Incidence of Statin Hepatotoxicity in Patients With Hepatitis C
Khorashadi S, Hasson NK, Cheung RC
Clin Gastroenterol Hepatol. 2006;4:902-907
Summary
Drug-related hepatotoxicity refers to an injury associated with impairment of liver function caused by exposure to a medication. Overall, drug-related hepatotoxicity is relatively uncommon, with an incidence ranging between 1/10,000 and 1/100,000.[1]
The statin class of medications — drugs used to treat hyperlipidemia — has been associated with a spectrum of liver injury, ranging from increased aminotransferase levels (0.2% to 2.7%) to rare reports of fatal hepatic failure. Usually, the hepatic enzyme elevation occurs early in the course of therapy — typically within the first 3-12 months of initiation of the medication. Most of these elevations are asymptomatic and associated with higher doses of drug.
This well-recognized association between statins and liver injury, albeit relatively rare, has led to recommendations by the pharmaceutical manufacturers as well as expert physician advisory panels for routine monitoring of liver enzyme levels in patients receiving statin medication and avoidance of statins in patients with active or chronic liver disease. However, there has been recent challenge to these recommendations, given data suggesting that at least in normal-risk patients, there was no difference in statin- and placebo-related hepatic enzyme elevation.[2] Indeed, the most recent clinical guidelines on the use of statins in patients with diabetes mellitus did not even recommend hepatic enzyme monitoring unless the baseline values were elevated.[3]
However, the clinical assessment of statin use in patients with chronic liver disease is less clear. The aim of this study by Khorashadi and colleagues was to assess the use of this class of medication in 3 cohorts: 166 patients with hepatitis C on statin therapy, 332 patients with hepatitis C not on statin therapy, and 332 patients on statin therapy but without hepatitis C.
The 3 study cohorts were appropriately matched for age, sex, and body mass index. For patients in the first cohort (hepatitis C, statin therapy), they found a higher incidence of mild-to-moderate elevations in aminotransferase levels compared with those not on statin therapy (22.9% vs 13.3%; P = .009), but a lower incidence of severe increases in liver biochemistry (1.2% vs 6.6%; P = .015). Overall, for patients on statin therapy there were no significant differences between the hepatitis C-positive or -negative cohorts, with regard to mild-to-moderate aminotransferase increases, severe increases in aminotransferases, or the need to discontinue statins as a result of hepatotoxicity. Therefore, statin therapy was not associated with a higher risk for severe hepatotoxicity.
Viewpoint
Drug-related hepatotoxicity cannot be viewed as a single disease. Many different mechanisms lead to hepatotoxicity, which may be predictable or unpredictable. In the case of statin-related injury, it seems to be an idiosyncratic reaction that is not predictable. Additionally, the evidence would support that no relation exists between the type of statin used and the occurrence of liver abnormalities. On the basis of these study findings, it also appears that in patients with hepatitis C and well-compensated liver disease, these agents can be used in a manner that is comparable to that in patients without chronic liver disease.
These findings are very much supported by a recent liver expert panel recommendation to the National Lipid Association.[4] This panel that (1) asymptomatic increases in aminotransferases represent a class effect associated with statin use and do not necessarily indicate liver dysfunction; (2) fulminant liver disease associated with statins is very rare; (3) routine monitoring of liver biochemistries is not warranted for patients receiving statin therapy; (4) well-compensated chronic liver disease and Child's A cirrhosis are not contraindications to statin use; and (5) statins can be used in patients with nonalcoholic fatty liver disease and steatohepatitis.
Appropriate use of statins in an expanded population of eligible patients should hopefully lead to improvement in the cardiovascular health of appropriately selected at-risk patients. Additionally, these agents may improve the hepatic disease — especially in those patients with hyperlipidemic-related nonalcoholic steatohepatitis.
Abstract
