Transcript
EVALUATION OF LIVER FUNCTION
TESTSGuide - Dr. Manohar Lal Prasad Presenter - Dr. Dhiraj Kumar
Source - Harrison’s principles of internal medicine 19th edition.Sleisenger and Fortrans textbook of gastrointestinal and liver disease.
LIVER FUNCTION TEST USED TO:
Detect presence of liver disesase
To know the extent of known liver diseases
Distinguish among different types of liver diseases
Follow the response to treatment
Liver function tests
Can be normal in pt. with serious liver diseases
Rarely suggests specific
diagnosis rather suggest
general categories of liver disease
Hepatocellular
Cholestatic , or infiltrative
They detect –liver cell damge,
interference with bile flow
Functions of liver
Metabolic functions
Excretory functions
Synthetic functions
Storage functions
Detoxification functions
Tests based on detoxification function:
Blood ammonia level
Tests based on excretory functions:
Sr. bilirubin Urine bilirubin
Urine and fecal
urobilinogen
Urine bile salts
Tests based on synthetic functions:
Plasma protein Prothrombin time
Tests based on metabolic functionsCarbohydrate metabolism• G
alactose tolerance test
Lipid metabolism• Sr
Cholesterol
Protein metabolism• S
r Protein
• Aminoaciduria
Enzymes in diagnosis of liver diseses
ENZYMES
•AST(SGOT)•ALT(SGPT)
ENZYMES•ALP•GGT•5’NT
Tests used in clinical practice
Sr . Bilirubin ALT(SGPT)
AST(SGOT) Alkaline phosphatase
Serum Albumin
Prothrombin time
Sr. Bilirubin• Breakdown product of porphyrin ring of heme containing
protein( myoglobin, cytochrome, peroxidase)• Two fractions:• Conjugated(Direct)(water soluble)(excreted by kidney)• Unconjugated (indirect)(water insoluble) (bound to
albumin)• Normal value- 1- 1.5mg/dl• In case of hyperbilirubinemia, if direct fraction <15% -
Unconjugated hyperbilirubinemia• Direct fraction- Upper limit of normal range is 0.3mg/dl
CAUSES OF HYPERBILIRUBINEMIA Isolated increase in unconjugated bilirubin is due to –1. Hemolytic disease2. Genetic disorders – crigler najjar and gilbert’s syndrome3. Neonatal jaundice/physiological jaundice
Isolated increase in conjugated bilirubin is due to –4. Cholestasis5. Genetic disorders – Dubin johnson syndrome and rotor’s
syndrome
Increase in both conjugated and unconjugated bilirubin is due to –
1. Intrahepatic /liver disorders
Degree of elevation of Sr bilirubin significant in:
Viral hepatitis
Alcoholic hepatitis
Drug induced liver disease
Model for End Stage Liver Disease(MELD) Score
• Criteria for listing a pt. for liver transplantation• Range of MELD score is 6 to 40• Liver tansplantation done in those pt who
have >15 MELD score• MELD score – bilirubin, creatinine, PT as INR• MELD score >= 21 high mortality in alcoholic
hepatitis
Urine Bilirubin:
Any bilirubin in urine- Conjugated bilirubin
Unconjugated fraction is water insoluble and albumin bound, hence not filtered
Phenothiazine give false positive
Recovering from jaundice urine bilirubin clears prior to Sr bilirubin
Bile salts:
• Are products of cholesterol metabolism• Facilitate absorption of fat from intestine• Primary bile salts- cholate & chenodeoxycholate,
produced in liver
• Metabolised by bacteria in intestine
• Produces secondary bile salts-lithocholate & deoxycholate
Bile salts
In cirrhosis- decreased ratio of primary to secondary bile salts
In cholestasis - secondary bile salts not formed – increased ratio of primary to secondary bile salts
Normally renal excretion of bile salt is negligible
Cholestasis increase renal excretion of bile salt
Measured by- Hay’s test, HPLC
BLOOD AMMONIA:Detoxification of ammonia
In liver – get converted to urea-excreted in kidney
In striated muscles- combines with glutamine – glutamic acid
Advanced liver disease •Significant muscle wasting•Contributes to hyperammonemia
Increased blood ammonia •Detect occult liver disease with mental status change
