Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a dismal prognosis. Interventional therapy serves as a main therapeutic approach for unresectable HCC. This study aimed to investigate the impact of post-interventional blood ammonia (BLA) levels on the prognosis of patients with unresectable HCC, to provide a reference for clinical risk stratification and individualized treatment.

A retrospective study was conducted, enrolling patients with unresectable HCC admitted to Senior Department of Hepatology, Chinese PLA General Hospital from August 2022 to September 2025. According to the BLA levels within 1 week after interventional therapy, the patients were divided into the BLA < 50 μmol/L group and the BLA ≥ 50 μmol/L group. The clinical characteristics, interventional treatment modalities (hepatic arterial infusion chemotherapy [HAIC] or transcatheter arterial chemoembolization [TACE]), and laboratory indicators of the patients were collected. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was applied to analyze the prognostic factors.

A total of 209 patients were enrolled in this study, including 178 males (85.2%); the mean age was 56.6 ± 9.5 years. By the last follow-up, 110 patients were still alive, and 99 had died. The objective response rate (ORR) and disease control rate (DCR) in the BLA ≥ 50 μmol/L group were significantly lower than those in the BLA < 50 μmol/L group after interventional therapy (ORR: 12.2% vs. 24.4%, p = 0.046; DCR: 28.1% vs. 48.1%, p = 0.004). Survival analysis showed that the overall survival (OS) and progression-free survival (PFS) in the BLA ≥ 50 μmol/L group were significantly shortened (p < 0.05). Multivariable Cox regression analysis revealed that BLA ≥ 50 μmol/L (HR = 1.572, 95% CI: 1.049–2.356, p = 0.029) was an independent risk factor for prognosis, while treatment with HAIC (HR = 0.648, 95% CI: 0.423–0.993, p = 0.046) was an independent protective factor.

Elevated BLA (≥ 50 μmol/L) after interventional therapy is an independent risk factor for poor prognosis in patients with unresectable HCC, and HAIC treatment may improve the survival of such patients.