VETC Phenotype and Advanced HCC: JHEP Reports | July 2026

Introduction:

Choosing the optimal first-line immunotherapy for advanced hepatocellular carcinoma (HCC) remains challenging because reliable predictive biomarkers are lacking. This study evaluated whether the Vessels Encapsulating Tumor Clusters (VETC) histological pattern could predict response to atezolizumab–bevacizumab and durvalumab–tremelimumab (STRIDE).

Why was this study needed?

• No validated tissue biomarker currently guides first-line immunotherapy selection in HCC.
• Multiple first-line regimens are available with similar overall efficacy.
• Molecular biomarkers remain expensive and are not routinely available.
• A simple biopsy-based marker could enable personalized treatment.
• Better patient selection may improve treatment outcomes.

Results:

• Patients with a complete VETC phenotype achieved higher response rates and significantly longer progression-free and overall survival with atezolizumab–bevacizumab.
• In contrast, patients with complete VETC treated with durvalumab–tremelimumab had inferior outcomes, suggesting that VETC may predict differential benefit between first-line immunotherapy regimens.
• Because VETC can be easily assessed on routine pretreatment biopsy, it represents a practical and clinically applicable predictive biomarker.

Clinical Impact:

This study introduces one of the first histopathology-based biomarkers capable of guiding first-line immunotherapy selection in advanced HCC. If prospectively validated, assessment of the VETC phenotype could help clinicians preferentially select atezolizumab–bevacizumab for patients with complete VETC while considering alternative regimens for others.

Bottom Line:

The VETC phenotype may become a practical precision medicine biomarker in advanced HCC. Patients with complete VETC appear to derive greater benefit from atezolizumab–bevacizumab than from durvalumab–tremelimumab, paving the way for biopsy-guided first-line treatment selection.