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  Ischemia
– Alcohol – Severe hypotension
– Medications – Vasoconstriction
 Tylenol – Sepsis
– Mushrooms
 Viral  Autoimmune
– Hepatitis A/B/C  Wilson’s
– EBV/HSV/CMV
 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  Intrahepatic
– Choledocholithiasis – TPN
– Malignancy – Sepsis
 Cholangiocarcinoma – Primary sclerosing
 Pancreatic cancer cholangitis
 Gallbladder cancer
– Primary biliary
 Ampullary cancer
cirrhosis
– Primary sclerosing – Intrahepatic mass
cholangitis
– AIDS Cholangiopathy
 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 long-
standing 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 well-
compensated 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