HBeAg阳性慢性乙型肝炎患者干扰素治疗24周应答不佳时的治疗方案

Treatment options in HBeAg-positive chronic hepatitis B patients with a poor response to 24-week interferon monotherapy

目的对干扰素单药治疗24周应答不佳的HBe Ag阳性慢性乙型肝炎（CHB）患者采用不同的治疗方案进行后续治疗,分析比较其疗效和安全性。方法回顾性分析2010年9月~2013年1月南方医科大学南方医院193例干扰素治疗24周时应答不佳的HBe Ag阳性的CHB患者,根据不同后续治疗方案分成：联用恩替卡韦（ETV）或阿德福韦（ADV）治疗（A组）,继续干扰素单药治疗（B组）,换为NAs治疗（C组）,直接停止治疗（D组）。观察比较第24、48、72周时各组患者的临床疗效与安全性。结果继续治疗至疗程48周时,A组和C组HBV DNA转阴率、ALT复常率均高于B组（A组：χ^2=26.808,P〈0.001和χ^2=5.485,P=0.017;C组：χ^2=21.257,P〈0.001和χ^2=5.369,P=0.018）;同时发现,加ETV组HBV DNA转阴率高于加ADV组（χ^2=8.255,P=0.004）。疗程72周时,A组患者有27例（39.7%）发生HBe Ag血清学转换,明显高于B、C两组（χ^2=4.238,P=0.04和χ^2=7.681,P=0.006）;58例（85.3%）获得HBV DNA转阴,59例（86.8%）ALT恢复正常,均高于B组（χ^2=23.018,P〈0.001和χ^2=5.987,P=0.014）,但与C组比较差异无统计学意义（P〉0.05）;同时发现,联合ETV组HBV DNA转阴率和HBe Ag血清学转换率均高于加ADV组（χ^2=9.823,P=0.002和χ^2=5.450,P=0.020）。D组,28例患者的HBV DNA均持续较高水平复制,HBe Ag水平升高,ALT反复波动。结论对于干扰素单药治疗24周时应答不佳的CHB患者,联用NAs并延长疗程可明显提高HBe Ag血清学转换率、HBV DNA转阴率及ALT复常率,特别是联用ETV并延长疗程时。

Objective To evaluate the efficacy and safety of 4 treatment options for HBe Ag- positive chronic hepatitis B（CHB）patients following a suboptimal response to 24-week interferon monotherapy. Methods The data of 193 HBe Ag-positive CHB patients with suboptimal response to 24- week interferon monotherapy were collected from Nanfang Hospital between September, 2010 and January, 2013. According to the subsequent treatments, the patients were divided into group A with additional entecavir or adefovir, group B with further interferon monotherapy, group C with conversion to NAs therapy, and group D with direct therapy withdrawal, and the biochemical and virological results at weeks 24, 48 and 72 were analyzed in the 4 groups. Results At week 48, the HBV DNA negative rates and serum alanine aminotransferase（ALT） normalization rates were both significantly higher in group A and C than in group B（P〈0.05）; in group A, ETV therapy subgroup had a significantly higher HBV DNA negative rate than ADV therapy subgroup at week 48（90.3% vs 59.5%, χ^2=8.255, P=0.004）. At week 72, 39.7%（27/68） of the patients in group A achieved HBe Ag seroconversion, a rate significantly higher than those in groups B（χ^2=4.238, P=0.040） and C（χ^2=7.681, P=0.006）; the HBV DNA negative rate and ALT normalization rate in group A were 85.3%（58/68） and 86.8%（59/68）, respectively, both significantly higher than those in group B（χ^2=23.018, P〈0.001; χ^2=5.987,P=0.014） but comparable to those in group C（P〈0.05）. In the two subgroups in group A, the HBV DNA negative rate and HBe Ag seroconversion rate were both significantly higher in ETV subgroup（χ^2=9.823, P=0.002; χ^2=5.450, P=0.020）. In group D,all the patients remained HBe Ag- positive with abnormal ALT levels and high level of HBV DNA.Conclusion For HBe Ag- positive CHB patients with suboptimal response to 24- week interferon monotherapy, combined treatment with NAs（especially ETV） and extension of the treatment course can significantly improve the HBe Ag seroconversion rates, HBV DNA negative rates, and ALT normalization rates.