Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore.
Duke-NUS Medical School, Singapore.
PLoS One. 2018 Jun 20;13(6):e0199166. doi: 10.1371/journal.pone.0199166. eCollection 2018.
Assessment of severity of liver fibrosis is essential in the management of non-alcoholic fatty liver disease (NAFLD). Second Harmonic Generation (SHG) microscopy is a novel optical tissue imaging system that provides automated quantification of fibrosis based on unique architectural features of collagen. This study aims to develop and validate a SHG-based index for automated staging of liver fibrosis in patients with NAFLD.
SHG microscopy was performed on archived liver biopsy specimens from 83 patients with NAFLD. A unique algorithm was developed to identify specific SHG parameters that correlated with fibrosis stage. The accuracy of the algorithm was compared against clinical assessment by experienced liver histopathologists using the Brunt fibrosis staging and further validated using the leave-one-out cross-validation method.
Mean age of the study cohort was 51.8 ± 11.7 years, with 41% males. A fibrosis index (SHG B-index) was developed comprising 14 unique SHG-based collagen parameters that correlated with severity of NAFLD fibrosis in a continuous fashion. The SHG B-index had excellent correlation with Brunt fibrosis stage (Spearman's correlation 0.820, p<0.001). AUROCs for prediction of Brunt fibrosis stages 1, 2, 3 and 4 were 0.853, 0.967, 0.985 and 0.941 respectively. In the cross-validation analysis, the SHG B-index demonstrated high specificity for diagnosis of all grades of fibrosis. A SHG B-index score of >1.76 had an overall diagnostic accuracy of 98.5% for prediction of presence of bridging fibrosis (Brunt stage ≥3) with sensitivity of 87.5%, specificity 98.0%, positive predictive value 96.6% and negative predictive value 92.6%.
The SHG B-index is a unique SHG-based index that provides accurate automated assessment of fibrosis stage in NAFLD patients.
非酒精性脂肪性肝病（NAFLD）的管理中，评估肝纤维化的严重程度至关重要。二次谐波产生（SHG）显微镜是一种新颖的光学组织成像系统，它基于胶原的独特结构特征提供纤维化的自动定量。本研究旨在开发和验证一种基于 SHG 的指数，用于自动分期 NAFLD 患者的肝纤维化。
对 83 例 NAFLD 患者的存档肝活检标本进行 SHG 显微镜检查。开发了一种独特的算法，以识别与纤维化分期相关的特定 SHG 参数。该算法的准确性通过经验丰富的肝组织病理学家对 Brunt 纤维化分期的临床评估进行比较，并使用留一法交叉验证方法进一步验证。
研究队列的平均年龄为 51.8±11.7 岁，男性占 41%。开发了一种纤维化指数（SHG B-指数），由 14 个独特的基于 SHG 的胶原参数组成，与 NAFLD 纤维化的严重程度呈连续相关。SHG B-指数与 Brunt 纤维化分期有很好的相关性（Spearman 相关系数 0.820，p<0.001）。预测 Brunt 纤维化分期 1、2、3 和 4 的 AUROC 分别为 0.853、0.967、0.985 和 0.941。在交叉验证分析中，SHG B-指数对所有纤维化程度的诊断具有很高的特异性。SHG B-指数>1.76 时，对桥接纤维化（Brunt 分期≥3）的存在具有 98.5%的总体诊断准确性，其敏感性为 87.5%，特异性为 98.0%，阳性预测值为 96.6%，阴性预测值为 92.6%。
SHG B-指数是一种独特的基于 SHG 的指数，可提供 NAFLD 患者纤维化分期的准确自动评估。
