Serum Interleukin-8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.
Serum Interleukin-8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.
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DOI：
10.1002/hep4.1237
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发表时间：
2018-11
影响因子：
5.1
通讯作者：
Abdelmalek MF
中科院分区：
文献类型：
--
作者：
Glass O;Henao R;Patel K;Guy CD;Gruss HJ;Syn WK;Moylan CA;Streilein R;Hall R;Mae Diehl A;Abdelmalek MF
肝纤维化的严重程度是非酒精性脂肪性肝病（NAFLD）患者肝脏相关发病率和死亡率的主要预测因素。不幸的是，NAFLD相关纤维化的非侵入性血清生物标志物有限。我们分析了97例经活检证实的NAFLD患者的基线血清样本中的24种细胞因子。这些患者前瞻性入组临床研究（ClinicalTrials.gov NCT 00794716），以确定与非酒精性脂肪性肝炎患者肝纤维化相关的细胞因子。根据肝纤维化的严重程度（轻度，0 - 1期，n = 37;中度，2期，n = 40;晚期，3 - 4期，n = 20）对患者进行分层，同时控制年龄、人种、性别、体重指数和糖尿病。白细胞介素-8（IL-8）、骨桥蛋白（OPN）和单核细胞趋化蛋白1（MCP 1）与肝纤维化相关（分别为P < 0.001，P = 0.005，P = 0.016）。在控制脂肪变性、小叶炎症、肝细胞气球样变、年龄、性别、体重指数、糖尿病、高血压和代谢综合征状态后，IL-8仍然与纤维化密切相关（P = 0.001）。此外，与已确定的肝纤维化标志物相比，IL-8也是纤维化肝损伤增加的强预测因子。来自杜克大学健康系统NAFLD临床数据库和生物储存库的72例NAFLD患者（n = 40例轻度纤维化; n = 32例晚期纤维化）的肝脏基因表达显示，IL-8、MCP 1和OPN基因表达增加，并且在晚期肝纤维化患者中表达差异。因此，血清IL-8、MCP 1和OPN可能反映了NAFLD肝纤维化过程中上调的基因表达。结论：血清IL-8、MCP 1和OPN可作为NAFLD中晚期肝纤维化的检测指标，从而揭示抗纤维化治疗的新靶点。与相关肝脏基因表达相对应的血清IL-8、MCP 1和OPN升高，为此类分析物作为肝纤维化严重程度的理想替代血清生物标志物提供了优势。
The severity of hepatic fibrosis is the primary predictor of liver‐related morbidity and mortality in patients with nonalcoholic fatty liver disease (NAFLD). Unfortunately, noninvasive serum biomarkers for NAFLD‐associated fibrosis are limited. We analyzed baseline serum samples for 24 cytokines of 97 patients with biopsy‐proven NAFLD. These patients were prospectively enrolled in a clinical study (ClinicalTrials.gov NCT00794716) to identify cytokines associated with liver fibrosis in patients with nonalcoholic steatohepatitis. Patients were stratified according to severity of hepatic fibrosis (mild, stage 0‐1, n = 37; moderate, stage 2, n = 40; and advanced, stage 3‐4, n = 20) while controlling for age, race, sex, body mass index, and diabetes mellitus. Interleukin‐8 (IL‐8), osteopontin (OPN), and monocyte chemoattractant protein 1 (MCP1) were associated with liver fibrosis (P < 0.001, P = 0.005, P = 0.016, respectively). After controlling for steatosis, lobular inflammation, hepatocyte ballooning, age, sex, body mass index, diabetes mellitus, hypertension, and metabolic syndrome status, IL‐8 remained strongly associated with fibrosis (P = 0.001). Furthermore, IL‐8 was also a strong predictor of increased fibrotic liver injury compared to established markers of hepatic fibrosis. Hepatic gene expression from 72 patients with NAFLD (n = 40 mild fibrosis; n = 32 advanced fibrosis) from the Duke University Health System NAFLD Clinical Database and Biorepository revealed IL‐8, MCP1, and OPN gene expression to be increased and differentially expressed in patients with advanced hepatic fibrosis. Thus, serum IL‐8, MCP1, and OPN may reflect up‐regulated gene expression during liver fibrosis in NAFLD. Conclusion: Serum IL‐8, MCP1, and OPN may serve as a test for advanced hepatic fibrosis in NAFLD and thus reveal novel targets for antifibrotic therapies. The increased serum IL‐8, MCP1, and OPN that correspond with associated hepatic gene expression lend strength to such analytes as ideal surrogate serum biomarkers for severity of hepatic fibrosis.
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DOI：
10.1097/00005176-200411000-00017
发表时间：
2004-11-01
影响因子：
2.9
作者：
Nobili, V;Marcellini, M;De Benedetti, T
通讯作者：
De Benedetti, T
影响因子：
3.6
作者：
Kirovski, Georgi;Dorn, Christoph;Hellerbrand, Claus
通讯作者：
Hellerbrand, Claus
影响因子：
4.3
作者：
Fitzpatrick, Emer;Dhawan, Anil
通讯作者：
Dhawan, Anil
影响因子：
24.5
作者：
Harrison, S. A.;Oliver, D.;Neuschwander-Tetri, B. A.
通讯作者：
Neuschwander-Tetri, B. A.
影响因子：
29.4
作者：
Matteoni, CA;Younossi, ZM;McCullough, AJ
通讯作者：
McCullough, AJ