Efficacy of N-acetylcysteine vs dexamethasone in preventing postembolization syndrome post-transarterial chemoembolization in hepatocellular carcinoma: A randomized controlled trial

BACKGROUND Hepatocellular carcinoma (HCC) is a major health concern in Thailand, with most patients diagnosed at the intermediate stage. Transarterial chemoembolization (TACE) is the standard treatment; however, postembolization syndrome (PES) remains a common complication. Although both dexamethasone (DEXA) and N-acetylcysteine (NAC) have shown efficacy in reducing PES, no study has directly compared their effects. AIM To compare the incidence of PES between DEXA and NAC in intermediate-stage HCC patients undergoing conventional TACE (cTACE). METHODS A randomized, double-blind, controlled trial was conducted at two tertiary hospitals in Thailand from November 2024 to April 2025. Eligible HCC patients (aged 18-70 years) were randomized (1:1) to receive either NAC (150 mg/kg/hour loading dose, followed by 50 mg/kg over 4 hours, then 6.25 mg/kg/ hour for 48 hours post-cTACE) or DEXA (8 mg IV 1 hour before cTACE). cTACE was performed by blinded interventional radiologists. The primary outcome was PES occurrence within 48 hours, assessed using South West Oncology Group toxicity coding and the Common Terminology Criteria for Adverse Events. The secondary outcomes were post-cTACE liver decompensation and the dynamic changes in the albumin-bilirubin (ALBI) score. RESULTS A total of 56 intermediate-stage HCC patients were included (DEXA, n = 28; NAC, n = 28). Most had preserved liver function, with 92.9% classified as Child-Pugh A. The maximum tumor size was 6.2 cm, and 85.7% had multiple lesions. Additionally, 39 patients (69.6%) met the beyond up-to-7 criteria. Overall, 27 patients (48.2%) developed PES. After adjusting for confounding factors, the NAC group had a significantly lower incidence of PES than the DEXA group (32.1% vs 64.3%; adjusted odds ratio = 0.17, 95% confidence interval: 0.03-0.87, P = 0.033). Only two patients (3.6%) developed post-cTACE liver decompensation. Furthermore, 51.8% patients experienced worsening ALBI scores within 48 hours post-procedure; however, the rate of ALBI score worsening did not significantly differ between the groups. CONCLUSION Compared with DEXA, NAC significantly reduces the incidence of PES, regardless of its impact on liver function recovery. Therefore, NAC is a preferable option for reducing PES in Barcelona Clinic Liver Cancer-B stage HCC patients with preserved liver function.