Today’s case involved a young man with no
medications and no past medical history who presented with a 2 week history of
malaise and jaundice on exam. He was found to have abnormal laboratory values
including AST and ALT in the 1000s and bilirubin in the 200s.
There were several teaching points for the
case:
We discussed the differential diagnosis
for jaundice. We discussed that there are two main categories of hyperbilirubinemia (i.e. jaundice):
1. Unconjugated
hyperbilirubinemia: caused by hemolysis or impaired hepatic bilirubin
uptake and/or conjuation such as from Gilbert syndrome or medications.
2. Conjugated
hyperbilirubinemia: the main cause is cholestasis
which can be extrahepatic cholestasis (i.e. biliary obstruction from
choledocholithiasis, primary sclerosing cholangitis, tumors, or other causes)
or intrahepatic cholestasis (i.e. from hepatitis, primary biliary cholangitis,
drugs and toxins, sepsis, infiltrative dieases and other causes)
In this case we were faced with a
conjugated hyperbilirubinemia in the context of acute liver injury. We
discussed the questions that are important on history that are based on the
differential diagnosis for acute liver injury. This includes asking about:
medications (including over-the-counter medications), toxins (including
acetaminophen and alcohol), other ingestions (specifically mushroom poisoning
for Amanita mushrooms), risk factors
for viral hepatitis (including travel, country of birth, tattoos, blood
transfusions, and injection drug-use), family history (including autoimmune
hepatitis, genetic diseases such as Wilson disease), or history of severe
illness that could result in hypoperfusion and ischemic hepatitis. We also
discussed that it would be important to rule out pregnancy and
pregnancy-related causes in a female patient.
The differential diagnosis of marked
transaminitis (i.e. AST and ALT in the 1000s) includes:
Top 3:
1. Acute viral hepatitis
2. Drug/toxin-induced liver injury
(including acetaminophen)
3. Acute ischemic hepatocellular
injury (i.e. “shock liver”)
Other causes (less common but possible):
autoimmune hepatitis, acute Budd Chiari, HELLP, acute fatty liver of pregnancy,
Wilson’s disease.
We discussed the key points on physical
exam which would include looking for signs of chronic liver disease, examining
for jaundice (look at the sclera for scleral icterus, look at the frenulum),
examination for hepatic encephalopathy with mental status exam and examination
for asterixis, and abdominal exam.
We discussed the investigations that
would be indicated, including a work up for the cause of acute liver injury
based on the differential diagnosis above (viral hepatitis serology,
acetaminophen level, tox screen, and abdominal ultrasound with doppler as a reasonable preliminary work up),
and the importance of the liver function
tests for prognosis. The liver function tests include: platelets, INR,
albumin, bilirubin and blood glucose. We talked about how liver function tests (i.e. the laboratory values related to the
liver’s function: produce albumin, coagulation factors, produce glucose in
states of starvation) and liver enzymes (AST, ALT, and ALP) are
not the same thing and how the terms are often confused.
We discussed the principles of management:
· - Ensure hemodynamic stability
· - Nutritional Support
· - Accuchecks and IV glucose
infusion if needed
· - Acetylcysteine infusion
**Especially if acetaminophen poisoning*** (there is limited evidence that
acetylcysteine may also benefit patients with non-acetaminophen-related acute
liver failure, possibly through its antioxidant and immunologic effects)
· - Monitor clinically and through
laboratory testing for prognostic evaluation
· - Involve liver transplantation
experts early
For further reading:
1. A review on acute liver failure
from NEJM: Bernal W, Wendon J. Acute liver failure. NEJM 2014;370(12):1170-1.
2. A RCT that provides evidence
for the use of N-acetylcysteine infusions in early stage
non-acetaminophen-related acute liver failure to improve transplant-free
survival: Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine
improves transplant-free survival in early stage non-acetaminophen acute liver
failure. Gastroenterology 2009;137:856-64
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