Liver Function Tests - An Approach for Primary Care

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This presentation is aimed at primary care physicians. It covers the fundamentals of liver function tests, including the basic principles of interpretation, and the key patterns of abnormalities. The focus is on how to approach liver function tests in a primary care setting.

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Liver Function Tests - An Approach for Primary Care

  1. 1. Liver Function Tests An Approach for Primary Care Dr Jarrod Lee Consultant Gastroenterologist & Advanced Endoscopist Mt Elizabeth Novena Hospital 1
  2. 2. Scope   Principles of interpreting LFTs Patterns of abnormal LFTs     Hepatocellular Damage Cholestasis Biosynthetic function Bilirubin 2
  3. 3. 'Traditional' Liver Function Test (LFT)  ALT: alanine transaminase (SGPT) AST: aspartate transaminase (SGOT) ALP: alkaline phosphatase GGT: gamma Glutamyl Transferase Albumin, bilirubin Total protein, globulin  Known as LFT, but they're really not!      3
  4. 4. Utility of LFTs • Advantages    Sensitive, non-invasive method to screen for liver dysfunction Patterns of abnormal LFTs can help recognized type of liver disorder Easy way to follow the course of liver diseases • Limitations – Poor sensitivity and specificity – Seldom leads to diagnosis 4
  5. 5. Interpreting LFTs the Principles 5
  6. 6. Broad Principles  Contextualization   Normal    LFT interpretation must be contextualized for each individual patient Different labs have different ‘normal’ values ‘Abnormal’ values may be ‘normal’ Patterns   LFTs rarely provide specific diagnosis Rather, suggests the general category of liver disorder through the pattern of abnormal LFT 6
  7. 7. Normal vs Abnormal Normal Abnormal 2 SD    Normal values = mean ± 2SD of normal population Normal: 95% of normal, asymptomatic patients have numbers in this range on a “bell shaped curve” Abnormal: By definition, 2.5% of normal patients have lab values either above or below the “normal” range 7
  8. 8. Patterns of Abnormal LFTs      Hepatocellular damage: ALT, AST, LDH Cholestasis: ALP, GGT, bilirubin, bile acids Biosynthetic function: PT/ INR, albumin, cholesterol Metabolic function: bilirubin, ammonia, lactate, glucose, ICG Clinical scores of decompensation: CPS, MELD 8
  9. 9. Patterns of Abnormal LFTs  Hepatocellular damage: ALT, AST, LDH Cholestasis: ALP, GGT, bilirubin, bile acids Biosynthetic function: PT/ INR, albumin, cholesterol Metabolic function: bilirubin, ammonia, glucose, ICG  Clinical scores of decompensation: CPS, MELD    9
  10. 10. Interpreting LFTs the Patterns 10
  11. 11. Hepatocellular Damage 11
  12. 12. Markers of Hepatocellular Damage    ALT & AST most frequently used Released when hepatocytes damaged Normal values:    ALT: 5 – 40 IU/L AST: 8 – 20 IU/L Patterns to note:    AST: ALT ratio Level of elevation Rate of decline 12
  13. 13. ALT vs AST ALT    Cytosol Half life: 47H Low concentration in other tissues:   Skeletal muscle, kidney, heart More specific for liver    AST Cytosol 20%, mitochondria 80% Half life: cytosol 17H, mitochondria 87H Other tissues:  heart, RBC, skeletal muscle, kidneys, pancreas, brain, lung 13
  14. 14. AST: ALT Ratio    Normal: 0.6 – 0.8 < 1: most liver disorders > 2:       Alcoholic hepatitis: AST < 300 Drugs & toxins Extra-hepatic source Ischemia Cirrhosis Fulminant Wilson’s disease (> 4) 14
  15. 15. AST: ALT Ratio 90 80 70 60 50 AST/ALT >1 AST/ALT >2 40 30 20 10 0 alcoholic post necrotic cirrhosis chronic hepatitis obstructive jaundice viral hepatitis
  16. 16. Level of Elevation  ALT > 600 (15x):   ALT < 200 (5x):   Acute hepatic injury Chronic hepatic injury, improved acute injury ALT 200-600 (5-15x):   Less useful Most common scenario! 16
  17. 17. ALT > 600 (15x)     Acute viral hepatitis Acetaminophen overdose Ischemic hepatitis aka shock liver      Drugs & toxins Autoimmune hepatitis Wilson's disease Acute bile duct obstruction Acute Budd Chiari Syndrome Can cause ALT > 3000 (75x) 17
  18. 18. ALT < 200 (5x) ALT Predominant     Chronic hepatitis B, C Acute viral hepatitis NASH Drugs, toxins  Autoimmune hepatitis Metabolic disorders  AST Predominant     Almost any liver disease   Alcoholic liver disease Drugs, toxins NASH Cirrhosis Non-hepatic source:   Haemolysis, myopathy, strenuous exercise Macro-AST: 15-60% of tertiary referrals 18
  19. 19. Rate of Decline FAST     Short half life drug Ischemic hepatitis Acute biliary tract obstruction Fulminant hepatitis SLOW     Acute viral hepatitis Long half life drug Autoimmune hepatitis Metabolic disorders Green: Ischemic hepatitis Blue: Acute viral hepatitis 19
  20. 20. Cholestasis 20
