Elevated Liver Damage Biomarkers in Long COVID: A Systematic Review and Meta-Analysis

Background Long COVID (LC) presents with complex pathophysiology, affecting multiple organs and producing a range of symptoms, from neuropsychiatric disturbances to multi-organ dysfunction. Liver damage has emerged as a notable feature, yet no systematic review or meta-analysis has comprehensively evaluated the biomarkers confirming liver injury in LC patients. Objective The present study aims to examine blood-based biomarkers of liver damage in LC disease. Methods A search of PubMed, Google Scholar, SciFinder, and SCOPUS identified 61 eligible studies, including 7172 participants, with 3404 LC patients and 3768 controls. Results Our analysis identified a significant increase in the liver damage index among LC patients, with a moderate effect size (standardized mean difference, SMD = 0.553; confidence intervals; 95% CI: 0.305–0.760) compared to normal controls. Additionally, LC patients exhibited marked elevations in alanine aminotransferase (SMD = 0.615; 95% CI: 0.351;0.878), aspartate aminotransferase (SMD = 0.352; 95% CI: 0.068;0.637), gamma-glutamyl transferase (SMD = 0.969; 95% CI: 0.194;1.745), and lactate dehydrogenase (SMD = 0.666; 95% CI: 0.332;0.999) activities. Moreover, significant reductions were observed in total protein (SMD = -0.326; 95% CI: -0.631; -0.021) and increases in prothrombin time (SMD = 0.633; 95% CI: 0.077;1.189), ferritin (SMD = 0.437; 95% CI: 0.069;0.805), D-dimer (SMD = 0.359; 95% CI: 0.144;0.573). Further studies are needed to confirm reductions in platelet count and elevations in fibrinogen levels Conclusion This study suggests that LC is associated with persistent liver damage and coagulopathy, highlighting the need to incorporate liver injury into treatment strategies to reduce potential risks.