Liver Function Tests
Steve Bradley
Chief Medical Resident, HMC
Inpatient Services
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
Tests of Liver Injury

AST/ALT
– 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
Patterns of Enzyme Elevation

Hepatocellular injury
– AST/ALT

Cholestatic
– Bilirubin/alkaline phosphatase
Mixed
 Isolated/predominant alkaline
phosphatase elevatioin

Caveats to Patterns

Hepatocellular injury
– 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!!
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
What targets the hepatocyte?

Toxins

– Alcohol
– Medications
– Severe hypotension
– Vasoconstriction
– Sepsis
 Tylenol
– Mushrooms

Viral
– Hepatitis A/B/C
– EBV/HSV/CMV
Ischemia
Autoimmune
 Wilson’s
 Alpha-1 antitrypsin
deficiency

Degree of elevation points to
etiology

>1000 to 2000
– 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
Back to our patient

Transaminases in the 1000s
– Suggests ischemia/toxin/viral

IVDU
– Risk of acute Hep B or acute Hep C

Cocaine
– Risk of ischemia

Recent infection
– Doxycycline
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
Increased Bilirubin

Sources
– 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
Biliary Obstruction

Canicular cell injury
– Alkaline phosphatase
 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
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
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?
Patient #3: Biggie Smalls
46 yo man with history of IVDU and longstanding alcohol use following up in clinic.
 Laboratory

– AST 68
– ALT 37
– Alk phos 194
– TBili 1.3
– Albumin 2.9
Mixed Patterns of Elevated Liver
Function

Chronic Liver disease
– Hepatitis B, Hepatitis C
– NASH
– Alcoholic liver disease
– Hemochromatosis
– Autoimmune hepatitis
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
What else do you want to know?

Where else is AST and ALT found?

How can you look for evidence of muscle
injury?
Additional Laboratory
CK 7260
 Myoglobin 23390
 UA – 2+ blood, microscopic no RBC


Diagnosis?
Isolated or Predominant Alk Phos

Chronic Biliary Disease
– Primary biliary cirrhosis
– Primary sclerosing cholangitis

Infiltrative disorder
– Amyloid
– Granulomatous diseases
– Metastatic carcinoma
– abscesses
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
Fulminant Hepatic Failure

Rapid development of severe acute liver
injury with impaired synthetic function and
encephalopathy
– Previously had a normal liver or had wellcompensated liver disease
Causes
Treatment

Directed therapy
– 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