Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
HIV Molecular Research Group, University College of Dublin, Ireland.
J Infect Dis. 2018 Sep 22;218(9):1394-1403. doi: 10.1093/infdis/jiy331.
Coinfection with human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV)-related liver fibrosis. Macrophages are triggered during both viral infections and are critical in liver inflammation/fibrogenesis. Liver fibrosis strongly associates with serum soluble CD163 (sCD163, a macrophage activation marker); comprehensive evaluation in HIV/HCV coinfection is lacking.
We retrospectively analyzed sCD163 (enzyme-linked immunosorbent assay) and hepatic CD163 (immunofluorescent CD163/CD68 costaining) in patients infected with HIV/HCV, HCV, or HIV, pre- and post-antiviral therapy.
sCD163 was significantly higher in HIV/HCV compared to either monoinfection, and decreased following successful antiviral therapy, although did not fully normalize. In HIV/HCV, sCD163 was associated with necroinflammation, Ishak fibrosis scores, and noninvasive fibrosis scores. We observed a novel trend whereby sCD163 levels progressively increase with increasing Ishak fibrosis score, peaking at stage 4, above which levels plateaued. Periportal CD163+ macrophage frequency was also higher with increasing fibrosis score. When stratified by fibrosis stage, sCD163 levels were higher in HIV/HCV than HCV but only in individuals with mild to moderate fibrosis.
In HIV/HCV, increasing sCD163 levels accompanied periportal CD163+ macrophage enrichment in mild to moderate fibrosis, but not in established cirrhosis, suggesting that sCD163 is a dynamic biomarker of fibrogenesis rather than accumulated fibrosis. Our findings implicate HIV-related macrophage activation in accelerated fibrosis progression in HIV/HCV coinfection.
人类免疫缺陷病毒（HIV）合并感染会加速丙型肝炎病毒（HCV）相关的肝纤维化。巨噬细胞在两种病毒感染时都会被激活，并在肝脏炎症/纤维化中起关键作用。肝纤维化与血清可溶性 CD163（sCD163，一种巨噬细胞激活标志物）密切相关；在 HIV/HCV 合并感染中缺乏全面评估。
我们回顾性分析了感染 HIV/HCV、HCV 或 HIV 的患者在抗病毒治疗前后的血清 sCD163（酶联免疫吸附试验）和肝 CD163（免疫荧光 CD163/CD68 双重染色）。
与单一感染相比，HIV/HCV 患者的 sCD163 显著升高，并且在成功抗病毒治疗后降低，但并未完全正常化。在 HIV/HCV 中，sCD163 与坏死性炎症、Ishak 纤维化评分和非侵入性纤维化评分相关。我们观察到一个新的趋势，即 sCD163 水平随着 Ishak 纤维化评分的增加而逐渐升高，在第 4 期达到峰值，之后水平趋于平稳。随着纤维化评分的增加，门脉周围 CD163+巨噬细胞的频率也更高。按纤维化分期分层，sCD163 水平在 HIV/HCV 中高于 HCV，但仅在轻度至中度纤维化患者中升高。
在 HIV/HCV 中，随着轻度至中度纤维化中门脉周围 CD163+巨噬细胞的富集，sCD163 水平逐渐升高，但在已建立的肝硬化中则没有升高，这表明 sCD163 是纤维化发生的动态生物标志物，而不是累积的纤维化。我们的研究结果表明，HIV 相关的巨噬细胞激活可能导致 HIV/HCV 合并感染中纤维化的加速进展。
