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

Abstract

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.

Graphical Abstract

Keywords:

• HBV-related HCC
• TACE
• TKI
• ICI
• liver injury
• survival time

Ethics Approval and Informed Consent

This study was approved by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University (Ethics number: xyfy2022-KL085-01). Given that this was a retrospective observational study of the patient’s anonymous clinical data and that no identifying information was used, the written informed consent was not necessary. We certify that this study was performed in accordance with the ethical standards outlined in the Declaration of Helsinki.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Jiaming Shen, Xia Wang and Guangde Yang are co-first authors of this study. The authors report no conflicts of interest related to this work.

Additional information

Funding

There is no funding to report.