Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Gastroenterology and Rheumatology, Section of Hepatology, University Hospital Leipzig, Leipzig, Germany.
J Viral Hepat. 2020 Jun;27(6):610-619. doi: 10.1111/jvh.13272. Epub 2020 Mar 17.
Hepatitis B virus (HBV) RNA in serum is a novel biomarker that reflects cccDNA activity. We investigated whether HBV RNA can predict serological response to peginterferon (PEG-IFN) treatment. Serum HBV RNA levels were retrospectively measured at weeks 0, 12, 24 and 52 of therapy and after treatment discontinuation (week 78) in 266 HBeAg-positive chronic HBV patients who had participated in a global randomized controlled trial (HBV99-01 study). Patients received 52 weeks PEG-IFN monotherapy (n = 136) or PEG-IFN and lamivudine (n = 130). The primary end point was HBeAg loss 24 weeks after PEG-IFN discontinuation. At baseline, the mean serum level of HBV RNA was 6.8 (SD 1.2) log c/mL. HBV RNA levels declined to 4.7 (1.7) log c/mL after one year of PEG-IFN therapy alone and to 3.3 (1.2)log c/mL after combination therapy. From week 12 onward, HBV RNA level was significantly lower in patients who achieved HBeAg loss at the end of follow-up as compared to those who did not, regardless of treatment allocation (week 12:4.4 vs 5.1 log c/mL, P = .01; week 24:3.7 vs 4.9 log c/mL, P < .001). The performance of a multivariable model based on HBV RNA level was comparable at week 12 (AUC 0.68) and 24 (AUC 0.72) of therapy. HBV RNA level above 5.5 log c/mL at week 12 showed negative predictive values of 93/67/90/64% for HBV genotypes A/B/C/D for the prediction of HBeAg loss. In conclusion, HBV RNA in serum declines profoundly during PEG-IFN treatment. Early on-treatment HBV RNA level may be used to predict nonresponse.
血清乙型肝炎病毒 (HBV) RNA 是反映cccDNA 活性的新型生物标志物。我们研究了 HBV RNA 是否可以预测聚乙二醇干扰素 (PEG-IFN) 治疗的血清学应答。266 例 HBeAg 阳性慢性乙型肝炎患者参与了一项全球随机对照试验 (HBV99-01 研究)，这些患者在治疗的第 0、12、24 和 52 周以及治疗停药后 78 周（第 52 周）时，血清 HBV RNA 水平被回顾性测量。患者接受 52 周 PEG-IFN 单药治疗（n=136）或 PEG-IFN 和拉米夫定联合治疗（n=130）。主要终点是 PEG-IFN 停药后 24 周时 HBeAg 丢失。基线时，血清 HBV RNA 平均水平为 6.8（标准差 1.2）log c/mL。单独使用 PEG-IFN 治疗 1 年后，HBV RNA 水平下降至 4.7（1.7）log c/mL，联合治疗后下降至 3.3（1.2）log c/mL。从第 12 周开始，与未达到随访终点时 HBeAg 丢失的患者相比，达到 HBeAg 丢失的患者的 HBV RNA 水平显著降低，无论治疗分配如何（第 12 周：4.4 与 5.1 log c/mL，P=.01；第 24 周：3.7 与 4.9 log c/mL，P<.001）。基于 HBV RNA 水平的多变量模型在治疗的第 12 周（AUC 0.68）和第 24 周（AUC 0.72）的表现相当。第 12 周 HBV RNA 水平>5.5 log c/mL 对 HBV 基因型 A/B/C/D 预测 HBeAg 丢失的阴性预测值分别为 93/67/90/64%。总之，HBV RNA 在 PEG-IFN 治疗期间明显下降。早期治疗中的 HBV RNA 水平可用于预测无应答。
