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Interpretation of Liver Function Test

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Interpretation of Liver Function Test , , M.D., Ph.D. Essential serum methods in hepato-biliary disease Noninvasive method ... – PowerPoint PPT presentation

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Title: Interpretation of Liver Function Test


1
Interpretation of Liver Function Test
  • ???? ??, ????
  • ? ? ?, M.D., Ph.D.

2
Liver Function Tests
Liver battery - cholesterol - protein -
albumin - bilirubin - alkaline
phosphatase - SGOT (AST) - SGPT (ALT) -
gamma-glutamyltransferase
3
Essential serum methods in hepato-biliary disease
  • Noninvasive method of screening
  • Patterns
  • Hepatocellular or cholestatic
  • Severity outcome
  • Response to treatment

4
Limitations
  • Not sensitive
  • CH/LC/HCC
  • Not specific
  • Albumin in IBD, AST in AMI
  • Not diagnostic but categorizable

5
Approximate Frequency of Liver Function Test
Abnormlity in Hospital General Medical Admissions
Overall () Unexpected () Albumin
10 5 Bilirubin 5
2 AST/ALT 5 2 ALP
10 5-10 GGT 5-15
5-15 AST aspartte aminotransferase ALT
alanine aminotransferase ALP alkaline
phosphatase GGT gamma-glutamyltransferase
6
General categories of LFTs
  • Transport organic anions metabolize drugs
  • Bilirubin, ICG
  • Hepatocyte injury
  • AST, ALT, LDH
  • Cholestasis
  • ALP, GGT
  • Biosynthetic capacity
  • Albumin, cholesterol, PT, clotting factor

7
Bilirubin
  • Production/hepatic removal
  • Overproduction
  • Uptake, conjugation, excretion? ??
  • Regurgitation
  • Uncomplicated hemolysis lt 3-5 mg/dL
  • Parenchymal liver dis, Calculi lt malignant
    obstruction
  • Clay color stool usually cholestatic,
    hepatocellular possible, not hemolytic
  • Dark urine direct hyperbilirubinemia, usually
    cholestatic
  • 30-50 mg/dL ?? renal failure

8
Unconjugated conjugated bilirubin
  • Unconju. Conjugated
  • Van den Bergh reaction Indirect Direct
  • Water solubility -
  • Lipid solubility -
  • Albumin attachment
  • Icteric urine -
  • Bile -
  • Brain affinity -
  • Hemolysis /-
  • Obstructive/hepatocellular

9
Albumin-linked bilirubin
  • Part of direct-reacting bilirubin fraction
  • Covalently linked to albumin
  • Important fraction of total serum bilirubin in
    cholestasis hepatobiliary disorder
  • Half-life 4 hours ? 14 days
  • ?? ??? conjugated bilirubinemia ?? bilirubinuria?
    ??? ???.
  • Decline more slowly than expected

10
N Eng J Med 1983309147
11
Urinary bilirubin
  • Unconjugated bilirubin
  • Tightly albumin bound
  • Not filtered ? not present in urine
  • 100 of serum bilirubin by new precise methods
  • Unconjugated bilirubin
  • Both healthy Gilbert syndrome
  • Urinary bilirubin
  • Conjugated bilirubinemia
  • Hepatobiliary disease? ??
  • Low renal threshold
  • Normal serum bil level, no jaundice ??? ??

12
Aminotransferase (transaminase)
  • Liver cell injury
  • AST (SGPT), ALT (SGOT)
  • Present in serum in low concentration source?
  • AST liver, cardiac m., skeletal m.,kidney,
    brain, pancreas, lung, WBC, RBC
  • No tissue specific isoenzyme
  • Damage or permeability
  • Clearing
  • AST gt ALT
  • By RES
  • Not biliary or urinary excretion

13
AST/ALT ratio
  • Location
  • ALT cytosol
  • AST cytosol most circulating AST in healthy
  • mitochondria 80 of activity in the
    liver
  • ALT more sensitive specific
  • ALT lt 300 IU, AST/ALT ratio gt2 or gt3 ALD
  • Pyridoxal phosphate deficiency
  • Noninvasive indicator of cirrhosis
  • Very specific (94-100) but Not sensitive
    (44-75)
  • AST/ALT lt 1 viral hepatitis, NASH

14
Other enzyme tests
  • Glutamate dehydrogenase
  • Isocitrate dehydrogenase
  • Lactate dehydrogenase
  • Sorbitol dehydrogenase

15
Alkaline phosphatase
  • Function, degradation site?
  • Canalicular membrane of hepatocyte, osteoblast,
    brush border of intestine, Proximal convoluted
    tubules, placenta, WBC
  • Half life 7 days
  • Higher in older men (15-50 years old)
  • Normally elevated in adolescents late pregnancy
  • Elevation hepatobiliary disease, bone or
    pregnancy gt intestine gt kidneys

