Cases That Test Your Skills

Young, angry, and in need of a liver transplant

Current Psychiatry. 2019 May;18(5):45-51

References

1. Depakote [package insert]. North Chicago, IL: AbbVie, Inc.; 2019.
2. National Institutes of Health. U.S. Department of Health and Human Services. Drug Record: Valproate. https://livertox.nlm.nih.gov/Valproate.htm. Updated October 30, 2018. Accessed March 21, 2019.
3. Schmid MM, Freudenmann RW, Keller F, et al. Non-fatal and fatal liver failure associated with valproic acid. Pharmacopsychiatry. 2013;46(2):63-68.
4. Patel N, Landry KB, Fargason RE, et al. Reversible encephalopathy due to valproic acid induced hyperammonemia in a patient with Bipolar I disorder: a cautionary report. Psychopharmacol Bull. 2017;47(1):40-44.
5. Eze E, Workman M, Donley B. Hyperammonemia and coma developed by a woman treated with valproic acid for affective disorder. Psychiatr Serv. 1998;49(10):1358-1359.
6. Darban M and Bagheri B. Drug reaction with eosinophilia and systemic symptoms induced by valproic acid: a case report. Iran Red Crescent Med J. 2016;18(9): e35825.
7. van Zoelen MA, de Graaf M, van Dijk MR, et al. Valproic acid-induced DRESS syndrome with acute liver failure. Neth J Med. 2012;70(3):155.
8. Lheureux PE, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol (Phila). 2009;47(2):101-111.
9. Bohan TP, Helton E, McDonald I, et al. Effect of L-carnitine treatment for valproate-induced hepatotoxicity. Neurology. 2001;56(10):1405-1409.
10. Böhles H, Sewell AC, Wenzel D. The effect of carnitine supplementation in valproate-induced hyperammonaemia. Acta Paediatr. 1996;85(4):446-449.
11. Raskind JY, El-Chaar GM. The role of carnitine supplementation during valproic acid therapy. Ann Pharmacother. 2000;34(5):630-638.
12. Romero-Falcón A, de la Santa-Belda E, García-Contreras R, et al. A case of valproate-associated hepatotoxicity treated with L-carnitine. Eur J Intern Med. 2003;14(5):338-340.
13. National Institute for Health and Clinical Excellence. Bipolar disorder: the management of bipolar disorder in adults, children, and adolescents, in primary and secondary care. https://www.nice.org.uk/guidance/cg185. Updated April 2018. Accessed March 21, 2019.
14 . Hirschfeld RMA, Bowden CL, Gitlin MJ, et al. Practice guideline for the treatment of patients with biopolar disorder: second edition. American Psychiatric Association. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar.pdf. Published 2002. Accessed March 21, 2019.

A review of the records from Visit 1 and Visit 2 at the outside hospital found no acetaminophen in Ms. L’s system and verified that there was no evidence of a current valproic acid overdose. Ms. L had stated that she had not overdosed on any other medications or used any illicit drugs or alcohol. Ms. L’s complex symptoms—namely fever, acute liver failure, and rash—were more consistent with an adverse effect of valproic acid or possibly an inherent autoimmune process.

Liver damage from valproic acid

Valproic acid is FDA-approved for treating bipolar disorder, epilepsy, and migraine headaches¹ (Table 2¹). Common adverse effects include nausea, vomiting, sleepiness, and dry mouth. Rarely, valproic acid can impair liver function. While receiving valproic acid, 5% to 10% of patients develop elevated ALT levels, but most are asymptomatic and resolve with time, even if the patient continues taking valproic acid.² Valproic acid hepatotoxicity resulting in liver transplantation for a healthy patient is extremely rare (Table 3¹). Liver failure, both fatal and non-fatal, is more prevalent in patients concurrently taking other medications, such as antiepileptics, benzodiazepines, and antipsychotics, as compared with patients receiving only valproic acid.³

There are 3 clinically distinguishable forms of hepatotoxicity due to valproic acid²:

hyperammonemia
acute liver failure and jaundice
Myriad ProReye-like syndrome, which is generally seen in children.

In case reports of hyperammonemia due to valproic acid, previously healthy patients experience confusion, lethargy, and eventual coma in the context of elevated serum ammonia levels; these symptoms resolved upon discontinuing valproic acid.^4,5 Liver function remained normal, with normal to near-normal liver enzymes and bilirubin.³ Hyperammonemia and resulting encephalopathy generally occurred within 1 to 3 weeks after initiation of valproate therapy, with resolution of hyperammonemia and resulting symptoms within a few days after stopping valproic acid.^2-4

At Visit 2, Ms. L’s presentation was not initially consistent with hepatic encephalopathy. She was alert and oriented to person, place, time, and situation. Additionally, Ms. L’s presenting problem was elevated liver function tests, not elevated ammonia levels. At Visit 2, her ammonia level was 58 µmol/L; on Day 2 (Visit 3) of her hospital stay, her ammonia level was 72 µmol/L (slightly elevated).

Continue to: At Visit 2 in the ED...

Young, angry, and in need of a liver transplant

References

Liver damage from valproic acid

Pages

Recommended Reading