The Efficacy of Dexamethasone Versus N‐Acetylcysteine in Prevention of Post‐Embolization Syndrome in Hepatocellular Carcinoma Patients: A Multicenter Randomized, Double‐Blind, Double‐Dummy, Non‐Inferiority Trial

Background and Aims Post‐embolization syndrome (PES) is a frequent complication after hepatocellular carcinoma (HCC) treatment. This study compared dexamethasone (DEX) versus N‐acetylcysteine (NAC) for efficacy and safety in preventing PES at 48 h after transcatheter arterial chemoembolization (TACE). Methods This Phase 3, randomized (1:1), double‐blind, double‐dummy, parallel‐group, non‐inferiority study, included patients with early‐ to intermediate‐stage HCC (BCLC Stages A–B) without macrovascular invasion who were candidates for TACE. Participants were randomly assigned to receive either an intravenous single dose of 8 mg DEX or NAC as part of the periprocedural TACE protocol. Results A total of 85 patients were included in the outcome analysis. PES incidence was non‐inferior between groups (difference proportion DEX‐NAC 0.02, [95% CI: −0.13 to 0.17]). However, subgroup symptoms’ analysis showed significantly greater reduction in abdominal pain (87.5% vs. 55.3%, p = 0.002) and fever (52.5% vs. 28.9%, p = 0.035) in DEX group compared to NAC group. Liver decompensation was significantly greater reduction in the DEX group than the NAC group (90% vs. 52.6%, p < 0.001). Anaphylactoid reactions (18.4%) were observed exclusively in the NAC group. Multivariate analysis showed preexisting high serum ALT was associated with an increased risk of developing PES (OR: 1.05; 95% CI: 1.01–1.08), and a higher chemotherapy dosage emerged as an independent risk factor for post‐TACE liver decompensation (OR: 1.00; 95% CI: 0.84–0.99). Conclusion PES incidence was non‐inferior between groups. However, at 48 h post‐TACE, the DEX regimen was associated with a significant reduction in fever, pain, and liver decompensation.