Autoimmune-like Drug-induced Liver Injury Caused by Atorvastatin and Demonstration of the Safety Profile of Pravastatin: A Case Report and Literature Review

Abstract

Statin-induced liver injury is a well-recognized but rare phenomenon with hepatocellular, cholestatic, and mixed phenotypes. Most studies do not recommend regular monitoring of liver function tests (LFTs) after starting statins unless clinically indicated. We report a case of autoimmune-like atorvastatin-induced liver injury (aminotransferases > 5 times the upper limit of normal) that was detected on routine follow-up after three months in an asymptomatic patient. In addition to elevation in transaminases, the patient had weakly positive ANAs. Antismooth muscle antibody (ASMA) was positive in titers of 1:680. Screening for viral hepatitis A-E was negative. Other diagnostic investigations showed complete blood examination, including eosinophils, renal function tests, electrolytes, total protein, albumin, prothrombin time, activated partial thromboplastin time (aPTT), international normalized ratio (INR), serum ferritin, and iron saturation to be in the normal range. Ultrasound and computed tomography (CT) abdomen showed normal liver, gall bladder, biliary tree, and pancreas. The patient was managed as a case of autoimmune-like drug-induced liver injury (DILI) caused by atorvastatin and the medication was discontinued. LFTs returned to completely normal 30 days after the discontinuation of atorvastatin. Furthermore, switching to pravastatin for dyslipidemia management four months after stopping atorvastatin did not lead to hepatotoxicity, illustrating the safety profile of pravastatin in patients who are unable to tolerate atorvastatin.

Statin-induced Liver Injury Patterns: A Clinical Review

“…Given the use of maintenance steroid administration, it is not possible to determine whether the persistent aminotransferase normalization after statin cessation was immune-mediated DILI or AIH controlled by steroid therapy. In the case described by Khan et al ., 12 however, statin cessation led to aminotransferase normalization without any further intervention, which is consistent with immune-mediated DILI secondary to statin administration. Interestingly, in that case, the patient was rechallenged with pravastatin rather than the previously administered agent, atorvastatin, after aminotransferase normalization.…”

“… 11 A third patient with presumed AIH did not have an IAHG score, but was weakly ANA positive and had a positive anti-smooth muscle antibody (ASMA) titer (1:640). 12 The fourth patient initially was only positive for ANA (1:160) 2 weeks after discontinuation of rosuvastatin, but subsequently became ASMA-positive (1:80) on repeat evaluation 1 month after medication discontinuation. The patient experienced a complete normalization of aminotransferases and negative auto-antibody titers within 3 months of statin discontinuation without any further intervention.…”

“…Only one of the six case patients was female. 12 While there were no data to explain the difference in adverse reactions associated with statins in men and women, the disproportion was also noted in cholestatic DILI, and is discussed below. The finding raises the question of whether the risk of hepatotoxicity from statins is higher for men or if it more reflective of sex differences in statin prescription rates, being higher in men than in women, as has been previously identified in studies evaluating patients with conditions ranging from heart failure to HCV and HIV.…”

“…Using the Scopus, PubMed, and Google Scholar databases, we identified 531 manuscripts using the key words "statin" and "liver injury". Of the 15 manuscripts evaluated, there were nine case reports, [10][11][12][13][14][15][16][17][18] two of which discussed two patients. 11,17 The case reports are summarized in Table 1.…”

Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants

“…Some drug-induced liver injuries (DILI) with autoimmune features have been related to statin use [11]. In most cases, it is characterised by a transient elevation less than three times the normal upper limit of liver transaminases which subsides spontaneously with treatment discontinuation [12]; in some other cases, it is characterised by an acute form of hepatitis with a significant rise in transaminases leading to hepatic failure [13,14]. The risk of statin-related liver toxicity seems to be higher in the elderly, especially when it is accompanied by alcohol consumption and hepatitis [15].…”