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Liver Function Test
Piyanant Chonmaitree, MD.
Department of Medicine
Srinakharinwirot University
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
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
Liver Function Test
• should be evaluated and Rx in more
expeditious manner
– marked abnormalities
– S&S of chronic liver disease or
decompensation
• mild elevation is nonspecific and usually
normal when repeated
– observe vs. additional evaluation
must be made in context of clinical scenario
Advantages
• sensitive, noninvasive
method of screening liver
dysfunction
• pattern of laboratory test
abnormalities to
recognize type of liver
disorder
• assess severity of liver
dysfunction
• follow cause of liver
disease
Disadvantages
• lack sensitivity
– normal results in serious
liver disease
• not specific for liver
dysfunction
• seldom lead to specific
diagnosis
Liver Function Test
Initial Approach
history
• patient’s symptoms
• risk factors for liver
disease
• concomitant conditions
• medications
• occupational exposure
to hepatotoxins
physical examination
• body habitus
• splenomegaly
• ascites
• cutaneous stigmata of
chronic liver disease
•history and physical examination
•algorithm approach useful mainly when
no clinical clues
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
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
ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย ถ่ายเหลว 2 เดือนก่อน
PE : T 37º C, markedly pale, no jaundice, koilonychia,
glossitis, coarse hair, no sign of chronic liver disease,
liver and spleen not palpated
LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 1.8 g/dl [3.5-5.5 g/dl] glob 2 g/dl [1.5-3.5 g/dL]
chol 80 mg/dl [<200]
จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว
Case 1
ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย บวม 2 เดือนก่อน
PE : T 37º C, not pale, no jaundice,
no sign of chronic liver disease,
liver and spleen not palpated
LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 1.8 g/dl [3.5-5.5 g/dl] glob 2 g/dl [1.5-3.5 g/dL]
chol 250 mg/dl [<200]
จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว
Case 2
ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย ท้องบวม 2 เดือนก่อน
PE : T 37.8º C, mildly pale, no jaundice
no sign of chronic liver disease,
liver and spleen not palpated, shifting dullness +
LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 1.8 g/dl [3.5-5.5 g/dl] glob 4.5 g/dl [1.5-3.5 g/dL]
chol 100 mg/dl [<200]
จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว
Case 3
ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย ท้องบวม 2 เดือนก่อน
PE : T 37º C, mildly pale, no jaundice,
spider nevi, palmar erythrema,
liver and spleen not palpated, shifting dullness +
LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 1.8 g/dl [3.5-5.5 g/dl] glob 4.5 g/dl [1.5-3.5 g/dL]
chol 100 mg/dl [<200]
จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว
Case 4
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
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
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
0
10
20
30
40
50
60
70
80
90
alcoholic post necrotic
cirrhosis
chronic
hepatitis
obstructive
jaundice
viral hepatitis
AST/ALT >1
AST/ALT >2
AST/ALT ratio
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
AST predominant
• Alcohol-related liver injury
• Steatohepatitis
• Cirrhosis
• Drug
• Nonhepatic
– Hemolysis
– Myopathy
– Thyroid disease
– Strenuous exercise
• Macro AST
*almost any types of liver disease
Risk factor of chronic viral hepatitis
• injection drug use
• birth to mother with HBV
• blood transfusion prior to 1992
• needle stick from a donor subsequently
testing positive for HBV or HCV
• chronic hemodialysis
• unvaccinated health care workers
• homosexual
• body piercing or tattooing
Common medication
• Acetaminophen overdose
• Statins
• NSAIDs
• Antibiotics
• Antiepileptics
• Antituberculosis drugs
• Herbal remedies, alternative
medications and substance abuse
ALT and AST < 5 times
• discontinue all nonessential medications
• if mild elevation and essential
medications must be continued
– if liver enzyme elevations continue to rise,
