Volume 176 - Issue 11
Cholestasis associated with the use of pravastatin sodium
Authors: Robert G Batey and Michelle Harvey
Med J Aust 2002; 176 (11): 561. || doi: 10.5694/j.1326-5377.2002.tb04559.x
Published online: 3 June 2002
Published online: 3 June 2002
To the Editor: Hydroxymethylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (or statins) are widely prescribed, and any class-specific side effect has the potential to affect many thousands of patients. The statin drugs are well recognised as a cause of mild and usually transient hepatitis.1-3 Cholestatic liver injury has been reported with simvastatin4 and atorvastatin,5 but pravastatin has only been implicated as a cause in one report.6
We report a 64-year-old woman who was twice treated with pravastatin sodium and who, on both occasions, demonstrated cholestasis, which, at its peak, was associated with minimal hepatocellular injury.
Our patient presented to the liver clinic of the John Hunter Hospital in 2001 for investigation of abnormal liver function test results. She was taking diltiazem, aspirin, irbesartan plus hydrochlorothiazide, and pravastatin as therapy for hypertension and hyperlipidaemia. She consumed less than 10 g alcohol per week. Liver function tests showed a predominant elevation of alkaline phosphatase and γ-glutamyltransferase, with a minimal rise in alanine and aspartate aminotransferases, a picture consistent with cholestasis rather than hepatocellular disease (see Box). She had started taking pravastatin in the three months preceding her referral, and commented that when she was taking the drug in the previous year she had also had abnormal liver test results. Her liver function test results in 1998 were normal.
Two ultrasound examinations of the liver, performed after five months of taking pravastatin in the first period and two months after beginning her second period of therapy, showed normal liver size and echogenicity, and no sign of obstructive liver disease. Tissue antibodies, viral studies for hepatitis viruses, α1-antitrypsin and iron studies were all either normal or negative. Renal function was normal throughout. She had no biochemical evidence of impaired hepatocellular function, and for this reason liver biopsy and endoscopic retrograde cholangiopancreatography were not undertaken.
In view of the association the patient made between previously ceasing therapy with the drug (because she felt unwell) and improving liver function, therapy (which was recommenced by the cardiologist for hyperlipidaemia) was again suspended and within two months liver test results improved markedly.
We believe that in the absence of other markers of liver disease and with improvement of liver function on both occasions that therapy with pravastatin was suspended, it is likely that this patient has twice developed a cholestatic response to pravastatin.
References
- Boccuzzi SJ, Bocanegra TS, Walker JF, et al. Long-term safety and efficacy profile of simvastatin. Am J Cardiol 1991; 68: 1127-1131.
- Nakad A, Bataille L, Hamoir V, et al. Atorvastatin-induced acute hepatitis with absence of cross-toxicity with simvastatin. Lancet 1999; 353: 1763-1764. pgfId-1187334
- Walker JF. Worldwide experience with simvastatin/lovastatin. Eur Heart J 1992; 13: Suppl B: 21-22. i1150096
- Ballare M, Campanini M, Catania E, et al. Acute cholestatic hepatitis during simvastatin administration. Recenti Prog Med 1991; 82: 233-235. i1150098
- Jiminez-Alonso J, Osorio JM, Gutierrez-Cabello F, et al. Atorvastatin-induced cholestatic hepatitis in a young woman with systemic lupus erythematosus. Grupo Lupus Virgen de las Nieves. Arch Intern Med 1999; 159: 1811-1812. i1150100
- Hartleb M, Rymarczyk G, Januszewski K. Acute cholestatic hepatitis associated with pravastatin. Am J Gastroenterol 1999; 94: 1388-1390. i1150102
Early-Onset Colorectal Cancer With Liver-Only Metastases: A Retrospective Cohort Study Integrating Prospectively Collected Real-World Clinical and Molecular Data From an Australian National Database (2009–2024) to Guide Treatment Planning
Savio G. Barreto, Christos S. Karapetis, Shahid Ullah, Matthew Burge, Susan Caird, Angus Campbell, Azim Jalali, Ross Jennens, Muhammad A. Khattak, Belinda Lee, Stephanie H. Lim, Shehara Mendis, Louise Nott, Timothy J. Price, Jeremy D. Shapiro, Jeanne Tie, Javier Torres, Colin Williams, Rachel Wong, Vanessa Wong, Peter Gibbs
Australian Pathways for Specialist Pain Management and Early Palliative Care for People With Pancreatic Cancer: Developed Using a Community Consensus Approach
Jennifer Philip, Melanie R. Lovell, Kylee Bellingham, Gail Garvey, Gregory B. Crawford, Nicole M. Rankin, Kara Burns, Isabel Young, Vivienne Milch, Dorothy Keefe, Katrina Anderson, James Lawson, Meinir Krishnasamy
Cause‐specific mortality among Queensland people with cirrhosis, by cirrhosis aetiology and decompensation status, 2007–22: a retrospective cohort study
Vikas Bhasker, Jessica R Fong, Paul J Clark, Gunter F Hartel, Richard Skoien, James O’Beirne, Elizabeth E Powell, Patricia C Valery
Clinical practice guidelines for hepatocellular carcinoma surveillance for people at high risk in Australia: summary of recommendations
Jacob George, Nicole L Allard, Stuart K Roberts, Leon A Adams, Jane Davies, Behzad Hajarizadeh, Jennifer H MacLachlan, Suzanne E Mahady, Rosalie Altus, Catherine Brown, David C Fry, Belinda Greenwood‐Smith, Natali Smud, Patricia C Valery, Nafisa Yussf, Kate Broun, Denise Campbell, Karen Canfell, Chelsea Carle Harrison, Victoria Freeman, Paul Grogan, Catherine Holliday, Suzanne Hughes, Anna Kelly, Cathelijne Kemenade, Claire Latumahina, Amanda McAtamney, Megan Varlow, Joachim Worthington, Susan Yuill, Eleonora Feletto
Assessment of metabolic dysfunction‐associated fatty liver disease in primary care: a consensus statement summary
Leon A Adams, William W Kemp, Kate R Muller, Elizabeth E Powell, Stuart K Roberts, Luis Calzadilla Bertot, Stephanie Best, Gary Deed, Jon D Emery, Samantha L Hocking, Graham R Jones, John S Lubel, Sinead Sheils, Stephen M Twigg, Gerald F Watts, Jacob George
Treatment outcomes for people with hepatitis C referred to tertiary care in Victoria, 2021–22: a retrospective observational study
Elly Layton, Nicole Matthews, Brendan Quinn, Nasra Higgins, Gabrielle Lindeman, Mielle Abbott, Jennifer MacLachlan, Elizabeth Birbilis, Margaret E Hellard, Joseph Doyle, Benjamin C Cowie, Mark Stoové