The potential of soluble CD14 in discriminating nonalcoholic steatohepatitis from nonalcoholic fatty liver disease
The potential of soluble CD14 in discriminating nonalcoholic steatohepatitis from nonalcoholic fatty liver disease
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可溶性CD 14在鉴别非酒精性脂肪性肝炎和非酒精性脂肪性肝病中的应用
DOI：
10.1111/hepr.13757
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发表时间：
2022-02-22
影响因子：
4.2
通讯作者：
Sakamoto, Naoya
中科院分区：
文献类型：
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作者：
Nakamura, Akihisa;Yamamoto, Koji;Sakamoto, Naoya
背景和目的虽然已经报道了各种非酒精性脂肪性肝炎（NASH）的非侵入性标志物和预测公式，但它们仅在NASH的晚期纤维化阶段的诊断中有价值。在这项研究中，我们使用动物模型和临床标本评估了可溶性CD 14（sCD 14）作为区分NASH和非酒精性脂肪性肝病（NAFLD）的诊断标志物。方法采用酶联免疫吸附法检测饮食诱导NASH小鼠和患者血清sCD 14水平。我们的队列入组了126例经肝穿刺活检证实的NAFLD患者。结果NASH模型小鼠独特的肠道环境导致肠道防御机制发生改变。在饮食诱导的NASH小鼠中观察到sCD 14的血清水平升高，并且由于暴露于肠源性内毒素，肝脏状况恶化。我们证实NAFL患者血清sCD 14水平与NASH患者血清sCD 14水平存在显著差异。用于区分NAFL和NASH的曲线下面积为0.891。此外，我们发现血清sCD 14水平与NAFLD患者中基于NAFLD活动性评分（NAS）的炎症分级、根据Brunt纤维化分类的纤维化分级弱相关，与基于NAS的气球样变分级正相关。结论sCD 14可作为鉴别NASH和NAFLD的病理生理标志物和辅助诊断指标。使用sCD 14可以筛查和识别NASH发展的高危人群，并支持早期治疗干预。
Background and Aims Although various noninvasive markers and prediction formulas for nonalcoholic steatohepatitis (NASH) have been reported, they are of value only in the diagnosis of the advanced fibrosis stage of NASH. In this study, we evaluated soluble CD14 (sCD14) as a diagnostic marker for discriminating NASH from nonalcoholic fatty liver disease (NAFLD) using an animal model and clinical specimens. Methods Serum sCD14 levels were measured in samples derived from mice with diet-induced NASH and patients using an enzyme-linked immunosorbent assay. Our cohort enrolled 126 patients with liver needle biopsy-proven NAFLD. Results The intestinal defense mechanism in NASH model mice was altered as a consequence of the unique gut environment. Elevated serum levels of sCD14 were observed in mice with diet-induced NASH, and the condition of the liver was exacerbated as a result of exposure to gut-derived endotoxin. We confirmed that the serum sCD14 levels in NAFL patients significantly differed from those in NASH patients. The area under the curve for distinguishing between NAFL and NASH was 0.891. Moreover, we found that serum sCD14 levels were weakly correlated with the inflammation grade based on the NAFLD activity score (NAS), the grade of fibrosis according to the Brunt fibrosis classification, and a positive correlation with the grade of ballooning based on NAS in patients with NAFLD. Conclusion sCD14 could be a useful pathophysiological marker and diagnostic adjunct distinguishing NASH from NAFLD. The use of sCD14 may allow the screening and identification of high-risk groups for NASH development and support early therapeutic interventions.