Statins hepatotoxicity

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. 

Regimens intended to increase HDL levels should include either gemfibrozil or niacin, bearing in mind that statins combined with either of these drugs may result in a greater incidence of hepatotoxicity or myositis. 

Patients receiving statins should have a fasting panel 4 to 8 weeks after the initial dose or dose changes. Liver function tests should be obtained at baseline and periodically thereafter based on package insert information. Some experts believe that monitoring for hepatotoxicity and myopathy should be triggered by symptoms. 

Like all drugs, the statins have their adverse effects. Hepatotoxicity is occasionally seen and potentially serious muscle problems arise rarely. See your doctor. 

Some investigators have concluded that rare drug-induced reversible hepatotoxicity calls for close monitoring of liver enzymes in long-term treatment with statin-fibrate combinations (75). 

Patients must be monitored carefnlly for signs of myopathy and hepatotoxicity. Elevations of transaminases as a possible pharmacodynamic effect of lipid-lowering therapy should be considered. Liver function tests (LFTs) shonld be monitored to identify possible hepatotoxicity. Statins shonld be withheld or changed if elevations in transaminases are persistently more than three times ULN or are accompanied by other signs of liver disease that might be iatrogenic. In addition, the patient mnst be adequately monitored in order to identify ... 

There is controversy about whether or not drugs are more likely to cause hepatotoxicity in patients with liver disease. There is little evidence that statins worsen pre-existing liver disease and hepatocellular damage is very rare, particularly given the high number of prescriptions written worldwide for these drugs [37, 38]. The SPCs... 

Russo and Jacobson [38] conclude that there is little evidence to suggest that statins are more hepatotoxic in patients with pre-existing liver disease, and that they may be used for the usual indications with increased monitoring. However, they go on to advise that their use should be avoided in patients with acute liver disease until the acute episode has passed, presumably to avoid the risk of reduced clearance of the drug causing accumulation and an increased risk of toxicity, such as myopathy or rhabdomyolysis. 

Chalasani N (2005) Statins and hepatotoxicity focus on patients with fatty liver. Hepatology 41 690-695. 

Liver toxicity is seen most often with use of the sustained release formulations. Concurrent therapy with an HMG-CoA reductase inhibitor (e.g., a statin) also results in increased incidence of hepatotoxicity. 

It has been suggested that danazol (and the doxycycline) were possibly hepatotoxic, which led to decreased lovastatin metabolism, or that the danazol had a direct toxic effect on the muscles. Efanazol inhibits the cytochrome P450 isoenzyme CYP3A4 by which simvastatin and lovastatin are metabolised, which would result in raised statin levels, and therefore myopathy and rhabdomyolysis. This seems a more likely explanation for the effects seen. 

Adrenaline hypertension Anticoagulants, oral skin necrosis Antituberculosis drugs hepatotoxicity Pseudoephedrine toxic epidermal necrolysis SSRIs suicidal behavior Statins acute pancreatitis Ximelagatran liver damage... 

Liver Hepatotoxic events occasionally have been reported when ezetimibe is used in conjunction with a statin, as in the case of a 70-year-old woman who developed fulminant hepatic failure, necessitating liver transplantation 10 weeks after switching from simvastatin to simvastatin 4- ezetimibe[25]. A study with 32 subjects with nonalcoholic fatty liver disease pathology showed that ezetimibe improved hepatic fibrosis but increased hepatic long-chain fatty acids and HbA c [26]. 

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