suspect medication should be stopped
– long-term effects of chronic, medication
induced hepatotoxicity are lacking for many
drugs
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ตรวจร่างกายปกติ
LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT และบอก management ในผู้ป่ วยรายนี้
Case 5
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ไม่มีอาการผิดปกติ
ใดๆ ไม่ดื่มสุรา ไม่กินยาใดๆ ไม่เคยได้รับเลือด ไม่เคยใช้สารเสพ
ติด
ตรวจร่างกายปกติ, BW 90 kg, Height 160 cm., truncal
obesity
LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
จงบอก management ในผู้ป่ วยรายนี้
Case 5.1
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ไม่มีอาการผิดปกติ
ใดๆ ไม่ดื่มสุรา ไม่กินยาใดๆ ไม่เคยได้รับเลือด ไม่เคยใช้สารเสพ
ติด
ตรวจร่างกายปกติ, BW 90 kg, Height 160 cm., truncal
obesity
LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
viral profile-negative
Case 5.1
NAFLD/NASH
• NAFLD = macrovesicular steatosis with mild
or without inflammation, no fibrosis
• NASH = NAFLD + inflammation/
ballooning/fibrosis
• alcohol <70 g/D in women, <140 g/D in men
• 2 hits hypothesis
– hyperinsulinemia  increased FFA in liver 
steatosis
– hepatocyte necrosis and inflammation
NAFLD/NASH
• asymptomatic, vague RUQ pain,
fatigue, malaise
• hepatomegaly, splenomegaly, spider
angiomata, palmar erythema, ascites
• AST, ALT 2-4x, AST/ALT<1
1/3 ALP slightly elevated
NAFLD/NASH
• U/S –bright liver
CT-lower density than spleen
MRI-bright on T1W
• biopsy (gold standard) :
macrovesicular steatosis, parenchymal
inflammation, hepatocyte necrosis,
ballooning hepatocyte degeneration
NAFLD/NASH
• weight reduction, exercise, control DM
and dyslipidemia
orlistat, sibutramine, Bariatric surgery
• avoidance of toxins : drugs, alcohol
• insulin sensitizing agents
– thiazolidinediones
– metformin
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี มีประวัติ IVDU
ตรวจร่างกายปกติ
LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
จงบอก investigation เพิ่มเติมในผู้ป่ วยรายนี้
Case 5.2
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี มีประวัติ IVDU
ตรวจร่างกายปกติ
LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
HBsAg positive
antiHCV negative
Case 5.2
ALT and AST < 5 times
and AST predominant
• history alcohol intake (history from
patient and family members)
• hemolysis studies
• aldolase
• CPK
• macro-AST
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี
ตรวจร่างกายปกติ
LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3
mg/dl]
AST 280 U/L [0-35 U/L] ALT 250 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT และบอก management ในผู้ป่ วยรายนี้
Case 6
Alcoholic hepatitis
• appropriate history of alcoholic
consumption, serologic exclusion of
other liver disease
• ♂ 40-80 g/D, ♀ 20-40 g/D 10-12 yrs.
• characteristic pattern
– AST rarely exceeds 300 IU/dl
– AST/ALT >1 in 92%, >2 in 70%
• pyridoxine deficiency
• alcohol induces release of mitochondrial AST
– GGT/ALP >2.5
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ดื่มสุรา ½ ขวดกลม
ต่อวัน 20 ปี
ตรวจร่างกายปกติ
LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 280 U/L [0-35 U/L] ALT 250 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT และบอก management ในผู้ป่ วยรายนี้
Case 6
Alcoholic hepatitis
Rx
• abstinence alcohol drinking
• severe alcoholic hepatitis (DF >32)
[DF = 4.6 x (PT-control) + serum bilirubin]
– glucocorticoid (no GI bleeding and active
infection) improve survival, not reduce
HRS
– pentoxyfilline reduce HRS
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)
ผู้ป่ วยหญิงอายุ 40 ปี underlying disease AF, HT มาด้วย CHF
LFT :TB 2 mg/dl [0.3-1 mg/dl] DB 1 mg/dl [0.1-0.3 mg/dl]
AST 2500 U/L [0-35 U/L] ALT 2200 U/L [0-35 U/L]
ALP 180 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT, DDx สาเหตุและบอก management ในผู้ป่ วยราย
นี้
Case 7
Ischemic hepatitis
• low-flow hemodynamic state
– hypotension, sepsis, cardiac arrhythmia,
MI, HF, hemorrhage, extensive burns,
severe trauma, heat stroke
• hypotension often not documented
• usually subclinical
(shock liver, acute hepatic circulatory insufficiency)
• sudden and massive (>2000) elevation
of liver enzyme, tend to decrease rapidly
and return normal within 1 wk.
