Transcript
Drug/Toxin Mediated Injury
Neil Theise, MDDepts. of Pathology and Medicine (Digestive Diseases)
Beth Israel Medical Center – Albert Einstein College of MedicineNew York City
Drug toxicities• Predictable hepatotoxins
• Unpredictable hepatoxins
Drug toxicities• Predictable hepatotoxins
- dose dependent, all species, all individuals
• Unpredictable hepatoxins
Drug toxicities• Predictable hepatotoxins
- dose dependent, all species, all individuals
e.g. Tylenol (acetaminophen)
• Unpredictable hepatoxins
Drug toxicities• Predictable hepatotoxins
- dose dependent, all species, all individuals
e.g. Tylenol (acetaminophen)
• Unpredictable hepatoxins- idiosyncratic, in rare patients,
not in all species, not dose dependent
Drug toxicities• Predictable hepatotoxins
- dose dependent, all species, all individuals
e.g. Tylenol (acetaminophen)
• Unpredictable hepatoxins- idiosyncratic, in rare patients,
not in all species, not dose dependent
e.g. Isoniazid (INH)
KNOWN DRUG TOXICITIES:Acute hepatitis, fulminant hepatic failure, chronic hepatitis, cirrhosis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, acute cholestasis, chronic cholestasis, gall stones, biliary obstruction, iron accumulation, hepatocellular adenomas, hepatocellular carcinomas, focal nodular hyperplasia, hepatocyte induction cells, macrovesicular steatosis, steatohepatitis, steatfibrosis, microvesicular steatosis, cholangiocarcinoma, stellate cell lipidosis and activation, peliosis hepatitis, angiosarcoma, idiopathic portal hypertension, nodular regenerative hyperplasia, fibrinogen inclusion disease,…………………..
Drug toxicities• Predictable hepatotoxins
- dose dependent, all species, all individuals
e.g. Tylenol (acetaminophen)
• Unpredictable hepatoxins- idiosyncratic, in rare patients,
not in all species, not dose dependent
e.g. Isoniazid (INH)
THEREFORE (KEY CONCEPT!!!):
IF YOU HAVE SIGNS OF LIVER DISEASE CLINICALLY OR IN A BIOPSY, DRUG TOXICITY IS ON YOUR DIFFERENTIAL!!!DRUG TOXICITY IS ON YOUR DIFFERENTIAL!!!
THEREFORE (KEY CONCEPT!!!):
IF YOU HAVE SIGNS OF LIVER DISEASE CLINICALLY OR IN A BIOPSY, DRUG TOXICITY IS ON YOUR DIFFERENTIAL!!!DRUG TOXICITY IS ON YOUR DIFFERENTIAL!!!
SO TALK TO YOUR PATIENT!
ASK ABOUT:
PRESCRIPTION MEDS
OVER THE COUNTER MEDICATIONS
HERBAL REMEDIES
SUPPLEMENTS
VITAMINS (or “VITAMINS”)
Examples
Oil Red O stain
Diffuse microvesicular steatosis
• Reye’s syndrome• Fatty liver of pregnancy• Tetracycline toxicity• Valproate toxicity• Vomiting sickness of Jamaica (from eating the unripened fruit of the Ackee tree)
Special Type of Fat!!!
Oil Red O stain
Diffuse microvesicular steatosis
• Reye’s syndrome• Fatty liver of pregnancy• Tetracycline toxicity• Valproate toxicity• Vomiting sickness of Jamaica (from eating the unripened fruit of the Ackee tree) • (HAART)
Special Type of Fat!!!
Case 1:42 y.o. woman with HCV.
Biopsy for staging and grading.
Case 1:Dx:1. Chronic hepatitis, mildly active with focal, mild portal fibrosis,
compatible with hepatitis C.2. Stellate cell lipidosis suggestive of hypervitaminosis A or other
retinoid use.
Case 2:28 y.o. man receives Ompeprazole; one week later notices yellow eyes.
ALT/AST: 70/83Alk Phos: 2x normal
Bilirubin: 11.2
Case 2:Dx:Acute cholestasis, marked, compatible with Omeprazole toxicity.
Case 3
2008: Now 22 years old, returns to emergency room with identical clinical picture:
nausea, vomiting, fatigue and jaundice; ALT/AST >8000
Again, negative for:HAV, HBV, HCV
ANA, AMA, ASMA, anti-LKM1Drugs or over the counter medications, etc.
Again, ceruloplamin and iron indices all normal.
Again, clinically: Fulminant failure of unknown cause. Receives supportive care AND a liver biopsy.
Again, patient recovers completelyand goes home well.
Case 3
2004: Without prior or family history of liver disease, this 18 year old female presents with nausea, vomiting, fatigue
and jaundice; ALT/AST >6000
Negative for:HAV, HBV, HCV
ANA, AMA, ASMA, anti-LKM1Drugs or over the counter medications, etc.
Ceruloplamin and iron indices all normal.
Clinically: Fulminant failure of unknown cause. Receives supportive care while awaiting donor organ,
but patient recovers completelyand is taken off transplant list; goes home well.
Case 3:Dx:Features of markedly active hepatitis, ? acute vs. chronic,? drug/toxin mediated injury
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