Yasui Yutaka, Abe Tokiya, Kurosaki Masayuki, Matsunaga Kotaro, Higuchi Mayu, Tamaki Nobuharu, Watakabe Keiya, Okada Mao, Wang Wan, Shimizu Takao, Takaura Kenta, Masugi Yohei, Nakanishi Hiroyuki, Tsuchiya Kaoru, Takahashi Yuka, Itakura Jun, Sakurai Urara, Hashiguchi Akinori, Sakamoto Michiie, Izumi Namiki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
Hepatol Res. 2019 Jan;49(1):33-41. doi: 10.1111/hepr.13286. Epub 2018 Dec 26.
Elastic fiber deposition is a cause of irreversibility of liver fibrosis. However, to date, its relevance to clinical features has not yet been clarified. This study aimed to clarify the correlation between non-invasive markers of fibrosis and fiber quantity, including elastic fiber, obtained from computational analysis.
This retrospective study included 270 patients evaluated by non-invasive liver fibrosis assessment prior to liver biopsy. Of these patients, 95 underwent magnetic resonance elastography (MRE) and 244 were assessed with Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA -M2BP). Using whole-slide imaging of Elastica van Gieson-stained liver biopsy sections, the quantity of collagen, elastin, and total fiber (elastin + collagen) was determined.
The total fiber quantity showed significant linear correlation with fibrosis stage F0-F4. Collagen fiber quantity increased from stage F0 to F4, whereas elastic fiber quantity increased significantly only from stage F2 to F3. Spearman's rank correlation test revealed that non-invasive liver fibrosis assessment significantly correlates with each fiber quantity, including correlation between total fiber quantity and the Fibrosis-4 (FIB-4) index (r = 0.361, P < 0.001), WFA -M2BP values (r = 0.404, P < 0.001), and liver stiffness value by MRE (r = 0.615, P < 0.001). Receiver operating characteristic (ROC) curve analyses revealed that the area under ROC for predicting higher elastic fiber (>3.6%) is 0.731 by FIB-4 index, 0.716 by WFA -M2BP, and 0.822 by liver stiffness by MRE.
Liver fibrosis correlates with fiber quantity through non-invasive assessment regardless of fiber type, including elastic fiber. Moreover, MRE is useful for predicting high amounts of elastic fiber.
弹性纤维沉积是肝纤维化不可逆的一个原因。然而，迄今为止，其与临床特征的相关性尚未阐明。本研究旨在阐明通过计算分析获得的纤维化非侵入性标志物与包括弹性纤维在内的纤维数量之间的相关性。
这项回顾性研究纳入了270例在肝活检前接受非侵入性肝纤维化评估的患者。其中，95例接受了磁共振弹性成像（MRE），244例接受了紫藤凝集素阳性Mac-2结合蛋白（WFA-M2BP）评估。使用弹性纤维染色的肝活检切片的全切片成像，测定胶原、弹性蛋白和总纤维（弹性蛋白+胶原）的数量。
总纤维数量与纤维化分期F0-F4呈显著线性相关。胶原纤维数量从F0期到F4期增加，而弹性纤维数量仅从F2期到F3期显著增加。Spearman等级相关检验显示，非侵入性肝纤维化评估与每种纤维数量显著相关，包括总纤维数量与纤维化-4（FIB-4）指数之间的相关性（r = 0.361，P < 0.001）、WFA-M2BP值（r = 0.404，P < 0.001）以及MRE测定的肝脏硬度值（r = 0.615，P < 0.001）。受试者工作特征（ROC）曲线分析显示，FIB-4指数预测较高弹性纤维（>3.6%）的ROC曲线下面积为0.731，WFA-M2BP为0.716，MRE测定的肝脏硬度为0.822。
无论纤维类型（包括弹性纤维）如何，肝纤维化通过非侵入性评估与纤维数量相关。此外，MRE有助于预测大量弹性纤维。