• mild and transient elevation of bilirubin
(80% < 2 mg/dl) and ALP
• extreme elevation LDH (>5000),
ALT/LDH < 1.5
• rare acute liver failure
• Rx and prognosis α underlying disease
Ischemic hepatitis
Ischemic hepatitis
ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย RUQ pain 12 ชั่วโมงก่อน
LFT :TB 2 mg/dl [0.3-1 mg/dl] DB 1.5 mg/dl [0.1-0.3 mg/dl]
AST 1200 U/L [0-35 U/L] ALT 1400 U/L [0-35 U/L]
ALP 180 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT, DDx สาเหตุและบอก management ในผู้ป่ วยราย
นี้
Case 8
Acute biliary obstruction
• aminotransferase peak early and
decline rapidly over 24-72 hr. despite
unresolved obstruction
• after aminotransferase decrease,
bilirubin and ALP increase
• 25% of patients with AST > 10X
Acute biliary obstruction
ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย RUQ pain 12 ชั่วโมงก่อน
LFT :TB 2 mg/dl [0.3-1 mg/dl] DB 1.5 mg/dl [0.1-0.3 mg/dl]
AST 1000 U/L [0-35 U/L] ALT 1300 U/L [0-35 U/L]
ALP 180 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
U/S : bile duct dilatation with gall stone
F/U LFT 72 hr. AST 300 U/L, ALT 600 U/L
Case 8
LDH
• non specific
• rhabdomyolysis, MI, hemolysis, stroke,
renal infarction, acute or chronic liver
disease
• use in
– ischemic hepatitis : transient, massive
elevation
– malignant infiltration of liver : sustained
elevation with ALP
RE cell plasma hepatocyte
HEME UCB UCB
+
albumin
UCB+ligandin
BMG
BDG
bile
urobilinogen stercobilinogen
Bilirubin
UDP-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
Diagnostic approach in elevated serum bilirubin
elevated bilirubin
History and PE
unconjugated bilirubin
normal ALP, ALT, AST
conjugated bilirubin
hemolysis studies,
review medications
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
• ineffective erythropoiesis : folate, IDA
• drug : rifampicin, ribavirin, probenecid
• resolution of hematoma
2. defects in hepatic uptake/conjugation
• Gilbert’s syndrome
• Crigler-Najjar syndrome
ผู้ป่ วยชายอายุ 30 ปี มาตรวจสุขภาพประจาปี
LFT :TB 3 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 30 U/L [0-35 U/L] ALT 30 U/L [0-35 U/L]
ALP 100 U/L [30-120 U/L]
alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT, DDx สาเหตุและบอก management ในผู้ป่ วย
รายนี้
Case 9
Gilbert’s syndrome
• benign, unconjugated
hyperbilirubinemia with otherwise
normal liver chemistries
• up to 5% of normal population
• polymorphism in TATA box of gene
encoding bilirubin UDP-GT
impair ability to conjugate bilirubin
• prominent in fasting state, systemic
illnesses, hemolysis, some medications
Gilbert’s syndrome
• Dx :
– asymptomatic, healthy
– mild unconjugated hyperbilirubinemia
(<4 mg/dl) with otherwise normal liver
chemistries test
– exclusion medications and hemolysis
Case 10
ผู้ป่ วยชายอายุ 30 ปี มาด้วยอ่อนเพลีย 3 วันก่อน
PE : T 38º C, markedly pale, mild jaundice, no sign of
chronic liver disease, liver and spleen not palpated
LFT : TB 5.4 mg/dl [0.3-1 mg/dl] DB 0.8 mg/dl [0.1-0.3 mg/dl]
AST 120 U/L [0-35 U/L] ALT 45 U/L [0-35 U/L]
ALP 110 U/L [30-120 U/L]
alb 3.6 g/dl [3.5-5.5 g/dl] glob 3.6 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT DDx สาเหตุและบอก management ในผู้ป่ วยรายนี้
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
Diagnostic approach in elevated serum bilirubin
elevated bilirubin
History and PE
unconjugated bilirubin
normal ALP, ALT, AST
conjugated bilirubin
• 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
Diagnostic approach in elevated serum bilirubin
elevated bilirubin
History and PE
unconjugated bilirubin
normal ALP, ALT, AST
conjugated bilirubin
normal ALP, ALT, AST abnormal ALP, ALT, AST
Rotor’s syndrome
Dubin-Johnson syndrome
Diagnostic approach in elevated serum bilirubin
elevated bilirubin
History and PE
unconjugated bilirubin
normal ALP, ALT, AST
conjugated bilirubin
normal ALP, ALT, AST abnormal ALP, ALT, AST
Rotor’s syndrome AST, ALT ALP
Dubin-Johnson syndrome predominate predominate
