S1383 Impact of Lipophilic vs Hydrophilic Statin on the Risk of Hepatocellular Carcinoma: A US Cohort Propensity-Matched Study

Introduction: The correlation between statin use and the risk of Hepatocellular Carcinoma (HCC) have been extensively investigated, revealing a potential protective effect. Our study aims to investigate the impact of lipophilic vs hydrophilic statin on the risk of HCC. Methods: Using TriNetX, which aggregates >90 million patients' medical records, we identified adults and categorized into 4 groups: HBV cirrhosis, HBV without cirrhosis, HCV cirrhosis, and NASH cirrhosis. Each group was further divided into 3: patients on lipophilic statins only (Atorvastatin, Simvastatin, Lovastatin or Fluvastatin), patients on hydrophilic statins only (Rosuvastatin or Pravastatin), and those not on statin therapy (control). We excluded patients with Alcoholic liver disease, hereditary hemochromatosis, PBC, PSC, AIH, Wilson's disease and A1AT deficiency. We conducted 1:1 propensity score matching for demographics, co-morbidities and medications like aspirin, metformin, NSAIDs and HBV or HCV antivirals, relevant to respective group. In NASH group, additional variables like Vitamin E, pioglitazone, obesity medications and bariatric surgery were included. We calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) to assess the risk of HCC. Results: Out of 26,145 patients with HBV cirrhosis, 1,429 (5.4%) were on lipophilic statin and 351 (1.3%) on hydrophilic statin. HBV without cirrhosis (n=116,296) had 14,071 (12.0%) on lipophilic statin and 3,346 (2.8%) on hydrophilic statin. HCV cirrhosis (n= 118,753) had 10,736 (9.0%) on lipophilic statin and 2,189 (1.8%) on hydrophilic statin. NASH cirrhosis (n= 138,296) had 21,236 (15.3%) on lipophilic statin and 6,403 (4.6%) on hydrophilic statin. Demographic and co-morbidity data were summarized in Table 1. After matching, lipophilic statin cohorts had a lower risk of HCC: HBV with cirrhosis (aOR 0.71 [0.57-0.88]), HBV without cirrhosis (aOR 0.49 [0.38-0.62]), HCV cirrhosis (aOR 0.70 [0.64-0.76]) and NASH cirrhosis (aOR 0.80 [0.73-0.87]). However, no significant difference in HCC risk in the hydrophilic statin cohorts: HBV cirrhosis (aOR 0.87 [0.58-1.32]), HBV without cirrhosis (aOR 0.68 [0.45-1.02]) and HCV cirrhosis (aOR 1.03 [0.87-1.22]). A protective effect was observed in the NASH cirrhosis cohort on hydrophilic statin (aOR 0.82 [0.72-0.94]), Figure 1. Conclusion: In our study, lipophilic statins showed a protective effect against hepatocellular carcinoma in HBV, HCV and NASH cirrhosis. Hydrophilic statins were only protective in NASH cirrhosis.Figure 1.: Adjusted odds ratio of hepatocellular carcinoma (HCC) on lipophilic vs hydrophilic statins across the major HCC etiologies. Table 1. - Demographics and characteristics of patients in cohort before matching Cohort Patients (% of cohort) Gender Race Condition Male Female White AA Hispanic DM Obesity HIV Smoking Alcohol HBV with cirrhosis Lipo statinN= 1,429 1,023 (71.6%) 405 (28.4%) 484 (33.9%) 300 (21%) 92 (6.4%) 626 (43.8%) 343 (24.0%) 68 (4.8%) 543 (37.9%) 91 (6.3%) Hydro statinN= 351 245 (69.8%) 106 (30.2%) 138 (39.3%) 58 (6.5%) 19 (5.4%) 141 (40.2%) 85 (24.2%) 38 (10.8%) 96 (27.3%) 20 (5.7%) HBV w/o cirrhosis Lipo statinN= 14,071 8,568 (61.1%) 5,454 (38.9%) 5,526 (39.4%) 3,390 (24.2%) 772 (5.5%) 4,785 (34.1%) 3,031 (21.5%) 1,050 (7.5%) 4,842 (34.4%) 989 (7.0%) Hydro statinN= 3,346 1,993 (59.6%) 1,349 (40.4%) 1,542 (45.6%) 724 (21.7%) 134 (4.0%) 969 (29.0%) 899 (26.8%) 448 (13.4%) 966 (28.8%) 120 (3.5%) HCV cirrhosis Lipo statinN= 10,736 7,508 (70.0%) 3,222 (30%) 5,119 (47.7%) 3,667 (34.3%) 949 (8.8%) 4,917 (45.8%) 3,679 (34.2%) 536 (5.0%) 7,304 (68.0%) 1,065 (9.9%) Hydro statinN= 2,189 1,481 (67.7%) 706 (32.3%) 1,158 (52.9%) 635 (29.0%) 192 (8.8%) 934 (42.7%) 549 (25.0%) 157 (7.2%) 1,150 (52.5%) 234 (10.6%) NASH cirrhosis Lipo statinN= 21,236 9,993 (47.1%) 11,229 (52.9%) 16,439 (77.5%) 1,295 (6.1%) 2,169 (10.2%) 13,453 (63.4%) 14,650 (68.9%) 140 (0.7%) 8,730 (41.1%) 1,337 (6.2%) Hydro statinN= 6,403 2,764 (43.2%) 3,636 (56.8%) 5,275 (82.4%) 270 (4.2%) 514 (8.0%) 3,814 (59.6%) 3,976 (62.0%) 60 (0.9%) 2,127 (33.2%) 229 (3.5%) AA: African American; HIV: human immunodeficiency virus; DM: diabetes mellitus; Lipo: lipophilic; Hydro: hydrophilic; NASH: non-alcoholic steatohepatitis.