1. Steve Bradley Chief Medical Resident, HMC Inpatient Services
Liver Function Tests
Steve Bradley
Chief Medical Resident, HMC Inpatient Services

2. What are “Liver Function Tests”
Few are truly associated with function
Albumin: protein synthetic function
INR: clotting factor synthesis
Most are related to cell injury
Patterns point to specific cell injury

3. Tests of Liver Injury AST/ALT Alkaline Phosphatase/GGT
Cytoplasmic enzymes found in hepatocytes
Very sensitive marker for hepatocyte injury
Specificity is poor (other sources, e.g. muscle)
Mitochondrial isoenzyme
AST increased by ethanol (explains 2:1 ratio)
Alkaline Phosphatase/GGT
Canicular enzymes
Gradual increase in plasma levels with obstruction of canicular flow

4. Patterns of Enzyme Elevation
Hepatocellular injury
AST/ALT
Cholestatic
Bilirubin/alkaline phosphatase
Mixed
Isolated/predominant alkaline phosphatase elevatioin

5. Caveats to Patterns Hepatocellular injury Cholestatic
Also results in release of bilirubin
Alkaline phosphatase also found in hepatocyte
Cholestatic
Biliary obstruction can lead to hepatocellular injury
History and Physical guide your thinking!!

6. Patient #1: Suzie Duzie
Presents with two days of fever, abdominal pain, yellow skin, nausea, vomiting.
Labs demonstrate the following:
AST 3210
ALT 3060
Alk phos 249
TBili 6.2 (Direct 4.3)
Albumin 3.1
INR 1.2

7. What targets the hepatocyte?
Toxins
Alcohol
Medications
Tylenol
Mushrooms
Viral
Hepatitis A/B/C
EBV/HSV/CMV
Ischemia
Severe hypotension
Vasoconstriction
Sepsis
Autoimmune
Wilson’s
Alpha-1 antitrypsin deficiency

8. Degree of elevation points to etiology
Ischemia
Toxin
Virus
>500 to 1000
Acute biliary obstruction
<300
Alcoholic liver disease, cirrhosis, chronic obstruction
AST/ALT>2 and each <300 suggests EtOH or cirrhosis
If >500, unlikely EtOH

9. Back to our patient Transaminases in the 1000s IVDU Cocaine
Suggests ischemia/toxin/viral
IVDU
Risk of acute Hep B or acute Hep C
Cocaine
Risk of ischemia
Recent infection
Doxycycline

10. Patient #2: Ima Hurtin
40 year-old overweight woman presents with right UQ abd pain, fever, chills. Previous episodes after fatty meals.
Laboratory Studies
AST 67
ALT 57
Alk Phos 293
TBili 4.1 (Direct 2)
Albumin 4
INR 1

11. Increased Bilirubin Sources Conjugated=direct=processed by liver
Increased production
Hemolysis, hematoma reabsorption
Impaired uptake/conjugation
Dubin-Johnson, Gilbert’s
Impaired excretion
Renal failure, biliary obstruction
Conjugated=direct=processed by liver
Unconjugated=indirect=not processed by liver
Fractionation – helpful to assess for unconjugated hyperbilirubinemia
< 20% direct AND indirect >1.2

12. Biliary Obstruction Canicular cell injury Alkaline phosphatase GGT
Liver and bone major sources
Increased synthesis and release in liver disease
Up to 3x normal in variety of liver disease
GGT
Sensitive indicator of canicular cell injury
Parallels alkaline phosphatase increase when of liver origin

13. Causes of Biliary Obstruction
Extrahepatic
Choledocholithiasis
Malignancy
Cholangiocarcinoma
Pancreatic cancer
Gallbladder cancer
Ampullary cancer
Primary sclerosing cholangitis
AIDS Cholangiopathy
Intrahepatic
TPN
Sepsis
Primary sclerosing cholangitis
Primary biliary cirrhosis
Intrahepatic mass

14. How would you like to approach this patient?
Finding the source of obstruction
Ultrasound: good for extrahepatic cause
CT/MRI/ERCP: for both intra or extrahepatic cause
In our patient?

15. Patient #3: Biggie Smalls
46 yo man with history of IVDU and long-standing alcohol use following up in clinic.
Laboratory
AST 68
ALT 37
Alk phos 194
TBili 1.3
Albumin 2.9

16. Mixed Patterns of Elevated Liver Function
Chronic Liver disease
Hepatitis B, Hepatitis C
NASH
Alcoholic liver disease
Hemochromatosis
Autoimmune hepatitis

17. Patient#4: Iva Fallen 72 yo man fell in bathroom. Found the next day.
Laboratory
AST 167
ALT 58
Alk phos 127
TBili 1.8
Albumin 3.9

18. What else do you want to know?
Where else is AST and ALT found?
How can you look for evidence of muscle injury?

19. Additional Laboratory
CK 7260
Myoglobin 23390
UA – 2+ blood, microscopic no RBC
Diagnosis?

20. Isolated or Predominant Alk Phos
Chronic Biliary Disease
Primary biliary cirrhosis
Primary sclerosing cholangitis
Infiltrative disorder
Amyloid
Granulomatous diseases
Metastatic carcinoma
abscesses

21. Last Case: Sue Sadd
32 yo woman, depressed, “took some pills” a few days ago
Laboratory
AST 1450
ALT 1620
Alk phos 242
TBili 8 (direct 4)
Albumin 2.9
INR 1.7

22. Fulminant Hepatic Failure
Rapid development of severe acute liver injury with impaired synthetic function and encephalopathy
Previously had a normal liver or had well-compensated liver disease

23. Causes

24. Treatment Directed therapy Liver transplant Acetaminophen - mucomyst
Acute fatty liver of pregnancy - delivery of infant
Amanita mushroom poisoning - penicillin and silibinin
Wilson's disease - D-penicillamine
Herpes Simplex Infection – acyclovir
Liver transplant