Tox in The Land: Toxicologic Causes of Acute Liver Failure

Source: https://badgut.org/information-centre/a-z-digestive-topics/the-liver-an-amazing-organ/

Definitions

  • Acute liver failure (ALF)

    • “Rapid deterioration of liver function”

    • INR > 1.5

    • Encephalopathy

  • King’s College Criteria for transplant:

    • Arterial pH < 7.30

    • INR > 6.5

    • Creatinine > 3.4mg/dL

    • Grade III or IV hepatic encephalopathy



Differential

  • What is on your differential for acute liver failure?

  • What labs should be ordered?

    • Do you always get an acetaminophen level...spoiler alert...you should.



Acetaminophen

  • #1 cause of acute liver failure in the United States

  • Single toxic ingestion >7.5g

  • Limited ability to clear NAPQI in large overdoses

  • 4 clinical phases:

    • Asymptomatic/mild symptoms

    • RUQ pain/worsening symptoms

    • Hepatic phase

    • Recovery

  • Start NAC within 8-10 hours

Source: https://www.tumbral.com/tag/nomogram

 

What about mushroom lovers and foragers out there? Are all mushrooms created equal? When in doubt, just get them from the grocery store

α-amanitin

  • Amanita phalloides (“death cap”)

  • Most potent amatoxin currently classified

  • RNA polymerase II inhibitor

  • Detectable in urine, serum, emesis

  • Clinical presentation:

    • Gastrointestinal symptoms in first 24 hours

    • Latent phase

    • Clinical hepatic +/- renal failure

Source: chemspider.com

Amanita phalloides. Source: wikipedia

 

J WS, et al. 2014 [5]

 

  • Treatment

    • Supportive

    • NAC

    • Transplant

    • Silibinin?

Perchloroethylene (PERC)

  • Chlorinated solvent used in dry cleaning and degreasing industries

  • Known carcinogen, hepatotoxicity in animal studies

  • Colorless, sweet odor

  • High VD

  • Presents clinically after oral ingestion or inhalation with AMS, hepatic and renal failure

  • Plasmapharesis

Copper

  • Essential trace mineral

  • RDA 1.5 mg/day

  • Single toxic ingestion >1-10g

  • Agricultural/marine fungicide

  • Mechanism:

    • Lipid peroxidation

    • Free radical production

    • Decreased cytochrome c oxidase activity

  • Case reports of acute liver failure developing within hours

  • Clinical presentation:

    • Gastrointestinal symptoms

    • Symptoms of hepatic encephalopathy within 24-72hrs

    • Multi-organ involvement

  • High mortality rate

  • ALF indicates poor prognosis

Source: https://www.carolina.com/specialty-chemicals-b-c/cupric-sulfate-pentahydrate-laboratory-grade-500-g/856550.pr

 

Source: https://www.factorydirectchemicals.com/products/copper-sulfate-pentahydrate-crystals

Source: https://en.wikipedia.org/wiki/Copper

 

Chloroform

  • Colorless, sweet-smelling liquid

  • Converted to phosgene gas in air

  • Original medical use as anesthetic

  • Presents with depressed CNS status, hepatotoxicity

  • Detectable in serum

  • Potential benefit of NAC

Source: https://www.henryschein.com/us-en/Shopping/ProductDetails.aspx?productid=3122137&CatalogName=DENTAL

 

Etc. Etc.

  • Carbon tetrachloride (CCl4)

  • Green tea extract

  • Halothane

  • Pennyroyal

  • Phosphorous

  • Black cohosh

  • Isoniazid

Take Home Points

  • Acetaminophen responsible for > 1/3 cases in the US

  • High index of suspicion

  • Use your social history!

  • When in doubt, NAC

POST BY: DR. EMILY CRAFT (PGY3)

FACULTY EDITING BY: DR. LAUREN PORTER (MEDICAL TOXICOLOGIST)

ToxLauren McCafferty