OMG my LFT’s!
How to Interpret and Use Them
René Romero, M.D.
Clinical Director, Pediatric Hepatology CPG‐Gastroenterology, Hepatology and Nutrition
Emory University School of Medicine
Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
• Objectives
– Understand the anatomy and microanatomy of the liver and its influence on clinical testing
– Understand the standard battery of tests used for clinical purposes
– Recognize general laboratory patterns of liver test results to aid in age‐specific evaluation
•Will be enhanced in the subsequent series of talks
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OMG my LFT’s!
• The liver has long been seen as a mysterious organ – Babylonian culture
•Foretold the future by reading sheep liver
– Prometheus
•Mythical recounting of liver regeneration
Let’s de-mystify the Liver and the reading of its signs
Let’s start with some facts about the liver
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The liver has a dual blood supply with 60-80% from the portal venous system and 20-40 % form the hepatic artery
Blood travels through the portal vein to the sinusoids and out the of the liver via the hepatic veins. Arterial blood is principal supply to the biliary system.
Excretion of products into systemic blood or biliary system
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A common theme is substances exchanged by the hepatocyte at the sinusoidal membrane, transported/transformed through hepatocyte, and excreted at canalicular membrane or back out into the blood.
FBS http://dx.doi.org/10.2741/E598
Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
• General functions of the liver – Guardian/Defender/command center – Filter/Detoxifier
– Warehouse – Distribution center – Factory
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“The functions of the liver are only exceeded by the number of investigations designed to test those functions.”
Dame Sheila Sherlock
Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
• Liver Function Tests
– Poor term as most routine clinical tests do not measure function
• Uses – Screening – Assess severity
• Not all of the common tests do this adequately
– Trending and follow up
• Limitations – Lack of sensitivity
• Normal “LFTs” ≠ normal liver
– Lack of specificity
• Similar abnormalities can be seen in different diseases 7
Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
• Liver Tests Categories – Liver cell “injury”
tests – Tests of liver
excretory or transport functions (transport of organic anions or drugs) – Tests of liver
synthetic functions
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OMG my LFT’s!
No single one test is sufficient to give the complete picture of liver To solve the puzzle you need more than one piece
Sometimes a pattern give a clue as to meaning And
How LFT’s
and WOF
are similar
Children’s Healthcare of Atlanta | Emory University
• Common Liver cell (hepatocyte) “injury” tests
• AST “aspartate aminotransferase” (serum glutamate oxaloacetic transaminase‐SGOT)”
– Transfers aspartate to a ketogroup in ketoglutaric acid
– Located in the mitochondria (80%) and cytosol (20%) in hepatocytes – Also present in heart, skeletal muscle, kidney, brain
• ALT “alanine aminotransferase” (serum glutamic pyruvate transaminase‐
SGPT
– Transfers alanine to a ketogroup in ketoglutaric acid – Located in cytosol of hepatocytes
– Also found in skeletal muscle
• Values in serum represent relative rate of entry in or out of circulation at the level of hepatic sinusoids
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TRANSAMINITIS
Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
• Common Tests of liver excretory or transport functions
–Bilirubin• Derived from hemoglobin degradation
• Total, indirect (unconjugated), direct (conjugated)
• Levels depend on the balance of production and clearance
• urine bilirubin – conjugated hyperbilirubinemia; Urobilinogen – unconjugated hyperbilirubinemia
– Alkaline phosphatase
• Found in the microvilli of the bile canaliculi
• Liver, kidney, bone, intestine
• Vary with age
–GGT (gamma glutamyl transferase)
• Membrane bound glycoprotein
• Large amount in biliary epithelium, kidneys, pancreas, intestine, prostate
• Inducible by AED and other drugs
–Ammonia/Bile Acid‐ other talks 11
Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
• Tests of liver synthetic functions
• Albumin
– Quantitatively largest amount of protein produced by liver – Half life is 20 days; not a reflection of recent disease – Altered by infection, nutrition, extrahepatic losses
• PT/INR
– Liver produces 11 of 13 factors measured in this test of coagulation
– As half life of most of these proteins are short, PT/INR is more indicative of recent synthetic capacity and therefore can have prognostic value
– Many are vitamin K dependent
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OMG my LFT’s!
