Bleeding Risk with Immunotherapy in Advanced HCC: JHEP Reports | July 2026

Introduction:

Atezolizumab–bevacizumab (A/B) and durvalumab–tremelimumab (STRIDE) are preferred first-line treatments for advanced hepatocellular carcinoma (HCC). Because bevacizumab inhibits VEGF, concerns remain regarding bleeding and thromboembolic complications in patients with underlying cirrhosis and portal hypertension.

Why was this study needed?

• Direct real-world safety comparisons between A/B and STRIDE are limited.
• The anti-VEGF component of bevacizumab may increase bleeding risk.
• Clinicians need evidence to guide treatment selection in patients at high bleeding risk.
• The comparative risk of variceal bleeding and thromboembolic events remains uncertain.
• Better safety data are needed to individualize first-line immunotherapy.

Results:

• Atezolizumab–bevacizumab was associated with significantly more overall and severe bleeding events, which also occurred earlier than with durvalumab–tremelimumab.
• Variceal bleeding and thromboembolic event rates were similar between the two treatment groups despite the higher overall bleeding risk with A/B.
• Treatment with A/B independently predicted bleeding risk, suggesting that the VEGF inhibitor contributes to this increased risk.

Clinical Impact:

These findings suggest that STRIDE may be the preferred first-line immunotherapy in patients with advanced HCC who have a high baseline bleeding risk, particularly those with portal hypertension or previous bleeding episodes. As this was a retrospective study, treatment decisions should still be individualized pending prospective confirmation.

Bottom Line:

Atezolizumab–bevacizumab increases overall bleeding risk compared with durvalumab–tremelimumab, while variceal bleeding and thromboembolic events remain similar. Careful bleeding risk assessment should guide first-line immunotherapy selection in advanced HCC.