Does elevated prothrombin time, alanine transaminase (ALT) and hyperammonemia warrant discontinuation of atorvastatin (atorvastatin) in a patient with cirrhosis?

From the Guidelines

Stopping atorvastatin is not necessarily warranted in a patient with cirrhosis solely based on elevated prothrombin time, ALT, and ammonia levels, as the current evidence suggests that a prolonged prothrombin time does not predict bleeding in patients with cirrhosis, and the decision to discontinue atorvastatin should be based on a comprehensive assessment of the patient's overall clinical condition and the potential risks and benefits of continuing the medication. The European Association for the Study of the Liver (EASL) clinical practice guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis, published in 2022 1, emphasize that basic haemostasis tests, such as prothrombin time, do not truly represent the haemostatic system operating in patients with liver disease. Key considerations in managing patients with cirrhosis include:

• The potential for bleeding complications, which are often unrelated to haemostatic failure but rather to portal hypertension or mechanical vessel injury
• The risk of thrombosis, which may require anticoagulant therapy for prevention or treatment
• The importance of a comprehensive assessment of the patient's overall clinical condition, including liver function tests, to guide management decisions In the context of atorvastatin use, it is essential to weigh the potential benefits of continuing the medication against the risks of hepatotoxicity and other adverse effects. While statins like atorvastatin are primarily metabolized by the liver, and cirrhosis can impair this metabolic function, the decision to discontinue atorvastatin should be based on a careful evaluation of the patient's individual circumstances, including the severity of liver disease, the presence of other comorbidities, and the potential alternatives for cardiovascular risk management. Close monitoring of liver function tests and consultation with hepatology and cardiology specialists may be necessary to develop a tailored approach for managing this complex patient.

From the FDA Drug Label

Hepatic Dysfunction:Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue atorvastatin calcium tablets ( 5.3). CONTRAINDICATIONS Acute liver failure or decompensated cirrhosis ( 4).

The patient has cirrhosis and is experiencing a high prothrombin time and ALT and ammonia, which may indicate hepatic dysfunction. Given the contraindication of atorvastatin in patients with decompensated cirrhosis, it is prudent to stop atorvastatin in this patient to avoid potential worsening of liver function 2.

From the Research

Patient Considerations

• A patient with cirrhosis experiencing a high prothrombin time and elevated ALT and ammonia levels may require careful consideration of their medication regimen, including the use of atorvastatin 3.
• The decision to stop atorvastatin in this patient should be based on a thorough evaluation of the potential benefits and risks of continuing the medication, as well as the patient's overall clinical condition.

Statin Use in Cirrhosis

• Current evidence suggests that statins, including atorvastatin, may have a positive impact on chronic liver disease and cirrhosis, with potential benefits including reduced mortality and decreased risk of hepatic decompensation 3, 4.
• However, the use of statins in patients with cirrhosis requires careful monitoring, as these patients may be at increased risk of adverse effects, such as elevated liver enzymes and worsening liver function.

Coagulation Abnormalities in Cirrhosis

• Patients with cirrhosis often experience coagulation abnormalities, including prolonged prothrombin time and activated partial thromboplastin time (aPTT) 5, 6.
• These abnormalities may be related to a prothrombotic rather than a prohaemorrhagic profile, and should be carefully evaluated in the context of the patient's overall clinical condition.

Management of Cirrhosis

• The management of cirrhosis typically involves a multifaceted approach, including directed counseling, laboratory testing, and ultrasound monitoring, as well as treatment of complications such as varices, ascites, and hepatic encephalopathy 7.
• The use of atorvastatin in patients with cirrhosis should be considered in the context of this overall management plan, and should be carefully monitored to minimize the risk of adverse effects.