Ajmera Veeral, Perito Emily R, Bass Nathan M, Terrault Norah A, Yates Katherine P, Gill Ryan, Loomba Rohit, Diehl Anna Mae, Aouizerat Bradley E
Division of Gastroenterology and, University of California-San Francisco, San Francisco, CA.
Division of Pediatric Gastroenterology, University of California-San Francisco, San Francisco, CA.
Hepatology. 2017 Jan;65(1):65-77. doi: 10.1002/hep.28776. Epub 2016 Oct 12.
Despite the high prevalence of nonalcoholic fatty liver disease (NAFLD), therapeutic options and noninvasive markers of disease activity and severity remain limited. We investigated the association between plasma biomarkers and liver histology in order to identify markers of disease activity and severity in patients with biopsy-proven NAFLD. Thirty-two plasma biomarkers chosen a priori as possible discriminators of NAFLD were measured in participants enrolled in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network. Dichotomized histologic outcomes were evaluated using centrally read biopsies. Biomarkers with statistically significant associations with NAFLD histology were evaluated in multivariable models adjusted for clinical factors. Of 648 participants (74.4% white, 61.7% female, mean age 47.7 years), 58.0% had definite NASH, 55.5% had mild/no fibrosis (stage 0-1), and 44.4% had significant fibrosis (stage 2-4). Increased activated plasminogen activator inhibitor 1 had a strong association with definite NASH compared to not NASH or borderline NASH in multivariable analysis (odds ratio = 1.20, 95% confidence interval 1.08-1.34, P < 0.001). Biomarkers associated with significant fibrosis (versus mild/no fibrosis) in multivariable analysis included higher levels of interleukin-8, monocyte chemoattractant protein-1, resistin, soluble interleukin-1 receptor I, soluble interleukin-2 receptor alpha, and tumor necrosis factor alpha and lower levels of insulin-like growth factor 2.
Specific plasma biomarkers are significantly associated with disease activity and severity of fibrosis in NAFLD and are potentially valuable tools for noninvasive stratification of patients with NAFLD and identification of targets for therapeutic intervention. (Hepatology 2017;65:65-77).
尽管非酒精性脂肪性肝病(NAFLD)的患病率很高,但疾病活动和严重程度的治疗选择及非侵入性标志物仍然有限。我们研究了血浆生物标志物与肝脏组织学之间的关联,以确定经活检证实的NAFLD患者疾病活动和严重程度的标志物。在非酒精性脂肪性肝炎(NASH)临床研究网络招募的参与者中,测量了32种预先选定的可能作为NAFLD鉴别指标的血浆生物标志物。使用集中阅片的活检评估二分法组织学结果。在针对临床因素进行调整的多变量模型中,评估与NAFLD组织学具有统计学显著关联的生物标志物。在648名参与者中(74.4%为白人,61.7%为女性,平均年龄47.7岁),58.0%患有明确的NASH,55.5%有轻度/无纤维化(0-1期),44.4%有显著纤维化(2-4期)。在多变量分析中,与未患NASH或临界NASH相比,活化纤溶酶原激活物抑制剂1升高与明确的NASH有很强的关联(比值比 = 1.20,95%置信区间1.08-1.34,P < 0.001)。在多变量分析中,与显著纤维化(相对于轻度/无纤维化)相关的生物标志物包括白细胞介素-8、单核细胞趋化蛋白-1、抵抗素、可溶性白细胞介素-1受体I、可溶性白细胞介素-2受体α和肿瘤坏死因子α水平较高,以及胰岛素样生长因子-2水平较低。
特定的血浆生物标志物与NAFLD的疾病活动和纤维化严重程度显著相关,是对NAFLD患者进行非侵入性分层及确定治疗干预靶点的潜在有价值工具。(《肝脏病学》2017年;65:65-77)