16
Normal Serum Alkaline Phosphatase Values
at Various Ages in Men and Women
17
Source of isoenzyme
  • Electrophoresis
  • Inactivation by heat
  • Placental or tumor origin heat stable
  • Other enzyme activity
  • GGT, 5-nucleotidase, leucine aminopeptidase

18
Principal diagnostic value
  • 75 of prolonged cholestasis pts gt ? 4 WNL
  • No difference between extra and intrahepatic
    obstruction
  • Isolated elevation
  • Partial bile duct obstruction stone, tumor
  • Infiltrative disease sarcoidosis, abscesses, Tb,
    metastatic carcinoma
  • Elevation in cancer patients
  • Bone or hepatic metastasis
  • Tumor secretion / leakage of hepatic phosphatase

19
Principal diagnostic value II
  • Elevation lt ? 4 WNL
  • Nonspecific
  • Viral hepatitis, CH, LC, infiltrative disease
  • Moderate elevations
  • Hodgkins disease, CHF, myeloid metaplasia,
    intraabdominal infections, osteomyelitis
  • Familial
  • Extremely low level
  • Wilson disease with hemolysis

20
?-Glutamyl Transpeptidase
  • Cell membrane in kidney, pancreas, liver, spleen,
    heart, brain, seminal vesicle not in bone
  • Normally exist in serum (0-30 IU/L)
  • No change during pregnancy
  • Clinically elevated in disease of liver, biliary
    tract, pancreas
  • Clinical value DDx of elevated ALP, alcohol
    abuse
  • Not elevated in bone disease
  • Not elevated in childhood pregnancy
  • GGT/ALP gt 3 alcohol, drug

21
?-Glutamyl Transpeptidase
  • Isolated elevation of GGT
  • Medication barbiturate, phenytoin,
    anticonvulsant, warfarin
  • Alcohol
  • Induction of hepatic microsomal GGT by EtOH or
    drugs
  • Leakage from hepatocyte by alcohol
  • Fatty liver disease
  • Insulin resistance, visceral fat, fatty liver

22
Immunoglobulin
  • Elevated in chronic liver disease
  • Impaired RES, Shunt
  • Antibodies to normal colonic flora
  • A/G ratio
  • Autoimmune hepatitis, cirrhosis (IgG, IgM),
    chronic inflammation, malignancy
  • Changes in liver disease
  • PBC IgM, ALD IgA, normal in obstructive
    jaundice
  • Clinical use Dx F/U of AIH

23
Albumin
  • 300-500 g in body fluids
  • Synthesize 15 g/d
  • Half life 20 days
  • 4 degraded daily
  • Regulation of synthesis Nutrition, osmotic
    pressure, systemic inflammation, hormone
  • ? AA, corticosteroid, thyroid hormone
  • ? Alcohol, inflammation
  • Chronic liver disease, heavy alcohol ingestion,
    chronic infection, malnutrition, protein loosing
    enteropathy, nephrotic syndrome

24
Prothrombin time
  • I, II, V, VII, IX, X, XII, XIII
  • Half life lt 24h
  • Congenital, consumption, warfarin, Vitamin K
    deficiency, parenchymal liver disease
  • Vitamin K 5- 10 mg parenteral injection
  • Improves 30 within 24 hours
  • Not sensitive but highly prognostic
  • Alcoholic steatonecrosis, hepatocellular disease,
    acetaminophen overdose
  • PT? ???? ??? ?? ?? ??? ??

25
Cholesterol
  • Synthesized in liver, small intestine
  • Cholestasis
  • 1.5-2 ? acute cholestasis
  • ? ? ? post-operative stricture, PBC
  • 5 ? xanthoma
  • Parenchymal injury
  • Usually normal in LC
  • Low level decompensation, malnutrition

26
Diagnositc approach
  • ??? ???? ??? ??????
  • ??? ??? ?? ??
  • AST/ALT, AP/GGT, albumin/PT/cholesterol
  • Categorization
  • ?? Hepatocellular Cholestatic Infiltrative
  • ALT - 0- 0-
  • AP 0- - -
  • Bil 0- 0- 0-
  • PT 0-?? 0-?? 0
  • Albumin ???? ?? 0 0
  • ????

27
?_? F/38
28
?? ???? ???
  • ??? ??
  • Pattern? ??
  • ????? ??
  • Biosynthetic capacity, Hepatocellular damage,
    excretory function, cholestasis ?? ???? ?? ?? ??
    ?? ????
  • ?? ?? ? ?? ???? ??(discrepancy)? ??? ? ??? ????
  • ?? ??, ?? ??? ????
  • ??? ??? ????
  • ??? ??? ????

29
? _? M/73
30
?_? M/71
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