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在长期恩替卡韦治疗期间,治疗初治慢性乙型肝炎患者的乙型肝炎表面抗原动力学的临床实用性。

Clinical utility of hepatitis B surface antigen kinetics in treatment-naïve chronic hepatitis B patients during long-term entecavir therapy.

机构信息

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, 70403, Taiwan.

Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 70403, Taiwan.

出版信息

World J Gastroenterol. 2018 Feb 14;24(6):725-736. doi: 10.3748/wjg.v24.i6.725.

Abstract

AIM

To investigate the utility of hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.

METHODS

This retrospective study included treatment-naïve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen (HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, one-year and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.

RESULTS

A total of 211 patients were enrolled. The median treatment time was 5.24 (2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen (HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients (cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients (cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline , but depended on lower baseline HBsAg levels.

CONCLUSION

Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

摘要

目的

研究慢性乙型肝炎患者长期接受恩替卡韦治疗期间乙型肝炎表面抗原(HBsAg)动力学的应用。

方法

本回顾性研究纳入了接受至少 2 年连续恩替卡韦治疗的初治慢性乙型肝炎患者。患者每 3 至 6 个月进行一次随访,检查肝功能、乙型肝炎病毒 DNA 和腹部超声。在乙型肝炎 e 抗原(HBeAg)阳性患者中,每 3 至 6 个月评估 HBeAg 水平,直至结果转为阴性。在基线、1 年和 5 年时间点检测血清 HBsAg 水平。通过肝活检、影像学检查或门静脉高压的临床发现诊断肝硬化。通过组织学检查或动态影像研究诊断肝细胞癌。

结果

共纳入 211 例患者。中位治疗时间为 5.24(2.00-9.62)年。多变量分析显示,基线 HBsAg 水平较低与 HBeAg 阳性患者更早的病毒学应答、更早的 HBeAg 血清学转换以及更早的生化学应答(临界值:4 log IU/mL)和 HBeAg 阴性非肝硬化患者更早的病毒学应答(临界值:2.4 log IU/mL)相关。尽管在长期恩替卡韦治疗期间 HBsAg 水平缓慢下降,但在 HBeAg 阳性非肝硬化患者中,在治疗的第一年 HBsAg 下降率更高,基线 HBsAg 水平更高的患者中 HBsAg 下降率更高。快速 HBsAg 下降并未观察到更有利的临床结局,但取决于较低的基线 HBsAg 水平。

结论

基线 HBsAg 可用于预测治疗反应。在解释 HBsAg 变化时,应根据疾病状态综合考虑 HBsAg 水平和下降率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba2/5807675/a87cebb62c92/WJG-24-725-g001.jpg

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