Transcript Document

Liver Function Test
Liver chemistry test
Clinical implication of abnormality
ALT
Hepatocellular damage
AST
Hepatocellular damage
Bilirubin
Cholestasis, impair conjugation, or biliary obstruction
ALP
Cholestasis, infiltrative disease, or biliary obstruction
PT
Synthetic function
Albumin
Synthetic function
GGT
Cholestasis or biliary obstruction
Bile acids
Cholestasis or biliary obstruction
5`-nucleotidase
Cholestasis or biliary obstruction
LDH
Hepatocellular damage, not specific
Normal Laboratory Values
Normal
Abnormal
2 SD
normal values = mean ± 2SD of normal population
Liver Function Test
• interpretation must be performed within
the context of the patient’s risk factors,
symptoms, concomitant conditions,
medications, and physical findings
• rarely provide specific Dx, but rather
suggest a general category of liver
disease
• differing laboratories  differing
normal values
Liver Function Test
Mild
(times)
Moderate
(times)
Marked
(times)
AST
<2-3
2-3 to 20
>20
ALT
<2-3
2-3 to 20
>20
ALP
<1.5-2
1.5-2 to 5
>5
GGT
<2-3
2-3 to 10
>10
Liver Function Test
classified in 3 groups
•synthetic function : albumin, PT
•hepatocyte injury : AST, ALT
•cholestasis : bilirubin, ALP, GGT
PT, albumin, bilirubin-most common
tests used as prognostic factors
AST and ALT
AST and ALT
• most frequent used markers of
hepatocellular necrosis, but not
correlate with eventual outcome
• decrease : recovery or poor prognosis
– poor prognosis : rapid fall with rising of
bilirubin and PT
AST
ALT
catalyze transfer amino
groups to form pyruvate
cytosol (20%) and
mitochondria (80%)
catalyze transfer amino
groups to form oxaloacetate
cytosol
T1/2 17 hr. (cytosol)
87 hr. (mitochondria)
liver, cardiac muscle,
skeletal muscle, kidneys,
brain, pancreas, lungs,
leucocytes, and RBC
T1/2 47 hr.
low concentration in other
tissues
AST, ALT
• level of transminase elevation
• predominant AST elevation
• rate of transaminase declination
• Peak values of transaminase activity occur
between the 7th and l2th days;
• activities then gradually decreaser,e
aching normal levelsb ythe 3rd to 5th week
if recovery is uneventful
• Persistenceo f increased A LT for more
than 6 months after an episode of acute
hepatitis is used to diagnose chronic
hepatitis
• After AMI, increased AST activity appears
in serum, as might be expected from the
high AST concentration in heart muscle.
AST activity also is increased in
progressive muscu-
• The ratio seems to clearly identify the
liver-cell "necrotic type" condition (i'e''
slight enzyme increase concomitant with
relatively high activities of mitochondrial
enzymes), typical of alcoholic hepatitis
• Several authors have described AST
linked to immunoglobulins, or macro-AST
• The typical findings are a persistent
increase of serum AST activity in an
asymptomatic subiect, with the absence of
any demonstrable pathology in organs rich
in AS
• The increased AST activity might reflect
decreased clearance of the abnormal
complex from plasma. Macro-AST has no
known clinical relevance
ALT and AST
• >15 times : acute hepatic injury
5-15 times : less useful
<5 times : chronic hepatic injury
improved acute hepatic injury
AST/ALT ratio
• < 1 : majority of liver disease
• >2
– extrahepatic source
– alcoholic hepatitis
– ischemic and toxin
– acute Wilson’s disease : hemolysis
– cirrhosis
• >4 : fulminant Wilson’s disease
Rate of Transaminase
