This study aimed to compare the prognosis and characteristics of patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab (AB) combination therapy and hepatic artery infusion chemotherapy (HAIC). We retrospectively assessed 193 and 114 patients treated with HAIC and AB combination therapy, respectively, between January 2018 and May 2023. The progression-free survival (PFS) of patients treated with AB combination therapy was significantly superior to that of patients treated with HAIC (p < 0.05), but there was no significant difference in overall survival (OS). After propensity score matching, our data revealed no significant differences in OS and PFS between patients who received AB combination therapy and those who received HAIC therapy (p = 0.5617 and 0.3522, respectively). In conclusion, our propensity score study reveals no significant differences in OS and PFS between patients treated with AB combination therapy and those treated with HAIC.

Background: Glypican-3 (GPC3) is overexpressed in most hepatocellular carcinoma (HCC) tissues but is absent in normal adult liver. We evaluated whether tumor GPC3 expression is associated with clinical outcomes in patients with advanced HCC treated with atezolizumab–bevacizumab (AB). Methods: We conducted a single-center retrospective cohort study of 139 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC who received AB between January 2022 and August 2025. Tumor GPC3 expression was assessed by immunohistochemistry. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: Baseline characteristics were largely balanced between GPC3-positive (n = 87) and GPC3-negative (n = 52) groups. Median OS was significantly shorter in patients with GPC3-positive tumors than in those with GPC3-negative tumors (p = 0.006). In multivariable analysis, GPC3 positivity remained independently associated with higher mortality (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.05–3.00; p = 0.033), along with Child–Pugh class B. PFS did not differ significantly between the groups (p = 0.712). ORR was lower in GPC3-positive tumors than in GPC3-negative tumors (approximately 17–18% vs. ~32%; p = 0.023). Membranous GPC3 localization was associated with inferior OS compared with cytoplasmic or absent expression (p = 0.025). Conclusions: Tumor GPC3 expression was associated with decreased OS and lower ORR among AB-treated patients with advanced HCC, suggesting potential clinical relevance and may help in risk stratification.

Purpose: Given the limited data on the effectiveness of atezolizumab plus bevacizumab (Ate/Bev) in patients with hepatocellular carcinoma with a Child-Pugh score (CPS) of 7, this study aims to evaluate the treatment’s efficacy in this population and identify specific CPS 7 subgroups that may benefit from it. Experimental Design: This study included patients with advanced hepatocellular carcinoma who received Ate/Bev as first-line therapy between September 2020 and December 2023 at seven university hospitals. The primary outcome was overall survival (OS), whereas secondary outcomes included progression-free survival (PFS) and treatment response. Results: Among the 374 included patients, those with CPS 5 (n = 169) demonstrated the highest OS and PFS, followed by patients with CPS 6 (n = 105) and CPS 7 (n = 100; P < 0.05). For the variables comprising CPS, the HR for OS increased with elevated total bilirubin levels and was lower in patients with mild ascites (P < 0.05). The HR for OS tended to increase as albumin levels dropped to 2.8 g/dL. Based on these findings, patients with CPS 7 were further classified into two subgroups: favorable (total bilirubin <2 mg/dL, 3.5 ≥ albumin ≥ 2.8 g/dL, mild ascites, and absence of hepatic encephalopathy) and unfavorable (other CPS 7). Compared with patients with CPS 6, those in the favorable CPS 7 group exhibited comparable OS and PFS, whereas patients with unfavorable CPS 7 had significantly lower OS and PFS (P < 0.05). These findings were consistently observed in the multivariate analysis. Conclusions: This study suggests that Ate/Bev treatment can be effective in a subset of patients with CPS 7, highlighting the potential to broaden treatment eligibility for this population. See related commentary by Li and Kelley, p. 4220

Background/Aims: Hepatic decompensation (HD) following systemic treatment, including atezolizumab + bevacizumab (Atezo/Bev) and tyrosine kinase inhibitors (TKIs), is a critical prognostic event in advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the predictive utility of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) for HD incidence post-treatment. Methods: This multicenter study included 396 HCC patients who received systemic therapy (Atezo/Bev or TKIs) and underwent VCTE prior to treatment at seven university-affiliated hospitals. Clinical outcomes including HD independent of tumor progression, variceal bleeding (VB), overall survival (OS), and progression-free survival (PFS) were assessed. A 25 kPa LSM threshold, based on Baveno VII criteria, stratified patients into high and low LSM groups. Results: Of the 396 patients, 176 received Atezo/Bev, while 45 and 175 received lenvatinib and sorafenib, respectively. Treatment distribution was similar between high and low LSM groups (p = 0.546). High LSM was associated with increased HD risk (HR = 3.00, p < 0.001), VB risk (HR = 2.34, p = 0.048), and a trend toward worse OS (HR = 1.27, p = 0.065). In the low LSM group, Atezo/Bev outperformed TKIs in OS and PFS (p < 0.05) without increasing HD risk. In contrast, in the high LSM group, Atezo/Bev and TKIs showed no OS or PFS differences, but Atezo/Bev significantly increased HD and VB risk (p < 0.05). A risk score based on four variables (Child-Pugh score 5, LSM ≥25 kPa, multiple tumors, and high-grade portal vein tumor thrombosis) showed good predictive accuracy for HD at 12 months (AUC = 0.832) and effectively identified patients at high risk for HD, VB, and poor survival (p < 0.005). Conclusion: LSM by VCTE predicts HD following systemic treatment in advanced HCC. In patients with high LSM, Atezo/Bev increases HD risk, warranting careful treatment selection.