Atezolizumab plus bevacizumab therapy has high response rates in patients with advanced hepatocellular carcinoma (HCC). It has been reported that HCC with immune exclusion associated with the signal activation of WNT/β-catenin is resistant to immune checkpoint inhibitors; however, to the best of our knowledge, the effectiveness of atezolizumab plus bevacizumab for HCC with WNT/β-catenin signal activation has not been reported. The present study aimed to analyze the efficacy of atezolizumab plus bevacizumab for HCC with WNT/β-catenin signal activation. A total of 24 patients who underwent liver tumor biopsy for HCC were classified into WNT/β-catenin signal activation and inactivation groups according to the expression levels of β-catenin and glutamine synthetase, which are indicative of WNT/β-catenin signal activation. The differences in the clinical responses to treatment between the groups were analyzed. A total of 15 patients had HCC with WNT/β-catenin signal activation, whereas 9 patients had HCC with WNT/β-catenin signal inactivation. There were no significant differences between both groups regarding objective responses (P=0.519) and disease control (P=0.586). In the WNT/β-catenin signal activation group, the median progression-free survival rate was 6.9 months compared with 6.2 months in the WNT/β-catenin signal inactivation group (P=0.674). Although a small number of patients was included in the present study, the present findings suggested that the efficacy of atezolizumab plus bevacizumab might be unaffected by WNT/β-catenin signal activation.

Atezolizumab plus bevacizumab and lenvatinib are approved frontline therapies for advanced hepatocellular carcinoma (HCC). Patients with advanced HCC continue to have a poor prognosis despite these therapeutic choices. Previous studies have reported CD8 + tumor-infiltrating lymphocytes (TILs) as a biomarker to predict responsiveness to systemic chemotherapy. The present study investigated whether evaluating CD8 + TILs by immunohistochemistry staining of liver tumor biopsy tissues could help predict the response of patients with HCC to atezolizumab plus bevacizumab and lenvatinib. In total, 39 patients with HCC who underwent liver tumor biopsy were classified into high and low CD8 + TILs groups and were then divided by therapy type. The clinical responses to treatment in both groups were evaluated for each therapy. There were 12 patients with high-level CD8 + TILs and 12 patients with low-level CD8 + TILs among those who received atezolizumab plus bevacizumab. An improved response rate was observed in the high-level group compared with the low-level group. The high-level CD8 + TILs group had a significantly longer median progression-free survival compared with the low-level group. Among the patients with HCC who received lenvatinib, five had high-level CD8 + TILs and 10 had low-level CD8 + TILs. There were no differences in response rate or progression-free survival between these groups. Although the present study included only a limited number of patients, the findings suggested that CD8 + TILs could be a biomarker for predicting response to systemic chemotherapy in HCC.

Background and Aim Direct‐acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection. Additionally, interferon‐free DAA treatment has improved liver function and reduced the risk of hepatocellular carcinoma (HCC) following HCV eradication. Previous studies on HCV have focused mainly on the treatment rate and the risk of developing HCC, and less attention has been given to loss to follow‐up (LTFU) after DAA treatment. Therefore, the present study aimed to identify the definitive risk factors for LTFU after the start of DAA treatment. Methods Between September 2017 and March 2022, 296 patients receiving glecaprevir and pibrentasvir for HCV infection were enrolled in this study. The incidence of LTFU following DAA treatment and the risk factors contributing to LTFU were identified using the patients' clinical characteristics. Results In the present study, 75 patients (25.3%) interrupted their follow‐up visits. Multivariate logistic analysis revealed a history of injection drug use (hazard ratio [HR], 1.81; P = 0.017), treatment duration (8 weeks) (HR, 3.51; P = 0.0033), and age <70 years (HR, 1.9; P = 0.0422) as independent factors associated with LTFU after the start of DAA treatment. Conclusion Young patients and those with injection drug use are likely to discontinue their follow‐up visits after the start of DAA treatment for HCV infection. Therefore, these patients require strict supervision.

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