Kashyap Sangeeta R, Diab Dima L, Baker Allison R, Yerian Lisa, Bajaj Harpreet, Gray-McGuire Courtney, Schauer Philip R, Gupta Manjula, Feldstein Ariel E, Hazen Stanley L, Stein Catherine M
Endocrinology Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Obesity (Silver Spring). 2009 Sep;17(9):1696-701. doi: 10.1038/oby.2009.89. Epub 2009 Apr 9.
Although nonalcoholic fatty liver disease (NAFLD) is frequent in obesity, the metabolic determinants of advanced liver disease remain unclear. Adipokines reflect inflammation and insulin resistance associated with obesity and may identify advanced NAFLD. At the time of obesity surgery, 142 consecutive patients underwent liver biopsy and had their preoperative demographic and clinical data obtained. Liver histology was scored by the NAFLD activity score, and patients subdivided into four groups. Concentrations of retinol-binding protein 4 (RBP4), adiponectin, tumor necrosis factor-alpha (TNF-alpha), and leptin were determined approximately 1 week prior to surgery and results were related to liver histology. The prevalence of no NAFLD was 30%, simple steatosis 23%, borderline nonalcoholic steatohepatitis (NASH) 28%, and definitive NASH 18%. Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) prevalence were 39 and 75%, respectively, and did not differ across the four histological groups (P = NS). Triglyceride (TG) and alanine transaminase (ALT) levels, strongly associated with advanced stages of NAFLD and NASH (P = 0.04). TG levels >150 mg/dl, increased the likelihood of NASH 3.4-fold, whereas high-density lipoprotein (HDL) levels predicted no NAFLD (P < 0.01). Concentrations of TNF-alpha, leptin, and RBP4 did not differ among histological groups and thus did not identify NASH; however, there was a trend for adiponectin to be lower in NASH vs. no NAFLD (P = 0.061). In summary, both TG and ALT levels assist in identification of NASH in an obesity surgery cohort. These findings underscore the importance of fatty acid delivery mechanisms to NASH development in severely obese individuals.
尽管非酒精性脂肪性肝病(NAFLD)在肥胖人群中很常见,但晚期肝病的代谢决定因素仍不清楚。脂肪因子反映了与肥胖相关的炎症和胰岛素抵抗,可能有助于识别晚期NAFLD。在肥胖手术时,142例连续患者接受了肝活检,并获取了他们术前的人口统计学和临床数据。肝脏组织学通过NAFLD活动评分进行评分,患者被分为四组。在手术前约1周测定视黄醇结合蛋白4(RBP4)、脂联素、肿瘤坏死因子-α(TNF-α)和瘦素的浓度,并将结果与肝脏组织学进行关联。无NAFLD的患病率为30%,单纯性脂肪变性为23%,临界非酒精性脂肪性肝炎(NASH)为28%,确诊NASH为18%。2型糖尿病(T2DM)和代谢综合征(MS)的患病率分别为39%和75%,在四个组织学组中无差异(P = 无显著性差异)。甘油三酯(TG)和丙氨酸转氨酶(ALT)水平与NAFLD和NASH的晚期阶段密切相关(P = 0.04)。TG水平>150 mg/dl,NASH的可能性增加3.4倍,而高密度脂蛋白(HDL)水平预测无NAFLD(P < 0.01)。TNF-α、瘦素和RBP4的浓度在组织学组之间没有差异,因此不能识别NASH;然而,与无NAFLD相比,NASH中脂联素水平有降低的趋势(P = 0.061)。总之,TG和ALT水平有助于在肥胖手术队列中识别NASH。这些发现强调了脂肪酸输送机制在严重肥胖个体NASH发展中的重要性。