Steatohepatitis and liver fibrosis are predicted by the characteristics of very low density lipoprotein in nonalcoholic fatty liver disease.
Steatohepatitis and liver fibrosis are predicted by the characteristics of very low density lipoprotein in nonalcoholic fatty liver disease.
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DOI：
10.1111/liv.13076
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Lai M
中科院分区：
文献类型：
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作者：
Jiang ZG;Tapper EB;Connelly MA;Pimentel CF;Feldbrügge L;Kim M;Krawczyk S;Afdhal N;Robson SC;Herman MA;Otvos JD;Mukamal KJ;Lai M
非酒精性脂肪性肝病（NAFLD）治疗的一个主要挑战是识别非酒精性脂肪性肝炎（NASH）和早期肝纤维化患者。NAFLD的进展伴随着极低密度脂蛋白（VLDL）的显著变化，VLDL是一种仅在肝脏中产生的脂蛋白颗粒。在此，我们试图确定与NASH和肝纤维化相关的VLDL谱的特征。我们评估了来自单中心NAFLD登记处的128名患者的VLDL特征，并检查了VLDL大小、总VLDL浓度和亚类VLDL浓度与NAFLD活动评分（NAS）、脂肪性肝炎和肝纤维化的关系。平均VLDL颗粒大小与NAFLD活性评分（NAS）呈近似线性关系。在多变量模型中，在调整BMI和糖尿病因素后，VLDL颗粒大小与NAS和NASH均显著相关。小VLDL颗粒浓度的降低与更严重的肝纤维化有关。在受试者手术特征分析中，平均VLDL大小与细胞角蛋白18在预测NASH方面的表现相似，而小VLDL颗粒浓度与NAFLD纤维化评分在预测2期或以上肝纤维化方面的表现相似。NASH中平均VLDL大小的增加和肝纤维化中小VLDL颗粒浓度的降低可能反映了与NASH和纤维化相关的肝细胞数量和状态的变化。除了在心血管疾病的风险分层中有价值外，循环VLDL谱还可以为NAFLD疾病严重程度的分期提供信息。
A major challenge in the management of nonalcoholic fatty liver disease (NAFLD) is to identify patients with nonalcoholic steatohepatitis (NASH) and early liver fibrosis. The progression of NAFLD is accompanied by distinctive changes in very low density lipoprotein (VLDL), a lipoprotein particle produced exclusively in the liver. Herein, we sought to determine the characteristics of VLDL profiles associated with NASH and liver fibrosis. We evaluated VLDL profiles of 128 patients from a single centre NAFLD registry, and examined VLDL size, total and subclass VLDL concentrations in relation to NAFLD activity score (NAS), steatohepatitis and liver fibrosis as determined by liver biopsy. A near linear relationship was observed between mean VLDL particle size and NAFLD activity score (NAS). In multivariate models, VLDL particle size was significantly associated with both NAS and NASH, after adjustment for BMI and diabetes. A decrease in small VLDL particle concentration was associated with more advanced liver fibrosis. In receiver operative characteristic analyses, mean VLDL size performed similarly to cytokeratin 18 in predicting NASH, whereas small VLDL particle concentration had similar performance to NAFLD fibrosis score in predicting stage 2 or above liver fibrosis. The increase in mean VLDL size in NASH and decrease in small VLDL particle concentration in liver fibrosis likely reflect changes in the number and state of hepatocytes associated with NASH and fibrosis. In addition to its value in risk stratification of cardiovascular diseases, circulating VLDL profile may provide information for the staging of NAFLD disease severity.