Mid-term Combination Immunotherapy and its Effect on the Albumin–Bilirubin Score in Unresectable Hepatocellular Carcinoma

Background/Aim: Combination immunotherapy has emerged as a standard approach for systemic chemotherapy in unresectable hepatocellular carcinoma (HCC). Preservation of liver function is crucial for prolonging survival during treatment. However, real-world data on liver function dynamics during combination immunotherapy remain limited. This study evaluated the mid-term impact of combination immunotherapy on liver function using the albumin–bilirubin (ALBI) score.

Patients and Methods: Patients receiving durvalumab plus tremelimumab (Dur/Tre group, n=13) or atezolizumab plus bevacizumab (Atez/Bev group, n=35) for at least six months were retrospectively analyzed. ALBI scores were assessed at the start of treatment (SOT), three months, and six months of treatment.

Results: In the Dur/Tre group, median (interquartile range) ALBI scores at SOT, three months, and six months of treatment were −2.09 (−2.39 to −1.78), −2.42 (−2.63 to −2.16), and −2.48 (−2.69 to −2.40), respectively, demonstrating a significant improvement at six months compared with SOT (p=0.002). In contrast, the Atez/Bev group exhibited ALBI scores of −2.44 (−2.73 to −2.14), −2.44 (−2.56 to −2.02), and −2.36 (−2.57 to −1.78), indicating significant deterioration at six months of treatment (p=0.010). Among patients with proteinuria, ALBI scores remained unchanged (p=0.171), whereas those without proteinuria experienced significant worsening (p=0.030). In both univariate and multivariate analyses, Dur/Tre treatment [hazard ratio (HR)= 0.022; p=0.005] and objective response rate (HR=0.091; p=0.031) were independently associated with reduced ALBI score deterioration.

Conclusion: Dur/Tre therapy may better preserve liver function compared with Atez/Bev therapy in patients with unresectable HCC.