Statin Monotherapy Not Inferior to Aspirin or Combined Aspirin and Statins Reducing the Incidences of Cirrhosis, HCC, and Mortality in MAFLD/MASH Patients: A Population Cohort Study

Chern-Horng Lee,1 Yu-Han Huang,2 Tzu-Ju Hsu,3 Tzung-Hai Yen,4 Sen-Yung Hsieh5,6 1Department of Geriatric Medicine and General Internal Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, 333, Taiwan; 2Department of Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, College of Medicine, China Medical University, Taichung, Taiwan; 3Management Office for Health Data (DryLab), Clinical Trial Research Center (CTC), China Medical University Hospital, Taichung, Taiwan; 4Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuanm, 333, Taiwan; 5Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, 333, Taiwan; 6College of Medicine, Chang Gung University, Taoyuan, 333, TaiwanCorrespondence: Sen-Yung Hsieh, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan, Tel +886-975368031, Fax +886-33272324, Email [email protected]; [email protected]: Metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatohepatitis (MASH) pose significant risks for liver cirrhosis and hepatocellular carcinoma (HCC). Daily aspirin and statins could reduce HCC in patients with MAFLD/MASH. We aimed to clarify whether combined aspirin and statins exert a synergistic effect on prevention of cirrhosis and HCC in patients with MAFLD/MASH.Patients and Methods: Patients and their clinical data were collected from the National Health Insurance Research Database (NHIRD), encompassing about 20 million population. A total of 735,574 MAFLD/MASH patients between January 1, 2009, and December 31, 2020 were identified. After applying exclusion criteria, 662,004 cases were enrolled, with a follow-up period of 3 years. Propensity score matching was employed for comparative analysis.Results: Our findings indicate that combined statin and aspirin use significantly reduced the incidence of liver cirrhosis (p < 0.001) compared to statin or aspirin alone, or non-use of both drugs. However, the combined therapy did not confer additional benefits in reducing mortality rates and HCC. Furthermore, statin monotherapy exhibited a more pronounced effect in reducing mortality and HCC compared to aspirin alone or combined therapy.Conclusion: Our study underscores that statin monotherapy was not inferior to aspirin or aspirin-statin combined therapies in terms of chemoprevention of cirrhosis, HCC, and overall mortality in MAFLD/MASH patients.Keywords: MAFLD, MASH, statin, aspirin, cirrhosis, hepatocellular carcinoma