Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Institute of Medical Education Research Rotterdam, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
J Viral Hepat. 2019 Sep;26(9):1076-1085. doi: 10.1111/jvh.13127. Epub 2019 Jun 3.
Pegylated IFNα (PEG-IFN) is one of the treatment options for chronic HBV (CHB) patients. However, the high patient treatment burden and limited response rate together clearly ask for biomarkers to predict PEG-IFN response. Soluble CD14 (sCD14) is considered a marker for immune activation and has been shown to predict clinical outcome of HIV infection. However, studies on sCD14 in CHB infection are inconclusive, and its relationship with clinical outcome is largely unknown. Here, we measured sCD14 levels in CHB patients and investigated whether changes in sCD14 level related to PEG-IFN response. Serum sCD14 levels were determined in 15 healthy controls, 15 acute self-limited HBV, 60 CHB patients in different disease phases and 94 HBeAg+ CHB patients at week 0 and week 12 of a 52-week PEG-IFN treatment. Response to PEG-IFN treatment was defined as HBeAg seroconversion or HBeAg loss at 26 weeks post-treatment. The mean sCD14 level in acute HBV patients (3.0 µg/mL) was significantly higher than in CHB patients (2.4 µg/mL) and healthy controls (2.4 µg/mL). In CHB patients receiving PEG-IFN, a significant increase in sCD14 was found after 12-week treatment (median week 0:2.1 µg/mL; week 12:3.7 µg/mL). After 12-week treatment, the fold change (FC = w12/w0) in sCD14 was significantly higher in responders compared to nonresponders (HBeAg seroconversion: median FC = 2.1 vs FC = 1.6; HBeAg loss: median FC = 2.2 vs FC = 1.5). Receiver operating characteristic curves demonstrated that FC-sCD14 levels can be of significant value as a stopping rule to select patients at week 12 who are not likely to benefit from further PEG-IFN treatment.
聚乙二醇干扰素α(PEG-IFN)是慢性乙型肝炎(CHB)患者的治疗选择之一。然而,高患者治疗负担和有限的反应率清楚地要求有生物标志物来预测 PEG-IFN 反应。可溶性 CD14(sCD14)被认为是免疫激活的标志物,并且已经显示出可以预测 HIV 感染的临床结果。然而,关于 CHB 感染中 sCD14 的研究尚无定论,其与临床结果的关系也知之甚少。在这里,我们测量了 CHB 患者的 sCD14 水平,并研究了 sCD14 水平的变化是否与 PEG-IFN 反应相关。在 0 周和 12 周的 52 周 PEG-IFN 治疗期间,测定了 15 名健康对照者、15 名急性自限性 HBV 患者、60 名处于不同疾病阶段的 CHB 患者和 94 名 HBeAg+CHB 患者的血清 sCD14 水平。PEG-IFN 治疗的反应定义为治疗后 26 周 HBeAg 血清学转换或 HBeAg 丢失。急性 HBV 患者(3.0μg/mL)的 sCD14 平均水平明显高于 CHB 患者(2.4μg/mL)和健康对照组(2.4μg/mL)。在接受 PEG-IFN 的 CHB 患者中,治疗 12 周后发现 sCD14 显著增加(中位数周 0:2.1μg/mL;周 12:3.7μg/mL)。在 12 周治疗后,与非应答者相比,应答者的 sCD14 (sCD14)的折叠变化(FC=w12/w0)显著更高(HBeAg 血清学转换:中位数 FC=2.1 vs FC=1.6;HBeAg 丢失:中位数 FC=2.2 vs FC=1.5)。受试者工作特征曲线表明,FC-sCD14 水平作为停止规则具有重要价值,可在第 12 周选择不太可能从进一步 PEG-IFN 治疗中获益的患者。