| Objective:To evaluate the difference of efficacy and safety for patients with LAM-resistent hepatitis B virus betwence ADV in combination with LAM and ADV alone.we used system review and Meta analysis to assess the evidence-based medicine results.Methods:We search the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE (1966 to present), EMBASE (1980 to present), Pubmed and the China Biological Medicine Database (1979 to present), VIP Chinese Journals Database (1968 to present), CNKI China National Knowledge Infrastructure Whole Article Database (1994 to present). We will also search the trials registers of the Cochrane Stroke Group and the Cochrane Complementary Medicine Field as well as the Chinese Stroke Trials Register. We searched five WHO ICTRP Primary Registers for ongoing trials.The references were investigated.the data and full text were traced with E-mail.Two reviewer 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 outeome indexes were biochemical response,virological response and HBeAg serocon version used as primary efficacy measures.The emergence of ADV associated mutation and the safety of two groups were used as secondary efficacy measures.The statistical analysis were done with Revman 5.2 software. Results:6 clinical trails that contained 426 patients were investigated,which were all randomized control trails.in which 2 trails contains the patients of liver cirrhosis. the study places contains China, England, American, France, Canada, Pennsylvania,Georgia,etal.the trials published in England and Chinese. the rate of drop out<10%,two groups are LAM+ADV vs ADV.Six trails were not reporting bias and attrition bias,with measured by 48 weeks and 48 months,the biochemical response rates in ADV+LAM combination group was higher as compared with that in ADV monotherapy OR=1.84[95%CI,1.12-3.00 p=0.02]/OR= 80.29 [95%CI,4.18-1541.64, p=0.004];greater virological response rates were observed in ADV+LAM combination group as compared with that in ADV monotherapy, and the difference in response rate between two groups were statistically significantly,RR=1.22[95%CI,1.06-1.39, p=0.004] /RR= 1.90[95%CI 1.10-3.30,p=0.02];the rates of HBeAg clearance and HBeAg seroconversion in two groups were similar, OR=1.02, (95%CI,0.40-2.58), p= 0.97/RR=1.30[95%CI,0.63-2.68], p=0.47.Greater emergence rates of ADV resistant mutants were observed in ADV monotherapy as compared with ADV+LAM combination therapy OR= 0.13 [95%CI0.03-0.58],p=0.008/OR= 0.07 [95%CI,0.01-0.40], p= 0.003. Only two studies reported that 2 patients with cirrhosis developed HCC,and 2 patients with cirrhosis had a decrease of creatinine clearance,but no statistically significant difference were seen between combination of ADV with LAM and ADV alone.No patients discontinued study treatment due to an adverse event.Conclusions:current studies for LAM-resisant CHB patients indicate that:1) combination therapy of ADV and LAM was superior in inhibiting HBV replication,biochemical response and preventing ADV drug resistance as compared with LAM monotherapy 2) the effect was similar in Hepatitis B e-antigen clearance and seroconversion eihter combination therapy or monotherapy.3) Long-term ADV treatment was general well tolerated,no people had to cause the therapy because of renal toxicity. |
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