Abstract
OBJECTIVE: To systematically evaluate the association between thyroid dysfunction and prognosis in patients with liver failure. METHODS: We systematically searched PubMed, Embase, Web of Science (WOS), and China National Knowledge Infrastructure (CNKI) till August 2025 to identify prospective or retrospective studies assessing the relationship between thyroid function-specifically, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4)-and outcomes in adult patients with liver failure, including mortality, intensive care unit (ICU) admission, and organ failure. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS). Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated, and heterogeneity, subgroup, and sensitivity analyses were conducted. RESULTS: Eleven studies, including 3,595 patients from four countries, were included. Thyroid dysfunction was significantly associated with increased mortality in patients with liver failure (RR = 3.56, 95% CI: 2.77-4.57; I² = 36%). Subgroup analyses by sex, FT3 cut-off, and etiology (hepatitis B virus [HBV] vs. non-hepatitis B virus acute-on-chronic liver failure [non-HBV ACLF]) showed consistent associations. Additionally, a subgroup analysis comparing FT3 concentrations between survival and death groups in liver failure patients revealed a significant difference in FT3 levels between the two groups (mean difference [MD] = 0.89 [0.41, 1.37] for short-term mortality and MD = 0.42 [0.23, 0.61] for long-term mortality). Sensitivity analyses confirmed the robustness of the results. No substantial publication bias was observed. CONCLUSIONS: Thyroid dysfunction, particularly low FT3 levels, is associated with higher mortality rates in patients with liver failure. These findings suggest that routine thyroid function assessment may help identify high-risk patients. Further well-designed prospective studies are needed to clarify the underlying mechanisms and evaluate the potential therapeutic implications.