OMG my LFT s! How to Interpret and Use Them. OMG my LFT s! OMG my LFT s!

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1 How to Interpret and Use Them René Romero, M.D. Clinical Director, Pediatric Hepatology CPG Gastroenterology, Hepatology and Nutrition Emory University School of Medicine 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 2 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 Ann Intern Med. 2008;149: https://web.stanford.edu/.../liverpages/livergallbladderspleen.html 3

2 The liver has a dual blood supply with 60-80% from the portal venous system and % 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 4 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 5 General functions of the liver Guardian/Defender/command center Filter/Detoxifier Warehouse Distribution center Factory The functions of the liver are only exceeded by the number of investigations designed to test those functions. Dame Sheila Sherlock 6

3 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 Children s in different Healthcare diseases of Atlanta Emory University 7 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 8 How LFT s and WOF are similar 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 You need context 9

4 TRANSAMINITIS 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 10 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 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 12

5 13 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 Sepsis Less commonly viral, chronic liver disease Adolescent Biliary obstruction Less commonly viral, chronic liver disease Sepsis 14 LFT patterns Hepatocyte injury TB and DB ± Alk Phos ± GGT ± AST and ALT - Synthetic parameters indicative of severity or chronicity Classical chronic primary liver disease may have this presentation Age Dependent Epidemiology Infant Sepsis/ischemia Viral Metabolic disease Older Child Sepsis/ischemia Viral NAFLD Metabolic disease Adolescent Sepsis/ischemia Viral NAFLD 15

6 Case 1 7 year old male Adopted Appears normal according to parents everyone says how strong he looks No jaundice, no pruritus No organomegaly CREATINE KINASE OSF: 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: 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 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 V O L R W N D L O L LFT s Age, History, Physical findings And use of a battery of tests (or buying a vowel) A CMP- Na, K, Cl, CO2, BUN, Cr, Glu, TP, Alb, ALK phos, AST, ALT, TB + GGT, DB + PT/INR WOF What is the category? What is context of the letter? Can you buy a vowel? or HFP- TP, Alb, Alk Phos, AST, ALT, TB, DB + GGT + PT/INR Higher likelihood of correct Diagnosis and Action 18

7 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? 19

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