Liver function dynamics in advanced hepatocellular carcinoma receiving immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization

Abstract

Background: The efficacy and safety of transarterial chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) have been established. However, it remains unclear whether the addition of TACE to systemic therapies exacerbates liver function deterioration and increases mortality risk.

Objectives: To assess liver function changes and their impact on prognosis in patients with advanced hepatocellular carcinoma (HCC) treated with ICIs and anti-VEGF antibody/TKIs with or without TACE as first-line therapy.

Design: This is a real-world retrospective cohort study.

Methods: Patients with advanced HCC treated with TACE combined with ICIs and anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or ICIs and anti-VEGF antibody/TKIs alone (ICI-VEGF) from January 2018 to June 2024 were retrospectively included. The primary outcomes were changes in albumin-bilirubin (ALBI) score and time to deterioration (TTD) of liver function. The secondary outcomes included overall survival (OS), progression-free survival (PFS), and the relationship between TTD and prognosis.

Results: A total of 111 patients were included, with 54 and 57 patients receiving TACE-ICI-VEGF and ICI-VEGF, respectively. Changes in ALBI score were similar between groups (difference in least squares mean, -0.075; 95% confidence interval (CI): -0.298 to 0.148). TTD was also comparable (median for TACE-ICI-VEGF 9.7 months vs. ICI-VEGF 8.5 months; hazard ratio (HR) = 1.19 (95% CI: 0.71-2.01); p = 0.512). TACE-ICI-VEGF group demonstrated a significantly improved median OS (18.3 vs. 11.8 months; HR = 0.60 (95% CI: 0.37-0.98); p = 0.041) and a trend toward prolonged median PFS (14.7 vs. 11.2 months; HR = 0.76 (95% CI: 0.47-1.25); p = 0.278). Patients with liver function deterioration had an increased risk of mortality (median OS: 13.2 vs. 17.0 months; HR = 1.44 (95% CI: 0.88-2.35); p = 0.139).

Conclusion: TACE combined with ICIs plus anti-VEGF antibodies/TKIs as first-line treatment generally did not adversely affect liver function. Liver function deterioration was associated with an increased risk of mortality.

Keywords: albumin-bilirubin score; hepatocellular carcinoma; liver function; systemic therapies; transarterial chemoembolization.

Figure 1.

Study cohort. BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma; ICIs, immune checkpoint inhibitors; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; TACE, transarterial chemoembolization; TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor.

Figure 2.

Time to deterioration in liver function.^{a a}Time to deterioration in liver function was defined as the time from baseline to a ⩾0.5-point increase in ALBI score sustained across two visits or disease progression. ALBI, albumin-bilirubin; CI, confidence interval; HR, hazard ratio; ICIs, immune checkpoint inhibitors; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; TACE, transarterial chemoembolization; TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor.

Figure 3.

Time to ALBI grade increase.^{a a}Time to ALBI grade increase was defined as the time from baseline to the first post-baseline ALBI measurement that was ⩾1 grade higher than baseline. ALBI, albumin-bilirubin; CI, confidence interval; HR, hazard ratio; ICIs, immune checkpoint inhibitors; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; TACE, transarterial chemoembolization; TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor.

Figure 4.

Time to deterioration in liver function by (a) ALBI grade 1 and (b) ALBI grade 2.^{a a}Time to deterioration in liver function was defined as the time from baseline to a ⩾0.5-point increase in ALBI score sustained across two visits or disease progression. ALBI, albumin-bilirubin; CI, confidence interval; HR, hazard ratio; ICIs, immune checkpoint inhibitors; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; TACE, transarterial chemoembolization; TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor.

Figure 5.

Time to ALBI grade increase by (a) ALBI grade 1 and (b) ALBI grade 2.^{a a}Time to ALBI grade increase was defined as the time from baseline to the first post-baseline ALBI measurement that was ⩾1 grade higher than baseline. ALBI, albumin-bilirubin; CI, confidence interval; HR, hazard ratio; ICIs, immune checkpoint inhibitors; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; TACE, transarterial chemoembolization; TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor.

Figure 6.

Kaplan-Meier estimates of (a) overall survival, and (b) progression-free survival assessed by mRECIST. CI, confidence interval; HR, hazard ratio; ICIs, immune checkpoint inhibitors; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; mRECIST, modified RECIST; TACE, transarterial chemoembolization; TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor.

Figure 7.

Impact of liver function during treatment on OS.^{a a}Patients with preserved or deteriorated liver function were defined as those who did not or did experience a ⩾0.5-point increase in ALBI score from baseline, sustained across two visits, or to disease progression. CI, confidence interval; HR, hazard ratio; OS, overall survival.

Figure 8.

Impact of liver function during treatment on OS by (a) TACE-ICI-VEGF group and (b) ICI-VEGF group.^{a a}Patients with preserved or deteriorated liver function were defined as those who did not or did experience a ⩾0.5-point increase in ALBI score from baseline, sustained across two visits, or due to disease progression. CI, confidence interval; HR, hazard ratio; ICIs, immune checkpoint inhibitors; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; OS, overall survival; TACE, transarterial chemoembolization; TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor.