Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19  

作　　者：Angus K Jacobs Steven D Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall David A Dorward Jonathan A Fallowfield Peter C Hayes John N Plevris 

机构地区：[1]Hepatology Laboratory,University of Edinburgh,Edinburgh EH164SB,United Kingdom [2]Scottish National Blood Transfusion Service,Jack Copland Centre,Edinburgh EH144BE,United Kingdom [3]Institute for Regeneration and Repair,University of Edinburgh,Edinburgh EH164UU,United Kingdom [4]Edinburgh Pathology,University of Edinburgh,Edinburgh EH164SB,United Kingdom

出　　处：《World Journal of Gastroenterology》2024年第31期3705-3716,共12页世界胃肠病学杂志（英文版）

基　　金：Supported by University of Edinburgh Hepatology Laboratory Internal Funding;the Liver Endowment Funds of the Edinburgh&Lothian Health Foundation.

摘　　要：BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 pa

关 键 词：Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 IMMUNOHISTOCHEMISTRY COVID-19 COVID-19-associated cholangiopathy 

分 类 号：R575[医药卫生—消化系统] R563.1[医药卫生—内科学]