Statin Use in Patients with Non-Alcoholic Steatohepatitis (NASH)

Introduction to Statin Therapy

The American Association for the Study of Liver Diseases and other major hepatology societies recommend that 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, 2, 3, 4.
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 2, 3.

Multiple guidelines from major hepatology societies consistently affirm that statins are not contraindicated in NAFLD/NASH patients, with a strength of evidence of 1 and quality of B 1, 2, 3, 4, 5, 6.
Over the past decade, one randomized controlled trial and several retrospective and prospective studies have established that statins are safe in patients with liver disease, and 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, 4.
Although elevated aminotransferases occur in up to 3% of patients receiving statins, serious liver injury from statins is rarely seen in clinical practice, with elevations typically being asymptomatic and recovering spontaneously 1, 2, 3, 4.

The critical clinical context is that cardiovascular disease, not liver disease, is the most common cause of death in NAFLD/NASH patients, and withholding statins due to unfounded concerns about hepatotoxicity actually increases mortality risk by leaving cardiovascular disease untreated 1, 2, 3, 4.
Patients with NAFLD should be risk-stratified for cardiovascular disease, and their cardiovascular risk factors should be managed accordingly, with statins recommended for dyslipidemia management (Strength 1, Quality B) 1, 4.
The treatment of dyslipidemia should be considered in the overall framework of cardiovascular risk reduction in patients with NAFLD, with post-hoc analysis of the GREACE cardiovascular outcomes study showing that statins significantly improved both liver biochemistries and cardiovascular outcomes in patients with elevated liver enzymes likely due to NAFLD 1, 4.

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, with a strength of evidence of 1 and quality of B 1, 4.
For dyslipidemia management, statins are recommended (Strength 1, Quality B), but for NASH treatment specifically, they are not recommended until further evidence is available 1, 4.

Several studies suggest statins may actually improve liver biochemistries and histology in NASH patients, though these studies were small and not rigorously designed, with a 2018 study in South Korea finding 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, 2, 4.

The only absolute contraindication for statins in the NAFLD/NASH spectrum is decompensated cirrhosis or acute liver failure, with statins able to be safely used in compensated cirrhosis (Child-Pugh class A) 2, 3, 7.
High-dose statins in decompensated cirrhosis confer increased risk of severe adverse events including liver toxicity and rhabdomyolysis, and hydrophilic statins (pravastatin, fluvastatin) are preferred in cirrhosis patients as they are not metabolized by CYP3A4 7.

Baseline liver function tests should be obtained before initiating statin therapy, with routine monitoring of liver enzymes not required unless clinically indicated 1, 2, 3, 4.
If aminotransferase elevations occur, they typically resolve spontaneously without discontinuation of therapy 1, 2, 3, 4.