The Hepatitis Post-Partum Flare Rates In The HBV Infected Mother Treated With Nucleoside Analogue During The Second And Third Trimester Of Pregnancy: A Meta-analysis

Object To investigate the effect of short-term antiviral therapy(AVT) during the second and third trimester of pregnancy on post-partum flare.To determine the safety of withdrawal in the HBV infected mother treated with nucleoside analogue during the second and third trimester of pregnancy. To guide the clinical use of antiviral drugs in pregnant women with HBV and nursing managementMethods All literature is searched on Databases(PUBMED, EMBASE, the Cochrane Library, Wang Fang and CNKI, up to January, 2016) regarding to antiviral therapy during pregnancy. Study selection and data extraction were done by pairs of independent reviewers. The post-partum flare rates within 3 month and 6 month were analyzed in the two groups, meanwhile, subgroup analyses were performed based on drug type, baseline liver function and the withdrawal time. Stata 12.0 software was used for assessing the risk of bias and statistical analysis.Results 10 relevant studies were involved, including 1939 mothers. Inclusive criteria: HBsAg positive more than 6 months, HBV-DNA>106 copy /ml, gestational age of 20-32 week. A number of 1066 women in treatment group: 316 women received LAM, 626 women received LDT and 124 women received TDF, then 953 women stopped within 4 weeks after delivery, 113 women stopped within 4-12 weeks after delivery. A number of 873 women in the control group who without antiviral treatment. We analyzed the post-partum flare rates within 3 and 6 month post withdraw/delivery, and subgroup analysis was performed based on drug type, baseline liver function and the withdrawal time. Compared with the control group, within 3 months post withdraw/delivery: RR=0.98, 95%CI(0.79,1.22);within 6 months post withdraw/delivery: RR=0.76, 95%CI(0.43-1.36);LAM treatment group compared with the control: within 3 months post withdraw/delivery: RR=0.49, 95%CI(0.30,0.78); within 6 months post withdraw/delivery: RR=0.33, 95%CI(0.18,0.61); LDT treatment group compared with the control: within 3 month post withdraw/delivery: RR=0.96, 95%CI(0.68,1.34), within 6 month post withdraw/delivery: RR=0.90, 95%CI(0.56,1.43); TDF treatment group compared with the control group: within 3 months post withdraw/delivery: RR=1.41, 95%CI(0.85,2.35); within 6 months post withdraw/delivery: RR=1.32, 95%CI(0.77,2.29); Stop within 4 weeks after delivery group compared with the control group: within 3 months post withdraw/delivery: RR=1.00, 95%CI(0.69,1.45);within 6 months post withdraw/delivery: RR=0.68, 95%CI(0.38,1.23); Stop after 4 weeks after delivery group compared with the control group: within 3 months post withdraw/delivery: RR=0.95, 95%CI(0.44,2.02); within 6 months post withdraw/delivery: RR=0.73, 95%CI(0.36,1.49); Comparison between the early cessation and late cessation group in treatment group: within 3 months post withdraw/delivery: RR=1.02, 95%CI(0.66,1.57); within 6 months post withdraw/delivery: RR=0.97, 95%CI(0.64,1.47); Comparison of treatment group and control group who ALT normal pregnant women :within 3 months post withdraw/delivery: RR=0.99, 95%CI(0.75,1.29); within 6 months post withdraw/delivery: RR=0.65, 95%CI(0.34,1.25). Comparison of treatment group and control group who ALT abnormal pregnant women : within 3 months post withdraw/delivery: RR=0.98, 95%CI(0.67,1.43); within 6 months post withdraw/delivery: RR=0.76, 95%CI(0.73,1.36). Funnel plots showed no publication bias in all studies.Conclusion Compared with the control group, antiviral therapy during pregnancy does not increase the post-partum ALT flare rates, and withdrawal is safe after short-term antiviral therapy. Furthermore, Lamivudine treatment in HBs Ag-positive mothers may reduce the post-partum ALT flare rates. In addition,extending antiviral therapy does not reduce the post-partum flares rates, Our result suggests that stop treatment soon after delivery is reasonable.