干扰素α-2b治疗HBeAg阳性慢性乙型肝炎的疗效观察

Clinical study of IFNα-2b alone or in combination with lamivudine for HBeAg positive chronic hepatitis B

目的比较干扰素α-2b联合拉米夫定与单用干扰素α-2b及单用拉米夫定三种不同疗法,治疗HBeAg阳性慢性乙型肝炎(CHB)的疗效。方法三个治疗中心针对259名HBeAg阳性CHB进行抗病毒治疗的临床研究。其中单用干扰素α-2b(A)组82名患者;干扰素α-2b联合拉米夫定(B)组88名患者;单用拉米夫定(C)组89名患者。对照分析各组治疗12、24、36、48周时以及随访第72周时,血清ALT复常率、HBV DNA阴转率和血清HBV标志物的变化。观察不良反应以及乙型肝炎病毒耐药情况。结果 (1)三组患者治疗各时间点血清ALT复常率比较,差异无统计学意义(P>0.05)。(2)干扰素α-2b联合拉米夫定组抗病毒治疗48周时,HBeAg阴转率和血清学转换率分别为39.67%和31.59%,与A组和C组比较差异有统计学意义(P<0.05)。(3)单用干扰素α-2b组抗病毒治疗48周时,血清HBeAg阴转率和转换率分别为30.29%和29.27%,与单用拉米夫定组的6.74%和5.62%比较差异具有统计学意义(P<0.05);(4)干扰素α-2b联合拉米夫定组和单用拉米夫定组治疗12周即可获得较高的HBVDNA检测下限率,伴随治疗时间越长,单用拉米夫定的患者48周耐药率12.21%,而联合用药组仅为3.23%;(5)干扰素治疗期间可出现白细胞明显减少现象,没有发生一起严重不良事件,入组患者均完成疗程。结论三组不同治疗方法均可获得一定的抗HBV疗效。但干扰素α-2b联合拉米夫定抗病毒治疗较单独使用干扰素α-2b或拉米夫定的疗效高。适当延长抗病毒治疗时间,患者能获得较高的HBeAg阴转率和HBeAg血清学转换率。干扰素α-2b联合拉米夫定还可以减少乙型肝炎病毒耐药率。

Objective To compare the efficacy of combination therapy of rh interferon α-2b（Kinferon） ＆ lamivudine,mono-therapy of Kinferon and mono-therapy of lamivudine,in the treatment of patients with hepatitis B e antigen（HBeAg） positive chronic hepatitis B（CHB）.Methods Total 344 HBeAg positive CHB patients were enrolled and randomly divided into three groups： mono-therapy of Kinferon（Group A,n=116）;combination therapy of Kinferon ＆ lamivudine（Group B,n=103）;mono-therapy of lamivudine（group C,n=125）.Changes of serum ALT normalization rate,no detection rate of HBV DNA and HBV virus serum marker were compared at week 12,24,36,48 and week 72（during follow-up visit）.Adverse reactions and drug resistance were also observed.Results（1） Serum ALT normalization rates in all three groups were not statistically significant.（P〉0.05）;（2） In group B,negative conversion ratio of HBeAg and seroconversion rate were 39.67% and 31.59% respectively at week 48,which had significant difference with group A ＆ C（P〈0.05）;（3） In group A,negative conversion ratio of HBeAg and seroconversion rate were 30.29% and 29.27% respectively at week 48,comparing with 6.74% and 5.62% in group C（P〈0.05）;（4） Both group B and C acquired high HBV DNA detection limit at week 12.But at week 48,the drug resistance rate in group C reached 12.21% while it was only 3.23% in group B;（5） During the treatment,some patients had mild leukopenia,but no severe ADR happened.All patients completed their therapy.Conclusion Anti-HBV effect is observed in all three groups but combined use of rh Interferon α-2b and lamivudine has better efficacy than mono-therapy of either interferon or lamivudine.Appropriate extension of the treatment course will help the patients acquire comparatively higher negative conversion ratio and seroconversion rate of HBeAg.Combination therapy of rh interferon α-2b and lamivudine also reduces patients’ drug resistance rate