Institute of Hepatology and Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, 410078, Hunan, China.
Hepatol Int. 2020 Mar;14(2):212-224. doi: 10.1007/s12072-020-10015-3. Epub 2020 Feb 25.
As an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses.
We analyzed a phase 3, multicenter, randomized cohort of 727 HBeAg-positive non-cirrhotic patients receiving a 48-week treatment of PegIFNα-2a or PegIFNα-2b and a 24-week treatment-free follow-up. Serum levels of HBV RNA, HBV DNA, HBeAg, and HBsAg were measured at weeks 0, 12, 24, 48, and 72.
HBeAg seroconversion and HBsAg loss at week 72 were observed in 217 (29.8%) and 21 (2.9%) patients, respectively. During the 48-week treatment, HBV RNA decreased more rapidly than HBV DNA and HBsAg, but HBV RNA and HBeAg shared similar dynamics with positive correlations. Multivariate regression analyses consistently revealed the significance of HBV RNA at weeks 0, 12, 24, and 48 to monitor HBeAg seroconversion but not HBsAg loss. Although baseline HBV RNA only showed a modest AUC performance, HBV RNA with a significant increase of AUC at week 12 outperformed other HBV biomarkers to forecast HBeAg seroconversion (p value < 0.05). HBV RNA ≤ 1000 copies/mL was an optimized cutoff at week 12 that offered better prediction than other HBV biomarkers. This optimized cutoff plus patient age, HBV genotype B, and HBeAg offered a strong estimation of HBeAg seroconversion (accuracy 95.2%, true negative rate 99.8%).
HBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons.
聚乙二醇干扰素α（PegIFNα）作为一种重要的抗乙型肝炎病毒药物，具有良好的临床疗效，但目前仍缺乏能准确预测治疗应答的生物标志物。本研究旨在评估乙型肝炎病毒（HBV）RNA 是否可作为聚乙二醇干扰素应答的早期监测指标。
我们分析了一项纳入 727 例 HBeAg 阳性非肝硬化患者的 3 期、多中心、随机队列研究，这些患者接受 PegIFNα-2a 或 PegIFNα-2b 治疗 48 周，随后停药随访 24 周。在第 0、12、24、48 和 72 周时检测血清 HBV RNA、HBV DNA、HBeAg 和 HBsAg 水平。
72 周时，217 例（29.8%）患者发生 HBeAg 血清学转换，21 例（2.9%）患者发生 HBsAg 丢失。在 48 周治疗期间，HBV RNA 下降速度快于 HBV DNA 和 HBsAg，但 HBV RNA 和 HBeAg 具有相似的动力学，呈正相关。多变量回归分析一致显示，治疗 0、12、24 和 48 周时 HBV RNA 对 HBeAg 血清学转换的监测具有显著意义，但对 HBsAg 丢失无显著意义。虽然基线 HBV RNA 的 AUC 性能仅为中等，但在第 12 周时 AUC 显著增加的 HBV RNA 优于其他 HBV 标志物，可更好地预测 HBeAg 血清学转换（p 值均<0.05）。第 12 周时，HBV RNA 水平≤1000 拷贝/ml 是一个优化的截断值，其预测 HBeAg 血清学转换的效果优于其他 HBV 标志物。将该优化截断值与患者年龄、HBV 基因型 B 和 HBeAg 相结合，可对 HBeAg 血清学转换进行强有力的预测（准确率为 95.2%，真阴性率为 99.8%）。
聚乙二醇干扰素治疗的 HBeAg 阳性患者中，第 12 周时的 HBV RNA 是 HBeAg 血清学转换的有效监测指标。
