核苷类似物治疗慢性乙肝患者停药后复发再治疗的观察

Observation on re-treatment of relapse after withdrawal of NAs in chronic hepatitis B patients

目的观察核苷类似物(NAs)治疗慢性乙肝患者停药后复发再治疗的疗效,探讨NAs治疗的多次疗程。方法选择符合条件(已经用NAs治疗3年以上且有停药意愿的深圳市第七人民医院2000—2016年间的住院或门诊慢性乙型肝炎患者)的患者50人为治疗组,选择另50人(已经服药2年以上并正在口服NAs又不愿停药)的患者为对照组,治疗组在患者乙型肝炎病毒DNA(HBV-DNA)出现病毒学反弹,ALT、AST出现异常后再次用抗病毒药(恩替卡韦或替诺福韦),对照组继续采用原治疗方案治疗。对比观察治疗效果和副作用,疗效比较采用χ~2检验。结果50例停药患者有6例没有复发,44例复发患者作为治疗组再抗病毒治疗,治疗组于48周时HBsAg滴度转阴率、HBeAg转阴率分别为13.6%、18.2%,对照组为0.0%、4.0%;复发时E抗原阴性和E抗原阳性患者48周的HBsAg转阴率分别为25.0%和4.2%,ALT≥2×ULN和ALT<2×ULN的患者48周HBsAg转阴率分别为28.6%和6.7%。治疗组副作用与对照组一样。结论NAs治疗患者停药后复发再治疗其疗效好、安全,HBsAg转阴率高,复发时E抗原阴性比E抗原阳性患者HBsAg转阴率高,ALT≥2×ULN比ALT<2×ULN的患者的HBsAg转阴率高,没有发现停药后病情反弹并加重现象;复发时ALT高,E抗原阴性,HBsAg滴度低是达到功能性治愈的独立因素。

Objective To observe the efficacy of relapse and retreatment for chronic hepatitis B patients with withdrawal of NAs,and to discuss the multiple courses of NAs treatment.Methods We selected 50 qualified patients(patients with hepatitis B who have been treated with NAs for more than three years and willing to discontinue drugs in Shenzhen Seventh People’s Hospital including inpatient and outpatient from 2000 to 2016)as treatment group,chose another 50 patients(patients have been treated with NAs for more than 2 years and reluctant to drug withdrawal)as control group,treatment group in patients with DNA virology bounce,retreatment of ALT and AST after abnormality(entecavir and tenofovior)and control group to continue using the original treatment plan.Their therapeutic effects and side effects were compared and observed.χ2 test was used for efficacy comparison.Results Six cases had no recurrence in 50 patients with drug withdrawal,44 cases of recurrent patients were treated as treatment group.The negative conversion rates of HBsAg titer and HBeAg in the treatment group at 48 weeks were 13.6%and 18.2%,and the control group were 0.0%and 4.0%,respectively.When relapse occured,the negative conversion rates of HBsAg in the patients with negative and positive E antigen at 48 weeks were 25.0%and 4.2%,respectively.The conversion rates of HBsAg titer in the patients with ALT≥2×ULN and ALT<2×ULN at 48 weeks were 28.6%and 6.7%,respectively.The side effects of the treatment group were the same as those of the control group.Conclusion NAs is effective and safe in treating patients with relapse after withdrawal of drugs,and has a high negative conversion rate of HBsAg.When recurrence,the negative conversion rate of HBsAg in E antigen negative patients is higher than that of positive patients.The HBsAg negative conversion rate of patients with ALT≥2×ULN is higher than that of patients with ALT<2×ULN.There is no rebound after stopping drug and aggravating phenomenon,when recurrence,high ALT,negative E antigen,low HBsAg titer are independent factors to achieve functional cure.