Electron microscopic observations in perfusion-fixed human non-alcoholic fatty liver disease biopsies
Pathology, vol. 53, pp. 220–228
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a widespread liver disease in Western society, but its multifactorial pathogenesis is not yet fully understood. Ultrastructural analysis of liver sinusoidal endothelial cells (LSECs) in animal models and in vitro studies shows defenestration early in the course of NAFLD, promoting steatosis. LSECs and fenestrae are important in the transport of lipids across the sinusoids. However, human ultrastructural data, especially on LSECs and fenestrae, are scarce. This study aimed to explore the ultrastructural changes in perfusion type fixed liver biopsies of NAFLD patients with and without non-alcoholic steatohepatitis (NASH), with a special focus on LSECs and their fenestration. Liver biopsies from patients with NAFLD were fixed using two perfusion techniques, jet and injection fixation, for needle and wedge biopsies, respectively. Ultrastructural changes were studied using transmission electron microscopy. NASH was diagnosed by bright-field microscopy using the SAF score (steatosis, activity, fibrosis). Thirty-seven patients were included, of which 12 (32.4%) had NASH. Significantly less defenestration was found in NASH compared to noNASH samples (p=0.002). Other features, i.e., giant mitochondria and fenestrae size did not differ between groups. Furthermore, we described new structures, i.e., single cell steatonecrosis and inflammatory fat follicles (IFF) that were observed in both groups. Concluding, defenestration was more common in noNASH compared to NASH in human liver samples. Defenestration was not related to the degree of steatosis or fibrosis. We speculate that defenestration can be a protective mechanism in simple steatosis which is lacking in NASH.
Authors 10
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Pauline L. M. Verhaegh corresponding
Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Internal Medicine, Division Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands; School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands. Electronic address: Pauline.verhaegh@mumc.nl
Department of Internal Medicine, Division Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands
School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
Division of Nanoscopy, Maastricht Multimodal Molecular Imaging Institute, and Department of Internal Medicine/Hepatology, The University of Maastricht, Maastricht, the Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Internal Medicine, Division Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands; School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
Department of Internal Medicine, Division Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands
School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
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Maastricht University Medical Centre · Maastricht University · Zuyderland Medisch Centrum
Affiliation as printed
Department of Surgery, Zuyderland MC, Heerlen, the Netherlands; Department of Gastro-Intestinal Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
Department of Gastro-Intestinal Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
Department of Surgery, Zuyderland MC, Heerlen, the Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers
Affiliation as printed
Department of Pathology, Amsterdam University Medical Center, Amsterdam, the Netherlands
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Affiliation as printed
Department of Pathology, Zuyderland MC, Heerlen, the Netherlands
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Affiliation as printed
Division of Nanoscopy, Maastricht Multimodal Molecular Imaging Institute, and Department of Internal Medicine/Hepatology, The University of Maastricht, Maastricht, the Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Internal Medicine, Division Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands; School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
Department of Internal Medicine, Division Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands
School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
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Ger H. Koek Aachen Department of Visceral and Transplantation Surgery Department of Visceral and Transplantation Surgery
Maastricht University Medical Centre · Maastricht University · Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Internal Medicine, Division Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands; School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Department of Visceral and Transplantation Surgery, Klinikum RWTH, Aachen, Germany
Department of Internal Medicine, Division Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands
Department of Visceral and Transplantation Surgery, Klinikum RWTH, Aachen, Germany
School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
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