Statin-induced Liver Injury Patterns: A Clinical Review

Abstract

Since their introduction in 1987, hydroxymethyl glutaryl coenzyme A reductase (HMG-CoA) inhibitors, more commonly known as statins, have become some of the most widely prescribed medications in the world. Though generally considered to be safe and well tolerated, statins have been associated with several side effects including mild liver dysfunction manifested by increases in aminotransferases. Rarely, statins have been noted to induce more serious hepatic injury, including liver injury with autoimmune features. Current literature supports statin induced liver injury presenting in either hepatocellular or cholestatic patterns, though with the former being the prevailing pattern of injury. Fortunately, severe liver injury is uncommon with statin use and is generally reversible without any intervention other than offending statin cessation. When evaluating cases of suspected statin-induced liver injury, a complete medical history, laboratory tests including a complete metabolic panel, autoimmune markers, and viral panel, as well as hepatic imaging, are crucial for a complete causality analysis with validated tools such as Roussel Uclaf Causality Assessment Method. The aim of this review is to review the current evidence for statin-induced liver injury and cholestasis.

Statins in Chronic Liver Disease: Review of the Literature and Future Role

“…[23][24][25] Statin-related DILI can manifest in both hepatocellular and cholestatic patterns and autoimmune liver injury. 26 Hepatotoxicity mechanisms are poorly understood but may occur by mitochondrial damage caused by an increased reactive oxygen species (ROS) and/or inhibition of the electron transport chain. 26,27 While CTP A patients benefit from the least increase in area under the curve and maximum plasma concentration of statin, these levels can increase by more than 10-fold in CTP B patients.…”

Understanding liver function tests: part 2

“…A rechallenge (when the acute injury has resolved) with atorvastatin is not recommended, and simvastatin should also be avoided as most reports of DILI are associated with atorvastatin and simvastatin. 10 A 2022 clinical review on statin-induced liver injury recommends that initiation of a different statin is an option for both hepatic and cholestatic liver injury, 11 but any re-initiation should also be supported with careful and frequent monitoring of LFTs, especially during the first six months of treatment. 12 Suitable alternative statins include pravastatin, which has a reported rate of hepatic injury with symptoms or jaundice of 1 per 100,000 users or less.…”

Risk Factors Analysis of Severe Liver Injury Induced by Statins

“…The latency of SILI patients was 8 (7,12) days, the weight was 67.00 (60.00, 72.00) kg, the ALT was 130.00 (93.00, 211.00) U/L, the AST was 90.00 (66.00, 143.00) U/L, and the TB was 47.00 (29.20, 64.10) umol/L.…”

“…The potential biological mechanism may be related to the different toxicity of drugs, the degree of influence by metabolic enzymes and the dosage of drugs [11]. Water-soluble statins and statins less metabolized through the liver have little effect on the liver [12]. Rosuvastatin is a water-soluble statin, and a small amount of it is metabolized by liver CYP2C9, so the incidence of SILI is low.…”