Declination
rapid
• ischemic
• short half life drug
• acute biliary tract
obstruction
• fulminant hepatitis
slow
• acute viral hepatitis
• long half life drug
• AIH
• metabolic disease
ALT and AST < 5 times
ALT predominant
• Chronic hepatitis B, C
• Acute hepatitis (A-E,
EBV, CMV)
• Steatohepatitis
• Hemochromatosis
• Medications/toxins
• Autoimmune hepatitis
• Alpha1-antitrypsin
deficiency
• Wilson’s disease
• Celiac disease
*almost any types of liver disease
AST predominant
• Alcohol-related liver injury
• Steatohepatitis
• Cirrhosis
• Drug
• Nonhepatic
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Hemolysis
Myopathy
Thyroid disease
Strenuous exercise
• Macro AST
Common medication
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Acetaminophen overdose
Statins
NSAIDs
Antibiotics
Antiepileptics
Antituberculosis drugs
Herbal remedies, alternative
medications and substance abuse
ALT and AST < 5 times
and AST predominant
• history alcohol intake (history from
patient and family members)
• hemolysis studies
• aldolase
• CPK
• macro-AST
ALT and AST > 15 times
• Acute viral hepatitis
(A-E, herpes)
• Medications/toxins
• Ischemic hepatitis
• Acute bile duct
obstruction
• Autoimmune
hepatitis
• Wilson’s disease
• Acute Budd-Chiari
syndrome
• Hepatic artery
ligation
• Heat stroke
AST predominate : medication/toxin, ischemic
 >75 times : ischemic, toxic, viral (less common)
Bilirubin
Bilirubin
UDP-glucoronyltransferase
RE cell
HEME UCB
plasma
UCB
+
albumin
hepatocyte
UCB+ligandin
BMG
BDG
bile
urobilinogen
stercobilinogen
Bilirubin
• Direct bilirubin : reacted directly with
reagent
Indirect bilirubin : require addition of
alcohol for color development
• Unconjugated bilirubin = indirect form
Conjugated bilirubin = bilirubin mono
and di-glucoronides
Isolated unconjugated
hyperbilirubinemia
• IDB fraction > 85% of total bilirubin
1. increase production :
•
hemolysis
chronic hemolysis-not sustained increase of
bilirubin >5 mg/dl in normal hepatic function
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•
•
ineffective erythropoiesis : folate, IDA
drug : rifampicin, ribavirin, probenecid
resolution of hematoma
2. defects in hepatic uptake/conjugation
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Gilbert’s syndrome
Crigler-Najjar syndrome
Indirect Hyperbilirubinemia
Bilirubin
AST, ALT
Alb
Glob
PT
hemolysis
5 mg/dl
increase AST
N
N
N
Gilbert’s
syndrome
5 mg/dl
normal
N
N
N
Conjugated hyperbilirubinemia
• DB > 50% of total bilirubin
• can’t differentiate obstruction and
parenchymal disease
• Delta fraction
– CB tightly bound to albumin
– tendency of hyperbilirubinemia to resolve
more slowly than other biochemical tests
Conjugated hyperbilirubinemia
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Bile duct obstruction
Hepatitis
Cirrhosis
Medications/Toxins
Primary biliary
cirrhosis
• Primary sclerosing
cholangitis
• Sepsis
• Total parenteral
nutrition
• Intrahepatic
cholestasis of
pregnancy
• Benign recurrent
cholestasis
• Vanishing bile duct
syndromes
• Dubin-Johnson
syndrome
• Rotor syndrome
Alkaline phosphatase
Alkaline phosphatase
• family of isoenzyme catalyze hydrolysis
of No. of P esters at alkaline pH
• require Zn for activity
• present in nearly all tissues (liver, bone,
intestinal, placenta, kidney)
• liver ALP
– isoenzyme, 5’-nucleotidase, GGT
Alkaline phosphatase
Physiologic
• >60 yr.
