Hepatitis, rhabdomyolysis and multi-organ failure resulting from statin use

This paper was published in the British Medical Journal Case Reports 2009;2009. pii: bcr07.2008.0412

Study title and authors:
Hepatitis, rhabdomyolysis and multi-organ failure resulting from statin use.

Rajaram M.
St Helens and Knowsley Hospitals NHS Trust, Medicine-Gastro, Whiston Hospital, Warrington Prescot, L35 5DR, UK.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21686823

This paper reports the case of of a woman who developed hepatitis, rhabdomyolysis and multi-organ failure resulting from the use of statins.

(i) A 77-year-old female patient was admitted to hospital with malaise, anorexia and generally feeling unwell for a week.
(ii) She was taking atorvastatin 80 mg daily.
(iii) The dose of atorvastatin was increased from 40 mg to 80 mg daily approximately six months before admission.
(iv) Examination revealed she was jaundiced.
(v) Laboratory tests revealed the following abnormalities (normal levels in brackets):
Creatine kinase: 523 iu/l (25–200)
Lactate dehydrogenase: 1241 iu/l (240–525)
Total bilirubin: 284 μmol/l (2–22)
Alanine transaminase: 2314 iu/l (11–55)
γ glutamyl transferase: 132 iu/l (5–50)
Aspartate transaminase: 1269 iu/l (12–42)
Alkaline phosphatase: 438 iu/l (40–125)
Urea: 15.9 mmol/l (3.6–7.3)
Creatinine: 290μmol/l (45–110)
(vi) A diagnosis of hepatitis related to statin use with accompanying kidney failure was made.
(vii) The statin was stopped and her liver biochemistry improved.
(viii) However on the fourth day after admission, her kidney function deteriorated.
(ix) Examination revealed excess fluid around the lungs and abdominal areas.
(x) The patient was transferred to the intensive care unit and required haemofiltration. (Hemofiltration is a kidney replacement therapy similar to hemodialysis).
(xi) Despite improvement in her kidney function, the creatine kinase levels continued to rise and peaked at 107178 iu/l.
(xii) Two weeks after admission to the hospital, the patient died of multi-organ failure.

Rajaram concludes: "The cause of hepatitis, rhabdomyolysis, and acute renal failure in this patient was the increase in dose of atorvastatin and subsequent elevation of serum atorvastatin concentration. We suggest that the elevation of atorvastatin concentrations resulted in skeletal muscle damage and rhabdomyolysis, as indicated by the elevation of creatine kinase and subsequent deposition of myoglobin in the kidneys, causing acute renal failure as indicated by the elevation of urea and creatinine".

Long-term exposure to statins may be associated with drug-induced lupus erythematosus and other autoimmune disorders

This study was published in the Journal of the European Academy of Dermatology and Venereology 2007 Jan;21(1):17-24

 

Study title and author:

Lupus erythematosus and other autoimmune diseases related to statin therapy: a systematic review.

Noël B.

Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. bernard.noel@chuv.hospvd.ch

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17207162

This paper reviewed the scientific literature concerning statin-induced autoimmune diseases including lupus erythematosus.

The review found:
(a) Statins were associated with various autoimmune diseases such as systemic lupus erythematosus, subacute cutaneous lupus erythematosus, dermatomyositis, polymyositis and lichen planus pemphigoides.
(b) Autoimmune hepatitis was observed in some patients with systemic lupus erythematosus.
(c) The average time of exposure before disease onset was 12 months, with a range from one month to six years.
(d) Aggressive immunosuppressive therapy was required in the majority of cases to aid clinical recovery.
(e) Some patients died despite the immunosuppressive therapy.

Noel concludes: "Long-term exposure to statins may be associated with drug-induced lupus erythematosus and other autoimmune disorders. Fatal cases have been reported despite early drug discontinuation and aggressive systemic immunosuppressive therapy".

Cholestatic jaundice induced by atorvastatin

This paper was published in the Israel Medical Association Journal 2009 Jul;11(7):440-1

Study title and authors:
Cholestatic jaundice induced by atorvastatin: a possible association with antimitochondrial antibodies.

