Evaluation of patients with elevated liver function test (LFT)
Liver Function Test
description
Transcript of Liver Function Test
Liver Function TestLiver 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
2 SD
Abnormal Normal
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
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
Liver Function Test
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
catalyze transfer amino groups to form oxaloacetate
cytosol (20%) and mitochondria (80%)
cytosol
T1/2 17 hr. (cytosol)
87 hr. (mitochondria)
T1/2 47 hr.
liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and RBC
low concentration in other tissues
• level of transminase elevation
• predominant AST elevation
• rate of transaminase declination
AST, ALT
• 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 timesALT 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
AST predominant• Alcohol-related liver injury• Steatohepatitis• Cirrhosis• Drug• Nonhepatic
– Hemolysis– Myopathy– Thyroid disease– Strenuous exercise
• Macro AST
*almost any types of liver disease
Common medication
• 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
RE cell plasma hepatocyte
HEME UCB UCB
+
albumin
UCB+ligandin
BMG
BDG
bile
urobilinogen stercobilinogen
BilirubinUDP-glucoronyltransferase
• 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
Bilirubin
Isolated unconjugated hyperbilirubinemia
• IDB fraction > 85% of total bilirubin1. increase production :
• hemolysischronic hemolysis-not sustained increase of bilirubin >5 mg/dl in normal hepatic function
• ineffective erythropoiesis : folate, IDA• drug : rifampicin, ribavirin, probenecid• resolution of hematoma
2. defects in hepatic uptake/conjugation• 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
• 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
Conjugated hyperbilirubinemia
• 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
Physiologic• >60 yr.• child and adolescent• pregnancy• blood group O• post meal (fatty meal)
Pathologic• intrahepatic • extrahepatic
Alkaline phosphatase
Alkaline phosphatase
Intrahepaticviral alcohol
drug pregnancy
PBC PSC
TPN sepsis
vanishing bile duct syndrome
benign recurrent cholestasis
benign post-op. cholestasis
paraneoplastic syndrome
venoocclusive disease
GVHD
Extrahepaticintraluminal 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
• Partial bile duct obstruction• Medications• Infiltrative liver disease• Hepatic metastasis• PBC• PSC• Hepatitis• Cirrhosis• Vanishing bile duct syndromes• Benign recurrent cholestasis
Infiltrative diseases
• TB• Fungal infection• HCC • Lymphoma• Metastatic malignancy• Amyloidosis • Sarcoidosis • Other granulomatous diseases
modest (up to 3x) rise in aminotransferase,
and up to 20x rise in ALP, bilirubin N-5x
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
• Anabolic steroid• Allopurinol• Amoxicillin-clavuronic acid• Captopril• Carbamazepine• Chlorpropamide• Cyproheptadine• Diltiazem• Erythromycin• Estrogens• Floxuridine• Flucloxacillin• Fluphenazine
• Gold salts• Imipramine• Indinavir• Iprindole• Nevirapine• Methytestosterone• Methylenedioxymethamphetam
ine• Oxaprozin• Pizotyline• Quinidine• Tolbutamide• TPN• Trimethoprim-
sulfamethoxazole
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 chol/TG Hb
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)
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
misnomer– not effectively assess actual function – not always specific for the liver– limited information regarding presence or
severity of complication
Liver Function Test
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