Liver Unit, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W2 1NY, UK.
Section of Endocrinology and Metabolic Medicine, St Mary's Hospital, Imperial College NHS Trust, London W2 1NY, UK.
Int J Mol Sci. 2023 Feb 10;24(4):3563. doi: 10.3390/ijms24043563.
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with fibrosis stage being the main predictor for clinical outcomes. Here, we present the metabolic profile of NAFLD patients with regards to fibrosis progression. We included all consecutive new referrals for NAFLD services between 2011 and 2019. Demographic, anthropometric and clinical features and noninvasive markers of fibrosis were recorded at baseline and at follow-up. Significant and advanced fibrosis were defined using liver stiffness measurement (LSM) as LSM ≥ 8.1 kPa and LSM ≥ 12.1 kPa, respectively. Cirrhosis was diagnosed either histologically or clinically. Fast progressors of fibrosis were defined as those with delta stiffness ≥ 1.03 kPa/year (25% upper quartile of delta stiffness distribution). Targeted and untargeted metabolic profiles were analysed on fasting serum samples using Proton nuclear magnetic resonance (H NMR). A total of 189 patients were included in the study; 111 (58.7%) underwent liver biopsy. Overall, 11.1% patients were diagnosed with cirrhosis, while 23.8% were classified as fast progressors. A combination of metabolites and lipoproteins could identify the fast fibrosis progressors (AUROC 0.788, 95% CI: 0.703-0.874, < 0.001) and performed better than noninvasive markers. Specific metabolic profiles predict fibrosis progression in patients with nonalcoholic fatty liver disease. Algorithms combining metabolites and lipids could be integrated in the risk-stratification of these patients.
非酒精性脂肪性肝病 (NAFLD) 是全球慢性肝病的主要病因，纤维化分期是临床结局的主要预测指标。在这里，我们介绍了 NAFLD 患者的代谢特征与纤维化进展的关系。我们纳入了 2011 年至 2019 年间所有连续新就诊的 NAFLD 患者。在基线和随访时记录了人口统计学、人体测量学和临床特征以及纤维化的非侵入性标志物。使用肝硬度测量 (LSM) 将显著和进展期纤维化定义为 LSM≥8.1kPa 和 LSM≥12.1kPa。肝硬化通过组织学或临床诊断。纤维化快速进展者定义为 delta 硬度≥1.03kPa/年（delta 硬度分布的第 25 个四分位数以上）。使用质子磁共振 (H NMR) 对空腹血清样本进行靶向和非靶向代谢谱分析。本研究共纳入 189 例患者，其中 111 例（58.7%）接受了肝活检。总体而言，11.1%的患者被诊断为肝硬化，而 23.8%的患者被归类为纤维化快速进展者。代谢物和脂蛋白的组合可以识别出纤维化快速进展者（AUROC 0.788，95%CI：0.703-0.874，<0.001），且其表现优于非侵入性标志物。特定的代谢谱可预测非酒精性脂肪性肝病患者的纤维化进展。结合代谢物和脂质的算法可整合到这些患者的风险分层中。
