Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Charles University, First Faculty of Medicine, Institute of Physiology, Prague, Czech Republic.
PLoS One. 2019 Nov 8;14(11):e0224820. doi: 10.1371/journal.pone.0224820. eCollection 2019.
BACKGROUND & AIMS: MiR-33a has emerged as a critical regulator of lipid homeostasis in the liver. Genetic deficiency of miR-33a aggravates liver steatosis in a preclinical model of non-alcoholic fatty liver disease (NAFLD), and relative expression of miR-33a is increased in the livers of patients with non-alcoholic steatohepatitis (NASH). It was unknown whether miR-33a is detectable in the serum of patients with NAFLD. We sought to determine whether circulating miR-33a is associated with histological hepatic steatosis, inflammation, ballooning or fibrosis, and whether it could be used as a serum marker in patients with NAFLD/NASH.
We analysed circulating miR-33a using quantitative PCR in 116 liver transplant recipients who underwent post-transplant protocol liver biopsy. Regression analysis was used to determine association of serum miR-33a with hepatic steatosis, inflammation, ballooning and fibrosis in liver biopsy.
Liver graft steatosis and inflammation, but not ballooning or fibrosis, were significantly associated with serum miR-33a, dyslipidemia and insulin resistance markers on univariate analysis. Multivariate analysis showed that steatosis was independently associated with serum miR-33a, ALT, glycaemia and waist circumference, whereas inflammation was independently associated with miR-33a, HbA1 and serum triglyceride levels. Receiver operating characteristic analysis showed that exclusion of serum miR-33a from multivariate analysis resulted in non-significant reduction of prediction model accuracy of liver steatosis or inflammation.
Our data indicate that circulating miR-33a is an independent predictor of liver steatosis and inflammation in patients after liver transplantation. Although statistically significant, its contribution to the accuracy of prediction model employing readily available clinical and biochemical variables was limited in our cohort.
miR-33a 已成为肝脏脂质稳态的关键调节因子。在非酒精性脂肪性肝病 (NAFLD) 的临床前模型中，miR-33a 的基因缺失会加重肝脏脂肪变性，非酒精性脂肪性肝炎 (NASH) 患者的肝脏中 miR-33a 的相对表达增加。尚不清楚 miR-33a 是否可在 NAFLD 患者的血清中检测到。我们旨在确定循环 miR-33a 是否与肝组织脂肪变性、炎症、气球样变或纤维化相关，以及它是否可作为 NAFLD/NASH 患者的血清标志物。
我们使用定量 PCR 分析了 116 例接受肝移植后行移植后方案肝活检的肝移植受者的循环 miR-33a。回归分析用于确定血清 miR-33a 与肝活检中肝脂肪变性、炎症、气球样变和纤维化的关系。
肝移植后肝脂肪变性和炎症，但不是气球样变或纤维化，与血清 miR-33a、血脂异常和胰岛素抵抗标志物在单因素分析中显著相关。多因素分析显示，脂肪变性与血清 miR-33a、ALT、血糖和腰围独立相关，而炎症与 miR-33a、HbA1 和血清三酰甘油水平独立相关。受试者工作特征分析显示，将血清 miR-33a 排除在多因素分析之外，会导致肝脂肪变性或炎症预测模型准确性的非显著降低。
我们的数据表明，循环 miR-33a 是肝移植后患者肝脂肪变性和炎症的独立预测因子。尽管具有统计学意义，但在我们的队列中，其对使用现有临床和生化变量的预测模型准确性的贡献有限。
