Imamura Yoshiki, Kumagi Teru, Kuroda Taira, Koizumi Mitsuhito, Yoshida Osamu, Kanemitsu Kozue, Tada Fujimasa, Tanaka Yoshinori, Hirooka Masashi, Hiasa Yoichi
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
Postgraduate Medical Education Center, Ehime University Hospital, Ehime, Japan.
Hepatol Res. 2021 Jul;51(7):775-785. doi: 10.1111/hepr.13672. Epub 2021 Jun 5.
Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion.
Shear wave elastography and contrast-enhanced ultrasonography were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was used for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl )-induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was carried out on human autopsy samples.
Pancreas stiffness measured by SWE was higher in patients with LC than in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C-peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC.
In patients with LC, pancreas stiffness measured by SWE could be a potential noninvasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and could aid in guiding the treatment for hepatogenous diabetes.
门静脉高压可导致肝硬化(LC)患者胰腺充血及胰岛素分泌受损。然而,其机制尚不清楚,目前尚无成熟的非侵入性成像方法用于评估其发病机制。本研究聚焦于通过剪切波弹性成像(SWE)评估的胰腺硬度,并探讨其与门静脉高压及胰岛素分泌的关系。
分别采用剪切波弹性成像和超声造影评估胰腺硬度和充血情况。采用胰高血糖素激发试验评估胰岛素分泌。此外,利用四氯化碳(CCl)诱导的LC和门静脉高压大鼠模型来确定胰腺充血的直接影响。对人体尸检样本进行胰腺免疫组织化学染色。
LC患者经SWE测量的胰腺硬度高于对照组,且与胰腺充血显著相关。胰高血糖素激发试验显示LC组C肽免疫反应性变化值较低,且与胰腺硬度和充血呈负相关。此外,在CCl大鼠模型中证实了门静脉高压和胰岛素分泌功能障碍。人体样本尸检显示胰腺存在充血和纤维化改变,以及LC患者胰岛素分泌与其相关因素之间的关系。
在LC患者中,经SWE测量的胰腺硬度可能是评估门静脉高压所致胰腺充血和纤维化的一种潜在非侵入性检查方法。此外,它与胰岛素分泌受损有关,有助于指导肝源性糖尿病的治疗。