Aldámiz-Echevarría Teresa, Berenguer Juan, Miralles Pilar, Jiménez-Sousa María A, Carrero Ana, Pineda-Tenor Daniel, Díez Cristina, Tejerina Francisco, Pérez-Latorre Leire, Bellón José M, Resino Salvador
Infectious Diseases and HIV Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
PLoS One. 2016 Feb 5;11(2):e0148537. doi: 10.1371/journal.pone.0148537. eCollection 2016.
Higher serum levels of adhesion molecules (sICAM-1 and sVCAM-1) are associated with advanced liver fibrosis in patients coinfected with human immunodeficiency virus and hepatitis C virus. We assessed the relationship between serum levels of adhesion molecules and liver-related events (LRE) or death, in coinfected patients.
We studied clinical characteristics and outcomes of 182 coinfected patients with a baseline liver biopsy (58 with advanced fibrosis) and simultaneous plasma samples who were followed for median of 9 years. We used receiver-operating characteristic (ROC) curves to calculate optimized cutoff values (OCV) of sICAM-1 and sVCAM-1, defined as the values with the highest combination of sensitivity and specificity for LRE. We used multivariate regression analysis to test the association between OCVs of sICAM-1 and sVCAM-1 and outcomes. The variables for adjustment were age, HIV transmission category, liver fibrosis, baseline CD4+ T-cell counts, antiretroviral therapy, and sustained virologic response (SVR).
During the study period 51 patients had SVR, 19 had LRE, and 16 died. The OCVs for LRE were 5.68 Log pg/mL for sICAM-1 and 6.25 Log pg/mL for sVCAM-1, respectively. The adjusted subhazard ratio (aSHR) (95% confidence interval [CI]) of death or LRE, whichever occurred first, for sICAM-1 and sVCAM-1 > OCV were 3.98 ([1.14; 13.89], P = 0.030) and 2.81 ([1.10; 7.19], respectively (P = 0.030).
Serum levels of sICAM-1 and sVCAM-1 can serve as markers of outcome in HIV/HCV-coinfected patients. Therapies targeting necroinflammatory damage and fibrogenesis may have a role in the management chronic hepatitis C.
血清中黏附分子（可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1）水平升高与人类免疫缺陷病毒和丙型肝炎病毒合并感染患者的晚期肝纤维化有关。我们评估了合并感染患者血清黏附分子水平与肝脏相关事件（LRE）或死亡之间的关系。
我们研究了182例合并感染患者的临床特征和结局，这些患者均进行了基线肝活检（58例有晚期纤维化）并同时采集了血浆样本，随访时间中位数为9年。我们使用受试者操作特征（ROC）曲线来计算可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1的最佳临界值（OCV），定义为对LRE具有最高敏感性和特异性组合的值。我们使用多变量回归分析来检验可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1的OCV与结局之间的关联。调整的变量包括年龄、HIV传播类别、肝纤维化、基线CD4 + T细胞计数、抗逆转录病毒治疗和持续病毒学应答（SVR）。
在研究期间，51例患者实现了SVR，19例发生了LRE，16例死亡。LRE的可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1的OCV分别为5.68 Log pg/mL和6.25 Log pg/mL。可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1> OCV时，死亡或LRE（以先发生者为准）的调整后亚风险比（aSHR）（95%置信区间[CI]）分别为3.98（[1.14；13.89]，P = 0.030）和2.81（[1.10；7.19]，P = 0.030）。
可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1的血清水平可作为HIV/HCV合并感染患者结局的标志物。针对坏死性炎症损伤和纤维化形成的治疗可能在慢性丙型肝炎的管理中发挥作用。