• child and adolescent
• pregnancy
• blood group O
• post meal (fatty meal)
Pathologic
• intrahepatic
• extrahepatic
Alkaline phosphatase
Intrahepatic
Extrahepatic
viral
alcohol
drug
pregnancy
PBC
PSC
TPN
sepsis
vanishing bile duct syndrome
benign recurrent cholestasis
benign post-op. cholestasis
paraneoplastic syndrome
venoocclusive disease
GVHD
intraluminal obstruction :
gall stones, ascariasis,
hemobilia
disease of BD :
PSC, choledochal cyst,
cholangioCA,
AIDS cholangiopathy
external compression :
LN, GB CA, Mirizzi’s syndrome,
CA pancreas, ampullar adenoma
Alkaline phosphatase
• initial evaluation : determine hepatic
or nonhepatic origin, concomitant
elevation of other serum LFT
• level not a reliable indicator of
severity of underlying liver disease
• degree not help to distinguish
intrahepatic and extrahepatic
Isolated hepatic ALP elevation
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Partial bile duct obstruction
Medications
Infiltrative liver disease
Hepatic metastasis
PBC
PSC
Hepatitis
Cirrhosis
Vanishing bile duct syndromes
Benign recurrent cholestasis
Infiltrative diseases
modest (up to 3x) rise in aminotransferase,
and up to 20x rise in ALP, bilirubin N-5x
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TB
Fungal infection
HCC
Lymphoma
Metastatic malignancy
Amyloidosis
Sarcoidosis
Other granulomatous diseases
Alkaline phosphatase
• ALP > 1000 : malignant biliary
obstruction, sepsis, AIDS with systemic
infection
• decrease : hypothyroidism, pernicious
anemia, Zn deficiency, congenital,
Wilson’s disease, severe hepatic
insufficiency
Medications  elevation of
bilirubin and ALP
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Anabolic steroid
Allopurinol
Amoxicillin-clavuronic acid
Captopril
Carbamazepine
Chlorpropamide
Cyproheptadine
Diltiazem
Erythromycin
Estrogens
Floxuridine
Flucloxacillin
Fluphenazine
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Gold salts
Imipramine
Indinavir
Iprindole
Nevirapine
Methytestosterone
Methylenedioxymethamphetam
ine
Oxaprozin
Pizotyline
Quinidine
Tolbutamide
TPN
Trimethoprimsulfamethoxazole
γ-glutamyltransferase (GGT)
γ-glutamyltransferase (GGT)
• catalyzed transfer of γ-glutamyl groups
of peptides to other amino acid
• abundant in liver, kidney, pancreas,
intestine, and prostate, spleen, heart,
brain but not in bone
• T1/2
– 7-10 days
– 28 days in alcohol-associated liver injury
γ-glutamyltransferase (GGT)
• increase
– alcohol
– drug
• anticonvulsant (CBZ, phenytoin, and
barbiturate), warfarin, OC
– almost all type of liver diseases
– COPD, renal failure, DM, hyperthyroidism,
RA, AMI, pancreatic disease
Summary
Hepatocellular necrosis
Biliary obstruction
Infiltration
toxin/
ischemia
viral
alcohol
complete
partial
AST/ALT
50-100X
5-50X
2-5X
1-5X
1-5X
1-3X
ALP
1-3X
1-3X
1-10X
2-20X
2-10X
1-20X
Bilirubin
1-5X
1-30X
1-30X
1-30X
1-5X
1-5X
PT
increase in severe,
unresponsive to vit K
increase,
responsive to vit K
normal
albumin
increase in subacute/chronic
usually normal,
decrease in advance
normal
Albumin
Albumin
• depend on nutrition, volume status,
vascular integrity, catabolism,
hormone, loss in stool and urine
• not specific for liver disease
• T1/2 19-21 D
– not reliable indicator of acute liver disease
Hypoalbuminemia
globulin
1.decrease synthesis
-protein malnutrition
-chronic liver disease
-chronic inflammation
2.increase loss
-PLE
-NS
3.increase Vd (ascites, overhydration)
4.increase turnover (catabolic state, steroid)
chol/TG Hb
Globulin
• produced by stimulated B lymphocyte
• elevation in
• chronic liver disease
• chronic inflammation and malignant
disease
Prothrombin time
• liver synthesize coagulation factor
except FVIII
• most present in excess, clotting
abnormal occur only when substantial
impairment in ability of liver to
synthesis
• PT : FI, II, V, VII, IX and X
• T1/2 FVII 6 hrs. (shortest)
• prognosis : acute, chronic
hepatocellular disease
Prothrombin time
prolonged :
• vitamin K deficiency (malnutrition,
malabsorption, antibiotics)
• massive transfusion
• congenital disease
• liver disease
• warfarin
• DIC
Prothrombin time
• in vit K deficiency, vit K 10 mg SC
decrease prolong PT >30% within 24
hrs.
• INR : no advantage over PT
Take home message
• initial evaluation : assess in clinical
context
• classified in 3 groups
 synthetic function : albumin, clotting
time
 cholestasis : bilirubin, ALP, GGT
 hepatocyte injury : AST, ALT
Liver Function Test
misnomer
– not effectively assess actual function
– not always specific for the liver
– limited information regarding presence or
severity of complication
Liver Chemistry Test
Liver Function Test
• normal may have abnormal test
• normal value not ensure that patient is
free of liver disease
• level of abnormality does not reflect
severity but may help in DDx
• decrease in the value does not mean
improvement
• limitation in sensitivity and specificity