Risk of Liver Fibrosis Is Associated with More Severe Strokes, Increased Complications with Thrombolysis, and Mortality

Abstract

The Fibrosis (FIB)-4 index is an established non-invasive test to detect liver fibrosis. Liver fibrosis is postulated to be one of the predictors of the risk of symptomatic Intracranial Haemorrhage (SICH) after intravenous tissue plasminogen activator (IV tPA) therapy, the mainstay of treatment following acute ischemic stroke (AIS). However, SICH is a feared complication of thrombolytic therapy. We aimed to evaluate the association of FIB-4 with outcomes of AIS after IV tPA. Consecutive AIS patients receiving IV tPA from 2006 to 2018 at a single stroke centre were studied in a retrospective cohort study. Multivariable adjusted logistic regression was performed to assess associations of FIB-4 with outcomes. The primary outcome was SICH, and secondary outcomes included functional independence (mRS of 0−2) and mortality measured at 90 days. Among 887 patients (median age: 67 (IQR: 57−77)), 342 had FIB-4 < 1.3 and 161 had FIB-4 > 2.67. A greater proportion of moderate to severe strokes (NIHSS ≥10) occurred in the FIB-4 > 2.67 group (n = 142, 88.8%) compared to the FIB-4 < 1.3 group (n = 208, 61.2%). Amongst the different stroke subtypes, median FIB-4 was highest in cardioembolic stroke (CES) compared to the 3 other non-CES stroke subtypes (1.90 (IQR: 1.41−2.69)). Following IV tPA, having FIB-4 > 2.67 was associated with an increased rate of SICH (adjusted OR: 4.09, 95% CI: 1.04−16.16, p = 0.045) and increased mortality (adjusted OR 3.05, 95% CI: 1.28−7.26, p = 0.012). Advanced liver fibrosis was associated with an increased rate of SICH and increased 90-day mortality after IV tPA. The FIB-4 score may be useful for prognostication after IV tPA.

Keywords: FIB-4; ischemic stroke; liver fibrosis; symptomatic intracranial haemorrhage; thrombolysis.

Figure 1

This figure is a boxplot depicting the median FIB-4 across the four different stroke mechanisms according to the TOAST classification, namely Cardioembolic stroke, Stroke of Undetermined Etiology, Large Artery Atherosclerosis and Small Vessel Occlusion. Error bars represent the 25th and 75th quartile of FIB-4 for each TOAST mechanism. Mann–Whitney U test determined that there was a significant difference between FIB-4 between Cardioembolic stroke and each of the four TOAST stroke subtypes groups at p < 0.001. The Kruskal–Wallis test, which determined if there was overall a statistically significant difference between any one of the four groups, was also statistically significant at p < 0.001.