Kirby Institute, University of New South Wales, Sydney, Australia.
PLoS One. 2013 Apr 9;8(4):e61297. doi: 10.1371/journal.pone.0061297. Print 2013.
Anti-HBe seroconversion and HBsAg loss are important therapeutic endpoints in patients with hepatitis B virus (HBV) infection. Quantitative measures of hepatitis B surface antigen (qHBsAg) and e antigen (qHBeAg) have been identified as potentially useful indicators of therapeutic response in HBV monoinfection. The aim of this study was to examine serological change including quantitative biomarkers in HIV-HBV coinfected patients initiating HBV active antiretroviral therapy (ART).
HIV-HBV coinfected individuals from Thailand were followed for up to 168 weeks post ART. Rates and associations of qualitative serological change were determined. Longitudinal changes in qHBsAg and qHBeAg were measured and their utility as predictors of response examined.
Forty seven patients were included of whom 27 (57%) were HBeAg positive at baseline. Median CD4 count was 48 cells/mm(3). Over a median follow-up of 108 weeks 48% (13/27) lost HBeAg, 12/27 (44%) achieved anti-HBe seroconversion and 13% (6/47) HBsAg loss. Anti-HBe seroconversion was associated with higher baseline ALT (p = 0.034), lower qHBsAg (p = 0.015), lower qHBeAg (p = 0.031) and greater HBV DNA decline to week 24 (p = 0.045). Sensitivity and specificity for qHBsAg and qHBeAg decline of >0.5 log at week 12 and >1.0 log at week 24 were high for both anti-HBe seroconversion and HBsAg loss.
Rates of serological change in these HIV-HBV coinfected individuals with advanced immunodeficiency initiating HBV-active ART were high. Baseline and on treatment factors were identified that were associated with a greater likelihood of subsequent anti-HBe seroconversion, including both quantitative HBsAg and HBeAg, suggesting these biomarkers may have utility in this clinical setting.
乙型肝炎病毒(HBV)感染者的抗-HBe 血清学转换和 HBsAg 丢失是重要的治疗终点。乙型肝炎表面抗原(qHBsAg)和 e 抗原(qHBeAg)的定量测量已被确定为 HBV 单感染患者治疗反应的潜在有用指标。本研究旨在研究接受 HBV 活性抗逆转录病毒治疗(ART)的 HIV-HBV 合并感染患者的血清学变化,包括定量生物标志物。
对来自泰国的 HIV-HBV 合并感染个体进行了长达 168 周的 ART 后随访。确定了定性血清学变化的发生率和相关性。测量了 qHBsAg 和 qHBeAg 的纵向变化,并研究了它们作为反应预测因子的效用。
共纳入 47 例患者,其中 27 例(57%)基线时 HBeAg 阳性。中位 CD4 计数为 48 个细胞/mm³。中位随访 108 周后,48%(13/27)的患者 HBeAg 丢失,12/27(44%)的患者抗-HBe 血清学转换,13%(6/47)的患者 HBsAg 丢失。抗-HBe 血清学转换与较高的基线 ALT(p=0.034)、较低的 qHBsAg(p=0.015)、较低的 qHBeAg(p=0.031)和更大的 HBV DNA 下降到第 24 周(p=0.045)相关。在第 12 周和第 24 周时,qHBsAg 和 qHBeAg 下降>0.5 log 和>1.0 log,对抗-HBe 血清学转换和 HBsAg 丢失的敏感性和特异性均较高。
在开始 HBV 活性 ART 的免疫功能严重受损的 HIV-HBV 合并感染个体中,血清学变化的发生率较高。确定了与随后发生抗-HBe 血清学转换的可能性更大相关的基线和治疗期间的因素,包括定量 HBsAg 和 HBeAg,这表明这些生物标志物在这种临床环境中可能具有一定的实用性。