THE MORNING REPORT

The Best in FOAM Education

  • Jia Jian Li, MD

Guide to Transaminitis

Introduction


AST

  • Liver, cardiac muscle, skeletal muscle, kidney, and brain


ALT

  • Present primarily in the liver

  • More specific marker of hepatocellular cell injury


Serum alkaline phosphatase

  • Predominantly from the liver and bones

  • Other sources

  • Women in the third trimester of pregnancy (due to an influx into blood of placental alkaline phosphatase)

  • Diabetes mellitus

  • Genetics

  • Age (generally higher in children and adolescents because of physiologic osteoblastic activity. Gradually increases from age 40 to 65 years, particularly in women)


Gamma-glutamyl Transferase (GGT)

  • Hepatocytes and biliary epithelial cells, kidney, seminal vesicles, pancreas, spleen, heart, and brain


Patterns


Hepatocellular

  • Disproportionate elevation in the serum aminotransferases compared with the alkaline phosphatase

  • Serum bilirubin may be elevated

  • Tests of synthetic function may be abnormal


Cholestatic

  • Disproportionate elevation in the alkaline phosphatase compared with the serum aminotransferases

  • Serum bilirubin may be elevated

  • Tests of synthetic function may be abnormal


Analyzing Lab Results


AST to ALT ratio

  • Most causes of hepatocellular injury are associated with a serum AST level that is lower than the ALT

  • An AST to ALT ratio of 2:1 or greater is suggestive of:

  • Alcoholic liver disease (elevated GGT)

  • Nonalcoholic steatohepatitis

  • Hepatitis C who have developed cirrhosis.

  • Wilson disease or cirrhosis due to viral hepatitis may have an AST that is greater than the ALT


Alcoholic fatty liver disease:

  • AST <8 times the upper limit of normal; ALT <5 times the upper limit of normal.


Nonalcoholic fatty liver disease:

  • AST and ALT <4 times the upper limit of normal.


Acute viral hepatitis or toxin-related hepatitis with jaundice:

  • AST and ALT >25 times the upper limit of normal.


Ischemic hepatitis (ischemic hepatopathy, shock liver, hypoxic hepatitis):

  • AST and ALT >50 times the upper limit of normal (in addition the lactate dehydrogenase is often markedly elevated).


Chronic hepatitis C virus infection:

  • Wide variability

  • Typically normal to less than twice the upper limit of normal,

  • Rarely more than 10 times the upper limit of normal


Chronic hepatitis B virus infection:

  • Levels vary

  • AST and ALT may be normal in inactive carriers, whereas most patients with chronic hepatitis B have mild to moderate elevations (approximately twice the upper limit of normal); with exacerbations, levels are more than 10 times the upper limit of normal


Emergencies


Acute liver failure

  • Typically more than 10 times the upper limit of normal

  • Hepatic encephalopathy

  • Prolonged prothrombin time (INR greater than or equal to 1.5)


Marked elevation without liver failure

  • Patients with marked or severe elevations in their aminotransferase levels (approximately 15 times the upper limit of normal or higher) often have acute hepatitis, although in some cases, there may be underlying chronic liver disease (eg, Wilson disease or an acute exacerbation of hepatitis B virus).

  • Massive elevations in aminotransferases (>5,000 U/L) are usually due to ischemic or drug-induced hepatitis.

  • Other causes of massive elevations in AST include rhabdomyolysis and heat stroke.


Alkaline Phosphatase


Alkaline Phosphatase

  • Acute or chronic elevation of the alkaline phosphatase in conjunction with other liver biochemical abnormalities may be due to:

  • Extrahepatic causes (eg, bile duct stones, primary sclerosing cholangitis, malignant biliary obstruction)

  • Intrahepatic causes (eg, PBC, primary sclerosing cholangitis, infiltrative disease)


  • Testing in patients with an elevated alkaline phosphatase of hepatic origin typically starts with right upper quadrant ultrasonography to assess the hepatic parenchyma and bile ducts

  • The presence of biliary dilatation on ultrasonography suggests extrahepatic cholestasis, whereas the absence of biliary dilatation suggests intrahepatic cholestasis


  • Only be used to evaluate elevations of other serum enzyme tests (eg, to confirm the liver origin of an elevated alkaline phosphatase or to support a suspicion of alcohol abuse in a patient with an elevated AST and an AST to ALT ratio of greater than 2:1


GGT


GGT

  • Only be used to evaluate elevations of other serum enzyme tests (eg, to confirm the liver origin of an elevated alkaline phosphatase or to support a suspicion of alcohol abuse in a patient with an elevated AST and an AST to ALT ratio of greater than 2:1.)


Conclusion


Take away #1: Not all transaminitis mean liver damage


Take away #2: AST to ALT ratio matters but must be interpreted in combination with other serum enzyme tests and clinical picture


Take away #3: GGT should only be used to evaluate elevations of other serum enzyme tests


References

https://www.uptodate.com/contents/approach-to-the-patient-with-abnormal-liver-biochemical-and-function-tests?search=transaminitis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1