Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.
Department and Institute of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Front Cell Infect Microbiol. 2023 Jun 16;13:1151899. doi: 10.3389/fcimb.2023.1151899. eCollection 2023.
The clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir.
A total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development.
Of the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment.
In conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578).
在接受抗病毒治疗的患者中，乙型肝炎病毒 (HBV) DNA 水平持续阳性的临床意义尚不清楚。我们研究了接受 78 周恩替卡韦治疗的慢性乙型肝炎 (CHB) 患者中与持续性病毒血症 (PV) 相关的因素。
本前瞻性多中心研究共分析了 394 例基线和治疗 78 周时接受肝活检的初治 CHB 患者。我们确定了在接受 78 周恩替卡韦治疗后 PV（高于定量下限，20 IU/ml）的患者。采用逐步、正向、多变量回归分析指定的基线参数，以确定与 PV 相关的因素。此外，我们使用 HCC 发生风险模型评估所有患者的肝细胞癌 (HCC) 发生率。
在 394 例患者中，90 例（22.8%）在抗病毒治疗 78 周后仍有 PV。与完全病毒学应答 (CVR) 相比，与 PV 显著相关的因素为 HBV DNA 水平≥8 log10 IU/ml（OR，3.727；95%CI，1.851-7.505；P<0.001）、抗-HBc 水平<3 log10 IU/ml（OR，2.384；95%CI，1.223-4.645；P=0.011）和 HBeAg 阳性（OR，2.871；95%CI，1.563-5.272；P<0.001）。与 CVR 相比，PV 患者的纤维化进展和 HCC 发生风险较低。在基线时 HBV DNA 水平≥8 log10 IU/ml 和抗-HBc 水平<3 log10 IU/ml 的 11 例 HBeAg 阳性患者中，9 例（81.8%）HBV DNA 水平持续阳性，9 例（81.8%）无纤维化进展。
综上所述，基线时 HBV DNA 水平≥8 log10 IU/ml、抗-HBc 水平<3 log10 IU/ml 和 HBeAg 阳性有助于接受 78 周抗病毒治疗的 CHB 患者发生 PV。此外，PV 患者的纤维化进展率和 HCC 发生风险较低。临床试验的完整方案已在 clinicaltrials.gov 注册（NCT01962155 和 NCT03568578）。
