Liver Function Test Abnormalities and Pruritus in a Patient Treated with Atorvastatin: Case Report and Review of the Literature

Abstract

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) are associated with elevated transaminase levels in 1-3% of patients. Therapy with these drugs requires monitoring of alanine aminotransferase (ALT) levels because animal studies and premarketing clinical trials showed signs of hepatotoxicity that were primarily minor elevations of ALT. Nevertheless, postmarketing experience suggests that hepatotoxicity is rare, and that elevated ALT levels are reversible with continued therapy and probably are related to cholesterol lowering. Based on the low occurrence of ALT elevations and the lack of clinical evidence of hepatotoxicity, some clinicians are calling for a change in the current practice of monitoring liver function tests. We report, however, the case of a 71-year-old woman who was receiving atorvastatin and experienced elevated transaminase levels on two occasions, and developed pruritus on rechallenge with the drug. Thus, clinicians should be aware of asymptomatic elevations in liver function tests in patients receiving atorvastatin who do not have known risk factors for liver damage.

Atorvastatin-induced acute elevation of hepatic enzymes and the absence of cross-toxicity of pravastatin

“…These patients had average ages > 60 years with a female/male ratio of 2: 1, and 6 out of them had a marked hyperbilirubinemia (> 100 μmol/l). In other 2 cases, one 72-year-old male from Spain and a 71 years old female from USA in the reports of de Castro and Gershovich [10, 11], atorvastatin-induced cholestatic injury was proven by rapid improvement with cessation of the drug and recurrence with re-initiation of atorvastatin. Besides advanced age, hepatic injury appeared associated with systemic diseases and medications.…”

Adverse Effects of Statins - Mechanisms and Consequences

“…Animal studies have demonstrated that statins induce hyperplasia of bile canaliculi, impair bile flow, induce gallstone formation, and elevate serum bile acids and conjugated bilirubin [119]. The incidence of cholestasis, associated with pruritus, jaundice, increased activity of alkaline phosphatase and glutamyltranspeptidase, in statin-treated individuals is about 1/150,000 patient-years [120]. Acute liver failure (ALF) is a life-threatening complication which develops with the incidence of about 1/100,000 patient-years [121].…”

Lipid-Lowering Agents That Cause Drug-Induced Hepatotoxicity

“…Atorvastatin-related hepatotoxicity has been associated with a mixed pattern of liver injury typically occurring several months after the initiation of the medication. [19][20][21][22] There has also been a recent case report of underlying autoimmune hepatitis apparently revealed by atorvastatin. 23 After broad experience with this medication (hundreds of thousands of treated patients), significantly increased transaminase levels greater than 3 times the upper limit of normal were only seen in 0.7% of cases.…”