Minha S, Golzman G, Adar I, Rapoport M.
Department of Internal Medicine C, Assaf Harofeh Medical Center, Zerifin, Israel. Minha.saar@gmail.com

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19911499

This paper describes the case of a man who developed cholestatic jaundice while taking atorvastatin. (Cholestatic jaundice is when the normal flow of bile from the liver to the small intestine is interupted).

(i) A 68 year old man was admitted to hospital complaining of fever, dark urine and hives (itchy rash).
(ii) He was taking atorvastatin 20 mg per day.
(iii) Physical examination revealed he had jaundice and large areas of hives.
(iv) Abnormal laboratory results included elevated liver function tests with a cholestatic pattern:
total bilirubin 7.4 mg/dl (normal 0.2–1.0 mg/dl)
alkaline phosphatase 555 U/L (normal 39–117 U/L)
alanine aminotransferase 250 U/L (normal 4–41 U/L)
aspartate aminotransferase 50 U/L (normal 5–38 U/L)
lactate dehydrogenase 540 U/L (normal 240–480 U/L)
(v) A diagnosis of drug-induced liver damage was made.
(vi) The patient stopped taking atorvastatin and he had a rapid biochemical and clinical improvement.
(vii) During the following four weeks the patient was discharged and readmitted twice with a similar clinical and laboratory findings.
(viii) A liver biopsy revealed on his next admission revealed severe inflammation.
(ix) Further investigation revealed that between admissions and prior to each recurrent bout of cholestatic hepatitis the patient had renewed his treatment with atorvastatin.  
(x) Complete cessation of atorvastatin was followed by a return to normal values of liver function tests and a complete clinical recovery.

Autoimmune hepatitis can be triggered by statins

This paper was published in the Journal of Clinical Gastroenterology 2006 Sep;40(8):757-61

 

Study title and authors:

Autoimmune hepatitis triggered by statins.

Alla V, Abraham J, Siddiqui J, Raina D, Wu GY, Chalasani NP, Bonkovsky HL.

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/16940892

This paper describes three patients in whom it is probable that statins initiated the development of autoimmune hepatitis. (Autoimmune hepatitis is inflammation of the liver that occurs when immune cells mistake the liver's normal cells for harmful invaders and attack them).

(i) Two men (aged 47 and 51) and one woman (aged 57) developed autoimmune hepatitis after the initiation of statin therapy.
(ii) The woman developed hepatitis due to statins on two separate occasions: the first in 1999, due to simvastatin, and the second in 2001 to 2002, due to atorvastatin, which was severe and persisted even after discontinuing medication.
(iii) In the two men, exposure to statins preceded development of autoimmune hepatitis, which persisted despite discontinuing medications.
(iv) Three similar previously reported cases were noted.

The researchers concluded that the three cases reported here and three similar previously reported cases, indicate that severe, ongoing autoimmune hepatitis can be triggered by statins.

Statins are a potential cause of cholestatic hepatitis

This paper was published in the American Journal of Gastroenterology 1999 May;94(5):1388-90

Study title and authors:
Acute cholestatic hepatitis associated with pravastatin.

Hartleb M, Rymarczyk G, Januszewski K.
Department of Gastroenterology, Silesian Medical School, Katowice, Poland.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/10235223

This paper describes a 57 year old man with acute cholestatic hepatitis. (Acute cholestatic hepatitis is where the bile ducts of the liver become obstructed by inflammation and may lead to jaundice).

The report found:
The man's symptoms had appeared 7 weeks after he was started on pravastatin 20 mg/day for "high cholesterol".

Investigations revealed a diagnosis of intrahepatic nonobstructive jaundice.

The liver function abnormalities normalized 7 weeks after cessation of therapy.

This paper shows that statins should be considered as a potential cause of cholestatic hepatitis.

Acute hepatitis induced by lovastatin

This study was published in Digestive Diseases and Sciences 1994 Sep;39(9):2032-3

Study title and authors:
Acute hepatitis induced by HMG-CoA reductase inhibitor, lovastatin.