hemolysis studies,
review medications
as elevated
ALT evaluation U/S
ERCP as elevated ALT evaluation
review medications
AMA, ERCP, liver biopsy
present absent
/ /
Case 11
ผู้ป่ วยชายอายุ 30 ปี มาด้วยจุกแน่นลิ้นปี่ 3 วันก่อน
PE : T 37º C, not pale, mild jaundice, no sign of chronic liver
disease, liver and spleen not palpated
LFT : TB 6.2 mg/dl [0.3-1 mg/dl] DB 4.8 mg/dl [0.1-0.3 mg/dl]
AST 100 U/L [0-35 U/L] ALT 120 U/L [0-35 U/L]
ALP 520 U/L [30-120 U/L]
alb 3.6 g/dl [3.5-5.5 g/dl] glob 3.6 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT และบอก management ในผู้ป่ วยรายนี้
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
Intrahepatic
viral alcohol
drug pregnancy
PBC PSC
TPN sepsis
vanishing bile duct syndrome
benign recurrent cholestasis
benign post-op. cholestasis
paraneoplastic syndrome
venoocclusive disease
GVHD
Extrahepatic
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
• in biliary obstruction
– induction of ALP synthesis 2° to enhanced
translation of mRNA ALP levels, may not
rise until 1-2 days
– T1/2 1 wk, take several days for levels to
normalise after resolution
• in malignancy “Regan isoenzyme”
• no identifiable liver/bone involvement
• biochemical distinct from liver ALP
• associated variety of different CA ex
lung CA
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
Diagnostic approach in elevated serum alkaline phosphatase
elevated ALP
History and PE
normal bilirubin, ALT, AST abnormal liver chemistries
GGT or 5’nucleotidase U/S
not hepatobiliary U/S
review medication
AMA
ERCP AMA
liver biopsy observation
as elevated ALT evaluation, liver
biopsy, ERCP
negative positive
no duct dilatation
yes no
negative
> 6 months
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี
ตรวจร่างกายปกติ
LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L]
ALP 320 U/L [30-120 U/L]
alb 1.8 g/dl [3.5-5.5 g/dl] glob 2 g/dl [1.5-3.5 g/dL]
จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว
Case 12
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
ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี กินคุมกาเนิดอยู่
ตรวจร่างกายปกติ
LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl]
AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L]
ALP 320 U/L [30-120 U/L]
alb 1.8 g/dl [3.5-5.5 g/dl] glob 2 g/dl [1.5-3.5 g/dL]
GGT 86 [0-50]
จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว
Case 12
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
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
Thank You

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Liver Function Test.ppt MBBS A healthcare provider draws a small amoun

  • 1. Liver Function Test Piyanant Chonmaitree, MD. Department of Medicine Srinakharinwirot University
  • 2. 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
  • 3. Normal Laboratory Values 2 SD Abnormal Normal normal values = mean ± 2SD of normal population
  • 4. 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
  • 5. 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
  • 6. Liver Function Test • should be evaluated and Rx in more expeditious manner – marked abnormalities – S&S of chronic liver disease or decompensation • mild elevation is nonspecific and usually normal when repeated – observe vs. additional evaluation must be made in context of clinical scenario
  • 7. Advantages • sensitive, noninvasive method of screening liver dysfunction • pattern of laboratory test abnormalities to recognize type of liver disorder • assess severity of liver dysfunction • follow cause of liver disease Disadvantages • lack sensitivity – normal results in serious liver disease • not specific for liver dysfunction • seldom lead to specific diagnosis Liver Function Test
