Cengiz Mustafa, Ozenirler Seren, Elbeg Sehri
Department of Gastroenterology, Dr. A.Y. Ankara Oncology Training and Research Hospital, Ankara, Turkey.
Department of Gastroenterology, Gazi University Faculty of Medicine, Ankara, Turkey.
J Gastroenterol Hepatol. 2015 Jul;30(7):1190-6. doi: 10.1111/jgh.12924.
Non-alcoholic fatty liver disease is a common cause of chronic liver disease, including non-alcoholic steatohepatitis (NASH). Our aim was to investigate whether serum toll-like receptors 2 and 4 (TLR2 and TLR4) levels are correlated with NASH and able to predict liver fibrosis, as well as to compare these markers with other non-invasive fibrosis scores (aspartate aminotransferase [AST] to alanine aminotransferase ratio, AST to platelet ratio index, fibrosis index, fibrosis 4, and fibrosis cirrhosis index).
Serum samples were obtained from consecutive biopsy proven NASH patients and healthy controls. Serum TLR2 and TLR4 were measured using ELISA. Stage of fibrosis was evaluated using the Brunt Criteria. The different non-invasive fibrosis scores were compared using areas under the curve.
Fifty-seven patients with NASH and 57 healthy individuals were enrolled in the study. Serum TLR2 levels were not significantly different between the healthy controls and NASH patients. The medians were 3.88 ng/mL ± 0.29 versus 3.81 ng/mL ± 0.32, respectively (P = 0.587). In comparing the levels of TLR4 between groups, the medians were 1.05 ng/mL ± 0.13 versus 1.46 ng/mL ± 0.27, respectively (P < 0.001). In NASH patients, the levels of serum TLR4 increased with the stage of fibrosis: TLR4 medians were F0:1.01, F1:1.46, F2:2.14, F3:3.74, F4:5.83 (P < 0.001). TLR4 produced AUCs for ≥ F1, ≥ F2, and ≥ F3 of 0.862, 0.810, and 0.905, respectively (P < 0.001). TLR4 levels were more predictive than other non-invasive fibrosis scores in liver fibrosis.
Serum TLR4 levels but not TLR2 were elevated in NASH patients in comparison with healthy controls. And in NASH patients, serum TLR4 levels both correlated with and were able to predict liver fibrosis.
非酒精性脂肪性肝病是慢性肝病的常见病因，包括非酒精性脂肪性肝炎（NASH）。我们的目的是研究血清Toll样受体2和4（TLR2和TLR4）水平是否与NASH相关并能够预测肝纤维化，以及将这些标志物与其他非侵入性纤维化评分（天冬氨酸转氨酶[AST]与丙氨酸转氨酶比值、AST与血小板比值指数、纤维化指数、纤维化4和纤维化肝硬化指数）进行比较。
从连续经活检证实的NASH患者和健康对照者中获取血清样本。使用酶联免疫吸附测定法（ELISA）检测血清TLR2和TLR4。采用布伦特标准评估纤维化阶段。使用曲线下面积比较不同的非侵入性纤维化评分。
本研究纳入了57例NASH患者和57名健康个体。健康对照者与NASH患者的血清TLR2水平无显著差异。中位数分别为3.88 ng/mL±0.29和3.81 ng/mL±0.32（P = 0.587）。比较两组间的TLR4水平，中位数分别为1.05 ng/mL±0.13和1.46 ng/mL±0.27（P < 0.001）。在NASH患者中，血清TLR4水平随纤维化阶段升高：TLR4中位数在F0期为1.01、F1期为1.46、F2期为2.14、F3期为3.74、F4期为5.83（P < 0.001）。TLR4对于≥F1、≥F2和≥F3期的曲线下面积分别为0.862、0.810和0.905（P < 0.001）。在肝纤维化方面，TLR4水平比其他非侵入性纤维化评分更具预测性。
与健康对照者相比，NASH患者血清TLR4水平升高，而TLR2水平未升高。并且在NASH患者中，血清TLR4水平与肝纤维化相关且能够预测肝纤维化。
