Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
J Formos Med Assoc. 2021 Sep;120(9):1676-1685. doi: 10.1016/j.jfma.2020.12.001. Epub 2020 Dec 16.
BACKGROUND/PURPOSE: Predictors of long-term outcomes of peginterferon (PegIFN) therapy for patients with chronic hepatitis B (CHB) remain to be explored. This study aimed to evaluate the predictive value of virological and immunological biomarkers and outcomes of PegIFN for CHB.
57 HBeAg-negative CHB patients receiving 48 weeks of PegIFN therapy were prospectively followed for a median period of 5.3 years after the end of treatment (EOT). Serum CXCL9 and IP-10 levels were measured. Flow cytometry analysis for T cell subsets was performed in 23 patients. Factors associated with long-term outcomes were analyzed.
The cumulative incidences of virological relapse, clinical relapse and HBsAg loss at year 7 were 18.1%, 0%, 31.6%, respectively, in patients with sustained off-treatment virological response (SVR), and 100%, 67.4%, 6.7%, respectively, in patients without SVR. By multivariate analysis, baseline CXCL9 > 80 pg/mL (hazard ratio (HR) = 0.418, p = 0.018) and on-treatment HBsAg declines were associated with a lower risk of virological relapse. Non-SVR was the only predictor of clinical relapse. CXCL9 >200 pg/mL (HR = 8.154, p = 0.038) and HBsAg <750 IU/mL (HR = 10.507, p = 0.036) were baseline predictors of HBsAg loss, while HBsAg decline >1 log at EOT (HR = 23.296, p = 0.005) was the on-treatment predictor of HBsAg loss. In subgroup patients with available PBMC, populations of T cell subsets correlated with virological and clinical relapses in univariate analysis.
Baseline serum CXCL9 and HBsAg levels could predict HBsAg loss after PegIFN therapy for HBeAg-negative CHB. Combining virological and immunological biomarkers could predict long-term outcomes of PegIFN therapy for HBeAg-negative CHB.
背景/目的：预测接受聚乙二醇干扰素（PegIFN）治疗的慢性乙型肝炎（CHB）患者的长期结局仍有待探索。本研究旨在评估病毒学和免疫学生物标志物以及 PegIFN 治疗 CHB 的结果对患者的预测价值。
57 例 HBeAg 阴性 CHB 患者接受 48 周 PegIFN 治疗，在治疗结束（EOT）后中位随访 5.3 年。检测血清 CXCL9 和 IP-10 水平。对 23 例患者进行 T 细胞亚群的流式细胞术分析。分析与长期结局相关的因素。
在获得持续病毒学应答（SVR）的患者中，第 7 年病毒学复发、临床复发和 HBsAg 丢失的累积发生率分别为 18.1%、0%和 31.6%，而未获得 SVR 的患者则分别为 100%、67.4%和 6.7%。多变量分析显示，基线 CXCL9>80pg/mL（风险比（HR）=0.418，p=0.018）和治疗期间 HBsAg 下降与病毒学复发风险降低相关。非 SVR 是临床复发的唯一预测因素。基线 CXCL9>200pg/mL（HR=8.154，p=0.038）和 HBsAg<750IU/mL（HR=10.507，p=0.036）是 HBsAg 丢失的预测因素，而 EOT 时 HBsAg 下降>1 log（HR=23.296，p=0.005）是 HBsAg 丢失的治疗预测因素。在有可用 PBMC 的亚组患者中，T 细胞亚群的数量在单变量分析中与病毒学和临床复发相关。
基线血清 CXCL9 和 HBsAg 水平可预测 HBeAg 阴性 CHB 患者接受 PegIFN 治疗后的 HBsAg 丢失。结合病毒学和免疫学生物标志物可预测 HBeAg 阴性 CHB 患者接受 PegIFN 治疗的长期结局。
