Crudele Lucilla, De Matteis Carlo, Piccinin Elena, Gadaleta Raffaella Maria, Cariello Marica, Di Buduo Ersilia, Piazzolla Giuseppina, Suppressa Patrizia, Berardi Elsa, Sabbà Carlo, Moschetta Antonio
Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy.
INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie d'Oro 305 - 00136 Roma, Italy.
JHEP Rep. 2022 Nov 15;5(1):100627. doi: 10.1016/j.jhepr.2022.100627. eCollection 2023 Jan.
BACKGROUND & AIMS: Dysmetabolic conditions could drive liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), increasing susceptibility to hepatocellular carcinoma (HCC). We therefore aimed to identify novel predictive biomarkers of HCC in patients with and without liver fibrosis.
A total of 1,234 patients with putative metabolic conditions and NAFLD were consecutively assessed in our outpatient clinic. Clinical and biochemical data were recorded, and then liver ultrasonography was performed annually for 5 years to detect HCC onset. For the analysis, the population was first divided according to HCC diagnosis; then a further subdivision of those who did not develop HCC was performed based on the presence or absence of liver fibrosis at time 0.
Sixteen HCC cases were recorded in 5 years. None of our patients had been diagnosed with cirrhosis before HCC was detected. Compared to patients who did not develop HCC, those who did had higher liver transaminases and fibrosis scores at time 0 ( <0.001). In addition, they presented with increased glycated haemoglobin levels and lower 25-OH vitamin D levels (0.05). Intriguingly, patients with higher liver fibrosis scores who subsequently developed HCC had lower HDL-cholesterol (HDL-c) levels at time 0 (0.001). Furthermore, in the 484 patients presenting with lower HDL-c at baseline, we found that waist circumference, and then vitamin D and glycated haemoglobin levels, were significantly different in those who developed HCC, regardless of liver fibrosis (0.05).
This study identifies HDL-c as a novel marker to predict HCC in patients with NAFLD. Increased waist circumference and deranged metabolic pathways represent additional predisposing factors among patients with low HDL-c, highlighting the importance of studying cholesterol metabolism and integrating clinical approaches with dietary regimens and a healthy lifestyle to prevent HCC.
Visceral adiposity and its associated conditions, such as chronic inflammation and insulin resistance, may play a pivotal role in hepatocellular carcinoma development in patients with non-alcoholic fatty liver disease. We provide new insights on the underlying mechanisms of its pathogenesis, shedding light on the involvement of low levels of "good" HDL-cholesterol. We recommend integrating dietary regimens and advice on healthy lifestyles into the clinical management of non-alcoholic fatty liver disease, with the goal of reducing the incidence of hepatocellular carcinoma.
代谢紊乱情况可能会促使非酒精性脂肪性肝病（NAFLD）患者发生肝纤维化，增加肝细胞癌（HCC）的易感性。因此，我们旨在确定有无肝纤维化的HCC患者的新型预测生物标志物。
在我们的门诊连续评估了总共1234例疑似代谢紊乱和NAFLD的患者。记录临床和生化数据，然后每年进行5年肝脏超声检查以检测HCC发病情况。为了进行分析，首先根据HCC诊断对人群进行划分；然后根据0时刻有无肝纤维化对未发生HCC的患者进行进一步细分。
5年内记录到16例HCC病例。在检测到HCC之前，我们的患者均未被诊断为肝硬化。与未发生HCC的患者相比，发生HCC的患者在0时刻的肝转氨酶和纤维化评分更高（<0.001）。此外，他们糖化血红蛋白水平升高，25-羟基维生素D水平降低（<0.05）。有趣的是，随后发生HCC且肝纤维化评分较高的患者在0时刻的高密度脂蛋白胆固醇（HDL-c）水平较低（<0.001）。此外，在基线时HDL-c较低的484例患者中，我们发现，无论有无肝纤维化，发生HCC的患者的腰围、维生素D和糖化血红蛋白水平均存在显著差异（<0.05）。
本研究确定HDL-c是预测NAFLD患者发生HCC的新型标志物。腰围增加和代谢途径紊乱是HDL-c水平低的患者中的其他易感因素，突出了研究胆固醇代谢以及将临床方法与饮食方案和健康生活方式相结合以预防HCC的重要性。
内脏肥胖及其相关情况，如慢性炎症和胰岛素抵抗，可能在非酒精性脂肪性肝病患者的肝细胞癌发生中起关键作用。我们对其发病机制的潜在机制提供了新的见解，揭示了低水平“好”的HDL-胆固醇的作用。我们建议将饮食方案和健康生活方式建议纳入非酒精性脂肪性肝病的临床管理，以降低肝细胞癌的发病率。
