%CI 1.74,3.13) but with more side effects and kindey dysfunctions.The other 2 trials divided patients into 3 groups and treated them at 4 periods,after the first double-blind 12 weeks 10 mg/d ADV administration,the "e" antigen transformation and "e" antigen/antibody serum transformation ratio had significant difference with control group(RR 1.17 95%CI 0.5,2.74),after the second double-blind 52 weeks 10 mg/d ADV treatment,the liver histological improvement was obvious and when changed into placebo,HBV DNA suddenly rebounded to baseline and decreased again when added ADV.Most patients quality of life were improved after treatment in all trials,with no death report.All trials had side effects,the incidence of which was no significantly different between ADV and placebo groups.Conclusions:The major trend of 4 ADV's RCTs were as follows:1)48 weeks after 10 mg/d ADV administration,the liver histological improvement,serum HBV DNA decrease,HbeAg seroconversion increase could be found in patients with no ADV related polymerase mutation which suggested good risk/efficacy ratio.2)The side effects and abnormal kidney laboratory examinations were seen more in 30 mg/d ADV administration group than 10 mg/d administration group.3)Due to articles quality,intervention therapies diversity,exprimental methods quality and current research conclusions uncertainty,the above-mentioned results should be carefully analyzed and applied.4)More large sample RCTs should be designed and investigated to make the final clincial treating therapy.