Ampuero Javier, Ranchal Isidora, Gallego-Durán Rocío, Pareja María Jesús, Del Campo Jose Antonio, Pastor-Ramírez Helena, Rico María Carmen, Picón Rocío, Pastor Luis, García-Monzón Carmelo, Andrade Raúl, Romero-Gómez Manuel
Inter-Centre Unit of Digestive Diseases & CIBERehd. Virgen Macarena - Virgen del Rocío University Hospitals, University of Sevilla, Sevilla, Spain.
Instituto de Biomedicina de Sevilla, Sevilla, Spain.
J Gastroenterol Hepatol. 2016 Sep;31(9):1611-8. doi: 10.1111/jgh.13335.
A small but significant proportion of patients with normal body mass index show non-alcoholic fatty liver disease (NAFLD). Oxidized low-density lipoprotein (LDL) is a powerful immunogenic molecule, which causes oxidative stress and produces antibodies (oxLDL-ab). We aimed to analyze the role of oxLDL-ab on histological features in lean-NAFLD patients.
Seventy-two biopsy-proven NAFLD patients were included. Lean patients showed body index mass of <30 kg/m(2) . Liver biopsies were assessed by one pathologist blinded to clinical data. Histological features were non-alcoholic steatohepatitis (NASH), steatosis, hepatocellular ballooning, and liver fibrosis. Metabolic and hepatic profiles were analyzed, and lipid-lowering medication was recorded. OxLDL-ab levels were measured by ELISA. OxLDL-ab-based lipid indexes analyzed: oxLDL-ab/total cholesterol ratio; oxLDL-ab/LDL-c ratio; oxLDL-ab/high-density lipoprotein cholesterol (HDL-c) ratio; and oxLDL-ab/oxLDL ratio.
Lean-NAFLD patients presented 26.5% (9/34) of NASH. OxLDL-ab/HDL-c ratio (r = 0.570; n = 34; P = 0.001) correlated with NAS score and was the only variable associated with NASH in the multivariate analysis [odds ratio, OR, 1.10 (95% confidence interval, CI: 1.01-1.21); P = 0.039]. Severe steatosis was present in 41.2% (14/34) of lean-NAFLD patients. OxLDL-ab/HDL-c ratio was higher in patients with grade-III steatosis (54.9 (37.3-124.6)) than those with grade II (37.1 (20.2-71.1)) and grade I (17.7 (13.1-22.8)) (P = 0.018). Hepatocellular ballooning was present in 20.6% (7/34) of lean-NAFLD patients, and OxLDL-ab/HDL-c ratio (OR 1.03 [95% CI: 1.01-1.05]; P = 0.050) was independently associated with histological features. OxLDL-ab/HDL-c ratio was higher in patients with advanced fibrosis (39.8 (22.9-121.6) vs 17.7 (13.9-30.9); P = 0.025), increasing gradually with the fibrosis stage (P = 0.042) and remained in the final multivariate model [OR 1.05 (95% CI: 1.00-1.11); P = 0.05]. However, in obese-NAFLD patients, oxLDL/HDL-c ratio was not associated with histological features.
Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio could represent an interesting biomarker associated with NASH, hepatocellular ballooning, and liver fibrosis, in lean patients. OxLDL-ab/HDL-c could play an important role for distinguishing patients with and without NAFLD complications.
一小部分但比例显著的体重指数正常的患者患有非酒精性脂肪性肝病(NAFLD)。氧化型低密度脂蛋白(LDL)是一种强大的免疫原性分子,可引起氧化应激并产生抗体(oxLDL-ab)。我们旨在分析oxLDL-ab在瘦型NAFLD患者组织学特征中的作用。
纳入72例经活检证实的NAFLD患者。瘦型患者的体重指数<30 kg/m²。由一位对临床数据不知情的病理学家对肝活检进行评估。组织学特征包括非酒精性脂肪性肝炎(NASH)、脂肪变性、肝细胞气球样变和肝纤维化。分析代谢和肝脏指标,并记录降脂药物使用情况。通过酶联免疫吸附测定(ELISA)测量oxLDL-ab水平。分析基于oxLDL-ab的脂质指数:oxLDL-ab/总胆固醇比值;oxLDL-ab/LDL-c比值;oxLDL-ab/高密度脂蛋白胆固醇(HDL-c)比值;以及oxLDL-ab/oxLDL比值。
瘦型NAFLD患者中NASH的发生率为26.5%(9/34)。oxLDL-ab/HDL-c比值(r = 0.570;n = 34;P = 0.001)与NAS评分相关,并且是多变量分析中与NASH相关的唯一变量[比值比,OR,1.10(95%置信区间,CI:1.01 - 1.21);P = 0.039]。41.2%(14/34)的瘦型NAFLD患者存在重度脂肪变性。III级脂肪变性患者的oxLDL-ab/HDL-c比值(54.9(37.3 - 124.6))高于II级(37.1(20.2 - 71.1))和I级(17.7(13.1 - 22.8))患者(P = 0.018)。20.6%(7/34)的瘦型NAFLD患者存在肝细胞气球样变,oxLDL-ab/HDL-c比值(OR 1.03 [95% CI:1.01 - 1.05];P = 0.050)与组织学特征独立相关。晚期纤维化患者的oxLDL-ab/HDL-c比值更高(39.8(22.9 - 121.6)对17.7(13.9 - 30.9);P = 0.025),并随纤维化阶段逐渐升高(P = 0.042),且保留在最终的多变量模型中[OR 1.05(95% CI:1.00 - 1.11);P = 0.05]。然而,在肥胖型NAFLD患者中,oxLDL/HDL-c比值与组织学特征无关。
氧化型低密度脂蛋白抗体/高密度脂蛋白胆固醇比值可能是一种与瘦型患者的NASH、肝细胞气球样变和肝纤维化相关的有趣生物标志物。oxLDL-ab/HDL-c可能在区分有无NAFLD并发症的患者中起重要作用。