More Related Content
Similar to Mattes noon conference (20)
More from Virginia Mason Internal Medicine Residency (20)
Mattes noon conference
- 2. © 2016 Virginia Mason Medical Center 2
Objectives
• Brief overview of liver biochemical and
function tests
• Differential diagnosis for jaundice
• List differential diagnosis for
transaminases in 1000s
• Discuss autoimmune hepatitis
- 3. © 2016 Virginia Mason Medical Center
Liver Biochemical and Function Tests
3
right lung nodules and infiltrates
Alkaline phosphatase:
• Present in liver, bone and placenta.
• Elevation does not distinguish between intra and extrahepatic cholestasis
• Confirm with GGT if in doubt
•Isolated elevation in AlkPhos should prompt consideration of high
bone turnover (i.e. Paget disease of bone, bone mets, osteogenic
sarcoma, etc)
•Intrahepatic cholestasis vs. extrahepatic cholestasis = ultrasound
•Extrahepatic – choledocholithiasis, malignancy, PSC, chronic
pancreatitis and AIDS cholangiopathy
•Intrahepatic – drugs, PBC, PSC, viral hepatitis, TPN,
pregnancy, infiltrative diseases
•Check AMA, ANA, ASMA
•If negative, MRCP to eval for PSC, viral hepatitis
serologies, EBV, CMV
GGT:
• Present in hepatocytes and biliary epithelial cells
•Also in kidney, pancreas, seminal vesicles, spleen, heart and brain
- 4. © 2016 Virginia Mason Medical Center
Liver Biochemical and Function Tests
4
- 5. © 2016 Virginia Mason Medical Center
Liver Biochemical and Function Tests
Bilirubin:
• Fractionate to determine conjugated (direct) or
unconjugated (indirect)
• Unconjugated
• Conjugated
5
- 6. © 2016 Virginia Mason Medical Center
Liver Biochemical and Function Tests
Aminotransferases:
• AST
• Present in liver, cardiac & skeletal muscle, brain, and kidney
• Isolated elevation think rhabdo
• ALT
• Present primarily in liver (low concentration in heart and kidney) therefore
more specific
• Correlates with gender and amount of adiposity
6
Mild <5x upper limit / Moderate 5-10x upper limit
• Medication, viral hepatitis, EtOH, NAFLD, Wilsons, A1AT, autoimmune, hemochromatosis, congestive
hepatopathy, celiac, adrenal insuff, thyroid disease, malignancy
Marked > 10x upper limit
• Tylenol overdose, drug toxicity, shock liver, autoimmune hepatitis, viral hepatitis, Budd-Chiari, rhabdo
- 7. © 2016 Virginia Mason Medical Center
Liver Biochemical and Function Tests
7
- 8. © 2016 Virginia Mason Medical Center
Liver Biochemical and Function Tests
8
- 9. © 2016 Virginia Mason Medical Center
Autoimmune Hepatitis
Epidemiology:
• Average age 40-50s. Female predominance (3.1:1). Incidence 1-2
per 100,000 population per year.
Presentation:
• Heterogeneous and fluctuating nature with a range of presentation
from asymptomatic to acute liver failure.
• Many have cirrhosis on biopsy given the subclinical course of the
disease for many years.
• Other presenting symptoms include lethargy, malaise, pruritus,
nausea, abdominal pain, jaundice.
• Associated with other autoimmune conditions (boards will give Hx
of DMI, thyroid disease, celiac disease, etc)
9
- 10. © 2016 Virginia Mason Medical Center
Autoimmune Hepatitis
10
Diagnosis: Clinical signs/symptoms, laboratory
data and exclusion of other chronic liver disease.
Biopsy if unclear or no response to therapy
(consider overlap syndrome).
Antibodies:
• ANA
• Anti-smooth muscle Ab (ASMA)
• Anti-actin (F-actin)
• Anti-liver-kidney-microsome-1 Ab (anti-LKM-1)
- 12. © 2016 Virginia Mason Medical Center
Autoimmune Hepatitis
Treatment: Based on severity of symptoms.
Treat if:
• Transaminases > 10 fold upper limit of normal
• Gamma globulin > 2 times upper limit
• Transaminases > 2x upper limit plus
• symptoms
• elevated gamma globulin 2x ULN
• elevated conjugated bilirubin
• interface hepatitis on biopsy
• Histologic features of necrosis
• Cirrhosis with any inflammation on biopsy
• Children
Otherwise, follow for disease progression/symptoms and consider
treatment if symptoms arise or increase in transaminases or gamma
globulins
12
- 13. © 2016 Virginia Mason Medical Center 13
Autoimmune Hepatitis
Treatment:
• Glucocorticoid monotherapy or glucocorticoid + azathioprine or
6-mercaptopurine
• Usually glucocorticoid monotherapy with 60 mg prednisone
tapered over 4 weeks to maintenance dose of 20 mg then
addition of azathioprine or 6-mercaptopurine.
• 65-80% have complete response
• 10% have no response
• 10% have incomplete response
• Maintenance dosing should be the lowest dose of azathioprine or
prednisone to maintain remission.
• Consider tapering therapy after 24 months of remission.
• 50-90% of patients relapse within 12 months of withdrawal of
therapy.
Editor's Notes
- Title your presentation “Noon Conference”
Prevents inadvertently giving away the case.
- Unconjugated: bilirubin overproduction or impaired uptake/conjugation (hemolysis, Gilbert (decreased glucuronosyltransferase activity), Crigler-Najjar (dysfunctional or minimally active glucuronosyltransferase), drugs)
Conjugated:
Elevated AlkPhos and GTT: Biliary obstruction (gallstones, pancreatic or biliary malignancy, AIDS cholangiopathy, parasites), viral hepatitis, alcoholic hepatitis, nonalcoholic steatohepatisis, PBC, ischemic hepatopathy, TPN, pregnancy, ESLD)
Normal AlkPhos and GGT: Very rare Dubin-Johnson (altered hepatocyte excretion of bilirubin into bile ducts), Rotor syndrome (defective hepatocyte reuptake of bilirubin)