Liver Injury and Its Impact on Prognosis in Patients with HBV-Related Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors

Purpose: Recently, the triple therapy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) has become a new treatment option for advanced or unresectable hepatocellular carcinoma (HCC) patients. We aimed to explore the liver injury and its effect on overall survival (OS) in patients treated with this combination therapy.

Patients and methods: Patients with HBV-related HCC who were treated with TACE-TKIs-ICIs from January 2020 to December 2021 were enrolled. Liver injury and survival time were the main endpoints of the study. Logistic regression analysis was used to analyze the factors associated with liver injury. Cox regression and Kaplan-Meier analysis were used to determine prognostic factors for OS.

Results: As of March 2022, 52 of the 119 enrolled patients developed any grade hepatotoxicity: 15 cases with grade 1, 19 cases with grade 2, 16 cases with grade 3 and 2 cases with grade 4. Our analysis indicated that lack of antiviral prevention was a risk factor for liver injury (OR = 0.149; 95% CI: 0.050-0.442; P = 0.001). The findings suggested that liver injury events (HR = 1.912; 95% CI: 1.031-3.546; P = 0.040) was associated with patient death. The median OS of patients without liver injury, grade 1-2 and grade 3-4 liver injury were undefined, 13.7 months and 11.1 months, respectively (log-rank P = 0.034).

Conclusion: Liver injury adverse events are common in HBV-related HCC patients treated with TACE-TKIs-ICIs. Patients who developed liver injury had a poor prognosis. For HBV-related HCC patients, effective prophylactic antiviral therapy and regular liver function testing are required before and during this triple therapy.