Association between the Risk of Hemorrhagic Stroke and Liver Enzymes Levels: A Systematic Review and Meta-analysis of 2,021,882 Patients.
Omnia Samy El-Sayed1, Abdelfattah Arafa2, Youssef Nader2, Ahmed A. Abo Elnaga3, Momen Syaj1, Hind EL AZZAZI4, Mohamed Ahmed Ali5, Mohamed Gaber Nada2, Ahmed M. Gazer6, Ahmed F Younis2, Assia Zanat7, Mohamed Ahmed Tolba8
1Faculty of Medicine, Zagazig University, Zagazig, Sharkia, Egypt, 2Faculty of Medicine, Al-Azhar University, Damietta, Egypt, 3Faculty of medicine, Mansoura university, Mansoura, Egypt, 4Faculty of Medicine and Pharmacy of Rabat, University Mohammed V, Rabat, Morocco, 5Qena Faculty of Medicine, South Valley University, Qena, Egypt, 6Faculty of medicine, Alexandria University, Egypt, 7Kyiv Medical University of UAFM, Kyiv, Kyiv City, UA, 8Faculty of Medicine, MUST university, 6th of October, Egypt
Objective:

This study aims to explore the association between elevated liver enzymes (GGT, ALP, AST, and ALT) and the risk of hemorrhagic stroke.

Background:

Hemorrhagic stroke is the second leading cause of death worldwide, accounting for 6.1 million deaths in 2019 with a case fatality rate ranging from 25% to 48%. Current literature suggests that liver enzymes are implicated in many disease processes, including stroke. However, conflicting evidence regarding the association of GGT, ALP, ALT, and AST and hemorrhagic stroke risk and prognosis have been proposed and the exact relationship between these two entities remains unclear. 

Design/Methods:

Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically searched four electronic databases (PubMed, Scopus, Embase, and Web of Science) to identify articles investigating the association between liver enzymes and hemorrhagic strokes up to February 2025. Newcastle Ottawa Scale was used to assess the quality of the included articles. Risk Ratio (RR), Hazard Ratio (HR), and Odds Ratio (OR) were statistically analyzed and reported using R (v4.4.2).

Results:

Increased levels of ALP and GGT were significantly associated with an increased risk of hemorrhagic stroke (RR = 1.45, 95% CI = 1.01-2.08, p = 0.043) and (RR = 1.36, 95% CI = 1.1-1.69, p = 0.0047). While AST was not significantly associated with hemorrhagic stroke (RR = 2.23, 95% CI = 0.87-5.76, p = 0.0961), higher levels of ALT demonstrated a significant association with higher risk of hemorrhagic stroke (RR = 1.18, 95% CI = 1.06-1.31, p = 0.0032). mRS 3-6 score and mortality were insignificantly associated with elevated ALP levels, (OR = 1.1, 95% CI = 0.99; 1.22, p = 0.0754) and (OR = 1.49, 95% CI = 0.58; 3.82, p = 0.4105).

Conclusions:
ALT, ALP, and GGT emerged as positive predictors of hemorrhagic stroke risk. while AST exhibited no significant association.
10.1212/WNL.0000000000216166
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