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Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy
Author(s) -
Wiese Signe,
Voiosu Andrei,
Hove Jens D.,
Danielsen Karen V.,
Voiosu Theodor,
Grønbæk Henning,
Møller Holger Jon,
Genovese Federica,
ReesePetersen Alexander Lynge,
Mookerjee Rajeshwar P.,
Clemmesen Jens Otto,
Gøtze Jens Peter,
Andersen Ove,
Møller Søren,
Bendtsen Flemming
Publication year - 2020
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15812
Subject(s) - medicine , inflammation , cirrhosis , fibrosis , pathogenesis , pathology , gastroenterology , endocrinology , cardiology
Summary Background Fibrogenesis and inflammation contribute to the progression of cirrhosis. However, it is unknown if these processes also contribute to the development of cirrhotic cardiomyopathy (CCM). Novel magnetic resonance imaging with quantification of the extracellular volume (ECV) provides an estimate of the fibrotic remodelling in the liver and heart. Aim To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation. Methods A prospective study of 52 patients with cirrhosis and 14 healthy controls. All patients underwent contrast‐enhanced MRI with T1‐mapping and quantification of myocardial and liver ECV, biochemical assessments of collagen turnover (PRO‐C3, PRO‐C5, PRO‐C6, collagen type IV degradation fragment, collagen type V degradation fragment, LG1M) and inflammation (TNFα, IL‐1β, IL‐6, IL‐8, IL‐18, SDF1α, sCD163, sMR, soluble macrophage mannose receptor). Results Myocardial and liver ECV were increased in patients compared with healthy controls (myocardial ECV 31.2 ± 5.5% vs 27.4 ± 2.9%, P = 0.037; liver ECV 44.1 ± 9.6% vs 33.7 ± 6.7%, P < 0.001). Myocardial ECV correlated strongly with liver ECV ( r = 0.48, P = 0.001) and biomarkers of collagen formation and inflammation ( P < 0.005). Similarly, liver ECV correlated with biomarkers of collagen formation and inflammation ( P < 0.003). In a multivariate analysis, liver ECV was predicted by biomarkers of collagen formation (PRO‐C3 and PRO‐C6), whereas myocardial ECV was predicted by biomarkers of collagen formation (PRO‐C6) and inflammation (IL‐6 and sMR). Conclusion Structural myocardial changes seem closely related to liver fibrosis in patients with cirrhosis. The strong associations with biomarkers of collagen formation and inflammation provide new insight into the role of inflammation and fibrogenesis in the development of structural cardiac abnormalities, potentially leading to CCM.