Proton pump inhibitors and clinical outcomes in hepatocellular carcinoma patients: A propensity score–matched analysis from a global federated dataset.

e16270 Background: Proton pump inhibitors (PPIs) are commonly prescribed in patients with hepatocellular carcinoma (HCC) to manage gastroesophageal reflux and stress ulcer prophylaxis. However, concerns have emerged regarding their potential association with adverse hepatic and thromboembolic events. This study aims to assess the impact of PPI use on the risks of mortality, thrombotic, hemorrhagic, and hepatic complications in HCC patients. Methods: This retrospective cohort study was conducted using the TriNetX global federated health research network, focusing on the US Collaborative Network comprising 68 healthcare organizations. We identified HCC patients and categorized them into two cohorts: Cohort 1 (HCC with PPI, N = 28,914) and Cohort 2 (HCC without PPI, N = 28,914) after propensity score matching (PSM). The primary outcome was all-cause mortality. Secondary outcomes included septic shock, acute kidney injury (AKI), ascites, hepatic encephalopathy (HE), portal hypertension (PHT), portal vein thrombosis (PVT), gastrointestinal bleeding (GIB), deep vein thrombosis (DVT), pulmonary embolism (PE), melena, acute liver failure, hepatorenal syndrome (HRS), and spontaneous bacterial peritonitis (SBP). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for these outcomes. Results: After PSM, HCC patients receiving PPIs had a significantly increased risk of all-cause mortality (HR 1.18, 95% CI 1.15-1.21, p < 0.001). The risk of thrombotic complications was higher in the PPI group, including PVT (HR 1.96, 95% CI 1.86-2.07, p < 0.001), DVT (HR 1.73, 95% CI 1.58-1.91, p < 0.001), and PE (HR 1.46, 95% CI 1.32-1.61, p < 0.001). The risks of septic shock (HR 3.36, 95% CI 3.03-3.74, p < 0.001), AKI (HR 2.29, 95% CI 2.21-2.38, p < 0.001), and ascites (HR 1.78, 95% CI 1.73-1.83, p < 0.001) were also significantly elevated. Regarding hemorrhagic events, PPI use was associated with a markedly increased risk of GIB (HR 4.43, 95% CI 4.08-4.80, p < 0.001) and melena (HR 3.82, 95% CI 3.48-4.18, p < 0.001), but not with increased risk of ICH. Additionally, HCC patients on PPIs had a significantly higher risk of hepatic complications, including HE (HR 3.26, 95% CI 3.03-3.52, p < 0.001), PHT (HR 2.11, 95% CI 2.04-2.18, p < 0.001), acute liver failure (HR 3.20, 95% CI 2.89-3.53, p < 0.001), and SBP (HR 3.33, 95% CI 2.99-3.71, p < 0.001). Conclusions: In HCC patients, PPI use is associated with significantly increased risks of mortality, thrombotic events, hemorrhagic complications, and hepatic decompensation. These findings suggest that caution should be exercised when prescribing PPIs in this population, and further studies are warranted to elucidate the mechanisms underlying these associations.