Balagopal Ashwin, Barin Burc, Quinn Jeffrey, Rogers Rodney, Sulkowski Mark S, Stock Peter G
Department of Medicine, Johns Hopkins University, Baltimore, MD, 21205, United States of America.
The EMMES Corporation, Rockville, MD, 20850, United States of America.
PLoS One. 2015 Aug 27;10(8):e0135882. doi: 10.1371/journal.pone.0135882. eCollection 2015.
Liver disease is a leading cause of mortality among HIV-infected persons in the highly active anti-retroviral therapy (HAART) era. Hepatitis C Virus (HCV) co-infection is prevalent in, and worsened by HIV; consequently many co-infected persons require liver transplantation (LT). Despite the need, post-LT outcomes are poor in co-infection. We examined predictors of outcomes post-LT. Immunologic biomarkers of immune activation, microbial translocation, and Th1/Th2 skewing were measured pre-LT in participants enrolled in a cohort of HIV infected persons requiring solid organ transplant (HIVTR). Predictive biomarkers were analyzed in Cox-proportional hazards models; multivariate models included known predictors of outcome and biomarkers from univariate analyses. Sixty-nine HIV-HCV co-infected persons with available pre-LT samples were tested: median (IQR) CD4+ T-cell count was 286 (210-429) cells mm-3; 6 (9%) had detectable HIV RNA. Median (IQR) follow-up was 2.1 (0.7-4.0) years, 29 (42%) people died, 35 (51%) had graft loss, 22 (32%) were treated for acute rejection, and 14 (20%) had severe recurrent HCV. In multivariate models, sCD14 levels were significantly lower in persons with graft loss post-LT (HR 0.10 [95%CI 0.02-0.68]). IL-10 levels were higher in persons with rejection (HR 2.10 [95%CI 1.01-4.34]). No markers predicted severe recurrent HCV. Monocyte activation pre-LT may be mechanistically linked to graft health in HIV-HCV co-infection.
在高效抗逆转录病毒治疗(HAART)时代,肝脏疾病是艾滋病毒感染者死亡的主要原因。丙型肝炎病毒(HCV)合并感染在艾滋病毒感染者中很普遍,且会因艾滋病毒而恶化;因此,许多合并感染者需要进行肝移植(LT)。尽管有需求,但合并感染患者肝移植后的预后较差。我们研究了肝移植后预后的预测因素。在一组需要实体器官移植的艾滋病毒感染者队列(HIVTR)中,对参与者肝移植前的免疫激活、微生物易位和Th1/Th2偏移的免疫生物标志物进行了测量。在Cox比例风险模型中分析预测生物标志物;多变量模型包括已知的预后预测因素和单变量分析中的生物标志物。对69例有肝移植前可用样本的艾滋病毒-HCV合并感染者进行了检测:CD4 + T细胞计数中位数(IQR)为286(210 - 429)个/mm³;6例(9%)可检测到艾滋病毒RNA。随访中位数(IQR)为2.1(0.7 - 4.0)年,29例(42%)患者死亡,35例(51%)发生移植物丢失,22例(32%)接受了急性排斥反应治疗,14例(20%)发生严重复发性HCV。在多变量模型中,肝移植后发生移植物丢失的患者中,可溶性CD14水平显著降低(风险比0.10 [95%置信区间0.02 - 0.68])。发生排斥反应的患者中,白细胞介素-10水平较高(风险比2.10 [95%置信区间1.01 - 4.34])。没有标志物可预测严重复发性HCV。肝移植前单核细胞激活可能在机制上与艾滋病毒-HCV合并感染中的移植物健康相关。