Departments of Infectious Diseases.
Reproductive Medicine Center, Changhai Hospital, Second Military Medical University, Shanghai, China.
J Clin Gastroenterol. 2020 Sep;54(8):e73-e82. doi: 10.1097/MCG.0000000000001376.
This study aimed to investigate the dynamic pattern of serum hepatitis B virus (HBV) RNA in chronic hepatitis B (CHB) patients on long-term nucleos(t)ide analogue (NA) therapy and evaluate predictor value of end-of-treatment (EOT) serum HBV RNA status on drug-withdrawal durability.
We carried out a real-life cohort study of 326 CHB patients on NA treatment between February 12, 2016 and February 21, 2018. Thirty of these patients discontinued NA treatment after enrollment, and were included in 2-year off-therapy follow-up. Serum HBV RNA levels were determined using the RNA simultaneous amplification testing method.
Both serum HBV RNA and DNA levels declined significantly in long-term antiviral progress. When the treatment duration was longer than 3 years, the undetectable rates of HBV RNA and DNA were 55.10% and 97.0%, respectively. The serum HBV RNA-negative rate was 39.5%. The cumulative 2-year off-therapy viral and clinical relapse rate was 40.56%; 95% confidence interval (95% CI), 21.51-59.61 and 31.31%; 95% CI, 11.32-51.29 in all patients, respectively. Patients with EOT hepatitis B surface antigen (HBsAg)≤1000 IU/mL plus HBV RNA negativity had a relatively lower cumulative 2-year off-therapy viral relapse rate (23.01%; 95% CI, 0.17-45.99). EOT HBsAg≤1000 IU/mL plus HBV RNA negativity showed obvious superiority for the EOT HBsAg≤1000 IU/mL single in drug withdrawal durability prediction, with better specificity (18.18% vs. 72.73%, P=0.03), and the positive predictive value and negative predictive value were 76.92% and 47.06%, respectively.
In the long-term antiviral process, both serum HBV RNA and DNA levels declined significantly. EOT serum HBV RNA negativity was not an independent drug withdrawal marker, but can complement the HBsAg titer to monitor drug withdrawal in CHB patients on long-term NA therapy.
本研究旨在探讨慢性乙型肝炎（CHB）患者长期核苷（酸）类似物（NA）治疗后血清乙型肝炎病毒（HBV）RNA 的动态变化模式，并评估治疗结束（EOT）时血清 HBV RNA 状态对停药后持久性的预测价值。
我们进行了一项真实队列研究，纳入了 2016 年 2 月 12 日至 2018 年 2 月 21 日期间接受 NA 治疗的 326 例 CHB 患者。其中 30 例患者在入组后停止 NA 治疗，并纳入 2 年停药随访。采用 RNA 同步扩增检测法检测血清 HBV RNA 水平。
在长期抗病毒过程中，血清 HBV RNA 和 DNA 水平均显著下降。当治疗时间超过 3 年时，HBV RNA 和 DNA 的不可检测率分别为 55.10%和 97.0%。HBV RNA 阴性率为 39.5%。所有患者的 2 年停药后病毒和临床复发累积率分别为 40.56%；95%置信区间（95%CI）为 21.51-59.61%和 31.31%；95%CI 为 11.32-51.29%。所有患者的 EOT 乙型肝炎表面抗原（HBsAg）≤1000 IU/mL 加 HBV RNA 阴性的 2 年停药后病毒累积复发率相对较低（23.01%；95%CI，0.17-45.99%）。EOT HBsAg≤1000 IU/mL 加 HBV RNA 阴性在预测停药持久性方面明显优于 EOT HBsAg≤1000 IU/mL 单一指标，具有更好的特异性（18.18%比 72.73%，P=0.03），阳性预测值和阴性预测值分别为 76.92%和 47.06%。
在长期抗病毒过程中，血清 HBV RNA 和 DNA 水平均显著下降。EOT 血清 HBV RNA 阴性不是独立的停药标志物，但可以补充 HBsAg 滴度，以监测长期 NA 治疗的 CHB 患者停药。
