Valva Pamela, Rios Daniela, Casciato Paola, Gadano Adrián, Galdame Omar, Mullen Eduardo, Bertot Gustavo, de Matteo Elena, Preciado María V
Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children's Hospital.
Liver Unit.
Eur J Gastroenterol Hepatol. 2018 Jun;30(6):637-644. doi: 10.1097/MEG.0000000000001079.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has been increasing constantly and linked to the global obesity epidemic. The NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Liver biopsy is the only reliable means to diagnose and stage NASH, but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition and cell-death markers, which correlate with liver injury in an NAFLD patient cohort.
Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. Matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloproteinase inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)] were measured in serum samples.
HA showed an association with fibrosis severity (P=0.03) and M30 with steatosis (P=0.013), inflammation (P=0.004), and fibrosis severity (P=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The evaluation of diagnostic accuracy showed good performance as less invasive markers of significant fibrosis of both HA (area under the receiver operating characteristic curve: 0.928) and M30 (area under the receiver operating characteristic curve: 0.848).
Biomarkers are essential tools that may provide a quick and accurate diagnosis for patients with life-threatening NAFLD and NASH. HA and M30, together or determined sequentially, have been found to be straightforward tests that may be sufficient to predict significant fibrosis even in a primary care center of an underdeveloped country.
非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病，其患病率一直在不断上升，且与全球肥胖流行有关。NAFLD的组织学谱范围从单纯性脂肪变性到非酒精性脂肪性肝炎（NASH），后者可进展为肝硬化和肝细胞癌。肝活检是诊断和分期NASH的唯一可靠方法，但其侵入性限制了其应用。因此，通过开发新的非侵入性检测手段来预测肝损伤代表了日益增长的医学需求。我们的目的是评估与NAFLD患者队列中的肝损伤相关的基质沉积和细胞死亡标志物。
分析了34例成年NAFLD患者的肝活检组织和血清。评估了组织学参数。在血清样本中测量了基质沉积[透明质酸（HA）和基质金属蛋白酶抑制剂-1（TIMP-1）]和细胞死亡标志物[细胞角蛋白-18（M65）和半胱天冬酶切割的细胞角蛋白-18（M30）]。
HA与纤维化严重程度相关（P=0.03），M30与脂肪变性（P=0.013）、炎症（P=0.004）和纤维化严重程度相关（P=0.04）。相比之下，TIMP-1和M65与肝损伤的任何组织学参数均无关联。诊断准确性评估显示，HA（受试者操作特征曲线下面积：0.928）和M30（受试者操作特征曲线下面积：0.848）作为显著纤维化的侵入性较小的标志物表现良好。
生物标志物是重要工具，可为患有危及生命的NAFLD和NASH的患者提供快速准确的诊断。已发现HA和M30一起或依次测定是简单的检测方法，即使在欠发达国家的初级保健中心，也可能足以预测显著纤维化。
