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不同效力的核苷(酸)类似物长期治疗慢性乙型肝炎患者期间HBsAg消失的动力学及预测

Kinetics and prediction of HBsAg loss during long-term therapy with nucleos(t)ide analogues of different potency in patients with chronic hepatitis B.

作者信息

Li Min-Ran, Xi Hong-Li, Wang Qin-Huan, Hou Feng-Qin, Huo Na, Zhang Xia-Xia, Li Fang, Xu Xiao-Yuan

机构信息

Department of Infectious Diseases, Peking University First Hospital, Beijing, China.

出版信息

PLoS One. 2014 Jun 6;9(6):e98476. doi: 10.1371/journal.pone.0098476. eCollection 2014.

Abstract

BACKGROUND & AIMS: About 350-400 million people are infected with hepatitis B virus (HBV) chronically and 1 million people die of hepatitis B virus (HBV)-related liver diseases. Nucleos(t)ide analogues (NAs) have been used for the treatment against HBV. However, few studies have investigated the long-term effects of different nucleos(t)ide analogues on levels of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB). The aims of this study were to measure the magnitude of HBsAg reduction by long-term monotherapy with adefovir dipivoxil (ADV) and entecavir (ETV), to compare HBsAg reduction between the two drugs of different potency and to predict the expected time needed to achieve HBsAg loss.

METHODS

We retrospectively evaluated the kinetics of HBsAg in 67 patients with CHB who all exhibited persistent viral suppression. These patients were treated with ADV or ETV for at least 6 years. HBV genotype was determined at baseline. Liver biochemistry, HBV serological markers, serum HBV DNA and HBsAg titers were determined at baseline, half year and yearly from year 1 to 6.

RESULTS

Serum HBsAg titers after treatment with ADV or ETV were significantly lower than the baseline titers (P<0.05). HBsAg reduction rate of patients treated with ETV (0.11 log10 IU/mL/ year) was higher than that treated with ADV (0.10 log10 IU/mL/year), and the calculated expected time to HBsAg loss for patients treated with ETV (approximate 24.99 years) was shorter than that with ADV (approximate 30.33 years), but there was no statistically significant difference between two groups (P>0.05).

CONCLUSION

Serum HBsAg titers gradually decreased during long-term treatment with either ADV or ETV. It appears that the potency of ADV on HBsAg reduction is close to that of ETV, as long as patients have achieved persistent viral suppression.

摘要

背景与目的

约3.5亿至4亿人长期感染乙型肝炎病毒(HBV),100万人死于HBV相关肝病。核苷(酸)类似物(NAs)已用于治疗HBV。然而,很少有研究调查不同核苷(酸)类似物对慢性乙型肝炎(CHB)患者乙型肝炎表面抗原(HBsAg)水平的长期影响。本研究的目的是测量阿德福韦酯(ADV)和恩替卡韦(ETV)长期单药治疗使HBsAg降低的幅度,比较两种不同效力药物之间HBsAg降低的情况,并预测实现HBsAg消失所需的预期时间。

方法

我们回顾性评估了67例均表现出持续病毒抑制的CHB患者的HBsAg动力学。这些患者接受ADV或ETV治疗至少6年。在基线时确定HBV基因型。在第1年至第6年的基线、半年和每年测定肝脏生化指标、HBV血清学标志物、血清HBV DNA和HBsAg滴度。

结果

用ADV或ETV治疗后的血清HBsAg滴度显著低于基线滴度(P<0.05)。接受ETV治疗患者的HBsAg降低率(0.11 log10 IU/mL/年)高于接受ADV治疗的患者(0.10 log10 IU/mL/年),并且计算得出接受ETV治疗患者实现HBsAg消失的预期时间(约24.99年)短于接受ADV治疗的患者(约30.33年),但两组之间无统计学显著差异(P>0.05)。

结论

在使用ADV或ETV进行长期治疗期间,血清HBsAg滴度逐渐下降。似乎只要患者实现了持续病毒抑制,ADV降低HBsAg的效力与ETV接近。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9541/4048200/cd81a2cf134d/pone.0098476.g001.jpg

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