Characterization of changes in intrahepatic immune cell populations during HCV treatment with sofosbuvir and ribavirin.
Characterization of changes in intrahepatic immune cell populations during HCV treatment with sofosbuvir and ribavirin.
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DOI：
10.1111/jvh.13034
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发表时间：
2019-03
影响因子：
2.5
通讯作者：
Meissner EG
中科院分区：
文献类型：
--
作者：
Orr C;Aartun J;Masur H;Kottilil S;Meissner EG
使用直接作用抗病毒药物（DAA）治疗慢性丙型肝炎病毒（HCV）感染可使大多数患者出现持续病毒学应答（SVR）。虽然非常有效，但约 3-5% 的患者尽管感染了看似易感的病毒，但并未实现 SVR。尽管先天性和适应性免疫可能发挥作用，但尚不清楚宿主因素是否会导致治疗失败。先前的研究表明，在 DAA 治疗后，即使达到 SVR，肝内免疫细胞的组成相对于健康志愿者也没有正常化。我们使用了 13 名接受索非布韦和利巴韦林治疗的患者（其中 4 名复发）的治疗前和治疗后配对肝活检，分析 DAA 治疗期间的细胞内免疫变化，并探讨与炎症和治疗结果的相关性。我们进行了单标记免疫组织化学，然后进行电子图像捕获、实质和非实质区域的手动注释以及定量图像分析。治疗期间主要的细胞变化是实质和非实质区域CD8+细胞密度的降低。 CD68+库普弗细胞密度与治疗前肝脏炎症（AST、ALT）相关，但在治疗期间没有变化。非实质区域的 CD4+ 细胞密度下降，有趣的是，在最终复发的受试者中，治疗前的 CD4+ 细胞密度较低。其他细胞标记物（CD56、CD20）以及凋亡标记物（TIA-1）和活化的星状细胞在治疗期间没有显着变化，或者因治疗结果而异。 DAA 治疗慢性 HCV 感染期间，主要的肝内细胞变化是 CD8+ 细胞密度的降低，但这与治疗结果无关。
Treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) results in a sustained virologic response (SVR) in most patients. While highly efficacious, ~3–5% of patients do not achieve SVR despite having virus that appears susceptible. It is unclear whether host factors contribute to treatment failures, although innate and adaptive immunity may play a role. Previous studies showed that after DAA treatment, the composition of intrahepatic immune cells does not normalize relative to healthy volunteers, even in cases where SVR is achieved. We used paired pre- and post-treatment liver biopsies from 13 patients treated with sofosbuvir and ribavirin, 4 of whom relapsed, to analyze intracellular immune changes during DAA treatment and explore correlations with inflammation and treatment outcome. We performed single marker immunohistochemistry followed by electronic image capture, manual annotation of parenchymal and non-parenchymal regions, and quantitative image analysis. The predominant cellular change during treatment was a decrease in CD8+ cellular density in both parenchymal and non-parenchymal regions. CD68+ Kupffer cell density correlated with hepatic inflammation (AST, ALT) pre-treatment, but did not change during treatment. CD4+ cellular density decreased in non-parenchymal regions and, intriguingly, was lower pre-treatment in subjects who eventually relapsed. Other cellular markers (CD56, CD20), as well as markers of apoptosis (TIA-1) and activated stellate cells, did not change significantly during treatment or differ by treatment outcome. The predominant intrahepatic cellular change during DAA treatment of chronic HCV infection is a reduction in CD8+ cellular density, but this did not correlate with treatment outcome.
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影响因子：
7.6
作者：
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通讯作者：
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影响因子：
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作者：
Meissner EG;Kohli A;Higgins J;Lee YJ;Prokunina O;Wu D;Orr C;Masur H;Kottilil S
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