Grimbert S, Pessayre D, Degott C, Benhamou JP.
Service d'Hépatologie, Unité de Recherches de Physiopathologie Hépatique (INSERM U 24), Hôpital Beaujon, Clichy, France.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/8082513

This paper reports the case of an adult who suffered from clinical hepatitis three months after the onset of lovastatin administration.

The patient suffered:
(i) Loss of strength and energy.
(ii) Jaundice.
(iii) Increased aminotransferase levels. (Elevated levels of aminotransferase (an enzyme) suggest the existence of medical problems such as viral hepatitis, diabetes, congestive heart failure, liver damage and bile duct problems).
(iv) Increased alkaline phosphatase levels. (Elevated levels of alkaline phosphatase (an enzyme) indicate the presence of liver disease or bone disorders).

Examination of the patients liver cells revealed:
(a) Cell death.
(b) Blocked bile ducts.
(c) Increased white blood cell levels. (Elevated white blood cells in the liver, suggest the existence of liver damage).

Withdrawal of lovastatin was followed by complete normalization of liver tests within two months.

This report shows that statins may induce hepatitis.

Statins increase the risk of many cancers, neurodegenerative disorders and a myriad of infectious diseases

This post features a summary of a study published in the International Journal of Cardiology 2009 June 12;135(1):128-30

Study title and authors:                                                                                                         Books:

The double-edged sword of statin immunomodulation.

Goldstein MR, Mascitelli L, Pezzetta F.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/18485499

Dr Mark Goldstein reviewed the evidence concerning statins and their effects on disease.

Dr Goldstein found:
(a) Statins may be harmful in certain segments of the population.
(b) Statins have been shown to increase the concentration of regulatory T cells (Tregs). There is evidence that this increases the risk of many cancers, particularly in the elderly.
(c) Furthermore, a statin induced increase in Tregs may be detrimental in neurodegenerative disorders, such as amyotrophic lateral sclerosis; and a myriad of infectious diseases. These include, but are not limited to, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and varicella zoster virus.

Dr Goldstein concludes: "These issues need our attention, and call for a heightened state of vigilance among those prescribing statins".

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Statins cause hepatitis in 65 year old woman

This post contains a summary of a paper published in the European Journal of Gastroenterology & Hepatology August 2003 - Volume 15 - Issue 8 - pp 921-924 and a recipe for balsamic glazed sticky lamb cutlets with thyme.

Books:

Study title and authors: 

Autoimmune hepatitis revealed by atorvastatin
Pelli, Nicoletta; Setti, Maurizio; Ceppa, Paola; Toncini, Carlo; Indiveri, Francesco

This paper can be accessed at: http://journals.lww.com/eurojgh/Abstract/2003/08000/Autoimmune_hepatitis_revealed_by_atorvastatin.14.aspx

This paper describes the case of autoimmune hepatitis induced by a statin.

(i) A 65-year-old woman was admitted to hospital because of fatigue, jaundice and altered liver function tests while on treatment with atorvastatin.
(ii) The doctor diagnosed autoimmune hepatitis and after investigations concluded that atorvastatin was the trigger of the disease.

The case shows the potential link between statins and autoimmune hepatitis.

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Recipe of the day

Balsamic Glazed Sticky Lamb Cutlets with Thyme

Ingredients:

Food Mall: Lamb

8 lamb cutlets, French trimmed

Salt and freshly milled black pepper

30ml/2tbsp finely chopped fresh thyme leaves

100ml/3½floz. good, aged balsamic vinegar

30ml/2tbsp fermented soy sauce

25g/1oz unsalted butter

Method:

1.Preheat the oven to Gas mark 6, 200°C, 400°F.

2.Season the cutlets and sprinkle with the thyme on both sides. Transfer to a metal rack in a roasting tin and cook for 15-20 minutes (depending on how you like your lamb).

3.Meanwhile, pour the vinegar and fermented soy sauce into a small pan. Bring to the boil, reduce the heat and simmer for about 10 minutes until the mixture is reduced by half. Whisk in the butter.

4.Remove the cutlets from the roasting tin and transfer to a large bowl. Drizzle the balsamic glaze over the cutlets.