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维生素D缺乏的纠正有助于抑制慢性丙型肝炎患者的IP-10和DPP IV水平:一项随机双盲、安慰剂对照试验。

Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial.

作者信息

Komolmit Piyawat, Charoensuk Kriangsak, Thanapirom Kessarin, Suksawatamnuay Sirinporn, Thaimai Panarat, Chirathaworn Chintana, Poovorawan Yong

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Division of Gastroenterology, Department of Internal medicine, Buddhachinaraj Hospital School of Medicine, Phitsanulok, Thailand.

出版信息

PLoS One. 2017 Apr 4;12(4):e0174608. doi: 10.1371/journal.pone.0174608. eCollection 2017.

Abstract

UNLABELLED

Vitamin D deficiency was common among patients with chronic hepatitis C (CHC) and had negative influence on treatment outcome. Correction of vitamin D deficiency improved treatment response. Interferon gamma-induced protein 10 (IP-10) and enzyme dipeptidyl peptidase-4 (DPP IV) involved in inflammatory responses in CHC. Their higher levels at pretreatment of CHC could predict poorer responses. Vitamin D suppressed expression of IP-10 from monocytes in vitro. In CHC patients, DPP IV involved in IP-10 regulation. We hypothesized that correction of vitamin D insufficiency or deficiency in CHC patients might restore immune dysregulation through a pathway linked to the TH1/Th2 cytokines, IP-10 or DPP IV. We conducted a double-blind, placebo-controlled trial. 80 CHC patients with vitamin D levels less than 30 ng/mL were assigned to receive vitamin D (40) or placebo (40) supplements for 6 weeks. The levels of 25-hydroxyvitamin D [25(OH)D], Th1/Th2 cytokines, IP-10 and DPP IV were measured at baseline and at the 6th week. At the end of study, the mean 25(OH)D level in vitamin D group was significantly increased and normalised. There were no changes in the level of Th1/Th2 cytokines. Our important finding revealed that upon correction of vitamin D insufficiency or deficiency, the serum IP-10 and DPP IV levels were decreased significantly as compare to the placebo group (delta changes; 83.27 vs -133.80; 95% CI [-326.910, -40.758], p = 0.0125, and 271.04 vs -518.69; 95% CI [-1179,15, -59.781], p = 0.0305, respectively. As previous evidences suggested that each factor individually influenced and predicted outcome of CHC treatment. Our results offer a new insight and help to piece the puzzle of vitamin D deficiency, IP-10 and DPP IV together in CHC.

TRIAL REGISTRATION

Thai Clinical Trials Registry TCTR20160429001.

摘要

未标注

维生素D缺乏在慢性丙型肝炎(CHC)患者中很常见,并且对治疗结果有负面影响。纠正维生素D缺乏可改善治疗反应。干扰素γ诱导蛋白10(IP-10)和二肽基肽酶4(DPP IV)参与慢性丙型肝炎的炎症反应。在慢性丙型肝炎治疗前它们的水平较高可预测较差的反应。维生素D在体外抑制单核细胞中IP-10的表达。在慢性丙型肝炎患者中,DPP IV参与IP-10的调节。我们假设纠正慢性丙型肝炎患者的维生素D不足或缺乏可能通过与TH1/Th2细胞因子、IP-10或DPP IV相关的途径恢复免疫失调。我们进行了一项双盲、安慰剂对照试验。80名维生素D水平低于30 ng/mL的慢性丙型肝炎患者被分配接受维生素D(40名)或安慰剂(40名)补充剂,为期6周。在基线和第6周时测量25-羟基维生素D [25(OH)D]、Th1/Th2细胞因子、IP-10和DPP IV的水平。在研究结束时,维生素D组的平均25(OH)D水平显著升高并恢复正常。Th1/Th2细胞因子水平没有变化。我们的重要发现表明,在纠正维生素D不足或缺乏后,与安慰剂组相比,血清IP-10和DPP IV水平显著降低(变化差值;83.27对-133.80;95% CI [-326.910, -40.758],p = 0.0125,以及271.04对-518.69;95% CI [-1179.15, -59.781],p = 0.0305)。如先前证据所示,每个因素单独影响并预测慢性丙型肝炎治疗的结果。我们的结果提供了新的见解,并有助于将慢性丙型肝炎中维生素D缺乏、IP-10和DPP IV的谜题拼凑在一起。

试验注册

泰国临床试验注册中心TCTR20160429001。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d394/5380326/39608295662a/pone.0174608.g001.jpg

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