The combination therapy of Durvalumab and Tremelimumab (Dur/Tre) has shown promise in treating advanced hepatocellular carcinoma (HCC). Nonetheless, reliable factors that predict therapeutic benefit and survival outcomes remain largely undefined. This study retrospectively assessed variables influencing clinical outcomes and treatment response in HCC patients receiving Dur/Tre. A total of 30 patients were retrospectively analyzed in this single-institution study to identify indicators of Dur/Tre effectiveness in advanced HCC. Clinical parameters associated with the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immune-mediated adverse events (imAEs) were evaluated. Particular emphasis was placed on the two-week change in circulating lymphocyte count from baseline (Δlymphocyte). Seventeen participants (56.7%) presented with BCLC stage C disease. The median observation period was 11 months. The ORR reached 30.0%, and the disease control rate (DCR) was 53.3%. Median PFS was 3.7 months, while OS had not yet been determined. A higher Δlymphocyte was independently correlated with improved objective response (hazard ratio [HR] 1.004; p = 0.016). Patients with Δlymphocyte ≥ +245/µL exhibited significantly longer PFS (HR 0.308; 95% CI 0.095-0.998; p = 0.049), with median PFS not reached compared to 1.96 months in those below +245/µL (log-rank p = 0.003). An early rise in lymphocyte count following Dur/Tre administration appears to be a strong indicator of favorable therapeutic response and prognosis in advanced HCC.
