Department of Gastroenterology, Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Authors contributed equally to this work.
Department of Gastroenterology, Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Authors contributed equally to this work.
Ann Hepatol. 2019 Jan-Feb;18(1):78-88. doi: 10.5604/01.3001.0012.7865.
The association between lysosomal acid lipase (LAL) activity and liver steatosis or fibrosis is poorly studied. The aim of our study was to determine the predictive power of LAL for cryptogenic liver steatosis and cryptogenic significant fibrosis/cirrhosis.
Cross-sectional observational study of 101 adult patients with unexplained elevated liver enzymes/hepatomegaly with or without dyslipidemia submitted to the determination of LAL activity and LIPA gene (E8SJM-C.894G^A) mutation. Seventy-one patients underwent liver biopsy or FibroScan®. Patients with an identifiable liver dysfunction cause and well-stablished NAFLD/NASH risk factors were excluded. Predictors for liver steatosis, significant fibrosis (> F2) or cirrhosis (F4) were evaluated.
Liver steatosis and fibrosis were mainly assessed by liver biopsy (74.6%; n = 53). Steatosis was present in 62.0% (n = 44), significant fibrosis in 47.9% (n = 34) and cirrhosis in 39.4% (n = 28). The median LAL was 0.36 (0.21-0.46)nmol/spot/h (vs. 0.29 (0.20-0.47); p = 0.558) for liver steatosis, 0.22 (0.11-0.29) nmol/spot/h (vs. 0.40 (0.34-0.51); p <0.001) for significant fibrosis and 0.21 (0.11-0.27) nmol/spot/h (vs. 0.40 (0.32-0.52); p < 0.001) for cirrhosis. No LIPA gene mutations were found. LAL activity was the strongest predictor of significant fibrosis (AUROC: 0.833; p < 0.001) with a cut-off of 0.265 (sensitivity: 85.9%; specificity: 75.0%) and cirrhosis (AUROC: 0.859; p < 0.001) with a cut-off of 0.235 (sensitivity: 86.2%; specificity: 75.0%), being higher than FIB4, GUCI or APRI. However, LAL activity was not associated with liver steatosis (AUROC: 0.536; p =0.558).
LAL activity can be considered a non-invasive new marker of cryptogenic liver fibrosis with higher accuracy than other known biomarkers. LAL activity < 0.265 nmol/spot/h was strongly associated with cryptogenic significant fibrosis and <0.235 nmol/spot/h with cryptogenic cirrhosis. LAL activity was not associated with cryptogenic liver steatosis.
溶酶体酸性脂肪酶（LAL）活性与肝脂肪变性或纤维化之间的关联尚未得到充分研究。我们的研究目的是确定 LAL 对隐源性肝脂肪变性和隐源性显著纤维化/肝硬化的预测能力。
对 101 例不明原因肝酶升高/肝肿大的成年患者进行横断面观察性研究，这些患者伴有或不伴有血脂异常，接受 LAL 活性和 LIPA 基因（E8SJM-C.894G^A）突变的测定。71 例患者进行了肝活检或 FibroScan®检查。排除有明确肝功能障碍原因和明确的非酒精性脂肪性肝病/非酒精性脂肪性肝炎（NASH）危险因素的患者。评估了肝脂肪变性、显著纤维化（> F2）或肝硬化（F4）的预测因素。
肝脂肪变性和纤维化主要通过肝活检评估（74.6%；n=53）。脂肪变性的发生率为 62.0%（n=44），显著纤维化的发生率为 47.9%（n=34），肝硬化的发生率为 39.4%（n=28）。LAL 的中位数为 0.36（0.21-0.46）nmol/spot/h（vs. 0.29（0.20-0.47）；p=0.558），显著纤维化的中位数为 0.22（0.11-0.29）nmol/spot/h（vs. 0.40（0.34-0.51）；p<0.001），肝硬化的中位数为 0.21（0.11-0.27）nmol/spot/h（vs. 0.40（0.32-0.52）；p<0.001）。未发现 LIPA 基因突变。LAL 活性是显著纤维化（AUROC：0.833；p<0.001）的最强预测因子，截断值为 0.265（敏感性：85.9%；特异性：75.0%）和肝硬化（AUROC：0.859；p<0.001）的截断值为 0.235（敏感性：86.2%；特异性：75.0%），高于 FIB4、GUCI 或 APRI。然而，LAL 活性与肝脂肪变性无关（AUROC：0.536；p=0.558）。
LAL 活性可作为隐源性肝纤维化的一种新的非侵入性标志物，其准确性高于其他已知生物标志物。LAL 活性<0.265 nmol/spot/h 与隐源性显著纤维化密切相关，<0.235 nmol/spot/h 与隐源性肝硬化密切相关。LAL 活性与隐源性肝脂肪变性无关。
