Department of Biochemistry, Medical College, Jiaxing University, Jiaxing, China.
Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Hepatol Commun. 2023 Jan 10;7(1):e0016. doi: 10.1097/HC9.0000000000000016. eCollection 2023 Jan 1.
Phenotypic heterogeneity among patients with NAFLD is poorly understood. We aim to identify clinically important phenotypes within NAFLD patients and assess the long-term outcomes among different phenotypes.
We analyzed the clinical data of 2311 participants from the Third National Health and Nutrition Examination Survey (NHANES III) and their linked mortality data through December 2019. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other liver diseases and excess alcohol use. A 2-stage cluster analysis was applied to identify clinical phenotypes. We used Cox proportional hazard models to explore all-cause and cause-specific mortality between clusters.
We identified 3 NAFLD phenotypes. Cluster 1 was characterized by young female patients with better metabolic profiles and lower prevalence of comorbidities; Cluster 2 by obese females with significant insulin resistance, diabetes, inflammation, and advanced fibrosis and Cluster 3 by male patients with hypertension, atherogenic dyslipidemia, and liver and kidney damage. In a median follow-up of 26 years, 989 (42.8%) all-cause mortality occurred. Cluster 1 patients presented the best prognosis, whereas Cluster 2 and 3 had higher risks of all-cause (Cluster 2-adjusted HR: 1.48, 95% CI: 1.16-1.90; Cluster 3-adjusted HR: 1.29, 95% CI: 1.01-1.64) and cardiovascular (Cluster 2-adjusted HR: 2.01, 95% CI: 1.18-3.44; Cluster 3-adjusted HR: 1.75, 95% CI: 1.03-2.97) mortality.
Three phenotypically distinct and clinically meaningful NAFLD subgroups have been identified with different characteristics of metabolic profiles. This study reveals the substantial disease heterogeneity that exists among NAFLD patients and underscores the need for granular assessments to define phenotypes and improve clinical practice.
非酒精性脂肪性肝病（NAFLD）患者的表型异质性尚不清楚。本研究旨在确定 NAFLD 患者中的临床重要表型，并评估不同表型的长期结局。
我们分析了来自第三次全国健康和营养调查（NHANES III）的 2311 名参与者的临床数据及其截至 2019 年 12 月的死亡相关数据。NAFLD 的诊断依据为超声检查有肝脂肪变性而无其他肝脏疾病和过量饮酒史。采用两阶段聚类分析来确定临床表型。我们使用 Cox 比例风险模型来探讨各聚类组之间的全因和特定原因死亡率。
我们确定了 3 种 NAFLD 表型。表型 1 以年轻女性患者为特征，代谢特征较好，合并症发生率较低；表型 2 以肥胖女性为主，存在显著的胰岛素抵抗、糖尿病、炎症和晚期纤维化；表型 3 以高血压、动脉粥样硬化性血脂异常和肝肾功能损害的男性患者为特征。在中位随访 26 年期间，989 例（42.8%）发生全因死亡。表型 1 患者的预后最好，而表型 2 和 3 的全因死亡率风险更高（表型 2 校正 HR：1.48，95%CI：1.16-1.90；表型 3 校正 HR：1.29，95%CI：1.01-1.64）和心血管死亡率（表型 2 校正 HR：2.01，95%CI：1.18-3.44；表型 3 校正 HR：1.75，95%CI：1.03-2.97）。
已确定 3 种表型明显不同且具有临床意义的 NAFLD 亚组，它们具有不同的代谢特征。本研究揭示了 NAFLD 患者中存在的大量疾病异质性，并强调需要进行精细评估以确定表型并改善临床实践。
