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

作者：Philipp Königshofer, Benedikt Hofer, Ksenia Brusilovskaya, Benedikt Simbrunner, Oleksandr Petrenko, Katharina Wöran, Merima Herac, Judith Stift, Katharina Lampichler, Gerald Timelthaler, David Bauer, Lukas Hartl, Bernhard Robl, Maria Sibila, Bruno K. Podesser, Georg Oberhuber, Philipp Schwabl, Mattias Mandorfer, Michael Trauner, Thomas Reiberger · 发表于：Hepatology · 年份：2021 · DOI：10.1002/hep.32220 · 被引用次数：52 · 研究领域：Liver Disease and Transplantation、Liver Diseases and Immunity、Liver Disease Diagnosis and Treatment

BACKGROUND AND AIMS: 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. APPROACH AND RESULTS: 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/angiogenes...