拉米夫定和α-干扰素序贯治疗e抗原阴性乙肝患者及其对拉米夫定耐药突变的抑制

Lamivudine and alpha interferon sequential treatment of e antigen negative hepatitis B patients and the inhibition of lamivudine resistance mutations

目的:评价拉米夫定和α-干扰素序贯治疗e抗原阴性乙肝患者的功效。方法:本研究共进行了162例e抗原阴性的慢性乙肝患者的治疗研究。其中98例患者采用拉米夫定单独用药,100 mg/d,持续治疗48周(B组)。64例患者先单独用拉米夫定,100 mg/d,持续治疗20周,然后联合用药,增加α-干扰素500万U,每周3次,持续治疗4周后,改为单独用α-干扰素(500万U,每周3次),持续治疗24周(A组)。所有的患者都再持续治疗24周。结果:经过48周的治疗,ALT水平复常和HBV-DNA降至<1 000 copies/ml的患者比例在两组中并没有明显不同。拉米夫定单独治疗组ALT水平复常和HBV-DNA<1 000 copies/ml的比例为55.1%,干扰素序贯治疗组两项的比例为59.36%和56.25%。而在治疗72周时,ALT水平复常的比例A组(53%)明显高于B组(36%)(P<0.05)。而且此时患者中发生拉米夫定耐药突变的比例B组(22.45%)明显高于A组(P<0.05)。结论:用拉米夫定和α-干扰素序贯治疗慢性乙肝患者与用拉米夫定单独治疗同样有效,序贯治疗更加抑制了拉米夫定耐药突变的产生。

Objective： To evaluate the effect of lamivudine and interferon sequential treatment of patients with chronic hepatitis be antigen negatie. Methods： 162 cases of e antigen negatie patients with chronic hepatiitis b treatment were studied. 98 cases were treated by lamivudine alone 100 mg, daily. Continuous treatment for 48 week：s （group B）. 64 pa- tients were first used alone lamivudine 100 mg every day, continuous treatment for 20 weeks, then corabination, increase of alpha interferon 5 million units, 3 times a week, continuous treatment after 4 weeks, instead of alpha interferon used alone （5 million units, 3 times a week）, continuous treatment 24 weeks （group A）. All patients corttinue treatment 24 weeks. Re suits： After 48 weeks of treatment, ALT complex and often HBV DNA reduced to less than 1 000 copies/ml in the per- centage of patients in both groups were not significantly different. Lamivudine treatment group ALT alone complex and of ten HBV DNA less than 1 000 copies/ml ratio for 55.1%, interferon sequential treatment group two ratio for 59.36% and 56.25%. And in the treatment of 72 weeks, ALT complex often proportion of group A （53%） was obviously higher than group B （36%） （P〈0.05）. And the patient was happened in lamivudine resistance mutations proportion of group B （22.45%） was obviously higher than group A （P〈0.05）. Conclusion： With sequential lamivudine and or interferon treatment of chron ic hepatitis B patients treated with lamivudine alone as effective. Sequential treatment of lamivudine more inhibited re strained mutants production.