When to initiate statin therapy for dyslipidemia in a patient with Metabolic Associated Steatohepatitis Liver Disease (MASLD) and elevated liver enzymes?

Statin Therapy for Dyslipidemia in MASLD Patients with Elevated Liver Enzymes

Statins can be safely used to treat dyslipidemia in patients with Metabolic Associated Steatotic Liver Disease (MASLD) despite elevated liver enzymes (SGOT/SGPT), as there is no evidence that these patients are at higher risk for serious drug-induced liver injury from statins than those without liver disease. 1

Safety of Statins in MASLD Patients

• Patients with MASLD are at increased risk for cardiovascular disease, which is their most common cause of death, making statin therapy an important intervention for risk reduction 1

• Despite common reluctance to use statins in patients with liver disease, multiple studies have established that statins are safe in these patients 1

• Elevated aminotransferases (SGOT/SGPT) are not uncommon in patients receiving statins, but serious liver injury from statins is rarely seen in clinical practice 1, 2

• The American Association for the Study of Liver Diseases (AASLD) guidelines explicitly state that there is no evidence that MASLD/NAFLD patients are at higher risk for serious statin-induced liver injury than those without liver disease 1

Monitoring Recommendations

• Before initiating statin therapy:

  • Obtain baseline liver function tests (LFTs) 3
  • Risk stratify patients for cardiovascular disease 1

• After initiating statin therapy:

  • Check liver function tests at 12 weeks after initiation 3
  • Monitor with any dose increase 3
  • Perform periodic monitoring during long-term maintenance therapy 3

• Interpretation of elevated enzymes:

  • Mild elevations of ALT or AST (<3 times the upper limit of normal) following statin therapy do not appear to lead to significant liver toxicity over time 3
  • If significant elevation occurs (>3 times ULN), consider dose reduction or temporary discontinuation with subsequent rechallenge 4

Additional Benefits of Statins in MASLD

• Several studies suggest that statins may actually improve liver biochemistries in patients with MASLD/NASH 1

• A post-hoc analysis of the GREACE cardiovascular outcomes study showed that statins significantly improved liver biochemistries and cardiovascular outcomes in patients with elevated liver enzymes likely due to NAFLD 1

• Statin treatment has been shown to be effective without worsening liver enzymes in patients with dyslipidemia and NAFLD 5

Important Caveats and Exceptions

• While statins are generally safe in MASLD with elevated enzymes, they should be avoided in:

  • Patients with advanced or end-stage parenchymal liver disease due to impaired metabolism 4
  • Patients with decompensated cirrhosis 1
  • Patients with acute liver disease of viral or alcoholic etiology (until normalization of cytolysis enzymes) 4

• Statins should not be used specifically to treat NASH itself, as there are no randomized controlled trials with histological endpoints proving their efficacy for this purpose 1

Algorithm for Statin Initiation in MASLD Patients with Elevated Enzymes

1. Assess cardiovascular risk and need for lipid-lowering therapy
2. Obtain baseline liver function tests
3. If liver enzymes are elevated but <3 times ULN:
   • Proceed with statin therapy at standard doses 1, 3
4. If liver enzymes are >3 times but <5 times ULN:
   • Consider starting with a lower dose and titrating up with close monitoring 4, 6
5. If liver enzymes are >5 times ULN:
   • Consider delaying statin therapy and investigating other causes of significant liver injury 4
   • Reassess once enzymes have improved
6. Monitor liver enzymes at 12 weeks after initiation and with any dose changes 3
7. For long-term therapy, periodic monitoring is recommended 3

In conclusion, dyslipidemia treatment should be considered within the overall framework of cardiovascular risk reduction in MASLD patients, and elevated liver enzymes alone should not prevent the use of statins when clinically indicated 1.