Fig. 5: Pitavastatin blocks liver cancer development in chronic inflammation marked by elevated IL-33 expression.

a Representative macroscopic images of pitavastatin- and PBS-treated WT liver exposed to HBV+DEN at 8 months post-infection. Arrows point to liver tumors. b Tumor burden measured as % liver surface area of pitavastatin- (n = 10) and PBS-treated (n = 5) WT mice that received HBV+DEN at 8 months post-infection. Each dot represents a mouse. Experimental data were verified in two independent experiments. c Representative images of H&E stained pitavastatin- and PBS-treated WT liver exposed to HBV+DEN at 8 months post-infection. d Representative images of PCNA stained pitavastatin- and PBS-treated WT liver exposed to HBV+DEN at 8 months post-infection. e Quantification of PCNA⁺ hepatocytes in pitavastatin- (n = 4) and PBS-treated (n = 5) WT mice that received HBV+DEN at 8 months post-infection. PCNA⁺ cells per 100 hepatocytes were counted in five to eight randomly selected HPF images of each liver. Each dot represents an HPF image. f Serum IL-33 levels in HBV-positive hepatitis patients (n = 40), HBV-negative hepatitis patients (n = 40), and healthy controls (n = 24). Each dot represents a patient serum sample. g Representative images of IL-33 stained liver tissues from HBV-positive hepatitis patients, HBV-negative hepatitis patients, and healthy control. h A retrospective cohort analysis of hepatitis and HCC in hepatitis risk in matched cohorts of patients treated with pitavastatin (test) versus ezetimibe (control) (two-sided two-proportion z-test). i The correlation between IL33 expression levels and CD8⁺ T cell and Treg cell infiltration in HCC samples (n = 371) from TCGA. j The correlation between IL1RL1 expression levels and CD8⁺ T cell and Treg cell infiltration in HCC samples (n = 371) from TCGA. k Schematic diagram outlining the mechanism that links HBV infection to increased hepatitis and HCC risk (Created in BioRender. Demehri, S. (2025) https://BioRender.com/taqks8w). Graphs show mean + SD, (b, e) two-sided unpaired t-test, (f) one-way ANOVA with Tukey’s multiple comparison test, (i, j) two-sided t-test for Pearson correlation coefficient, scale bars: 1 cm (liver images) and 100 μm (histology). Source data are provided as a Source Data file.