Is a statin (HMG-CoA reductase inhibitor) okay for a patient with liver cirrhosis and elevated alanine transaminase (ALT)?

From the Guidelines

Statin therapy is not recommended for patients with decompensated cirrhosis, but it can be considered in patients with compensated cirrhosis and high ALT levels, with close monitoring and caution. The presence of cirrhosis with high ALT indicates ongoing liver inflammation and dysfunction, which may be worsened by statins' potential hepatotoxicity. According to the most recent and highest quality study, statin therapy is safe in adults with type 2 diabetes and compensated cirrhosis from nonalcoholic fatty liver disease and should be initiated or continued for cardiovascular risk reduction as clinically indicated 1. However, statin therapy should be used with caution and close monitoring in people with decompensated cirrhosis, given limited safety and efficacy data.

Some key points to consider when deciding to use statins in patients with liver cirrhosis and high ALT levels include:

• The patient's overall cardiovascular risk must be weighed against the potential for worsening liver function 1.
• The decision to use statins should be made in consultation with both hepatology and cardiology specialists.
• If cholesterol management is necessary, non-statin alternatives like ezetimibe might be considered instead.
• Any decision to use statins in liver disease should involve careful risk-benefit assessment, starting with the lowest effective dose, using less hepatotoxic statins (like pravastatin or rosuvastatin), and implementing frequent liver function monitoring 1.

It is essential to note that the administration of statins to patients with decompensated cirrhosis or acute liver failure should be avoided, as stated in the study published in the Clinical and Molecular Hepatology journal 1.

From the FDA Drug Label

Adverse reactions (regardless of causality) reported in ≥2% of pravastatin-treated patients in placebo-controlled trials of up to 8 months duration are identified in Table 1: ALT Increased 1.2 2.9 Gastrointestinal: abdominal pain, constipation, pancreatitis, hepatitis (including chronic active hepatitis), cholestatic jaundice, fatty change in liver, cirrhosis, fulminant hepatic necrosis, hepatoma, fatal and non-fatal hepatic failure.

The use of pravastatin in patients with liver cirrhosis and high ALT is not explicitly recommended or contraindicated in the provided drug label. However, given the potential for increased risk of liver damage, as evidenced by reports of hepatitis, cirrhosis, and fulminant hepatic necrosis, caution is advised.

• Key considerations:
  • Elevated ALT levels were observed in 2.9% of patients treated with pravastatin.
  • Postmarketing reports include cases of liver damage, including cirrhosis and fulminant hepatic necrosis.
• Clinical decision: In the absence of explicit guidance, it is prudent to exercise caution when considering the use of pravastatin in patients with liver cirrhosis and high ALT. 2

From the Research

Statin Use in Patients with Liver Cirrhosis and High ALT

• The use of statins in patients with liver cirrhosis and high ALT (alanine transaminase) levels has been a topic of discussion due to concerns about hepatotoxicity 3, 4, 5, 6, 7.
• However, recent studies have shown that statins can be safe and beneficial for patients with compensated cirrhosis, with potential benefits including reduced fibrosis, lower incidence of hepatocellular carcinoma, and improved survival 4, 6, 7.
• In patients with decompensated cirrhosis, statins should be prescribed with caution and at low doses, with frequent monitoring of creatinine phosphokinase levels to detect adverse events 3.
• The pharmacokinetics of statins can be altered in cirrhosis, creating challenges with their use in liver disease, but emerging data suggests that statin therapy appears to be safe and effective in patients with chronic liver disease and compensated cirrhosis 5.
• Statins have pleiotropic properties that are independent of their effect on cholesterol levels, including improving endothelial dysfunction, antioxidant, antifibrotic, anti-inflammatory, antiproliferative, antiangiogenic, proapoptotic, or immunomodulation properties, which may contribute to their beneficial effects in patients with liver cirrhosis 3, 4, 7.

Safety and Efficacy of Statins in Liver Cirrhosis

• Several retrospective studies have shown that statin use in chronic liver disease and cirrhosis is safe, and even associated with lower mortality and lower rate of hepatic decompensation 6.
• Moderate-quality evidence suggests that statins reduce the risk of hepatic decompensation, variceal bleeding, and mortality, especially among patients with compensated cirrhosis 7.
• Low-quality evidence supports the fact that statins reduce mortality in chronic liver disease 7.
• The current evidence from preclinical and clinical studies suggests that statins might have a positive impact on chronic liver disease, and hepatologists might soon rely on statins to achieve better outcomes in their patients with liver cirrhosis without significant additional costs 7.