Statin use is associated with lower prevalence of advanced liver fibrosis in patients with type 2 diabetes


      • NAFLD and advanced fibrosis are highly prevalent in US adults with type 2 diabetes.
      • Statin use was associated with lower odds of advanced liver fibrosis and cirrhosis.
      • The association was stronger among women and younger patients.
      • Clinical trials on the effect of statin therapy on liver histology are justified.



      Patients with type 2 diabetes (T2D) are at increased risk of both cardiovascular disease (CVD) and advanced liver fibrosis related to non-alcoholic fatty liver disease (NAFLD). Statin use is known to reduce the incidence of CVD while evidence on an effect on NAFLD severity is limited.


      This is a cross-sectional study performed with data from the 2017–2018 cycle of the National Health and Nutrition Examination Survey (NHANES). The target population consisted in adult patients with T2D and reliable vibration-controlled transient elastography (VCTE) results. Presence of liver fibrosis and steatosis were assessed by the median values of liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), respectively. Patients with evidence of viral hepatitis and significant alcohol consumption were excluded. Logistic regression analysis was performed to evaluate the association between statin treatment and both steatosis and advanced (≥F3) liver fibrosis after adjustment for potential confounders.


      The study population consisted in 744 patients (age: 61 ± 1 years, BMI: 33.3 ± 0.5 kg/m2). NAFLD (CAP≥274 dB/m) was present in 74.9% of patients (95% CI 69.2–79.8) and 14.5% (95% CI 10.8–19.2) had advanced fibrosis (LSM ≥ 9.7 kPa). After adjustment for age, sex, race-ethnicity, BMI, albumin, total cholesterol, HbA1c, triglycerides and liver enzymes, statin use was associated with lower odds of advanced fibrosis (OR 0.35, 95% CI 0.13–0.90, p = 0.03). No significant interaction was found between statin use and steatosis.


