Background Transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKI) are usually used in treatment of hepatocellular carcinoma (HCC). However, there is a lack of clinical studies examining the influence of TACE and TACE-TKI on postoperative liver function and prognosis in intermediate HCC.

Objective To compare the short-term changes in liver function, complications, and survival outcomes (progression-free survival, PFS) associated with TACE and TACE-TKI (Sorafenib or Lenvatinib) treatments for intermediate HCC and identify their associated factors.

Methods The medical records of 149 patients with intermediate HCC who underwent TACE or TACE-TKI in the Fifth Medical Center of Chinese PLA General Hospital were collected from June 2010 to January 2023. According to different therapies, patients were divided into TACE group and TACE-TKI group. The PFS was followed up to June 2023. Liver function before TACE, 48 h and 2 months after TACE, complications and survival outcomes were compared between the two groups.

Results The baseline characteristics were not significantly different between TACE group (n=97) and TACE-TKI group (n=52). The percentage of hepatic dysfunction was higher in the TACE-TKI group than that in the TACE group at 48 h after TACE (42.3% vs 21.6%, P=0.008). At 48 h after TACE, white blood cell count (WBC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in the two groups were all higher than those before TACE (P<0.05), while the levels of platelet (Plt) and albumin (ALB) in both groups were lower compared with those before TACE (P<0.05). At 2 months after TACE, TBIL was higher in the TACE-TKI group than that in the TACE group (19.1μmol/L vs 14.4μmol/L, P=0.001). The TACE-TKI group had a higher incidence of postoperative complications than that of the TACE group (30.7% vs 15.5%, P<0.05). The median follow-up time was 6.08 years. PFS was longer in the TACE group than that in the TACE-TKI group (47 months vs 32 months, P<0.05). Multivariate COX analysis showed that Alpha fetoprotein (AFP) ≤ 647 ng/mL (HR:0.570, 95% CI: 0.357-0.909, P=0.018), AST≤31 μ/L (HR:0.527, 95% CI: 0.319-0.872, P=0.013), prothrombin activity (PTA) ≤ 93% (HR: 0.507, 95% CI: 0.310-0.832, P=0.007), TACE treatment>twice (HR: 2.104, 95% CI: 1.359-3.259, P=0.001) and the TACE therapy (HR: 0.598, 95% CI:0.380-0.942, P=0.027) were associated with longer PFS.

Conclusion TACE-TKI (Sorafenib or Lenvatinib) group has a higher occurrence of liver dysfunction and postoperative complications than that of the TACE group during the treatment of intermediate HCC. AFP>647 ng/mL, TACE treatment ≤twice, AST>31μ/L, the TACE-TKI therapy and PTA>93% may be associated with worse PFS in intermediate HCC patients treated with TACE or TACE-TKI.