摘要目的 观察慢性乙型肝炎(chronic hepatitis B, CHB)患者进行干扰素治疗过程中乙型肝炎核心抗体(hepatitis B core antibody ,抗-HBc)效价的动力学特点并分析其对预测抗病毒疗效的意义.方法 收集2011年10月至2014年10月在西安交通大学医学院第一附属医院感染性疾病科就诊的CHB患者的临床资料.动态监测干扰素治疗期间及停药后的乙型肝炎病毒( hepatitis B virus, HBV) DNA水平、肝功能和血清学标志物变化,分析不同病毒学应答结局时抗-HBc效价的动态变化特点,采用二分类logistic回归分析抗-HBc效价对干扰素治疗CHB疗效的预测价值.结果 42例CHB患者年龄(30.8 ±10.1)岁,乙型肝炎e抗原(hepatitis B e antigen, HBeAg)阳性患者34例, HBeAg阴性患者8例.所有患者均完成48周干扰素治疗及停药24周的随访,其中28.6%(12/42)患者获得持续病毒学应答(sustained virological response , SVR), 26.2%(11/42)患者发生病毒学复发, 45.2%(19/42)患者无应答.不同应答结局的抗-HBc效价变化特点不同, SVR组患者在基线和治疗12周时抗-HBc效价均高于无应答组,差异均有统计学意义[基线时: (4.93 ±0.30)比(4.70 ±0.33)lg IU/mL, t＝2.147, P＝0.013;治疗12周: (4.83 ±0.23)比(4.44 ±0.41) lg IU/mL, t＝3.032, P＝0.007]. SVR组在治疗12周和24周时抗-HBc效价显著高于病毒学复发组,差异均有统计学意义[治疗12周: (4.83 ±0.23)比(4.67 ±0.51)lg IU/mL, t＝2.400, P＝0.039;治疗24周: (4.73 ±0.21)比(4.55 ±0.50)lg IU/mL, t＝2.542, P＝0.039].多因素logistic回归分析发现,基线抗-HBc效价是干扰素治疗CHB获得SVR的独立预测因素( OR＝6.000, 95%CI: 1.118～20.486, P＝0.037),其受试者工作特征曲线下面积为0.753,最佳临界值为5.03 lg IU/mL,阳性预测值为64.3%,阴性预测值为89.3%.结论 抗-HBc效价动态变化特征与干扰素治疗CHB出现不同病毒学应答结局密切相关,基线抗-HBc效价为抗病毒治疗获得SVR的独立预测因素.

abstractsObjective To observe the dynamic characteristics of hepatitis B core antibody (anti-HBc) titers in chronic hepatitis B (CHB) patients treated with interferon and to explore the predictive value of anti-HBc for response to interferon.Methods The clinical information of the patients diagnosed with CHB in Department of Infectious Diseases , the First Affiliated Hospital of Xi′an Jiaotong University from October 2011 to October 2014 were collected.HBV DNA, liver function and HBV serological markers of CHB patients were tested dynamically during and after interferon treatment.The dynamic characteristics of anti-HBc titers in patients with different virological responses were analyzed.The predictive values of anti-HBc titer for the efficacy of interferon treatment of CHB patients were analyzed by binary logistic regression .Results Of the 42 CHB patients aging(30.8 ±10.1) years old, 34 patients were hepatitis B e antigen (HBeAg) positive and 8 were negative.All patients completed 48-week interferon treatment and 24-week follow-up after the end of treatment. Among them, 28.6%( 12/42), 26.2%( 11/42 ) and 45.2%( 19/42 ) of patients achieved sustained virological response (SVR), virological relapse ( VR) and non-response ( NR), respectively.Patients with different virological response presented various characteristics of anti -HBc titers.Compared with NR group, the anti-HBc titers at baseline and week 12 were significantly higher in SVR group (at baseline: [4.93 ±0.30] vs [4.70 ±0.33] lg IU/mL, t ＝2.147, P ＝0.013; at week 12: [4.83 ± 0.23] vs [4.44 ± 0.41] lg IU/mL, t＝3.032, P＝0.007).The anti-HBc titers in SVR group at week 12 and week 24 were significantly higher than those in VR group (at week 12: [4.83 ±0.23] vs [4.67 ±0.51] lg IU/mL, t＝2.400, P＝0.039; at week 24: [4.73 ±0.21] vs [4.55 ±0.50] lg IU/mL, t＝2.542, P＝0.039).By multivariate logistic regression analysis, the anti-HBc titer at baseline was the independent predictive factor for SVR in CHB patients treated with interferon (OR＝6.000, 95%CI: 1.118 -20.486, P＝0.037).The area under receiver operating characteristics curve was 0.753 and the optimal cutoff value of anti-HBc titer for the response to interferons in CHB patients was 5.03 lg IU/mL, with positive predictive value of 64.3%and negative predictive value of 89.3%.Conclusions Dynamic pattern of anti-HBc titers is correlated with different virological responses in CHB patients treated with interferon , and the baseline anti-HBc titer is the independent predictive factor for SVR.