Statins and the Liver

Herrick, Cynthia; Bahrainy, Samira; Gill, Edward A.

doi:10.1016/j.ecl.2015.09.008

Cited by 10 publications

(8 citation statements)

References 45 publications

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“…Liver function tests have been found abnormally elevated (in a dose-dependent way) in 0.5–2% of statin-treated patients (Catapano et al, 2016 ). Although statin-induced elevations in transaminases, especially without parallel bilirubin elevations, are not associated with hepatotoxicity (Herrick et al, 2016 ), ALT and AST should be assessed, together with CK, at baseline (before the initiation of statin treatment). Then the levels of transaminases should only be reassessed after 8–12 weeks of treatment initiation or increase.…”

Section: Management Of Fhmentioning

confidence: 99%

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

et al. 2018

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Familial hypercholesterolemia (FH) is a common genetic cause of premature cardiovascular disease (CVD). The reported prevalence rates for both heterozygous FH (HeFH) and homozygous FH (HoFH) vary significantly, and this can be attributed, at least in part, to the variable diagnostic criteria used across different populations. Due to lack of consistent data, new global registries and unified guidelines are being formed, which are expected to advance current knowledge and improve the care of FH patients. This review presents a comprehensive overview of the pathophysiology, epidemiology, manifestations, and pharmacological treatment of FH, whilst summarizing the up-to-date relevant recommendations and guidelines. Ongoing research in FH seems promising and novel therapies are expected to be introduced in clinical practice in order to compliment or even substitute current treatment options, aiming for better lipid-lowering effects, fewer side effects, and improved clinical outcomes.

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Section: Management Of Fhmentioning

confidence: 99%

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

et al. 2018

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“…Liver adverse symptoms are unspecific and most patients remain asymptomatic [186]. A 3-fold increase in serum aspartate (AST) and alanine (ALT) aminotransferases activities have been described in less than 1% of patients receiving starting and intermediate statins doses [187][188][189][190][191] and this alteration may be accompanied by bilirubin elevation [192]. Two factors are frequently related to the hepatotoxic effects of statins: (a) the lipophilicity of these medicines and (b) alterations in cytochrome P450 system [193][194][195].…”

Section: Statins Toxicity To Livermentioning

confidence: 99%

Mitochondrial Oxidative Stress and Calcium-Dependent Permeability Transition are Key Players in the Mechanisms of Statins-Associated Side Effects

Busanello¹,

Marques²,

Lorza‐Gil³

et al. 2018

Mitochondrial Diseases

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Statins are cholesterol-lowering medicines utilized worldwide and are associated with reduced risk of cardiovascular mortality and events. However, 0.5-10% of patients suffer from adverse effects especially on skeletal muscle. Recently, new onset of diabetes has been reported in subjects on statin therapy. Pro-and anti-oxidant effects of statins have been reported, thus fostering a debate. Previously reported data provide evidence that statins induce alterations in intracellular calcium homeostasis and mitochondrial dysfunctions that can be counteracted by antioxidants (e.g., CoQ10, creatine, and L-carnitine). Therefore, we have proposed that statin-induced inhibition of mitochondrial respiration leads to oxidative stress that opens a calcium-dependent permeability transition pore, an event that may lead to cell death. In addition, mitochondrial oxidative stress caused by statin treatment may be a signal for cellular antioxidant system responses such as catalase upregulation, possibly explaining the alleged statins' antioxidant properties. Muscle mitochondrial dysfunction induced by statin treatment may be associated with the peripheral insulin resistance and may explain statins-induced new onset of diabetes. Together, the data presented in this review suggest that the statins' detrimental effects can be prevented by co-administration of antioxidants.

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“…Liver adverse symptoms are in general unspecific and most patients remain asymptomatic ( Tzefos and Olin, 2011 ). An increase in plasma aspartate (AST) and alanine (ALT) aminotransferases that may be accompanied by bilirubin elevation ( Herrick et al, 2016 ) was described in less than 1% of treated patients ( Aguirre et al, 2013 ). Two factors are frequently related to the hepatotoxic effects of statins: their lipophilicity and metabolism by the cytochrome P450 system ( Bhardwaj and Chalasani, 2007 ; Herrick et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…An increase in plasma aspartate (AST) and alanine (ALT) aminotransferases that may be accompanied by bilirubin elevation ( Herrick et al, 2016 ) was described in less than 1% of treated patients ( Aguirre et al, 2013 ). Two factors are frequently related to the hepatotoxic effects of statins: their lipophilicity and metabolism by the cytochrome P450 system ( Bhardwaj and Chalasani, 2007 ; Herrick et al, 2016 ). Accordingly, prospective studies showed an association between statins, especially lipophilic, with drug-induced liver injury (DILI).…”

Section: Introductionmentioning

confidence: 99%

Coenzyme Q10 or Creatine Counteract Pravastatin-Induced Liver Redox Changes in Hypercholesterolemic Mice

et al. 2018

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Statins are the preferred therapy to treat hypercholesterolemia. Their main action consists of inhibiting the cholesterol biosynthesis pathway. Previous studies report mitochondrial oxidative stress and membrane permeability transition (MPT) of several experimental models submitted to diverse statins treatments. The aim of the present study was to investigate whether chronic treatment with the hydrophilic pravastatin induces hepatotoxicity in LDL receptor knockout mice (LDLr-/-), a model for human familial hypercholesterolemia. We evaluated respiration and reactive oxygen production rates, cyclosporine-A sensitive mitochondrial calcium release, antioxidant enzyme activities in liver mitochondria or homogenates obtained from LDLr-/- mice treated with pravastatin for 3 months. We observed that pravastatin induced higher H2O2 production rate (40%), decreased activity of aconitase (28%), a superoxide-sensitive Krebs cycle enzyme, and increased susceptibility to Ca2+-induced MPT (32%) in liver mitochondria. Among several antioxidant enzymes, only glucose-6-phosphate dehydrogenase (G6PD) activity was increased (44%) in the liver of treated mice. Reduced glutathione content and reduced to oxidized glutathione ratio were increased in livers of pravastatin treated mice (1.5- and 2-fold, respectively). The presence of oxidized lipid species were detected in pravastatin group but protein oxidation markers (carbonyl and SH- groups) were not altered. Diet supplementation with the antioxidants CoQ10 or creatine fully reversed all pravastatin effects (reduced H2O2 generation, susceptibility to MPT and normalized aconitase and G6PD activity). Taken together, these results suggest that 1- pravastatin induces liver mitochondrial redox imbalance that may explain the hepatic side effects reported in a small number of patients, and 2- the co-treatment with safe antioxidants neutralize these side effects.

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Statins and the Liver

Cited by 10 publications

References 45 publications

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

Mitochondrial Oxidative Stress and Calcium-Dependent Permeability Transition are Key Players in the Mechanisms of Statins-Associated Side Effects

Coenzyme Q10 or Creatine Counteract Pravastatin-Induced Liver Redox Changes in Hypercholesterolemic Mice

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