Unveiling the role of sodium glucose cotransporter-2 inhibitors in hepatocellular carcinoma patients with cirrhosis: A comparative global cohort study.

4138 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and is often associated with chronic liver disease and cirrhosis. Despite advancements in therapeutic options, the prognosis for HCC patients remains poor. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exhibit anti-inflammatory, anti-fibrotic, and anti-carcinogenic properties, potentially influencing cancer biology via metabolic and oxidative stress modulation. Our study aimed to evaluate the impact of SGLT2i on outcomes of HCC patients with underlying cirrhosis using a large global database. Methods: We conducted a retrospective, propensity score-matched cohort study using TriNetX Analytics Network database. We compared patients aged > 18 years with HCC and cirrhosis who received SGLT2i to those who did not receive SGLT2i from 1/1/2014 to 1/1/2023 for one year. The study cohort included 1,254 cirrhotic HCC patients on SGLT2i, while the control cohort comprised 40,820 cirrhotic HCC patients not on SGLT2i. Propensity score matching was applied to balance demographics, HCC-directed therapies, comorbidities, laboratory values, and medications. Kaplan-Meier analysis estimated event-free survival and overall survival, with comparisons using log-rank tests. The primary outcomes were all-cause mortality, venous thromboembolism (VTE), and all-cause hospitalization rates. Secondary outcomes included all-cause ICU admissions, ischemic stroke/TIA, acute kidney injury (AKI), and septic shock. Results: Propensity score matching adjusted for key characteristics resulted in 1,020 matched pairs for each cohort. Our comparative analysis showed that the SGLT2i group had significantly lower all-cause mortality, with a hazard ratio (HR) of 0.399 (95% confidence interval [CI] 0.314, 0.507). Specific outcomes associated with improvement in the SGLT2i group: VTE (HR 0.607, 95% CI 0.481, 0.765), all-cause hospitalization rates (HR 0.568, 95% CI 0.501, 0.644), all-cause ICU admissions (HR 0.522, 95% CI 0.396, 0.689), ischemic stroke/TIA (HR 0.585, 95% CI 0.389, 0.878), thrombocytopenia (HR 0.578, 95% CI 0.470, 0.711), AKI (HR 0.708, 95% CI 0.588, 0.852), and septic shock (HR 0.528, 95% CI 0.382, 0.728). Conclusions: Our study highlights the association of SGLT2i with significant improvements in clinical outcomes for HCC patients with cirrhosis. SGLT2i use was linked to reduced all-cause mortality, VTE, hospitalizations, ICU admissions, and complications such as ischemic stroke/TIA, thrombocytopenia, AKI, and septic shock. These findings suggest SGLT2i may offer therapeutic benefits beyond their cardiovascular and renal effects, potentially influencing cancer biology and systemic complications in this high-risk population. Prospective trials are warranted to validate these findings and assess their safety and efficacy.