慢性乙型肝炎患者长期应用核苷(酸)药物抗病毒疗效观察

Outcomes of nucleos(t)ide long-term therapy in patients with chronic hepatitis B

目的观察恩替卡韦(ETV)与拉米夫定/替比夫定(LAM/LdT)治疗慢性乙型肝炎(CHB)患者的长期疗效及耐药情况。方法回顾性分析本院肝炎门诊所收治的52例CHB患者,最长随访168周,每12周评估1次其ALT水平、HBV DNA和乙型肝炎病毒表面标志物的变化情况。结果 ETV组患者治疗48周、96周和144周HBV DNA抑制率分别为76.9%(10/13)、100%(5/5)和100%(5/5),ALT复常率分别为80%(12/15)、57.1%(4/7)和60%(3/5)。LAM/LdT组患者治疗48周、96周和144周HBV DNA抑制率分别为72%(18/25)、90%(9/10)和62.5%(5/8),ALT复常率分别为86.4%(19/22)、100.0%(11/11)和88.9%(8/9)。两组患者治疗144周时,e抗原血清学转换率分别为25%(1/4)和66.7%(4/6)。ETV组患者未见病毒学突破者,LAM/LdT组病毒学突破率为25%(7/28)。结论长期经核苷(酸)类药物治疗的CHB患者,能获得较好的病毒学抑制和ALT复常;ETV组患者的耐药性优于LAM/LdT组,但e抗原血清学转换率较LAM/LdT组差。

Objective To observe the long-term outcomes of nucleos（t）ide therapy in patients with chronic hepatitis B （CHB） and to compare the response and drug-resistance between patients in entecavir （ETV） group and lamivudine/telbivudine （LAM/LdT） group. Methods Total of 52 patients with CHB were enrolled, with follow-up of 168 weeks. The viral response and biochemical response were detected every 12 weeks. Results At the 48th, 96th and 144th week in treatment, the rates of HBV DNA undetectable were 72% （18/25）, 90% （9/10） and 62.5% （5/8） in LAM/LdT group, while 76.9% （10/13）, 100% （5/5） and 100% （5/5） in ETV group, respectively. The rates of ALT normalization were 80% （12/15）, 57.1% （4/7） and 60% （3/5） in ETV group and 86.4% （19/22）, 100.0% （11/11） and 88.9% （8/9） in LAM/LdT group, respectively. At the 144th week, the rates of HBeAg seroconversion in ETV group and LAM/LdT group were 25% （1/4） and 66.7% （4/6）, respectively. No virological breakthrough was observed in ETV group. However, seven （7/28, 25%） patients developed virological breakthrough in LAM/LdT group, among whom 4 patients were detected of drug-mutations. Conclusions Continuous treatment with nucleos（t）ide over 3 years was associated with high rates of HBV DNA undetectable and ALT normalization in patients with chronic hepatitis B. Less drug-resistant mutations developed in ETV group, while more HBeAg seroconversion was found in LAM/LdT group.