丙型肝炎病毒持续病毒学应答对接受抗逆转录病毒治疗的HIV/HCV合并感染患者免疫抑制性色氨酸分解代谢的影响
Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients.
作者信息
Jenabian Mohammad-Ali, Mehraj Vikram, Costiniuk Cecilia T, Vyboh Kishanda, Kema Ido, Rollet Kathleen, Paulino Ramirez Robert, Klein Marina B, Routy Jean-Pierre
机构信息
*Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec, Canada; †Currently, Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal (UQAM), Québec, Canada; ‡Research Institute McGill University Health Centre, Montreal, Quebec, Canada; §Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; ‖Research Department, School of Medicine, Universidad Iberoamericana, Santo Domingo, Dominican Republic; and ¶Division of Hematology, McGill University Health Centre, Montreal, Quebec, Canada.
出版信息
J Acquir Immune Defic Syndr. 2016 Mar 1;71(3):254-62. doi: 10.1097/QAI.0000000000000859.
BACKGROUND
We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)-associated liver disease despite antiretroviral therapy (ART), possibly due to immune dysregulation. We hypothesized that liver fibrosis in HIV/HCV coinfection would be associated with immune dysfunction and alterations in Trp metabolism.
METHODS
Trp catabolism and inflammatory soluble markers were assessed in plasma samples from ART-treated HIV/HCV-coinfected patients (n = 90) compared with ART-treated HIV-monoinfected patients and noninfected subjects. Furthermore, 17 additional coinfected patients with sustained virological response (SVR) were assessed longitudinally 6 months after completion of interferon-α/ribavirin treatment.
RESULTS
HIV/HCV patients had higher Trp catabolism compared with HIV-monoinfected and healthy individuals. Elevated kynurenine levels in HIV/HCV patients with liver fibrosis correlated with the prognostic aspartate aminotransaminase to platelet ratio (APRI scores) and insulin levels. Furthermore, HIV/HCV patients had elevated levels of disease progression markers interleukin-6 and induced protein 10 and shared similar levels of markers of microbial translocation (intestinal fatty acid-binding protein, soluble CD14 and lipopolysaccharide-binding protein) compared with HIV-monoinfected and healthy individuals. Successful HCV treatment improved APRI score and markers of disease progression and microbial translocation although elevated Trp catabolism remained unchanged 6 months after SVR.
CONCLUSION
ART-treated HIV/HCV-coinfected patients had elevated immunosuppressive Trp catabolism when compared with monoinfected HIV-treated patients, which did not normalize after SVR. These findings suggest that a necroinflammatory liver syndrome persists through inflammation by Trp catabolism after 6 month of SVR.
背景
我们之前报道了色氨酸（Trp）分解代谢与HIV单一感染中的免疫功能障碍之间的关联。尽管接受了抗逆转录病毒疗法（ART），但HIV合并感染丙型肝炎病毒（HCV）与HCV相关肝病的更快进展相关，这可能是由于免疫失调所致。我们推测，HIV/HCV合并感染中的肝纤维化与免疫功能障碍及Trp代谢改变有关。
方法
与接受ART治疗的HIV单一感染患者和未感染受试者相比，对接受ART治疗的HIV/HCV合并感染患者（n = 90）的血浆样本进行Trp分解代谢和炎症可溶性标志物评估。此外，对另外17例获得持续病毒学应答（SVR）的合并感染患者在完成干扰素-α/利巴韦林治疗6个月后进行纵向评估。
结果
与HIV单一感染患者和健康个体相比，HIV/HCV患者的Trp分解代谢更高。肝纤维化的HIV/HCV患者中犬尿氨酸水平升高与预后性天冬氨酸转氨酶与血小板比值（APRI评分）及胰岛素水平相关。此外，与HIV单一感染患者和健康个体相比，HIV/HCV患者的疾病进展标志物白细胞介素-6和诱导蛋白10水平升高，且微生物易位标志物（肠道脂肪酸结合蛋白、可溶性CD14和脂多糖结合蛋白）水平相似。成功的HCV治疗改善了APRI评分、疾病进展标志物和微生物易位，尽管在SVR后6个月Trp分解代谢升高仍未改变。
结论
与接受ART治疗的HIV单一感染患者相比，接受ART治疗的HIV/HCV合并感染患者的免疫抑制性Trp分解代谢升高，且在SVR后未恢复正常。这些发现表明，在SVR 6个月后，坏死性炎症性肝综合征通过Trp分解代谢导致的炎症持续存在。
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