拉米夫定与阿德福韦酯初始与优化联合治疗慢性乙型肝炎144周疗效及经济学分析

Efficacy and economics analysis of lamivudine plus adefovir dipivoxil de-novo and optimize combination therapy of 144 weeks for chronic hepatitis B patients

目的观察拉米夫定（LAM）与阿德福韦酯（ADV）初始联合与优化联合方案治疗慢性乙型肝炎144周的疗效及经济学效果。方法将慢性乙型肝炎患者83例分为3组：初始联合组（A组）28例、单药治疗24周后优化联合组（B组）32例及单药治疗48周后优化联合组（C组）23例。共观察144周，分别检测基线、24、48、96、144周的病毒学、血清学、生化学指标，并于96、144周时对HBVDNA≥10^3拷贝／mL者行HBVP区耐药基因测序。运用药物经济学中的成本一效果分析对3组资料进行分析。结果治疗96周时3组HBVDNA转阴率分别为92．9％、90．6％、87．0％，组间比较差异无统计学意义（X^2=0．509，P〉0．05）；治疗144周时3组HBVDNA转阴率分别为96．4％、93.8％、91．3％，组间比较差异无统计学意义（X^2=0．590，P〉0．05）。治疗144周时初始联合组有1例患者发生了病毒学突破，检测出HBVP区基因的变异位点是L180M，M204V。HBeAg阳性的患者治疗96周时3组的血清学转换率分别为27．8％、19．2％、35．7％，组间比较差异无统计学意义（X^2=1．340，P〉0．05）；治疗144周时3组血清学转换率分别为38．9％、30．8％、42．9％，组间比较差异无统计学意义（X^2=0．364，P〉0．05）。治疗96周时3组ALT复常率分别为94．1％、90．9％、88．9％，组间比较差异无统计学意义（X^2=0．303，P〉0．05）；治疗144周时3组ALT复常率分别为100％、95．5％、94．4％，组间比较差异无统计学意义（X^2=0．911，P〉0．05）。3组患者的成本．效果分析，初始联合组高于优化联合组。结论LAM和ADV初始联合与优化联合方案在病毒学转阴率，血清学转换率，ALT复常率、减少耐药的发生率方面均有较好的疗效；优化联合方案治疗慢乙型肝炎的药物经济学分析优于初始联合方案，建议推广使用。

Objective To compare the 144-week efficacy of de-novo combination therapy with lamivudine （LAM） and adefovir dipivoxil （ADV） to that of optimize combination for chronic hepatitis B （CHB） patients. Methods A total of 83 cases with CHB were divided into 3 groups： the de-novo combination group （group A, 28 cases）, after 24- week mono-therapy to optimize combination group （group B, 32 cases）, after 48-week mono-therapy to optimize combination group（group C, 23 cases）. The virological, serological, biochemical indicators at baseline, week 24, 48, 96 and 144 were detected respectively. The gene resistance mutations of HBV P region were analyzed for the patients whose HBV DNA were still positive （HBV DNA≥10^3 copies/mL） at week 96, 144, respectively. Data of 3 groups were analyzed by the pharmacoeconomics cost-effectiveness analysis. Results HBV DNA negative conversion rates in 3 groups after 96- week therapy were 92.9%, 90.6%, 87.0%. There were no significant differences among 3 groups （X^2= 0.509, P 〉 0.05）; HBV DNA negative conversion rates in 3 groups after 144-week therapy were 96.4%, 93.8%, 91.3%, and the differences among them were not statistically significant（X^2 = 0.590, P 〉 0.05）. There was 1 patient with virologic breakthrough at 144-week treatment in group A. The mutation sites in I-IBV P genes were L180M and M204V. HBeAg- positive patients with seroconversion rates in 3 groups after 96-week therapy were 27.8%, 19.2%, 35.7%, and the dif- ferences were not statistically significant （ X^2 = 1.340, P 〉 0.05）. The rates in 3 groups at week 144 were 38.9%, 30.8%, 42.9%, and the differences were not statistically significant （ X^2= 0.364, P 〉 0.05）. The ALT normalization rates in 3 groups at week 96 were 94.1%, 90.9%, 88.9%, and the differences were not statistically signifi- eant（ X2 = 0.303, P 〉 0.05） ; The ALT normalization rates in 3 groups after 144-week therapy were 100.0 %, 95.5 %, 94.4%, and the differences were not statistically significant（ X^2 = 0.911, P 〉 0.05）. The eest-effeet analysis showed that the initial combination group was superior to the optimize combination group. Conclusions The effects of virology negative conversion rate, seroconversion rate, ALT normalization rate and reduction the incidence of drug resistance in LAM ＋ ADV de-novo combination therapy and optimized combination therapy axe good, but optimized combination therapy is more economic than de-novo combination therapy, so optimized combination therapy can be recommended for use.