Hepatotoxicity associated with statins

Abstract

Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies. Most of investigations have focused on both these adverse effects and mechanisms of drug induced toxicity. The present review has attempted to compile almost all of the existing studies on the hepatotoxicity of statins but not rhabdomyolysis. The aim of our study is to provide an overview of the studies on the statin-associated hepatotoxicity and to discuss the published studies. The researchers are of the opinion that the research on this topic is incomplete but extremely necessary.

Protective effect of atorvastatin on oxidative stress in streptozotocin‐induced diabetic rats independently their lipid‐lowering effects

“…The exact mechanism by which statins cause ALT elevation is not well understood and liver injury is extremely rare. Animal experiments suggest that liver toxicity is not seen at therapeutic doses, but is seen in higher doses of statins . In a study, it was aimed to determine the effects of atorvastatin therapy on ALT and AST levels in patients with type 2 diabetes and chronic hepatitis C. On the basis of the results of the study, atorvastatin was suggested to improve liver profile by decreasing ALT and AST enzyme activities in both diseases .…”

Drugs-Inducing Hepatotoxicity

“…Statins may cause hepatotoxicity by causing mitochondrial dysfunction; after treatment with statins, it causes a huge increase in mitochondrial superoxide which leads to mitochondrial impairment 24 . In a study involving 185 patients treated with statins, at clinical presentation, 57.8 % presented with a hepatocellular pattern, 18.3 % a cholestatic, and 23.2 % a mixed one 25 .…”

The problem of safety of lipid-lowering therapy

“…Предрасполагающими факторами к развитию как повре ждения печени, так и миопатии являются высокоинтенсивная терапия статинами, комбинированная терапия дислипидемии, сопутствующая терапия другими лекарствами, которые метаболизируются с участием цитохрома Р450, предшествующая печеночная или почечная недостаточность, пожилой возраст [54,55].…”