Introduction: Atezolizumab, an immune checkpoint inhibitor, plus bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), is an approved first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Immune checkpoint inhibitors are more effective in patients with HCC when administered with anti-VEGF drugs; however, these drugs affect host immunity. Lenvatinib is an anti-VEGF agent used to treat HCC; therefore, this study evaluated the effect of treatment of HCC with lenvatinib on host immunity in patients with chronic liver disease (CLD). Methods: We studied adult Japanese patients with CLD and unresectable HCC treated with lenvatinib at our hospital. Lenvatinib was administered for 4 weeks (8 mg/day for bodyweight 60 kg). Blood samples were collected at baseline and at four weeks of treatment and examined for immune-related changes. Results: Forty-three patients were enrolled in this study. We found a significant increase T helper (Th) 1 cells following 4 weeks of lenvatinib treatment, although there were no significantly difference in Th2 cells and regulatory T cells. We also found a significant increase serum levels of TNF-alpha, soluble TNF-alpha receptor I, and endothelial growth factor following 4 weeks of lenvatinib treatment. Furthermore, an increase in Th1 cells and serum levels of TNF-alpha were found in patients with partial response. Conclusion: Lenvatinib might induce Th1 dominant host immunity in patients with CLD and unresectable HCC treatment who showed a partial response. These changes in host immunity may be a biomarker in HCC patients treated with lenvatinib.

The Author(s). Published by S. Karger AG, Basel