Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
J Gastroenterol. 2019 Feb;54(2):182-193. doi: 10.1007/s00535-018-1502-y. Epub 2018 Aug 22.
We determined the antiviral potency and viral breakthrough rate after 10 years of continuous entecavir treatment in patients with chronic hepatitis B (CHB) infection.
The cumulative rates of undetectable hepatitis B virus DNA (HBV-DNA, < 2.1 log copies/mL), alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroclearance, hepatitis B surface antigen (HBsAg) seroclearance, and viral breakthrough of 1094 nucleos(t)ide analogue-naïve CHB patients (HBeAg-positive: 47%) who were on continuous entecavir treatment for 10 years were calculated.
The median age was 50 years and follow-up period was 5.5 years, with 999, 804, 591, 390, 182 and 87 patients followed up for at least 1, 3, 5, 7, 9 and 10 years, respectively. Incremental increases were noted in the rates of undetectable HBV-DNA, ALT normalization, HBeAg seroclearance, and HBsAg seroclearance, reaching 96, 79, 38 and 3.7%, respectively, by the tenth year. The mean decline in HBsAg level from baseline was - 0.08 log IU/mL/year. Multivariate analysis identified HBsAg level and genotype (A) as independent predictors of HBsAg seroclearance. Sixteen patients experienced viral breakthrough. The cumulative percentages of patients with viral breakthrough analyzed by the Kaplan-Meier test were 1.5 and 2.5% at years 5 and 10, respectively. There were no serious adverse events during treatment.
Long-term entecavir treatment of nucleos(t)ide analogue-naïve CHB patients was associated with an excellent viral response and a low rate of entecavir-resistant mutations at 10 years. Baseline HBsAg levels and genotype were predictors of HBsAg seroclearance during entecavir treatment.
我们确定了连续恩替卡韦治疗 10 年后慢性乙型肝炎（CHB）感染患者的抗病毒效力和病毒突破率。
计算了 1094 例核苷（酸）类似物初治 CHB 患者（HBeAg 阳性：47%）连续恩替卡韦治疗 10 年的累积无乙型肝炎病毒 DNA（HBV-DNA，<2.1log 拷贝/mL）、丙氨酸氨基转移酶（ALT）正常化、HBeAg 血清学清除、HBsAg 血清学清除和病毒突破率。
中位年龄为 50 岁，随访时间为 5.5 年，分别有 999、804、591、390、182 和 87 例患者至少随访 1、3、5、7、9 和 10 年。HBV-DNA 不可检测、ALT 正常化、HBeAg 血清学清除和 HBsAg 血清学清除的比率逐渐增加，第 10 年分别达到 96%、79%、38%和 3.7%。HBsAg 水平从基线的平均下降为-0.08logIU/mL/年。多变量分析确定 HBsAg 水平和基因型（A）是 HBsAg 血清学清除的独立预测因子。16 例患者发生病毒突破。Kaplan-Meier 检验分析的病毒突破患者累积百分比分别为第 5 年和第 10 年的 1.5%和 2.5%。治疗期间无严重不良事件。
核苷（酸）类似物初治 CHB 患者长期接受恩替卡韦治疗，10 年后病毒应答良好，恩替卡韦耐药突变率低。基线 HBsAg 水平和基因型是恩替卡韦治疗期间 HBsAg 血清学清除的预测因子。
