Biomaterial Database

Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies. 2022

Philipp Königshofer, and Benedikt Silvester Hofer, and Ksenia Brusilovskaya, and Benedikt Simbrunner, and Oleksandr Petrenko, and Katharina Wöran, and Merima Herac, and Judith Stift, and Katharina Lampichler, and Gerald Timelthaler, and David Bauer, and Lukas Hartl, and Bernhard Robl, and Maria Sibila, and Bruno K Podesser, and Georg Oberhuber, and Philipp Schwabl, and Mattias Mandorfer, and Michael Trauner, and Thomas Reiberger

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients. Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies. Based on CPA-to-PP/HVPG correlation, potential dynamic components were identified in subgroups of animals/patients with lower-than-expected and higher-than-expected PP/HVPG. Dynamic PH components were validated in a patient cohort (n = 245) using liver stiffness measurement (LSM) instead of CPA. CPA significantly correlated with PP in animal models (Rho = 0.531; p < 0.001) and HVPG in patients (Rho = 0.439; p < 0.001). Correlation of CPA with PP/HVPG varied across different animal models and etiologies in patients. In models, severity of hyperdynamic circulation and specific fibrosis pattern (portal fibrosis: p = 0.02; septa width: p = 0.03) were associated with PH severity. In patients, hyperdynamic circulation (p = 0.04), vascular dysfunction/angiogenesis (VWF-Ag: p = 0.03; soluble vascular endothelial growth factor receptor 1: p = 0.03), and bile acids (p = 0.04) were dynamic modulators of PH. The LSM-HVPG validation cohort confirmed these and also indicated IL-6 (p = 0.008) and hyaluronic acid (HA: p < 0.001) as dynamic PH components. The relative contribution of "static" fibrosis on PH severity varies by type of liver injury. Next to hyperdynamic circulation, increased bile acids, VWF-Ag, IL-6, and HA seem to indicate a pronounced dynamic component of PH in patients.

UI	MeSH Term	Description	Entries
D006975	Hypertension, Portal	Abnormal increase of resistance to blood flow within the hepatic PORTAL SYSTEM, frequently seen in LIVER CIRRHOSIS and conditions with obstruction of the PORTAL VEIN.	Cruveilhier-Baumgarten Disease,Cruveilhier-Baumgarten Syndrome,Cruveilhier Baumgarten Disease,Cruveilhier Baumgarten Syndrome,Disease, Cruveilhier-Baumgarten,Portal Hypertension,Portal Hypertensions,Syndrome, Cruveilhier-Baumgarten
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008102	Liver Circulation	The circulation of BLOOD through the LIVER.	Hepatic Circulation,Circulation, Liver,Circulation, Hepatic
D008103	Liver Cirrhosis	Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.	Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D002492	Central Nervous System Depressants	A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents).	CNS Depressants,Depressants, CNS
D002779	Cholestasis	Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).	Bile Duct Obstruction,Biliary Stasis,Bile Duct Obstructions,Biliary Stases,Cholestases,Duct Obstruction, Bile,Duct Obstructions, Bile,Obstruction, Bile Duct,Obstructions, Bile Duct,Stases, Biliary,Stasis, Biliary
D003094	Collagen	A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).	Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D006439	Hemodynamics	The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.	Hemodynamic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000431	Ethanol	A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.	Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol