Rationale for the use of statins in liver disease

Abstract

The evolution of chronic liver injuries from benign and manageable dysfunction to life threatening end-stage liver disease with severe complications renders chronic liver disease a global health burden. Because of the lack of effective medication, transplantation remains the only and final curative option for end-stage liver disease. Since the demand for organ transplants by far exceeds the supply, other treatment options are urgently required to prevent progression and improve end-stage liver disease. Statins are primarily cholesterol-lowering drugs used for primary or secondary prevention of cardiovascular diseases. In addition to the primary effect, statins act beneficially through different pleiotropic mechanisms on inflammation, fibrosis, endothelial function, thrombosis, and coagulation to improve chronic liver diseases. However, concerns remain about the efficacy and safety of statin treatment because of their potential hepatotoxic risks, and as of now, these risks impede broader use of statins in the treatment of chronic liver diseases. The aim of this review is to comprehensively describe the mechanisms by which statins improve prospects for different chronic liver diseases with special focus on the pathophysiological rationale and the clinical experience of statin use in the treatment of liver diseases.

Monocyte-Macrophages and T Cells in Atherosclerosis

“…Advanced atherosclerotic lesions contain cells with markers of senescence, including senescence-associated β-galactosidase, p16 Ink4a , p53, p21, and shortened telomeres (Minamino and Komuro, 2007). While indirect causation studies in mice originally suggested a pro-atherogenic role of senescent lesional cells, genetic association studies in mice and humans have called into question this conclusion (Schierwagen et al, 2017). However, a more definitive causation study has been recently conducted using Western diet-fed Ldlr -/- mice in which lesional macrophages, VSMCs, and endothelial cells expressing p16 Ink were genetically eliminated (Childs et al, 2016).…”

Treatment of Oesophageal Varices in Liver Cirrhosis

“…However, intrahepatic inflammatory stimuli and portal hypertension can persist [13,14]. Larger trials are required to investigate whether patients successfully treated for hepatitis B and hepatitis C infections and those with non-alcoholic steatohepatitis with persistent metabolic damage can profit from adjuvant medications, such as non-selective beta blockers (NSBB) [15], renin-angiotensin system inhibitors [16], statins [17] or rifaximin [18], alone or in combination [19,20]. All these drugs blunt inflammatory stimuli and reduce portal pressure.…”

Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects

“…In light of current literature, this fear seems unjustified since statin liver toxicity is a rare event [8••]. Moreover, recent data point to potentially beneficial and previously unexpected effects of statins in CLD and cirrhosis [9]. In this review, we summarize current evidence regarding the influence of statins in endothelial dysfunction in CLD, their ability to modulate hepatic fibrogenesis, and their vasoprotective effects in portal hypertension as well as on existing data about the impact of statins in cirrhosis development, progression, and complications.…”