  • 8. Initial Approach history • patient’s symptoms • risk factors for liver disease • concomitant conditions • medications • occupational exposure to hepatotoxins physical examination • body habitus • splenomegaly • ascites • cutaneous stigmata of chronic liver disease •history and physical examination •algorithm approach useful mainly when no clinical clues
  • 9. 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
  • 10. 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
  • 11. 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)
  • 12. Globulin • produced by stimulated B lymphocyte • elevation in • chronic liver disease • chronic inflammation and malignant disease
  • 13. ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย ถ่ายเหลว 2 เดือนก่อน PE : T 37º C, markedly pale, no jaundice, koilonychia, glossitis, coarse hair, no sign of chronic liver disease, liver and spleen not palpated LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 1.8 g/dl [3.5-5.5 g/dl] glob 2 g/dl [1.5-3.5 g/dL] chol 80 mg/dl [<200] จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว Case 1
  • 14. ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย บวม 2 เดือนก่อน PE : T 37º C, not pale, no jaundice, no sign of chronic liver disease, liver and spleen not palpated LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 1.8 g/dl [3.5-5.5 g/dl] glob 2 g/dl [1.5-3.5 g/dL] chol 250 mg/dl [<200] จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว Case 2
  • 15. ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย ท้องบวม 2 เดือนก่อน PE : T 37.8º C, mildly pale, no jaundice no sign of chronic liver disease, liver and spleen not palpated, shifting dullness + LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 1.8 g/dl [3.5-5.5 g/dl] glob 4.5 g/dl [1.5-3.5 g/dL] chol 100 mg/dl [<200] จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว Case 3
  • 16. ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย ท้องบวม 2 เดือนก่อน PE : T 37º C, mildly pale, no jaundice, spider nevi, palmar erythrema, liver and spleen not palpated, shifting dullness + LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 1.8 g/dl [3.5-5.5 g/dl] glob 4.5 g/dl [1.5-3.5 g/dL] chol 100 mg/dl [<200] จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว Case 4
  • 17. 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
  • 18. Prothrombin time prolonged : • vitamin K deficiency (malnutrition, malabsorption, antibiotics) • massive transfusion • congenital disease • liver disease • warfarin • DIC
  • 19. Prothrombin time • in vit K deficiency, vit K 10 mg SC decrease prolong PT >30% within 24 hrs. • INR : no advantage over PT
  • 20. 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
  • 21. 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
  • 22. • level of transminase elevation • predominant AST elevation • rate of transaminase declination AST, ALT
  • 23. ALT and AST • >15 times : acute hepatic injury 5-15 times : less useful <5 times : chronic hepatic injury improved acute hepatic injury
  • 24. 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
  • 26. 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
  • 27. 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 AST predominant • Alcohol-related liver injury • Steatohepatitis • Cirrhosis • Drug • Nonhepatic – Hemolysis – Myopathy – Thyroid disease – Strenuous exercise • Macro AST *almost any types of liver disease
  • 28. Risk factor of chronic viral hepatitis • injection drug use • birth to mother with HBV • blood transfusion prior to 1992 • needle stick from a donor subsequently testing positive for HBV or HCV • chronic hemodialysis • unvaccinated health care workers • homosexual • body piercing or tattooing
  • 29. Common medication • Acetaminophen overdose • Statins • NSAIDs • Antibiotics • Antiepileptics • Antituberculosis drugs • Herbal remedies, alternative medications and substance abuse
