Are Statins Contraindicated in Patients with NASH?
No, statins are not contraindicated in patients with NASH and should be actively used to treat dyslipidemia and reduce cardiovascular disease risk, which is the leading cause of death in this population. 1
Primary Recommendation
Statins can and should be used to treat dyslipidemia in patients with NAFLD and NASH, as there is no evidence that these patients are at increased risk for serious drug-induced liver injury from statins compared to those without liver disease. 1 The 2021 Korean Association for the Study of the Liver (KASL) guidelines explicitly state that statins can be used in NAFLD and NASH and are considered first-line treatment to lower LDL-C and prevent atherosclerotic cardiovascular disease. 1
Key Evidence Supporting Statin Safety
Multiple guidelines from major hepatology societies (American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, EASL, KASL) consistently affirm that statins are not contraindicated in NAFLD/NASH patients. 1
Over the past decade, one randomized controlled trial and several retrospective and prospective studies have established that: (a) statins are safe in patients with liver disease, and (b) patients with chronic liver disease including NAFLD and NASH are not at higher risk for serious liver injury from statins than those without liver disease. 1
Although elevated aminotransferases occur in up to 3% of patients receiving statins, serious liver injury from statins is rarely seen in clinical practice. 1 These elevations are typically asymptomatic, appear within 1 year of starting statins, and recover spontaneously. 1
Cardiovascular Risk Prioritization
The critical clinical context is that cardiovascular disease, not liver disease, is the most common cause of death in NAFLD/NASH patients. 1 Therefore, withholding statins due to unfounded concerns about hepatotoxicity actually increases mortality risk by leaving cardiovascular disease untreated. 1
Patients with NAFLD should be risk-stratified for cardiovascular disease, and their cardiovascular risk factors should be managed accordingly. 1
The treatment of dyslipidemia should be considered in the overall framework of cardiovascular risk reduction in patients with NAFLD. 1
Post-hoc analysis of the GREACE cardiovascular outcomes study showed that statins significantly improved both liver biochemistries and cardiovascular outcomes in patients with elevated liver enzymes likely due to NAFLD. 1
Important Distinction: Treatment vs. Specific Therapy
While statins are safe and indicated for cardiovascular risk reduction in NASH patients, statins should not be used specifically to treat NASH itself until randomized controlled trials with histological endpoints prove their efficacy. 1 This distinction is crucial:
- For dyslipidemia management: Statins are recommended (Strength 1, Quality B). 1
- For NASH treatment specifically: Not recommended until further evidence (Strength 1, Quality B). 1
Potential Hepatic Benefits (Secondary Finding)
Several studies suggest statins may actually improve liver biochemistries and histology in NASH patients, though these studies were small and not rigorously designed. 1, 2, 3 A 2018 study in South Korea found that statin treatment decreased not only the risk of NAFLD occurrence but also the development of fibrosis attributed to NAFLD, regardless of diabetes mellitus status. 1
Critical Contraindication: Decompensated Cirrhosis
The only absolute contraindication for statins in the NAFLD/NASH spectrum is decompensated cirrhosis or acute liver failure. 1, 4
- Statins can be safely used in compensated cirrhosis (Child-Pugh class A). 4
- High-dose statins in decompensated cirrhosis confer increased risk of severe adverse events including liver toxicity and rhabdomyolysis. 4
- Hydrophilic statins (pravastatin, fluvastatin) are preferred in cirrhosis patients as they are not metabolized by CYP3A4. 4
Common Clinical Pitfall to Avoid
The most dangerous pitfall is the continued reluctance to use statins in patients with suspected or established chronic liver disease, including NAFLD and NASH, based on unfounded fears of hepatotoxicity. 1 This reluctance directly contributes to increased cardiovascular mortality in a population already at high risk. 1
- A 2017 prospective study found that only 37% of NASH patients were receiving statins at enrollment despite their high cardiovascular risk. 5
- Statin users and nonusers had similar rates of aminotransferase elevations during follow-up, and all elevations returned to normal without active intervention. 5