  21. 21. Alkaline Phosphatase (ALP)     Main marker of cholestasis Normal: 20-70 IU/L Half life: 7 days Sources:    Hepatocytes Osteoblasts, gut, kidney, placenta Biliary obstruction:   Raised levels due to induction of ALP synthesis May not rise until 1-2 days later 21
  22. 22. Raised ALP: Causes Physiologic Causes  Age > 60 yrs  Children, adolescents  Pregnancy  Blood group O  Post meal (fatty meal) Pathologic Causes  Intrahepatic cholestasis  Extrahepatic cholestasis (bile duct obstruction) 22
  23. 23. Normal ALP Values vs Age 23
  24. 24. Raised ALP: Pathologic Causes Intrahepatic Obstruction    Drugs Sepsis Others  Infiltrative liver disease  Primary biliary cirrhosis  Primary sclerosing cholangitis (PSC)  Paraneoplastic syndromes Extrahepatic Obstruction  Intraluminal:   Bile duct wall:   Gallstones Cholangiocarcinoma Extraluminal:  Pancreatic cancer, lymph nodes, gallstones (Mirizzi's Syndrome) 24
  25. 25. -Glutamyl Transpeptidase (GGT)  Main utility      Differentiate ALP source Not found in bone; not raised in pregnancy/ childhood Sources: liver, kidney, pancreas, intestine, prostate, spleen, heart, brain Half life: 7-10 days; 28 days in alcohol liver injury Isolated GGT elevation:    Due to induction of hepatic microsomal GGT Drugs: warfarin, anticonvulsants, barbiturates Alcohol: also causes hepatocyte leakage 25
  26. 26. Biosynthetic Function 26
  27. 27. Coagulation Factors    All synthesized in liver except Factor VIII Mostly present in excess Prothrombin Time (PT): Factors I, II, V, VII, IX, X    Half life: Factor VII – 6H (shortest) Abnormalities only occur when liver's biosynthetic ability substantially impaired Common causes:   Vit K deficiency (malnutrition, malabsorption) Warfarin 27
  28. 28. Albumin       300 – 500 g in body fluid Synthesis: 15 g/ day Degradation: 4% daily Half life: 19 – 21 days Not reliable indicator of acute liver disease Not specific  Depends on nutrition, volume status, vascular integrity, catabolism, hormones, stool/ urine losses 28
  29. 29. Hypoalbuminemia  Decreased synthesis: protein malnutrition, chronic liver disease, chronic inflammation  Increased loss: nephrotic syndrome, protein losing enteropathy  Increased volume: ascites, over-hydration Increased turnover: catabolic states, steroids  Clues: globulin, cholesterol/ TG  29
  30. 30. Bilirubin 30
  31. 31. 'Bilirubin' Pathway RE Cell Plasma Heme → UCB UCB – Albumin Hepatocyte UCB + 'gluconate' → CB Urobilinogen Stercobilinogen UCB: Unconjugated bilirubin CB: Conjugated bilirubin 31
  32. 32. Bilirubin Unconjugated Bilirubin      Indirect bilirubin Normal: < 0.8 mg/ dL (< 13.6 µmol/L) Lipid soluble, water insoluble Bound to albumin in plasma Not filtered by kidney → not present in urine Conjugated Bilirubin      Direct bilirubin Normal: 0.3 – 1.0 mg/dL (5.1 – 17.0 µmol/L) Water soluble, lipid insoluble Excreted in bile Filtered by glomerulus → majority reabsorbed, small amount excreted in urine 32
  33. 33. Isolated Unconjugated Hyperbilirubinemia   Unconjugated bilirubin > 85% of total bilirubin Increased production:      Haemolysis: rarely > 5 mg/dL (85 µmol/L) Ineffective erythropoiesis: folate/ iron deficiency Drugs: rifampicin, ribavirin Resolution of hematoma Defects in hepatic uptake or conjugation:  Gilbert's syndrome, Criggler – Najjar syndrome 33
  34. 34. Conjugated Hyperbilirubinemia     Conjugated bilirubin > 50% total bilirubin Cannot differentiate between obstructive & parenchymal causes Tea coloured urine + clay coloured stool: usually cholestatic cause, although parenchymal cause possible Malignant obstruction usually higher values 34
  35. 35. Delta Bilirubin  Conjugated bilirubin covalently bound to albumin     Important fraction of total bilirubin in patients with cholestasis & hepatobiliary disease Prolonged half life: 19 – 21 days (albumin) Late recovery phase: all bilirubin may be in this form Explains 2 enigmas in patients with raised conjugated bilirubin:   CB declines slowly in patients who are recovering well No bilirubinuria during recovery phase as delta bilirubin not filtered by glomeruli 35
  36. 36. Summary  Principles of LFTs:   Contextualization, Normal Values, Abnormal Patterns Patterns of Abnormal LFTs     Hepatocellular injury: ALT, AST  AST: ALT ratio  Level of elevation  Rate of decline Cholestasis: ALP, GGT Biosynthetic function: PT, albumin Bilirubin 36
  37. 37. Conclusion       'LFT's are numerous & somewhat confusing Have limited sensitivity & specificity Not all liver ds have abnormal LFT Not all normal LFTs have normal livers Decrease in values may not mean improvement What to do?    All abnormal LFTs should be investigated LFTs must be contextualized for each patient Refer when unsure 37
  38. 38. Thank You 38

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