Inflammation in liver fibrosis and atrial fibrillation: A prospective population-based proteomic study
Joost Boeckmans, Maurice Stephan Michel, Alexander Gieswinkel, Oliver Tüscher, Stavros Konstantinides, J. König, Thomas Münzel, Karl J. Lackner, Jasmin Ghaemi Kerahrodi, Alexander K. Schuster, Philipp S. Wild, Peter R. Galle, Jörn M. Schattenberg
Abstract
Background & Aims: Elevated liver stiffness has been associated with atrial fibrillation (AFib) in the general population. The mechanism underlying this association is unclear. Methods: Participants were recruited from the general population and prospectively enrolled with follow-up for 5 years. The fibrosis-4 (FIB-4) index was used as a surrogate marker for liver fibrosis. Proteomics analysis was performed using the 92-target Olink inflammation panel. Validation was performed using the NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet index (APRI), and repeat confirmation proteomics. Results: <0.0001), reproduced using the NFS and APRI, and corresponding to increased serum levels. Conclusions: CXCL10 is linked to liver fibrosis, as determined by the FIB-4 index, and to prevalent AFib. Impact and implications: How elevated liver stiffness relates to atrial fibrillation in the general population remains to be clarified. We hypothesized that systemic inflammation against a background of liver fibrosis produced from metabolic dysfunction-associated steatotic liver disease (MASLD), is involved in the pathophysiology of atrial fibrillation. Using large-scale targeted proteomics, we found that CXCL10 is related to both liver fibrosis, as defined by the fibrosis-4 index, and to atrial fibrillation. These results can aid evidence-based drug development for patients with atrial fibrillation and MASLD-related liver fibrosis.