  • 30. ALT and AST < 5 times • discontinue all nonessential medications • if mild elevation and essential medications must be continued – if liver enzyme elevations continue to rise, suspect medication should be stopped – long-term effects of chronic, medication induced hepatotoxicity are lacking for many drugs
  • 31. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ตรวจร่างกายปกติ LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] จงแปลผล LFT และบอก management ในผู้ป่ วยรายนี้ Case 5
  • 32. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ไม่มีอาการผิดปกติ ใดๆ ไม่ดื่มสุรา ไม่กินยาใดๆ ไม่เคยได้รับเลือด ไม่เคยใช้สารเสพ ติด ตรวจร่างกายปกติ, BW 90 kg, Height 160 cm., truncal obesity LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] จงบอก management ในผู้ป่ วยรายนี้ Case 5.1
  • 33. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ไม่มีอาการผิดปกติ ใดๆ ไม่ดื่มสุรา ไม่กินยาใดๆ ไม่เคยได้รับเลือด ไม่เคยใช้สารเสพ ติด ตรวจร่างกายปกติ, BW 90 kg, Height 160 cm., truncal obesity LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] viral profile-negative Case 5.1
  • 34. NAFLD/NASH • NAFLD = macrovesicular steatosis with mild or without inflammation, no fibrosis • NASH = NAFLD + inflammation/ ballooning/fibrosis • alcohol <70 g/D in women, <140 g/D in men • 2 hits hypothesis – hyperinsulinemia  increased FFA in liver  steatosis – hepatocyte necrosis and inflammation
  • 35. NAFLD/NASH • asymptomatic, vague RUQ pain, fatigue, malaise • hepatomegaly, splenomegaly, spider angiomata, palmar erythema, ascites • AST, ALT 2-4x, AST/ALT<1 1/3 ALP slightly elevated
  • 36. NAFLD/NASH • U/S –bright liver CT-lower density than spleen MRI-bright on T1W • biopsy (gold standard) : macrovesicular steatosis, parenchymal inflammation, hepatocyte necrosis, ballooning hepatocyte degeneration
  • 37. NAFLD/NASH • weight reduction, exercise, control DM and dyslipidemia orlistat, sibutramine, Bariatric surgery • avoidance of toxins : drugs, alcohol • insulin sensitizing agents – thiazolidinediones – metformin
  • 38. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี มีประวัติ IVDU ตรวจร่างกายปกติ LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] จงบอก investigation เพิ่มเติมในผู้ป่ วยรายนี้ Case 5.2
  • 39. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี มีประวัติ IVDU ตรวจร่างกายปกติ LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 75 U/L [0-35 U/L] ALT 90 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] HBsAg positive antiHCV negative Case 5.2
  • 40. ALT and AST < 5 times and AST predominant • history alcohol intake (history from patient and family members) • hemolysis studies • aldolase • CPK • macro-AST
  • 41. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ตรวจร่างกายปกติ LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 280 U/L [0-35 U/L] ALT 250 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] จงแปลผล LFT และบอก management ในผู้ป่ วยรายนี้ Case 6
  • 42. Alcoholic hepatitis • appropriate history of alcoholic consumption, serologic exclusion of other liver disease • ♂ 40-80 g/D, ♀ 20-40 g/D 10-12 yrs. • characteristic pattern – AST rarely exceeds 300 IU/dl – AST/ALT >1 in 92%, >2 in 70% • pyridoxine deficiency • alcohol induces release of mitochondrial AST – GGT/ALP >2.5
  • 43. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ดื่มสุรา ½ ขวดกลม ต่อวัน 20 ปี ตรวจร่างกายปกติ LFT :TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 280 U/L [0-35 U/L] ALT 250 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] จงแปลผล LFT และบอก management ในผู้ป่ วยรายนี้ Case 6
  • 44. Alcoholic hepatitis Rx • abstinence alcohol drinking • severe alcoholic hepatitis (DF >32) [DF = 4.6 x (PT-control) + serum bilirubin] – glucocorticoid (no GI bleeding and active infection) improve survival, not reduce HRS – pentoxyfilline reduce HRS
  • 45. 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)
