Sex Differences in the Association between Liver Fibrosis and Clinical Outcomes in Acute Cardioembolic Stroke Patients with Nonvalvular Atrial Fibrillation

Abstract Background: Liver cirrhosis is a confirmed risk factor for clinical outcomes of stroke patients. However, the contribution of liver fibrosis to cardioembolic stroke (CES) and its short-term outcomes are poorly understood. This study aimed to investigate the association between liver fibrosis and short-term clinical outcomes of acute CES patients, due to nonvalvular atrial fibrillation (NVAF), as well as the impacts of sex on the association. Methods: Using data of 522 patients with NVAF admitted within 48 hours after acute symptom of CES onset. We calculated Fibrosis-4 score (FIB-4) and defined liver fibrosis as: likely advanced fibrosis (FIB-4>3.25), indeterminate (FIB-4, 1.45-3.25), unlikely advanced fibrosis (FIB-4<1.45). We investigated the impact of liver fibrosis degree on stroke severity, major disability at discharge and all cause death at 90 days stratified by sex. Results: Among 522 acute CES patients with NVAF, the mean FIB-4 on admission reflected intermediate fibrosis with largely normal liver enzymes. After adjusting for all confounders, multivariate analyses revealed that likely advanced liver fibrosis was associated with severe stroke (OR=2.21, 95% CI: 1.04-3.54), major disability at discharge (OR=4.59, 95% CI: 1.88-11.18), and 90-days mortality (HR=1.25, 95% CI: 1.10-1.56). Further grouped by sex, these associations were stronger in males but not significant in females.Conclusions: In patients with largely normal liver enzyme, likely advanced liver fibrosis is associated with severe stroke, major disability and all cause death after acute CES due to NVAF, and the association unfolded more obvious in males, but not for females.