The Liver Unit, Gastroenterology Institute, Hadassah Medical Center, Hadassah Medical School, The Hebrew University, Jerusalem 9112001, Israel.
Pediatric Gastroenterology Institute, Shaare Zedek Medical Center, Hadassah Medical School, The Hebrew University, Jerusalem 9103102, Israel.
Int J Mol Sci. 2016 Feb 27;17(3):312. doi: 10.3390/ijms17030312.
Fatty liver has become the most common liver disorder and is recognized as a major health burden in the Western world. The causes for disease progression are not fully elucidated but lysosomal impairment is suggested. Here we evaluate a possible role for lysosomal acid lipase (LAL) activity in liver disease. To study LAL levels in patients with microvesicular, idiopathic cirrhosis and nonalcoholic fatty liver disease (NAFLD). Medical records of patients with microvesicular steatosis, cryptogenic cirrhosis and NAFLD, diagnosed on the basis of liver biopsies, were included in the study. Measured serum LAL activity was correlated to clinical, laboratory, imaging and pathological data. No patient exhibited LAL activity compatible with genetic LAL deficiency. However, serum LAL activity inversely predicted liver disease severity. A LAL level of 0.5 was the most sensitive for detecting both histologic and noninvasive markers for disease severity, including lower white blood cell count and calcium, and elevated γ-glutamyltransferase, creatinine, glucose, glycated hemoglobin, uric acid and coagulation function. Serum LAL activity <0.5 indicates severe liver injury in patients with fatty liver and cirrhosis. Further studies should define the direct role of LAL in liver disease severity and consider the possibility of replacement therapy.
脂肪肝已成为最常见的肝脏疾病，并被认为是西方世界的主要健康负担。疾病进展的原因尚未完全阐明，但溶酶体功能障碍被认为与之相关。在这里，我们评估溶酶体酸性脂肪酶 (LAL) 活性在肝脏疾病中的可能作用。研究微泡性、特发性肝硬化和非酒精性脂肪性肝病 (NAFLD) 患者的 LAL 水平。本研究纳入了根据肝活检诊断为微泡性脂肪变性、隐源性肝硬化和非酒精性脂肪性肝病的患者的病历。测量的血清 LAL 活性与临床、实验室、影像学和病理学数据相关。没有患者表现出与遗传 LAL 缺乏一致的 LAL 活性。然而，血清 LAL 活性与肝病严重程度呈负相关。LAL 水平为 0.5 时对检测组织学和非侵入性疾病严重程度标志物最敏感，包括白细胞计数和钙降低，以及γ-谷氨酰转移酶、肌酐、葡萄糖、糖化血红蛋白、尿酸和凝血功能升高。血清 LAL 活性<0.5 表明脂肪肝和肝硬化患者存在严重的肝损伤。进一步的研究应确定 LAL 在肝病严重程度中的直接作用，并考虑替代治疗的可能性。