      Given the absence of approved therapies for NAFLD-fibrosis, it would be reasonable to initiate specific randomized controlled trials with statins.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Metabolism - Clinical and Experimental
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Sarwar N.
        • Gao P.
        • Seshasai S.R.
        • Gobin R.
        • Kaptoge S.
        • Di Angelantonio E.
        • et al.
        Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.
        Lancet. 2010; 375: 2215-2222
        • de Marco R.
        • Locatelli F.
        • Zoppini G.
        • Verlato G.
        • Bonora E.
        • Muggeo M.
        Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study.
        Diabetes Care. 1999; 22: 756-761
        • Zoppini G.
        • Fedeli U.
        • Gennaro N.
        • Saugo M.
        • Targher G.
        • Bonora E.
        Mortality from chronic liver diseases in diabetes.
        Am J Gastroenterol. 2014; 109: 1020-1025
        • Younossi Z.M.
        • Golabi P.
        • de Avila L.
        • Paik J.M.
        • Srishord M.
        • Fukui N.
        • et al.
        The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis.
        J Hepatol. 2019; 71: 793-801
        • Ciardullo S.
        • Monti T.
        • Perseghin G.
        High prevalence of advanced liver fibrosis assessed by transient elastography among U.S. adults with type 2 diabetes.
        Diabetes Care. 2021; 44: 519-525
        • Collins R.
        • Reith C.
        • Emberson J.
        • Armitage J.
        • Baigent C.
        • Blackwell L.
        • et al.
        Interpretation of the evidence for the efficacy and safety of statin therapy.
        Lancet. 2016; 388: 2532-2561
      1. 10.
        Cardiovascular disease and risk management: standards of medical care in diabetes-2020.
        Diabetes Care. 2020; 43: S111-s34
        • Cosentino F.
        • Grant P.J.
        • Aboyans V.
        • Bailey C.J.
        • Ceriello A.
        • Delgado V.
        • et al.
        2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD).
        Eur Heart J. 2019; 41: 255-323
        • Huang Y.W.
        • Lee C.L.
        • Yang S.S.
        • Fu S.C.
        • Chen Y.Y.
        • Wang T.C.
        • et al.
        Statins reduce the risk of cirrhosis and its decompensation in chronic hepatitis B patients: a nationwide cohort study.
        Am J Gastroenterol. 2016; 111: 976-985
        • Yang Y.-H.
        • Chen W.-C.
        • Tsan Y.-T.
        • Chen M.-J.
        • Shih W.-T.
        • Tsai Y.-H.
        • et al.
        Statin use and the risk of cirrhosis development in patients with hepatitis C virus infection.
        J Hepatol. 2015; 63: 1111-1117
        • Pose E.
        • Trebicka J.
        • Mookerjee R.P.
        • Angeli P.
        • Gines P.
        Statins: old drugs as new therapy for liver diseases?.
        J Hepatol. 2019; 70: 194-202
        • Nascimbeni F.
        • Pellegrini E.
        • Lugari S.
        • Mondelli A.
        • Bursi S.
        • Onfiani G.
        • et al.
        Statins and nonalcoholic fatty liver disease in the era of precision medicine: more friends than foes.
        Atherosclerosis. 2019; 284: 66-74
        • Centers for disease control and prevention
        2017: National Health and Nutrition Examination Survey (NHANES).
        U.S. Department of health and human services, 2017 (Available from)
        • American Diabetes Association
        2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2020.
        Diabetes Care. 2020; 43: S14-S31
        • National Center for Health Statistics
        National Health and Nutrition Examination Survey 2017–2018 laboratory data.
        • Grundy S.M.
        • Brewer Jr., H.B.
        • Cleeman J.I.
        • Smith Jr., S.C.
        • Lenfant C.
        Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition.
        Arterioscler Thromb Vasc Biol. 2004; 24: e13-e18
        • Chalasani N.
        • Younossi Z.
        • Lavine J.E.
        • Charlton M.
        • Cusi K.
        • Rinella M.
        • et al.
        The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases.
        Hepatology. 2018; 67: 328-357
        • Castera L.
        • Friedrich-Rust M.
        • Loomba R.
        Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease.
        Gastroenterology. 2019; 156 (e4): 1264-1281
        • Eddowes P.J.
        • Sasso M.
        • Allison M.
        • Tsochatzis E.
        • Anstee Q.M.
        • Sheridan D.
        • et al.
        Accuracy of FibroScan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease.
        Gastroenterology. 2019; 156: 1717-1730
        • Dulai P.S.
        • Singh S.
        • Patel J.
        • Soni M.
        • Prokop L.J.
        • Younossi Z.
        • et al.
        Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis.
        Hepatology. 2017; 65: 1557-1565
        • Ridker P.M.
        • Danielson E.
        • Fonseca F.A.H.
        • Genest J.
        • Gotto A.M.
        • Kastelein J.J.P.
        • et al.
        Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
        N Engl J Med. 2008; 359: 2195-2207
        • Seif el-Din S.H.
        • El-Lakkany N.M.
        • El-Naggar A.A.
        • Hammam O.A.
        • Abd El-Latif H.A.
        • Ain-Shoka A.A.
        • et al.
        Effects of rosuvastatin and/or β-carotene on non-alcoholic fatty liver in rats.
        Res Pharm Sci. 2015; 10: 275-287
        • Kabel A.M.
        • Abd Elmaaboud M.A.
        • Albarraq A.A.
        Ameliorative potential of omega 3 fatty acids and HMG-CoA reductase inhibitors on experimentally-induced non-alcoholic steatohepatitis.
        Prostaglandins Leukot Essent Fat Acids. 2015; 96: 1-9
        • Athyros V.G.
        • Alexandrides T.K.
        • Bilianou H.
        • Cholongitas E.
        • Doumas M.
        • Ganotakis E.S.
        • et al.
        The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement.
        Metabolism. 2017; 71: 17-32
        • Nascimbeni F.
        • Aron-Wisnewsky J.
        • Pais R.
        • Tordjman J.
        • Poitou C.
        • Charlotte F.
        • et al.
        Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease.
        BMJ Open Gastroenterol. 2016; 3
        • Dongiovanni P.
        • Petta S.
        • Mannisto V.
        • Mancina R.M.
        • Pipitone R.
        • Karja V.
        • et al.
        Statin use and non-alcoholic steatohepatitis in at risk individuals.
        J Hepatol. 2015; 63: 705-712
        • Kargiotis K.
        • Athyros V.G.
        • Giouleme O.
        • Katsiki N.
        • Katsiki E.
        • Anagnostis P.
        • et al.
        Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome.
        World J Gastroenterol. 2015; 21: 7860-7868
        • Kamal S.
        • Khan M.A.
        • Seth A.
        • Cholankeril G.
        • Gupta D.
        • Singh U.
        • et al.
        Beneficial effects of statins on the rates of hepatic fibrosis, hepatic decompensation, and mortality in chronic liver disease: a systematic review and meta-analysis.
        Am J Gastroenterol. 2017; 112: 1495-1505
        • Lee J.I.
        • Lee H.W.
        • Lee K.S.
        • Lee H.S.
        • Park J.-Y.
        Effects of statin use on the development and progression of nonalcoholic fatty liver disease: a nationwide nested case-control study.
        Official journal of the American College of Gastroenterology| ACG. 2021; 116: 116-124
        • de Keyser C.E.
        • Koehler E.M.
        • Schouten J.N.
        • Visser L.E.
        • Hofman A.
        • Janssen H.L.
        • et al.
        Statin therapy is associated with a reduced risk of non-alcoholic fatty liver in overweight individuals.
        Dig Liver Dis. 2014; 46: 720-725
        • Singh A.
        • Garg R.
        • Lopez R.
        • Alkhouri N.
        Diabetes liver fibrosis score to detect advanced fibrosis in diabetics with non-alcoholic fatty liver disease.
        Clin Gastroenterol Hepatol. 2021;
        • Rockey D.C.
        • Caldwell S.H.
        • Goodman Z.D.
        • Nelson R.C.
        • Smith A.D.
        Liver biopsy.
        Hepatology. 2009; 49: 1017-1044