Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: A pilot trial of interferon nonresponders
Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: A pilot trial of interferon nonresponders
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DOI：
10.1016/s0016-5085(00)70134-x
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发表时间：
2000-04-01
期刊：
影响因子：
29.4
通讯作者：
Davis, GL
中科院分区：
文献类型：
--
作者：
Nelson, DR;Lauwers, GY;Davis, GL
背景和目标：白细胞介素（IL）-10是一种下调促炎反应并对肝纤维化具有调节作用的细胞因子。本研究的目的是确定IL-10对慢性丙型肝炎患者肝损伤的影响。24例既往对干扰素治疗无反应的慢性丙型肝炎患者被纳入一项随机，双盲2剂量试验，其中他们每天皮下接受4或8 μ g/kg IL-10，持续90天。在治疗前和治疗结束时进行肝活检。结果：IL-10耐受良好，22例患者完成了研究。治疗结束时，22名患者中有19名患者的血清ALT水平恢复正常，22名患者中有5名患者的血清ALT水平维持正常。22名患者中有19名患者的肝脏炎症减轻，其中11名患者的减轻幅度大于或等于2。22例患者中有14例纤维化程度减轻（平均变化3.6-2.6; P = 0.001），血清HCVRNA水平无变化。IL-10治疗与血清学标志物的变化相关，表明免疫反应和纤维化的减少，结论：IL-10治疗慢性丙型肝炎患者是安全的，耐受性良好，虽然它没有明显的抗病毒活性，IL-10使血清ALT水平正常化，改善肝组织学，并减少肝纤维化在很大比例的患者接受治疗。因此，IL-10可能对干扰素治疗无效的慢性丙型肝炎患者具有治疗潜力。
Background & Aims: Interleukin (IL)-10 is a cytokine that down-regulates the proinflammatory response and has a modulatory effect on hepatic fibrogenesis, The aim of this study was to determine the effect of IL-10 on hepatic injury in patients with chronic hepatitis C, Methods: Twenty-four patients with chronic hepatitis C who had not previously responded to interferon-based therapy were enrolled in a randomized, double-blinded 2-dose trial in which they received either 4 or 8 mu g/kg IL-10 subcutaneously daily for 90 days. Liver biopsies were performed before and at the end of therapy. Results: IL-10 was well tolerated with 22 patients completing the study. Serum ALT levels normalized in 19 of 22 patients by the end of therapy and were sustained in 5 of 22, Hepatic inflammation decreased in 19 of 22 patients, with 11 having a decrease by greater than or equal to 2. Fibrosis decreased in 14 of 22 patients (mean change, 3.6-2.6; P = 0.001), There was no change in serum HCV RNA levels. IL-10 therapy was associated with changes in serological markers, suggesting a reduction of immune response and fibrogenesis, Conclusions: IL-10 therapy is safe and well tolerated in patients with chronic hepatitis C, Although it has no apparent antiviral activity, IL-10 normalizes serum ALT levels, improves liver histology, and reduces liver fibrosis in a large proportion of patients receiving treatment. Therefore, IL-10 may have therapeutic potential in patients with chronic hepatitis C patients who do not respond to interferon-based therapy.