Statins cirrhosis

In cirrhosis the first-pass effect is significantly reduced, and this may lead to greatly elevated concentrations of drug reaching the systemic circulation. Most statins and fibrates have a high first-pass extraction. 

Nonetheless, statins can probably be used safely in liver disease where there is no synthetic dysfunction, and even where there is a degree of liver dysfunction, provided the appropriate agent is used at an appropriate dose. This is in direct contradiction to the SPC for each product and must be borne in mind by clinicians when considering statin therapy. Starting doses shonld be low (e.g. pravastatin 10 mg or simvastatin 10 mg at night) and the dose mnst be increased cautiously. Simvastatin may be used in patients with no synthetic dysfunction, although if cirrhosis and synthetic dysfimction snbsequently develop, pravastatin would be a more suitable choice. 

The first-pass effect may be reduced in cirrhosis and portal hypertension owing to reduced blood flow through the liver. Additionally, in cirrhosis and acute hepatitis the number of functional hepatocytes may be reduced. Drugs with a high first-pass extraction ratio and a narrow therapeutic window, such as the statins, are more likely to be toxic in patients with liver dysfunction [20]. In liver disease, an increase in the percentage of drug reaching the systemic circulation is an important factor in statin toxicity. 

Fibric adds Clofibrate Gemfibrozil Fenofibrate Increase VLtt-catabolism PPAR , agonist LDLi 5-20% HDL t 10%-20% TG i 20%-S0% Gl upset, dyspepsia, gallstones, T LFTs, myopathy Nonmetabolism Warfarin Cyclosporine Statins Liver or severe renal disease primary biliary cirrhosis preexisting gallbladder disease... 

Cirrhosis of the liver is one of the most well-known adverse effects of chronic alcohol abuse. The cholesterol-lowering, life-prolonging statin drugs must be monitored routinely for hepatotoxicity and rhabdomyolosis. A Google search on the terms statins, hepatotoxicity, and review produced over 22,000 hits indicating this is a very active field of interest. 

The situation with respect to the uncommon liver disorder of bihary cirrhosis is uncertain. Hypercholesterolemia, mainly as a rise in LDL cholesterol, is a common characteristic, although increased cardiovascular risk is not proportionate to the dyslipidemia. In 603 patients with primary biliary cirrhosis who took a statin for a mean duration of 41 months hepatic enzymes actually fell [30 ]. 

Rajab MU, Kaplan MM. Statins in primary biliary cirrhosis are they safe Dig Dis Sci 2010 55 2086-8. 

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