拉米夫定联合阿德福韦酯治疗高病毒载量慢性乙型肝炎初治患者的疗效分析

Curative effect of lamivudine combined with adefovir dipivoxil in patients with initial treatment for chronic hepatitis B of high viral load

目的对比拉米夫定(LAM)联合阿德福韦(ADV)与恩替卡韦(ETV)单药治疗高病毒载量慢性乙型肝炎初治患者的疗效及安全性。方法选取我院2012年10月至2013年6月收治的122例高病毒载量慢性乙型肝炎初治患者为研究对象,采用随机数表法将其分成A、B两组,每组各61例。A组采用LAM联合ADV方案治疗,B组采用ETV单一用药方案治疗,疗程24个月。比较两组患者治疗3个月(T1)、6个月(T2)、12个月(T3)和24个月(T4)时段的乙肝病毒基因(HBV-DNA)下降值及HBV-DNA<103copies/ml比率等病毒学应答情况,记录其T1~T4时段乙型肝炎e抗原(HBe Ag)血清转换率、丙氨酸氨基转移酶(ALT)复常率等指标变化,分析两组患者病毒突破及病毒耐药发生差异。结果 1 T1~T4各时段内两组患者HBV-DNA下降值及HBV-DNA<103copies/ml比率等病毒学应答情况比较差异均无统计学意义(P>0.05);但T2~T4时段时,两组患者上述两项病毒学应答指标均较T1时显著提升,差异均有统计学意义(P<0.05);2 T1~T4各时段内,两组患者ALT复常率比较差异均无统计学意义(P>0.05);A组各时段内HBe Ag血清转换率均明显高于B组,差异均有统计学意义(P<0.05);T2~T4时段时,两组患者HBe Ag血清转换率及ALT复常率均较T1时显著提升,差异均有统计学意义(P<0.05);3持续治疗24个月后,A组未见病毒突破及病毒耐药发生,B组累计发生病毒学突破5例,其中4例检测到耐药基因变异点,组间比较差异具有统计学意义(P<0.05)。结论对高病毒载量慢性乙型肝炎初治患者予以LAM联合ADV方案,疗效确切,可有效提高其HBe Ag血清转换率、降低乙肝病毒载量,病毒突破及病毒耐药风险较低,于患者预后提升有利,值得临床推广。

Objective To compare the curative effects and safety of lamivudine(LAM) combined with adefovir dipivoxil(ADV) and entecavir(ETV) alone in patients with initial treatment for chronic hepatitis B of high viral load.Methods One hundred and twenty-two patients with initial treatment for chronic hepatitis B of high viral load treated in our hospital from October 2012 to June 2013 were selected as the research objects. According to the random number table,the patients were divided into group A and group B, with 61 patients in each group. Group A was treated with LAM combined with ADV, while group B was treated with ETV only. The treatment course was 24 months. The decreased values of hepatitis B virus gene(HBV-DNA), the ratio of HBV-DNA <103copy/ml and other virological response during periods of 3months(T1), 6 months(T2), 12 months(T3) and 24 months(T4) of treatment were compared between the two groups. The changes of serum conversion rate of hepatitis B e antigen(HBe Ag), normalizing rate of alanine aminotransferase(ALT) and other indexes during T1 to T4 were recorded. The differences in the occurrence of viral breakthrough and viral drug resistance in the two groups were analyzed. Results 1 During each period from T1 to T4, the differences in the decreased value of HBV-DNA, the ratio of HBV-DNA <103copy/ml and other virological response between the two groups were not statistically significant(P>0.05), but the two virological response indexes mentioned above during T2 to T4 were significantly improved. Compared with those during T1, the differences were statistically significant(P<0.05). 2 During each period from T1 to T4, the differences in ALT normalizing rates between the two groups were not statistically significant(P>0.05).The serum conversion rate of HBe Ag in group A during each period was significantly higher than that in group B and the differences were statistically significant(P<0.05). During T2 to T4, the serum conversion rate of HBe Ag and ALT normalizing rate in the two groups were significantly higher than those during T1(P<0.05). 3 After 24 months of continuous treatment, there was no viral breakthrough and viral drug resistance occurring in group A. There were a total of 5 cases of viral breakthrough in group B, including 4 cases which were detected with variation of drug resistance gene. The differences between groups were statistically significant(P<0.05). Conclusion For patients with initial treatment for chronic hepatitis B of high viral load, the curative effect was definite to adopt LAM combined with ADV regimen. It can effectively improve the serum conversion rate of HBe Ag and reduce the viral load of hepatitis B. The risk of viral breakthrough and viral drug resistance is relatively lower, which is good for patient’s prognosis and is worthy of clinical promotion.