Research Unit of Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand.
Department of Pathology, Chulalongkorn University, Bangkok, Thailand.
J Med Virol. 2017 Jan;89(1):130-138. doi: 10.1002/jmv.24601. Epub 2016 Jun 21.
This study was aimed at comparing clinical applicability of serum HBsAg quantification in relation to intrahepatic covalently closed-circular DNA (cccDNA) in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) treated with pegylated interferon (PEG-IFN) monotherapy for 48 weeks. Overall, 32 and 36 patients with HBeAg-positive and HBeAg-negative CHB, respectively were recruited. Paired liver biopsies at baseline and end of therapy were analyzed for cccDNA. Virological response (VR) at 48 weeks post-treatment was defined as HBeAg clearance (for HBeAg-positive CHB) and HBV DNA <2,000 IU/ml (for both groups). The results demonstrated that baseline levels of all viral markers were higher in the HBeAg-positive group than the HBeAg-negative group. Baseline HBsAg correlated with cccDNA in the HBeAg-positive group (r = 0.452, P = 0.009) but not in the HBeAg-negative group (r = 0.018, P = 0.919). However, the magnitude of cccDNA and HBsAg decline at end of treatment was not different between groups. The reduction of HBsAg showed a positive correlation with cccDNA decline in HBeAg-positive and HBeAg-negative CHB (r = 0.544, P = 0.001 and r = 0.364, P = 0.029, respectively). Overall, responders had more decline in cccDNA and HBsAg levels compared with non-responders. Patients with serum HBsAg decline of >1.0 log IU/ml during treatment archived VR and HBsAg clearance of 80% and 30%, respectively. In conclusion, serum HBsAg represented a better surrogate marker of intrahepatic cccDNA in patients with HBeAg-positive CHB compared to those with HBeAg-negative CHB. On-treatment, HBsAg reduction of 1.0 log IU/mL was associated with a high probability of subsequent VR and HBsAg clearance in patients receiving PEG-IFN therapy. J. Med. Virol. 89:130-138, 2017. © 2016 Wiley Periodicals, Inc.
本研究旨在比较 HBeAg 阳性和 HBeAg 阴性慢性乙型肝炎（CHB）患者接受聚乙二醇干扰素（PEG-IFN）单药治疗 48 周时，血清 HBsAg 定量与肝内共价闭合环状 DNA（cccDNA）的临床适用性。共有 32 例 HBeAg 阳性和 36 例 HBeAg 阴性 CHB 患者入组。基线和治疗结束时进行配对肝活检以分析 cccDNA。治疗后 48 周的病毒学应答（VR）定义为 HBeAg 清除（HBeAg 阳性 CHB）和 HBV DNA <2000IU/ml（两组）。结果表明，HBeAg 阳性组的所有病毒标志物基线水平均高于 HBeAg 阴性组。HBeAg 阳性组的 HBsAg 基线与 cccDNA 相关（r=0.452，P=0.009），而 HBeAg 阴性组则无相关性（r=0.018，P=0.919）。然而，两组之间治疗结束时 cccDNA 和 HBsAg 下降的幅度并无差异。HBsAg 的减少与 HBeAg 阳性和 HBeAg 阴性 CHB 中 cccDNA 的减少呈正相关（r=0.544，P=0.001 和 r=0.364，P=0.029）。总体而言，应答者与无应答者相比，cccDNA 和 HBsAg 水平下降更多。治疗过程中血清 HBsAg 下降>1.0logIU/ml 的患者分别实现了 VR 和 HBsAg 清除率 80%和 30%。结论：与 HBeAg 阴性 CHB 患者相比，血清 HBsAg 更能代表 HBeAg 阳性 CHB 患者肝内 cccDNA 的替代标志物。治疗过程中，HBsAg 下降 1.0logIU/ml 与接受 PEG-IFN 治疗的患者随后发生 VR 和 HBsAg 清除的可能性较高相关。J. Med. Virol. 89:130-138, 2017. © 2016 Wiley Periodicals, Inc.