Increased blood ammonia •In severe portal hypertension•Portal blood shunts around liver
Increased arterial ammonia •Correlates with fulminant hepatic failure outcome
ENZYMES IN LIVER DISEASES
• Sr transaminases• Aspartate
aminotransferases (AST)(SGOT)
• Alanine aminotransferases (ALT)(SGPT)
• Alkaline phosphatase(ALP)• Gamma glutamyl
transpeptidase(GGT)• 5’ Nucleotidase(5’NT)
Sr enzyme test grouped in two categories:
Enzymes whose elevation reflect damage to hepatocytes
Enzyme whose elevation reflect cholestasis
Enzyme showing infiltrative pattern
Enzymes that reflect damage to hepatocytes:
Aspartate aminotransfersase(AST)(SGOT)
Alanine aminotransferases(ALT)(SGPT)
AST(SGPT) is found in liver > cardiac muscles > skeletal muscles> kidney> brain >pancreas> lungs> WBC >RBC
ALT(SGPT) is found primarily in liver.( more liver specific)
Normal range is 10-40 IU/L
• Sr aminotransferases upto 300 IU/L are non specific
• Minimal ALT elevation Fatty liver disease• If levels >1000 IU/L reflects extensive
hepatocellular injury seen in:1. Viral hepatitis2. Ischemic liver injury( prolonged hypotension
or acute heart failure3. Toxin/drug induced liver injuryIn most acute hepatocellular disorder ALT >=AST
AST/ALT Ratio:• Normal ratio 0.7 to 1.4• Useful in 1. Wilson disease 2. Chronic liver disease 3. Alcoholic liver disease• AST/ALT <1 seen in 1.Chronic viral hepatitis 2.NAFLD • AST/ALT >2:1 suggestive & 3:1 is highly suggestive of alcoholic
liver disease• In alcoholic liver disease : ALT rarely >300 & ALT often
normal( alcohol induced deficiency of PYRIDOXAL PHOSPHATE)
Aminotransf-erases
not increased
in obstructive jaundice
except
During the
acute phase
of biliary
obstruction
Due to passage of gall
stone into CBD
In this aminotran-sferases
1000-2000 IU/L
AST(SGOT)
• 2 forms 1. Cytosolic 2. Mitochondrial (mAST) – synthesized in precursor
form( pre-mAST)
converted to mature form• Account for 80% of total AST activity in liver cells• mAST/ total AST ratio- marker of chronic alcohol
consumption
• Isolated rise of ALT is seen in1. Chronic HepC infection2. Fatty liver• Isolated AST elevation1. Alcohol related 2. Drug induced liver injury3. Hemolysis4. Myopathic processesThese enzymes distinguish hepatocellular from cholestatic
jaundice• Increase in ALT and AST (>500 IU/L) in hepatocellular
jaundice than in cholestatic jaundice(>200 IU/L)• Persistence of elevated AST & ALT beyond 6 month in
case of hepatitis – chronic hepatitis
Enzymes showing cholestasis:• 3 enzymes are elevation in cholestasis 1. Alkaline phosphatase(ALP)2. 5’Nucleotidase(5’NT)3. Gamma glutamyl transpeptidases(GGT)
ALP & 5’NT – in or near bile canalicular membrane of hepatocytes
GGT located in ER & bile duct epithelial cells(less specific for cholestasis)
GGT (sometimes) used to identify occult alcohol use
• ALP isoenzyme is found in 1. Liver 2. Bone 3.Placenta 4. Small intestine• Physiological rise in ALP 1. Age >60 years ( 1-1.5 times)2. Blood type O & B (after eating a fatty meal
due to influx of intestinal ALP in blood)3. Children and adolescents ( rapid bone growth)4. Late in normal pregnancies( placental ALP)
• ALP < 3 times – any liver disease• ALP> 4 times 1. Cholestatic liver disease 2. Infiltrative liver disease(cancer & amyloidosis) 3. Pagets disease of bone( rapid bone turnover)If ALP is raised – source of isoenzyme by:1. Fractionation of ALP by electrophoresis2. Measure GGT &5’NT –elevated only in liver disease3. Different isoenzymes have different heat susceptibilityi. Increased heat stable fraction – MC from placentaii. Sensitive to heat inactivation- Bone ALP
Normal levels
Sr GGT 10 to 47 IU/L
Sr 5’ NT 2 to 17 IU/L
Sr ALP 39 to 117IU/L
Tests based on Biosynthetic function
Plasma proteins
Coagulation factors(Prothrombin time P.T.)
