Esophagogastric Variceal Bleeding in Cirrhotic Patients with Hepatocellular Carcinoma Receiving Systemic Therapy: A...

Systemic therapy has improved outcomes in advanced hepatocellular carcinoma (HCC), but the risk of esophagogastric variceal (EGV) bleeding remains a concern. This study investigated the incidence and risk factors for EGV bleeding and mortality in cirrhotic HCC patients receiving systemic therapy.

This single-center retrospective study included cirrhotic patients with intermediate to advanced HCC who initially received systemic therapy with tyrosine kinase inhibitors (TKIs) alone or in combination with anti-programmed cell death-1 antibodies (anti-PD-1). HCC was diagnosed based on histology or typical radiological findings and staged according to the Barcelona Clinic Liver Cancer (BCLC) classification system. EGV bleeding was confirmed by oesophagogastroduodenoscopy. The treatment efficacy was evaluated using the modified Response Evaluation Criteria in Solid Tumors.

A total of 263 patients were included, predominantly male (85.9%), with a median age of 59 years. BCLC stages B and C accounted for 59.3% and 40.7% of cases, respectively. The 1-year and 2-year cumulative incidence of EGV bleeding were 16.7% and 21.6%, respectively. Portal vein thrombosis (PVT), ascites, and severe varices were independently associated with 1-year EGV bleeding. The 1-year mortality rate was 6.1%. The mortality was independently associated with EGV bleeding, AFP levels >400 ng/mL, type of portal vein tumor thrombus, and tumor progression. The overall objective response rate (ORR) was 32.0%, with TKIs plus anti-PD-1 achieving higher ORR than TKIs alone (39.5% vs. 27.7%, P=0.017) without increasing the bleeding risk or mortality (all P>0.05). Among 162 HBV-related HCC patients receiving long-term antiviral therapy, HBV DNA negative conversion (37.5% vs. 29.6%, P=0.739) and HBsAg decline (-15.1% vs. -14.3%, P=0.883) were comparable between TKIs plus anti-PD-1 and TKIs alone group.

In cirrhotic patients with advanced HCC, PVT, ascites and high-risk EGV were predictors of variceal bleeding, regardless of the tumor response. TKIs plus anti-PD-1 achieved higher ORR than TKIs alone without increasing EGV bleeding risk or mortality, supporting their use in selected patients with careful assessment of EGV bleeding risk.