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接受核苷/核苷酸类似物治疗的乙肝e抗原阴性慢性乙型肝炎患者严重再激活时的血清乙肝表面抗原动力学

Serum hepatitis B surface antigen kinetics in severe reactivation of hepatitis B e antigen negative chronic hepatitis B patients receiving nucleoside/nucleotide analogues.

作者信息

Wong Grace L-H, Chan Henry L-Y, Lo Angeline O-S, Chan Hoi-Yun, Tse Chi-Hang, Chim Angel M-L, Wong Vincent W-S

机构信息

Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.

出版信息

Antivir Ther. 2013;18(8):979-86. doi: 10.3851/IMP2615. Epub 2013 Jun 6.

DOI:10.3851/IMP2615
PMID:23744529
Abstract

BACKGROUND

Kinetics of serum hepatitis B surface antigen (HBsAg) level in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients presented with severe reactivation and received oral antiviral therapy is unknown. We aimed to investigate the kinetics of HBsAg level among these patients.

METHODS

HBeAg-negative patients on antiviral therapy with follow-up for 2 years were studied. Those presented with severe reactivation (alanine aminotransferase [ALT] ≥5 times of normal) were compared to those with mild hepatitis. Serum HBsAg level was measured by Elecsys HBsAg II Quant assay (Roche) at baseline and 6-monthly.

RESULTS

A total of 192 (74 severe reactivation) patients were studied. Eighty-one (42%), 74 (39%) and 37 (19%) patients were on lamivudine, entecavir and telbivudine, respectively. Forty-four (23%) patients had early HBsAg decline, that is, ≥0.5 log10 reduction, at month 6. Patients with severe reactivation had higher serum baseline ALT (1,415 ±897 versus 73 ±39 IU/l), HBV DNA (6.4 ±1.6 versus 5.2 ±1.2 log10 IU/ml) and HBsAg (3.3 ±1.0 versus 2.9 ±0.6 log10 IU/ml), as well as an earlier HBsAg decline (50% versus 6%; all P<0.001) than those without. The HBsAg change of patients with severe reactivation was higher at months 0-6 (-0.58 ±-1.26 versus -0.01 ±-0.26 log10 IU/ml; P<0.001) but then became comparable from months 6-24 (-0.19 ±-0.60 versus -0.13 ±-0.19 log10 IU/ml; P=0.85), compared to those presented with mild hepatitis.

CONCLUSIONS

Patients who presented with severe reactivation of HBeAg-negative hepatitis were more likely to develop early HBsAg decline during antiviral therapy. It may indicate a transient strong immune clearance with rapid initial reduction in serum HBsAg, which cannot be sustained due to a faster clearance of serum HBsAg.

摘要

背景

乙肝e抗原(HBeAg)阴性的慢性乙型肝炎患者出现严重再激活并接受口服抗病毒治疗时,血清乙肝表面抗原(HBsAg)水平的动力学尚不清楚。我们旨在研究这些患者中HBsAg水平的动力学。

方法

对接受抗病毒治疗并随访2年的HBeAg阴性患者进行研究。将出现严重再激活(丙氨酸氨基转移酶[ALT]≥正常上限5倍)的患者与轻度肝炎患者进行比较。在基线和每6个月时,采用电化学发光免疫分析法(Elecsys HBsAg II Quant assay,罗氏公司)检测血清HBsAg水平。

结果

共研究了192例患者(74例严重再激活)。分别有81例(42%)、74例(39%)和37例(19%)患者使用拉米夫定、恩替卡韦和替比夫定。44例(23%)患者在第6个月时出现早期HBsAg下降,即下降≥0.5 log10。严重再激活患者的血清基线ALT(1415±897 vs 73±39 IU/L)、HBV DNA(6.4±1.6 vs 5.2±1.2 log10 IU/ml)和HBsAg(3.3±1.0 vs 2.9±0.6 log10 IU/ml)水平更高,且与未出现严重再激活的患者相比,HBsAg下降更早(50% vs 6%;所有P<0.001)。与轻度肝炎患者相比严重再激活患者在0至6个月时的HBsAg变化更大(-0.58±1.26 vs -0.01±0.26 log10 IU/ml;P<0.001),但在6至24个月时变得相当(-0.19±0.60 vs -0.13±0.19 log10 IU/ml;P=0.85)。

结论

HBeAg阴性肝炎出现严重再激活的患者在抗病毒治疗期间更有可能出现早期HBsAg下降。这可能表明存在短暂的强烈免疫清除,血清HBsAg迅速初始降低,但由于血清HBsAg清除更快,这种情况无法持续。

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