  • 46. ผู้ป่ วยหญิงอายุ 40 ปี underlying disease AF, HT มาด้วย CHF LFT :TB 2 mg/dl [0.3-1 mg/dl] DB 1 mg/dl [0.1-0.3 mg/dl] AST 2500 U/L [0-35 U/L] ALT 2200 U/L [0-35 U/L] ALP 180 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] จงแปลผล LFT, DDx สาเหตุและบอก management ในผู้ป่ วยราย นี้ Case 7
  • 47. Ischemic hepatitis • low-flow hemodynamic state – hypotension, sepsis, cardiac arrhythmia, MI, HF, hemorrhage, extensive burns, severe trauma, heat stroke • hypotension often not documented • usually subclinical (shock liver, acute hepatic circulatory insufficiency)
  • 48. • sudden and massive (>2000) elevation of liver enzyme, tend to decrease rapidly and return normal within 1 wk. • mild and transient elevation of bilirubin (80% < 2 mg/dl) and ALP • extreme elevation LDH (>5000), ALT/LDH < 1.5 • rare acute liver failure • Rx and prognosis α underlying disease Ischemic hepatitis
  • 50. ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย RUQ pain 12 ชั่วโมงก่อน LFT :TB 2 mg/dl [0.3-1 mg/dl] DB 1.5 mg/dl [0.1-0.3 mg/dl] AST 1200 U/L [0-35 U/L] ALT 1400 U/L [0-35 U/L] ALP 180 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] จงแปลผล LFT, DDx สาเหตุและบอก management ในผู้ป่ วยราย นี้ Case 8
  • 51. Acute biliary obstruction • aminotransferase peak early and decline rapidly over 24-72 hr. despite unresolved obstruction • after aminotransferase decrease, bilirubin and ALP increase • 25% of patients with AST > 10X
  • 53. ผู้ป่ วยหญิงอายุ 40 ปี มาด้วย RUQ pain 12 ชั่วโมงก่อน LFT :TB 2 mg/dl [0.3-1 mg/dl] DB 1.5 mg/dl [0.1-0.3 mg/dl] AST 1000 U/L [0-35 U/L] ALT 1300 U/L [0-35 U/L] ALP 180 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] U/S : bile duct dilatation with gall stone F/U LFT 72 hr. AST 300 U/L, ALT 600 U/L Case 8
  • 54. LDH • non specific • rhabdomyolysis, MI, hemolysis, stroke, renal infarction, acute or chronic liver disease • use in – ischemic hepatitis : transient, massive elevation – malignant infiltration of liver : sustained elevation with ALP
  • 55. RE cell plasma hepatocyte HEME UCB UCB + albumin UCB+ligandin BMG BDG bile urobilinogen stercobilinogen Bilirubin UDP-glucoronyltransferase
  • 56. • 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
  • 57. Diagnostic approach in elevated serum bilirubin elevated bilirubin History and PE unconjugated bilirubin normal ALP, ALT, AST conjugated bilirubin hemolysis studies, review medications
  • 58. 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 • ineffective erythropoiesis : folate, IDA • drug : rifampicin, ribavirin, probenecid • resolution of hematoma 2. defects in hepatic uptake/conjugation • Gilbert’s syndrome • Crigler-Najjar syndrome
  • 59. ผู้ป่ วยชายอายุ 30 ปี มาตรวจสุขภาพประจาปี LFT :TB 3 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 30 U/L [0-35 U/L] ALT 30 U/L [0-35 U/L] ALP 100 U/L [30-120 U/L] alb 4 g/dl [3.5-5.5 g/dl] glob 3 g/dl [1.5-3.5 g/dL] จงแปลผล LFT, DDx สาเหตุและบอก management ในผู้ป่ วย รายนี้ Case 9
  • 60. Gilbert’s syndrome • benign, unconjugated hyperbilirubinemia with otherwise normal liver chemistries • up to 5% of normal population • polymorphism in TATA box of gene encoding bilirubin UDP-GT impair ability to conjugate bilirubin • prominent in fasting state, systemic illnesses, hemolysis, some medications
  • 61. Gilbert’s syndrome • Dx : – asymptomatic, healthy – mild unconjugated hyperbilirubinemia (<4 mg/dl) with otherwise normal liver chemistries test – exclusion medications and hemolysis
  • 62. Case 10 ผู้ป่ วยชายอายุ 30 ปี มาด้วยอ่อนเพลีย 3 วันก่อน PE : T 38º C, markedly pale, mild jaundice, no sign of chronic liver disease, liver and spleen not palpated LFT : TB 5.4 mg/dl [0.3-1 mg/dl] DB 0.8 mg/dl [0.1-0.3 mg/dl] AST 120 U/L [0-35 U/L] ALT 45 U/L [0-35 U/L] ALP 110 U/L [30-120 U/L] alb 3.6 g/dl [3.5-5.5 g/dl] glob 3.6 g/dl [1.5-3.5 g/dL] จงแปลผล LFT DDx สาเหตุและบอก management ในผู้ป่ วยรายนี้
  • 63. 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