Plasma proteins• Liver is the sole source of plasma proteins except for
immunoglobulins( by plasma cells)• Sr albumin comprises 60% of all plasma proteins• Tests of plasma protein include:1. Total Sr protein2. Sr albumin 3. Sr globulin4. Sr A/G ratio5. Pre albumin6. Pro collagen III peptide 7. Ceruloplasmin
Albumin• Synthesized exclusively by hepatocytes• Long half life 18 – 20 days; 4% is degraded per day• Slow turn over – not a good indicator of acute or mild hepatic
dysfunction• In hepatitis , albumin < 3 mg/dl – Chronic liver disease like
cirrhosis, reflects liver damage and decreased albumin synthesis• Non hepatic cause of low albumin:1. Protein malnutrition2. Protein losing enteropathy3. Nephrotic syndrome4. Chronic infection(increased levels of IL-1, TNF, Cytokines- inhibit
albumin synthesis
Sr Globulin
• Made of alpha, beta , gamma globulin• Alpha & beta globulin produced primarily in hepatocytes• Gamma globulin produced by B lymphocytes• In Cirrhosis and Chronic hepatitis – gamma globulin is
increased ( Cirrhotic liver fails to clear bacterial antigen from intestine which come through hepatic circulation)
• Diffuse polyclonal IgG – Auto immune hepatitis• Increased IgM – Primary biliary cirrhosis• Increased IgA- Alcoholic liver disease
• Pre Albumin1. Level falls in liver diseases2. Half life 2 days3. Sensitive indicator of change in synthetic & catabolic function4. Useful in drug induced hepato toxicity• Ceruloplasmin 1. Acute phase protein2. Normal plasma level 0.2 – 0.4g/l• Decreased in Increased in 1. Wilson disease 1.Copper toxicity2. Menke’s disease 2. Pregnancy3. Aceruloplasminemia 3. OCPs4. Copper deficiency
Pro collagen III peptide
• Cleavage product of type III procollagen molecule• Radioimmuno assay• Increased when there is transformation of viable
hepatic tissue into connective tissue / fibrosis• Used in evolution of liver disease like:1. Chronic active hepatitis2. Liver fibrosis 3. Liver cirrhosis
Coagulation factors• Except factor VIII, clotting factors synthesized in
liver• Half life ranges 6 hrs( factor VII) to 5 days
(fibrinogen)• Measurement is single best measure of hepatic
synthetic function• Diagnosis and prognosis of acute parenchymal liver
diseases• Test – Prothrombin time(PT)• PT measures II, VII, IX, X activity - Vit K dependent
PT & INR• INR- Degree of anti coagulation on warfarin therpy• International Sensitivity index(ISI): INR standardise PT
measured according to thromboplastin reagent used in any lab expressed as ISI.
• ISI is used to calculate INR• PT is increased in 1. Hepatitis2. Cirrhosis3. Vit k deficiency- obstructive jaundice, fat malabsorption4. If PT > 5 times , not corrected by parenteral Vit k - poor
prognostic sign in acute viral hepatitis & other liver diseaseINR is part of MELD Score
LFT in Anti TB treatment• LFT should be preferred before starting anti TB treatment• With use of rifampicin & isoniazid , onset of liver damage
may be as soon as 10 days or may be upto 1yr after commencing therapy
• So LFT should be repeated routinely• High risk groups are –1. Malnourished 2. Children and elderly3. Known liver disease - Alcoholic liver disease - Hepatitis B &C
Percutaneous liver biopsyCan be performed bedside with LADone in• Hepatocellular disease of uncertain cause• Prolonged hepatitis with possibility of auto immune hepatitis• Unexplained hepatitis• Fever of known origin• Staging of malignant lymphomaContradiction of percutaneous liver biopsy• Significant ascites• Prolonged INRIn these conditions transjugular approach is done.
Transient Elastography (FibroScan)
• Ultra sound waves to measure hepatic stiffness non invasively
• Useful for early fibrosis in1. Chronic Hep C2. Primary Biliary Cirrhosis3. Hemochromatosis4. NAFLD5. Recurent chronic hepatitis after liver
transplantation
Evaluation of chronically abnormal liver tests
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