Clinically significant portal hypertension rather than ALBI grade predicts prognosis in advanced hepatocellular carcinoma.
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INTRODUCTION AND OBJECTIVES: Clinical trials in advanced hepatocellular carcinoma (HCC) typically include patients with preserved liver function (Child-Pugh A), without adequately considering cirrhosis or clinically significant portal hypertension (CSPH). We aimed to compare prognostic models in Child-Pugh A patients. PATIENTS AND METHODS: This prospective multicenter cohort study included patients with advanced HCC treated with systemic therapy (2018-2024) in Latin America. Survival was analyzed using Kaplan-Meier and Cox proportional multivariate hazards models and competing risk analysis for cause-specific mortality and hepatic decompensation. RESULTS: From 306 patients receiving systemic therapy, 79.1% (n=242) were Child-Pugh A (sorafenib 60.3%, atezolizumab plus bevacizumab 30.6%, and lenvatinib 8.7%). Among these, cirrhosis was observed in 78.9%, and CSPH in 51.6%. No survival differences were observed between ALBI 1 vs 2-3 grades (HR 1.08; P=0.685), or Child-Pugh A5 vs A6. In multivariable analysis, atezolizumab plus bevacizumab was independently associated with improved OS (HR 0.64, 95% CI 0.42-0.99), adjusted for AFP ≥400 ng/mL and CSPH. Other models, including the ALBI score as a continuous or categorical variable, showed no significant independent association with mortality, nor did they improve model performance. In a competing risk regression analysis accounting for death due to tumor progression as a competing event, CSPH was the only independent variable associated with hepatic decompensation, sHR 1.98 (95% CI 1.01-3.89). CONCLUSIONS: Accurate reporting of cirrhosis and CSPH is essential, even for Child-Pugh A patients, as both are independent prognostic factors that should be considered for therapeutic decision-making in advanced HCC.