From the Guidelines
Statin-induced hepatitis is a rare but serious side effect of statin medications that requires immediate discontinuation of the statin and close monitoring. The relationship between statin use and the development of hepatitis is well-tolerated by most persons, with elevated hepatic transaminases generally occurring in 0.5% to 2.0% of cases and are dose-dependent 1.
Key Considerations
- Statins can rarely cause idiosyncratic liver injury through unclear mechanisms, possibly related to metabolic stress or immune-mediated reactions 1.
- Prompt discontinuation is crucial to prevent progression of liver damage.
- Most cases resolve with cessation of the medication, but continued monitoring is necessary to ensure recovery and rule out other causes of hepatitis.
- LFT elevations more than 3 times the upper limit of normal are concerning for hepatotoxicity 1.
- Recovery usually occurs within weeks to months after stopping the statin.
- Alternative lipid-lowering therapies (e.g., ezetimibe, PCSK9 inhibitors) may be considered if needed.
Management Strategy
If statin-induced hepatitis is suspected:
- Stop the statin medication immediately.
- Perform liver function tests (LFTs) to assess the extent of liver damage.
- Monitor LFTs regularly until they normalize, typically every 2-4 weeks.
- Avoid restarting the same statin or other statins without careful consideration and consultation with a hepatologist. According to the most recent guideline, statins can be used in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and they are considered as a first-line treatment to lower LDL-C and prevent atherosclerotic cardiovascular disease 1.
From the FDA Drug Label
Increases in serum transaminases have been reported with use of pravastatin [see Adverse Reactions (6. 1)]. In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. Persistent increases to more than three times the ULN in serum transaminases have occurred in approximately 1% of patients receiving either pravastatin or placebo in clinical studies Marked persistent increases of hepatic transaminases have also occurred with pravastatin. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pravastatin. Increases in serum transaminases have been reported with use of rosuvastatin [see Adverse Reactions (6. 1)] . In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. In a pooled analysis of placebo-controlled trials, increases in serum transaminases to more than three times the ULN occurred in 1.1% of patients taking rosuvastatin versus 0. 5% of patients treated with placebo.
Statin use and hepatitis: The use of statins, including pravastatin and rosuvastatin, has been associated with increases in serum transaminases, which can be a sign of hepatitis. However, these changes are often transient and resolve with continued therapy or after a brief interruption.
- Key points:
- Increases in serum transaminases have been reported with statin use
- These changes are often transient and resolve with continued therapy or after a brief interruption
- Rare cases of fatal and non-fatal hepatic failure have been reported with statin use, including pravastatin and rosuvastatin
- Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury 2 3
- Clinical decision: When prescribing statins, including pravastatin and rosuvastatin, consider liver enzyme testing before initiation and when clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue the statin.
From the Research
Statin Use and Hepatitis Development
- Statins are generally well tolerated and have a good safety profile, with a similar proportion of patients developing abnormal liver tests as those treated with placebo 4, 5, 6.
- However, idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction, and clinical trials are underpowered to detect uncommon side effects 4, 5, 6.
- Statin hepatotoxicity has been reported, with a summary of 40 cases and a series of 76 cases suspected statin-induced liver injury published 4.
- The risk of jaundice caused by statin drugs is estimated to be one in 17,434 users per year, which is higher than previously estimated 7.
- Clinically apparent drug-induced liver injury due to statins is rare, but can present with variable patterns of injury, including hepatocellular and cholestatic hepatitis, and autoimmune features in some cases 8.
Patterns of Liver Injury
- Idiosyncratic liver injury due to statins has been reported to occur in 1.9%-5.5% of patients in prospective series of drug-induced liver injury 5.
- Atorvastatin and simvastatin have been associated with positive rechallenge and some case reports have described liver injury following dose escalation of the implicated statin 5.
- Drug-induced liver injury from statins can present with an acute hepatocellular liver injury pattern, although mixed or cholestatic injury patterns have also been reported 6, 8.
Outcomes and Risks
- Mortality from liver injury and/or liver transplantation has been documented in a few patients with statin-induced liver injury, although the vast majority of patients with liver injury have recovered after cessation of therapy 4, 5, 8.
- Statin therapy appears to be safe in the treatment of non-alcoholic fatty liver disease, in compensated patients with chronic hepatitis B or C, and may have an inhibitory effect on hepatitis C virus replication in vitro 4.
- Statin therapy seems to be related to a reduced risk for hepatocellular carcinoma in patients with chronic liver disease, but randomized data are lacking 4.