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Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
• LFT patterns – Cholestatic
•TB and DB
•Alk Phos
•GGT
•AST and ALT Variable
•Synthetic parameters indicative of severity or chronicity
• Age Dependent Epidemiology – Infant
•Sepsis
•BA/ other anatomic biliary obstruction
•A1AT, ALGS, PFIC, CF
•Metabolic disease – Older Child
•Biliary obstruction
•Drug
•Sepsis
•Less commonly viral, chronic liver disease
– Adolescent
•Biliary obstruction
•Drug
•Less commonly viral, chronic liver disease
•Sepsis
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OMG my LFT’s!
• LFT patterns – Hepatocyte injury
•TB and DB ±
•Alk Phos ±
•GGT ±
•AST and ALT
•Synthetic parameters indicative of severity or chronicity
• Age Dependent Epidemiology – Infant
•Sepsis/ischemia
•Viral
•Metabolic disease
•Drug – Older Child
•Sepsis/ischemia
•Viral
•NAFLD
•Drug
•Metabolic disease – Adolescent
•Sepsis/ischemia
•Viral
•Drug -
Classical chronic primary liver disease
Children’s Healthcare of Atlanta | Emory University
• Case 1
• 7 year old male – Adopted – Appears normal
according to parents
•“everyone says how strong he looks”
•No jaundice, no pruritus
•No organomegaly
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CREATINE KINASE OSF: 16726
CREATININE : 0.25 CALCIUM : 9.2 TOTAL PROTEIN : 6.6 ALBUMIN : 4.5 ALKALINE PHOS : 117 AST (SGOT) : 343 ALT (SGPT) : 712 Bilirubin Total : 0.3 GAMMA GGT : 10 Bile Acids : 11.4
PT (Prothrombin Time) : 10.6 INR OSF: 1.0 WBC OSF: 3.6
HGB OSF: 12.4 HCT OSF: 37.4 RDW OSF: 13.8 PLATELET COUNT OSF: 298
Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
• Case 2
• 7 year old boy – URI for three days – Complaining of
abdominal pain and feeling warm
– Mom using Tylenol and a cold pain reliever steadily past three days every 6 hours
– He is ill appearing a little confused
17 CREATININE : 0.8
CALCIUM : 9.2 TOTAL PROTEIN : 6.6 ALBUMIN : 4.0 ALKALINE PHOS : 250 AST (SGOT) : 1898 ALT (SGPT) : 2578 Bilirubin Total : 2.5 GAMMA GGT : 40
PT (Prothrombin Time) : 25.7 INR 2.5 WBC OSF: 8.3
HGB OSF: 13.4 HCT OSF: 38.4 PLATELET COUNT OSF: 195
Acetaminophen level -25
Children’s Healthcare of Atlanta | Emory University
OMG my LFT’s!
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LFT’s
Age, History, Physical findings And use of a battery of tests (or buying a vowel)
CMP- Na, K, Cl, CO2, BUN, Cr, Glu, TP, Alb, ALK phos, AST, ALT, TB + GGT, DB
+ PT/INR
or
HFP- TP, Alb, Alk Phos, AST, ALT, TB, DB
+ GGT + PT/INR
Higher likelihood of correct Diagnosis and Action A
A
O L V R
W ND L
O
WOF
What is the category?
What is context of the letter?
Can you buy a vowel?
L
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OMG my LFT’s!
• As the next speakers discuss their subjects – What is the age specific epidemiology?
– How does standard testing help categorize?
•How might the tests fall short?
– What do I feel comfortable performing myself?
– When should referral should be made?
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