Tovoli Francesco, Napoli Lucia, Negrini Giulia, D'Addato Sergio, Tozzi Giulia, D'Amico Jessica, Piscaglia Fabio, Bolondi Luigi
Unit of Internal Medicine, Departmentt of Medical and Surgical Sciences, University of Bologna, 40136 Bologna, Italy.
Unit of Neuromuscolar and Neurodegenerative Diseases, Children's Hospital and Research Institute "Bambino Gesù", 00165 Rome, Italy.
Int J Mol Sci. 2017 May 25;18(6):1134. doi: 10.3390/ijms18061134.
Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.
溶酶体酸性脂肪酶（LAL）是脂质代谢中的关键酶。初步报告表明，相对获得性LAL缺乏在非酒精性脂肪性肝病（NAFLD）中起一定作用——然而，这种机制是否特定于NAFLD仍不清楚。我们旨在确定一组NAFLD患者和丙型肝炎病毒（HCV）感染患者对照组中的LAL活性，研究肝硬化的作用。共纳入81例诊断为NAFLD的患者和78例匹配的HCV相关肝病对照组。对每位患者，在外周干血斑（DBS）上测定LAL活性，并将其与临床和实验室数据相关联。还对肝硬化患者进行了亚组分析。与HCV患者相比，NAFLD患者的LAL活性显著降低。这一发现在疾病的肝硬化前期尤为明显。LAL活性还与血小板和白细胞计数相关，提示门静脉高压引起的全血细胞减少对DBS测定的LAL活性存在分析干扰。NAFLD的特征是LAL活性存在特定缺陷，提示LAL具有致病作用。我们建议，未来关于该主题的研究应依赖于组织特异性分析，因为外周血检测也会受到混杂因素的影响。
