Long-Lasting Imprint in the Soluble Inflammatory Milieu Despite Early Treatment of Acute Symptomatic Hepatitis C.
Long-Lasting Imprint in the Soluble Inflammatory Milieu Despite Early Treatment of Acute Symptomatic Hepatitis C.
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DOI：
10.1093/infdis/jiab048
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发表时间：
2022-08-26
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--
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慢性丙型肝炎感染患者接受直接作用抗病毒药物（DAA）治疗可导致可溶性炎症介质（西姆斯）部分恢复。与此相反，我们假设，早期DAA治疗急性丙型肝炎病毒（HCV）与DAA可能会正常化大多数西姆斯。在这项研究中，我们使用了一个独特的队列的急性症状性丙型肝炎患者清除丙型肝炎病毒与6周疗程ledipasvir/sofosbuvir。血浆样品用于邻近延伸测定，测量92种蛋白质。在急性HCV患者中观察到了深刻的SIM改变，白细胞介素（IL）-6和CXCL-10显著上调，而某些介质下调（如单核细胞趋化蛋白-4，IL-7）。在治疗和随访期间，大多数西姆斯降低，但并非全部恢复正常（例如，CDCP 1、IL-18）。值得注意的是，在DAA治疗前下调的西姆斯仍然受到抑制，而其他最初不变的SIM在治疗和随访期间下降至较低的值（例如，CD 244）。与慢性肝炎患者和健康对照组相比，急性丙型肝炎与可溶性炎症环境的显著变化相关。尽管早期DAA治疗部分地使这种改变的特征正常化，但HCV的持久印记仍然存在。
Treatment with direct-acting antivirals (DAAs) in patients with chronic hepatitis C infection leads to partial restoration of soluble inflammatory mediators (SIMs). In contrast, we hypothesized that early DAA treatment of acute hepatitis C virus (HCV) with DAAs may normalize most SIMs. In this study, we made use of a unique cohort of acute symptomatic hepatitis C patients who cleared HCV with a 6-week course of ledipasvir/sofosbuvir. Plasma samples were used for proximity extension assay measuring 92 proteins. Profound SIM alterations were observed in acute HCV patients, with marked upregulation of interleukin (IL)-6 and CXCL-10, whereas certain mediators were downregulated (eg, monocyte chemoattractant protein-4, IL-7). During treatment and follow-up, the majority of SIMs decreased but not all normalized (eg, CDCP1, IL-18). Of note, SIMs that were downregulated before DAA treatment remained suppressed, whereas others that were initially unchanged declined to lower values during treatment and follow-up (eg, CD244). Acute hepatitis C was associated with marked changes in the soluble inflammatory milieu compared with both chronic hepatitis patients and healthy controls. Whereas early DAA treatment partly normalized this altered signature, long-lasting imprints of HCV remained.
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