Impact of neutrophil-to-lymphocyte ratio on survival outcomes among cirrhotic and non-cirrhotic patients with advanced hepatocellular carcinoma under atezolizumab–bevacizumab combination therapy

Spyridon Pantzios; Orestis Sidiropoulos; Antonia Syriha; Ioanna Stathopoulou; Sofia Rellou; Emmanouil Nychas; Georgia Barla; Nikolaos Ptohis; Ioannis Elefsiniotis

Authors Spyridon Pantzios, Orestis Sidiropoulos, Antonia Syriha, Ioanna Stathopoulou, Sofia Rellou, Emmanouil Nychas, Georgia Barla, Nikolaos Ptohis, Ioannis Elefsiniotis.

Abstract

Background The efficacy of atezolizumab–bevacizumab in patients with hepatocellular carcinoma (HCC) has not been studied separately in cirrhotic and non-cirrhotic patients. Our aim was to evaluate the efficacy of atezolizumab–bevacizumab in these patients, in relation to baseline values of the neutrophil-to-lymphocyte ratio (NLR).

Methods We divided 57 atezolizumab–bevacizumab-treated HCC patients according to baseline NLR (>3: NLR-H, ≤3: NLR-L) and studied overall survival (OS) and progression-free survival (PFS) in 4 groups: group A, non-cirrhotic/NLR-L; group B, non-cirrhotic/NLR-H; group C, cirrhotic/NLR-L; and group D, cirrhotic/NLR-H.

Results The 4 groups were comparable except for etiology, ALBI grade, macrovascular invasion, Barcelona Clinic Liver Cancer stage and prior therapy. Median OS and PFS were 30, 10, 12 and 5 months, and 14, 4, 8 and 2 months, for groups A, B, C, D, respectively (P<0.001). By Cox regression, cirrhotic/NLR-H patients showed significantly worse OS and PFS. Cirrhotic/NLR-L patients had better OS (12 vs. 5 months, P=0.002) and PFS (8 vs. 2 months, P=0.028) compared to cirrhotic/NLR-H. NLR was significantly correlated with OS (P=0.015). Non-cirrhotic/NLR-L patients had better OS (30 vs. 10 months, P=0.006) and PFS (15 vs. 4 months, P=0.01) compared to non-cirrhotic/NLR-H patients. Prior therapy was significantly correlated with better OS (30 vs. 8 months, P<0.001) and PFS (24 vs. 4 months, P<0.001) in non-cirrhotic patients.

Conclusions Cirrhotic/NLR-H HCC patients presented the worst survival. NLR is an independent risk factor for worse survival in cirrhotic patients. Prior therapy is the only factor significantly correlated with OS and PFS in non-cirrhotic patients.

Keywords Hepatocellular carcinoma, immunotherapy, cirrhosis, neutrophil-to-lymphocyte ratio

Ann Gastroenterol 2025; 38 (3): 319-327