Interpretation of Liver Function Test

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Interpretation of Liver Function Test

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• ? ? ?, M.D., Ph.D.

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Liver Function Tests
Liver battery - cholesterol - protein -
albumin - bilirubin - alkaline
phosphatase - SGOT (AST) - SGPT (ALT) -
gamma-glutamyltransferase
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Essential serum methods in hepato-biliary disease

• Noninvasive method of screening
• Patterns
• Hepatocellular or cholestatic
• Severity outcome
• Response to treatment

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Limitations

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

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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
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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

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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

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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

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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

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N Eng J Med 1983309147
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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 ??? ??

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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

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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

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Other enzyme tests

• Glutamate dehydrogenase
• Isocitrate dehydrogenase
• Lactate dehydrogenase
• Sorbitol dehydrogenase

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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

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Normal Serum Alkaline Phosphatase Values
at Various Ages in Men and Women
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Source of isoenzyme

• Electrophoresis
• Inactivation by heat
• Placental or tumor origin heat stable
• Other enzyme activity
• GGT, 5-nucleotidase, leucine aminopeptidase

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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

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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

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?-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

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?-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

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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

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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

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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? ???? ??? ?? ?? ??? ??

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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

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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
• ????

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

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? _? M/73
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?_? M/71