Spontaneous regression of hepatocellular carcinoma with reduction in angiogenesis-related cytokines after treatment with sodium-glucose cotransporter 2 inhibitor in a cirrhotic patient with diabetes mellitus.

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event, and the pathogenesis remains unclear. Here, we present a case of spontaneous regression of HCC after treatment with sodium-glucose cotransporter 2 inhibitor (SGLT2i) in a cirrhotic patient with diabetes mellitus (DM). A 68-year-old man regularly visited our hospital for follow-up of HCC after treatment with transcatheter arterial chemoembolization, and management of liver cirrhosis and type 2 DM. Contrast-enhanced computed tomography scan showed a hypervascular tumor in the liver and elevated serum α-fetoprotein levels, indicating the recurrence of HCC. Simultaneously, the hemoglobin A1c value increased to 8.0%; therefore, he was treated with SGLT2i (canagliflozin 100 mg/day). Ten weeks after the initiation of SGLT2i treatment, he was admitted to our hospital for treatment of recurrent HCC. However, the hypervascular tumor had disappeared, and the elevated serum α-fetoprotein level had decreased to normal limits, indicating spontaneous regression of HCC. In addition, an angiogenesis array analysis revealed downregulated protein expression of matrix metalloproteinase-8, angiopoietin-1/2, platelet-derived growth factor-AA, and prolactin at 10 weeks after SGLT2i treatment. In this report, we first describe a case of spontaneous regression of HCC with reduction in angiogenesis-related cytokines after SGLT2i treatment.