Early Biochemical Response in Advanced Hepatocellular Carcinoma Treated with Lenvatinib Combined with Adjunctive Hydrogen-Oxygen Nanobubble Therapy: A Case Report

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with limited survival rates in advanced stages. Systemic therapy using tyrosine kinase inhibitors such as lenvatinib is a standard treatment; however, therapeutic response may be suboptimal due to tumor hypoxia and an immunosuppressive tumor microenvironment. Hydrogen–oxygen (HHO) nanobubble therapy has emerged as a novel approach, although evidence remains limited. Case Presentation. A 55-year-old male was diagnosed with multifocal HCC following medical evaluation. Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels were 5,748.71 ng/mL and 14,433.16 mAU/mL, respectively. Abdominal CT demonstrated multiple hepatic lesions involving both lobes, with the largest measuring 15.7 × 10.35 × 13.93 cm. The patient received lenvatinib 10 mg once daily combined with 10 sessions of adjunctive intravenous HHO nanobubble therapy using escalating doses. After approximately one month, AFP decreased to 2,800 ng/mL (51.3%) and PIVKA-II to 2,102 mAU/mL (85.4%). Follow-up PET imaging demonstrated metabolically active hepatic lesions with necrotic components. Conclusions. This case describes a marked early biochemical response during combined treatment. However, the independent contribution of HHO nanobubble therapy cannot be determined from a single case without a comparator. Further controlled studies are required to assess safety and efficacy.