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目的:探讨核苷酸类似物(NAs)初治的HBeAg阳性患者发生HBeAg血清学转换的影响因素。方法:回顾性分析169例初次应用NAs抗病毒治疗至少2年且无病毒学突破的HBeAg阳性患者(中度慢性乙型肝炎患者153例,代偿性肝硬化患者16例),定期随访。应用寿命表法计算累计HBeAg血清学转换率,对影响HBeAg血清学转换的因素进行单因素、多因素Cox比例风险模型和Log-rank分层分析。结果:(1)HBeAg累积血清学转换率随着治疗时间的延长逐渐增高,1年、2年、3年HBeAg血清学累积转换率分别为21.07%、39.92%、54.48%。(2)基线年龄(P=0.005)、ALT(P=0.000)及病毒学应答时间(P=0.038)是影响HBeAg血清学转换的独立因素。(3)Log-rank分析结果:性别、家族史、基线诊断及NAs对HBeAg血清学转换无影响(P>0.05);基线ALT水平越高,越易获得HBeAg血清学转换(P<0.01);随着患者年龄的增加,其获得HBeAg血清学转换的概率越小(P=0.041);较晚获得病毒学应答的患者,其发生HBeAg血清学转换困难、滞后(P<0.01)。结论:延长抗病毒治疗时间有望获得更高的HBeAg血清学转换率,患者的年龄、基线ALT水平及病毒学应答发生的早晚可作为HBeAg血清学转换的预测因素。
Objective: To investigate the influencing factors of HBeAg seroconversion in patients with newly diagnosed HBeAg in nucleotide analogues (NAs). METHODS: A total of 169 HBeAg positive patients (153 with moderate chronic hepatitis B and 16 patients with compensated cirrhosis) who were initially treated with antiviral NAs for at least 2 years without any virological breakthrough were retrospectively analyzed. The patients were followed up regularly. The cumulative HBeAg seroconversion rate was calculated using the life table method. Univariate and multivariate Cox proportional hazards models and Log-rank stratification analysis were used to analyze the factors influencing HBeAg seroconversion. Results: (1) HBeAg cumulative seroconversion rate increased with the prolongation of treatment time. The cumulative HBeAg seroconversion rates at 1 year, 2 years and 3 years were 21.07%, 39.92% and 54.48%, respectively. (2) Baseline age (P = 0.005), ALT (P = 0.000) and virological response time (P = 0.038) were independent factors affecting HBeAg seroconversion. (3) The results of Log-rank analysis showed that gender, family history, baseline diagnosis and NAs had no effect on HBeAg seroconversion (P> 0.05). The higher baseline ALT was, the easier the HBeAg seroconversion was. As the patient’s age increased, the probability of HBeAg seroconversion was lower (P = 0.041). Patients with later virological response had difficulty in HBeAg seroconversion and lag (P <0.01). CONCLUSION: Prolonged antiviral therapy is expected to achieve a higher HBeAg seroconversion rate. The age of patients, baseline ALT levels, and the rate of virological response may be used as predictors of HBeAg seroconversion.