CAJ | 학술논문

目的：观察重组人干扰素α-2b（INFα-2b）单药治疗及恩替卡韦（ETV）与阿德福韦酯（ADV）联合治疗拉米夫定（LAM）与ADV联合治疗应答不佳的慢性乙型肝炎患者的疗效和安全性。方法选择我院2008年6月~2011年1月LAM与ADV联合治疗应答不佳的慢性乙型肝炎患者161例，随机分为A、B两组，A组给予INFα-2b 5×106，每周3次；B组ETV（0.5 mg，1次/d）与ADV （10 mg，1次/d）联合应用。所有病例治疗48周为观察终点。采用化学发光法定量检测HBsAg和HBeAg，采用实时荧光定量PCR检测HBV DNA水平，采用PCR产物直接测序法检测病毒耐药基因。组间比较采用配对t检验，率的比较采用χ2检验。结果治疗48周，A组与B组患者血清HBV DNA水平中位数均明显下降，下降幅度分别为2.06±1.15log10拷贝/ml与1.77±1.28log10拷贝/ml；A组与B组血清病毒学应答率、血清学应答率、生化学应答率分别为：48.15%（39/81）与53.75%（43/80）、61.70%（50/81）与53.75%（43/80）、49.38%（40/81）与60.00%（48/80），两组间差异均无统计学意义（P>0.05）；基因耐药变异率分别为30.95%（13/42）与64.86%（24/37），差异有统计学意义（P<0.05）。结论LAM联合ADV治疗应答不佳的慢性乙型肝炎患者，选择改用INF或改用ETV与ADV联合治疗，均能获得较好的临床疗效。若患者无干扰素禁忌证，尽可能选择干扰素治疗。
목적：관찰중조인간우소α-2b（INFα-2b）단약치료급은체잡위（ETV）여아덕복위지（ADV）연합치료랍미부정（LAM）여ADV연합치료응답불가적만성을형간염환자적료효화안전성。방법선택아원2008년6월~2011년1월LAM여ADV연합치료응답불가적만성을형간염환자161례，수궤분위A、B량조，A조급여INFα-2b 5×106，매주3차；B조ETV（0.5 mg，1차/d）여ADV （10 mg，1차/d）연합응용。소유병례치료48주위관찰종점。채용화학발광법정량검측HBsAg화HBeAg，채용실시형광정량PCR검측HBV DNA수평，채용PCR산물직접측서법검측병독내약기인。조간비교채용배대t검험，솔적비교채용χ2검험。결과치료48주，A조여B조환자혈청HBV DNA수평중위수균명현하강，하강폭도분별위2.06±1.15log10고패/ml여1.77±1.28log10고패/ml；A조여B조혈청병독학응답솔、혈청학응답솔、생화학응답솔분별위：48.15%（39/81）여53.75%（43/80）、61.70%（50/81）여53.75%（43/80）、49.38%（40/81）여60.00%（48/80），량조간차이균무통계학의의（P>0.05）；기인내약변이솔분별위30.95%（13/42）여64.86%（24/37），차이유통계학의의（P<0.05）。결론LAM연합ADV치료응답불가적만성을형간염환자，선택개용INF혹개용ETV여ADV연합치료，균능획득교호적림상료효。약환자무간우소금기증，진가능선택간우소치료。
Objective To compare the efficacy and safety of recombinant human interferon α-2b (INFα-2b) monotherapy and combined therapy with entecavir (ETV) plus adefovir dipivoxil (ADV) in chronic hepatitis B patients with poor response to combined therapy with lamivudine and ADV. Methods A total of 161 patients with chronic hepatitis B refractory to to combined therapy with lamivudine (LAM) and ADV were randomized to receive INFα-2b monotherapy (5 × 106, three times a week) (group A) or combined therapy with entecavir (0.5 mg/day) plus adefovir (10 mg/day) (group B). Serum levels of HBsAg, HBeAg and HBV viral load were analyzed at 48 weeks using chemiluminescence assay and by real-time PCR as appropriate. The drug resistance genes in HBV was tested by direct DNA sequencing. Results At 48 weeks of treatment, HBV DNA decreased significantly in groups A and B to 2.06 ± 1.15log10 copies/ml and 1.77 ± 1.28log10 copies/ml, respectively. The rates of viral response, serological response, and biochemical response in groups A and B were 48.15%(39/81) vs 53.75%(43/80), 61.70%(50/81) vs 53.75%(43/80), and 49.38%(40/81) vs 60.00%(48/80), showing no significant differences between the two groups (P>0.05). The drug resistance gene mutation rate was significanty higher in group B (64.86%, 24/37) than in group A (30.95%, 13/42, P<0.05). Conclusions Chronic hepatitis B patients refractory to lamivudine combined with ADV have a good response to INFα-2b monotherapy and combined therapy with entecavir and ADV , and interferon treatment is preferred to reduce potential drug resistance gene mutations.