Factors influencing subclinical atherosclerosis in patients with biopsy-proven nonalcoholic fatty liver disease

Although the presence of nonalcoholic fatty liver disease (NAFLD) is known to be related to subclinical atherosclerosis, the relationship between the severity of NAFLD and subclinical atherosclerosis is not clear. This study aimed to clarify the factors related to subclinical arteriosclerosis, including the histopathological severity of the disease and PNPLA3 gene polymorphisms, in NAFLD patients. We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness in 153 biopsy-proven NAFLD patients. The baPWV values were significantly higher in the advanced fibrosis group than in the less advanced group (median, 1679 cm/s vs 1489 cm/s; p = 5.49×10−4). Multiple logistic regression analysis revealed that older age (≥55 years) (p = 8.57×10−3; OR = 3.03), hypertension (p = 1.05×10−3; OR = 3.46), and advanced fibrosis (p = 9.22×10−3; OR = 2.94) were independently linked to baPWV ≥1600 cm/s. NAFLD patients were categorized into low-risk group (number of risk factors = 0), intermediate-risk group (= 1), and high-risk group (≥2) based on their risk factors, including older age, hypertension, and biopsy-confirmed advanced fibrosis. The prevalence of baPWV ≥1600 cm/s was 7.1% (3/42) in the low-risk group, 30.8% (12/39) in the intermediate-risk group, and 63.9% (46/72) in the high-risk group. Non-invasive liver fibrosis markers and scores, including the FIB-4 index, NAFLD fibrosis score, hyaluronic acid, Wisteria floribunda agglutinin positive Mac-2-binding protein, and type IV collagen 7s, were feasible substitutes for invasive liver biopsy. Older age, hypertension, and advanced fibrosis are independently related to arterial stiffness, and a combination of these three factors may predict risk of arteriosclerosis in NAFLD patients.尽管目前已知非酒精性脂肪性肝病（nonalcoholic fatty liver disease, NAFLD）的发生与亚临床动脉粥样硬化存在关联，但NAFLD病情严重程度与亚临床动脉粥样硬化之间的具体关联仍未明确。本研究旨在明确非酒精性脂肪性肝病患者中亚临床动脉硬化的相关影响因素，包括该病的组织病理学严重程度与PNPLA3基因多态性。本研究对153例经活检证实的非酒精性脂肪性肝病患者进行了臂踝脉搏波速度（brachial-ankle pulse wave velocity, baPWV）检测，以此作为动脉僵硬度的评估指标。进展期纤维化组的baPWV值显著高于非进展期纤维化组（中位数：1679 cm/s vs 1489 cm/s；p=5.49×10^-4）。多因素logistic回归分析结果显示，年龄≥55岁（p=8.57×10^-3；比值比OR=3.03）、高血压（p=1.05×10^-3；OR=3.46）以及进展期纤维化（p=9.22×10^-3；OR=2.94）均与baPWV≥1600 cm/s独立相关。研究人员基于年龄≥55岁、高血压及活检证实的进展期纤维化这三项危险因素，将非酒精性脂肪性肝病患者划分为低风险组（危险因素数量=0）、中风险组（危险因素数量=1）及高风险组（危险因素数量≥2）。低风险组中baPWV≥1600 cm/s的患病率为7.1%（3/42），中风险组为30.8%（12/39），高风险组则为63.9%（46/72）。包括FIB-4指数、非酒精性脂肪性肝病纤维化评分、透明质酸、紫藤凝集素阳性Mac-2结合蛋白以及IV型胶原7s在内的无创肝纤维化标志物及评分体系，可作为有创肝活检的可行替代检测手段。年龄≥55岁、高血压及进展期纤维化均与动脉僵硬度独立相关，将这三项因素联合起来可用于预测非酒精性脂肪性肝病患者的动脉硬化风险。