  • 64. Diagnostic approach in elevated serum bilirubin elevated bilirubin History and PE unconjugated bilirubin normal ALP, ALT, AST conjugated bilirubin
  • 65. • 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
  • 66. 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
  • 67. Diagnostic approach in elevated serum bilirubin elevated bilirubin History and PE unconjugated bilirubin normal ALP, ALT, AST conjugated bilirubin normal ALP, ALT, AST abnormal ALP, ALT, AST Rotor’s syndrome Dubin-Johnson syndrome
  • 68. Diagnostic approach in elevated serum bilirubin elevated bilirubin History and PE unconjugated bilirubin normal ALP, ALT, AST conjugated bilirubin normal ALP, ALT, AST abnormal ALP, ALT, AST Rotor’s syndrome AST, ALT ALP Dubin-Johnson syndrome predominate predominate hemolysis studies, review medications as elevated ALT evaluation U/S ERCP as elevated ALT evaluation review medications AMA, ERCP, liver biopsy present absent / /
  • 69. Case 11 ผู้ป่ วยชายอายุ 30 ปี มาด้วยจุกแน่นลิ้นปี่ 3 วันก่อน PE : T 37º C, not pale, mild jaundice, no sign of chronic liver disease, liver and spleen not palpated LFT : TB 6.2 mg/dl [0.3-1 mg/dl] DB 4.8 mg/dl [0.1-0.3 mg/dl] AST 100 U/L [0-35 U/L] ALT 120 U/L [0-35 U/L] ALP 520 U/L [30-120 U/L] alb 3.6 g/dl [3.5-5.5 g/dl] glob 3.6 g/dl [1.5-3.5 g/dL] จงแปลผล LFT และบอก management ในผู้ป่ วยรายนี้
  • 70. 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
  • 71. Physiologic • >60 yr. • child and adolescent • pregnancy • blood group O • post meal (fatty meal) Pathologic • intrahepatic • extrahepatic Alkaline phosphatase
  • 72. Alkaline phosphatase Intrahepatic viral alcohol drug pregnancy PBC PSC TPN sepsis vanishing bile duct syndrome benign recurrent cholestasis benign post-op. cholestasis paraneoplastic syndrome venoocclusive disease GVHD Extrahepatic 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
  • 73. Alkaline phosphatase • in biliary obstruction – induction of ALP synthesis 2° to enhanced translation of mRNA ALP levels, may not rise until 1-2 days – T1/2 1 wk, take several days for levels to normalise after resolution • in malignancy “Regan isoenzyme” • no identifiable liver/bone involvement • biochemical distinct from liver ALP • associated variety of different CA ex lung CA
  • 74. 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
  • 75. 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
  • 76. 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
  • 77. 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
  • 78. 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
  • 79. Diagnostic approach in elevated serum alkaline phosphatase elevated ALP History and PE normal bilirubin, ALT, AST abnormal liver chemistries GGT or 5’nucleotidase U/S not hepatobiliary U/S review medication AMA ERCP AMA liver biopsy observation as elevated ALT evaluation, liver biopsy, ERCP negative positive no duct dilatation yes no negative > 6 months
  • 80. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ตรวจร่างกายปกติ LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L] ALP 320 U/L [30-120 U/L] alb 1.8 g/dl [3.5-5.5 g/dl] glob 2 g/dl [1.5-3.5 g/dL] จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว Case 12
  • 81. 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
  • 82. 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
  • 83. ผู้ป่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี กินคุมกาเนิดอยู่ ตรวจร่างกายปกติ LFT : TB 1 mg/dl [0.3-1 mg/dl] DB 0.2 mg/dl [0.1-0.3 mg/dl] AST 35 U/L [0-35 U/L] ALT 35 U/L [0-35 U/L] ALP 320 U/L [30-120 U/L] alb 1.8 g/dl [3.5-5.5 g/dl] glob 2 g/dl [1.5-3.5 g/dL] GGT 86 [0-50] จงแปลผล LFT และบอกสาเหตุของความผิดปกติดังกล่าว Case 12
  • 84. 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
  • 85. 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
  • 86. 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
  • 87. 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