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

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 Moderate Marked
(times) (times) (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
 Liver Function Test
Advantages Disadvantages
• sensitive, noninvasive • lack sensitivity
method of screening liver – normal results in serious
dysfunction liver disease
• pattern of laboratory test • not specific for liver
abnormalities to
dysfunction
recognize type of liver
disorder • seldom lead to specific
• assess severity of liver diagnosis
dysfunction
• follow cause of liver
disease
 Initial Approach
•history and physical examination
•algorithm approach useful mainly when
no clinical clues
history physical examination
• patient’s symptoms • body habitus
• risk factors for liver • splenomegaly
disease • ascites
• concomitant conditions • cutaneous stigmata of
• medications chronic liver disease
• occupational exposure
to hepatotoxins
 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
 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
 Case 1
ผู ป
้ ่ 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 และบอกสาเหตุของความผิดปกติดงั กล่าว
 Case 2
ผู ป
้ ่ 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 และบอกสาเหตุของความผิดปกติดงั กล่าว
 Case 3
ผู ป
้ ่ 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 และบอกสาเหตุของความผิดปกติดงั กล่าว
 Case 4
ผู ป
้ ่ 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 และบอกสาเหตุของความผิดปกติด ังกล่าว
 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 catalyze transfer amino

groups to form pyruvate groups to form oxaloacetate
cytosol (20%) and cytosol
mitochondria (80%)
T1/2 17 hr. (cytosol) T1/2 47 hr.
87 hr. (mitochondria)
liver, cardiac muscle, low concentration in other
skeletal muscle, kidneys, tissues
brain, pancreas, lungs,
leucocytes, and RBC
 AST, ALT
• level of transminase elevation
• predominant AST elevation
• rate of transaminase declination
 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
 AST/ALT ratio
90

80

70

60

50

AST/ALT >1
40
AST/ALT >2
30

20

10

0
alcoholic post necrotic chronic obstructive viral hepatitis
cirrhosis hepatitis jaundice
 Rate of Transaminase
Declination
rapid slow
• ischemic • acute viral hepatitis
• short half life drug • long half life drug
• acute biliary tract • AIH
obstruction • metabolic disease
• fulminant hepatitis
 ALT and AST < 5 times
ALT predominant AST predominant
• Chronic hepatitis B, C • Alcohol-related liver injury
• Acute hepatitis (A-E, • Steatohepatitis
EBV, CMV)
• Steatohepatitis • Cirrhosis
• Hemochromatosis • Drug
• Medications/toxins • Nonhepatic
• Autoimmune hepatitis – Hemolysis
• Alpha1-antitrypsin – Myopathy
deficiency – Thyroid disease
• Wilson’s disease – Strenuous exercise
• Celiac disease • 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
 Case 5
ผู ป
้ ่ 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 ในผู ป ้ ่ วยรายนี ้
 Case 5.1
ผู ป
้ ่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ไม่มอ ี าการผิดปกติ
ใดๆ ไม่ดมสุ ื่ รา ไม่กนิ ยาใดๆ ไม่เคยได้ร ับเลือด 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 ในผู ป ้ ่ วยรายนี ้
 Case 5.1
ผู ป
้ ่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ไม่มอ ี าการผิดปกติ
ใดๆ ไม่ดมสุ ื่ รา ไม่กนิ ยาใดๆ ไม่เคยได้ร ับเลือด 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
 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
 Case 5.2
ผู ป
้ ่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี มีประวัต ิ 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 เพิมเติ ่ ้ ่ วยรายนี ้
มในผู ป
 Case 5.2
ผู ป
้ ่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี มีประวัต ิ 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
 ALT and AST < 5 times
and AST predominant
• history alcohol intake (history from
patient and family members)
• hemolysis studies
• aldolase
• CPK
• macro-AST
 Case 6
ผู ป
้ ่ 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 ในผู ป ้ ่ วยรายนี ้
 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
 Case 6
้ ่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี ดืมสุ
ผู ป ่ รา ½ ขวดกลม
ต่อว ัน 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 ในผู ป ้ ่ วยรายนี ้
 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 • Autoimmune
(A-E, herpes) hepatitis
• Medications/toxins • Wilson’s disease
• Ischemic hepatitis • Acute Budd-Chiari
• Acute bile duct syndrome
obstruction
• Hepatic artery
ligation
• Heat stroke
AST predominate : medication/toxin, ischemic
 >75 times : ischemic, toxic, viral (less common)
 Case 7
ผู ป ้ ่ 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 ในผู ป ้ ่ วยราย
นี ้
 Ischemic hepatitis
(shock liver, acute hepatic circulatory insufficiency)
• low-flow hemodynamic state
– hypotension, sepsis, cardiac arrhythmia,
MI, HF, hemorrhage, extensive burns,
severe trauma, heat stroke
• hypotension often not documented
• usually subclinical
 Ischemic hepatitis
• 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
 Case 8
ผู ป ่ั
้ ่ วยหญิงอายุ 40 ปี มาด้วย RUQ pain 12 ชวโมงก่ อน
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 ในผู ป ้ ่ วยราย
นี ้
 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
 Case 8
ผู ป ่ั
้ ่ วยหญิงอายุ 40 ปี มาด้วย RUQ pain 12 ชวโมงก่ อน
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
 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
 Bilirubin
UDP-glucoronyltransferase

RE cell plasma hepatocyte

HEME UCB UCB UCB+ligandin
+ BMG
albumin 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
 Diagnostic approach in elevated serum bilirubin

elevated bilirubin

History and PE

unconjugated bilirubin conjugated bilirubin

normal ALP, ALT, AST

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
 Case 9
ผู ป
้ ่ 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 ในผู ป ้ ่ วย
รายนี ้
 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
ผู ป
้ ่ 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 ในผู ป ้ ่ วยรายนี ้
 Indirect Hyperbilirubinemia

Bilirubin AST, ALT Alb Glob PT

hemolysis 5 mg/dl increase AST N N N

Gilbert’s 5 mg/dl normal N N N

syndrome
 Diagnostic approach in elevated serum bilirubin

elevated bilirubin

History and PE

unconjugated bilirubin conjugated bilirubin

normal ALP, ALT, AST
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
• Bile duct obstruction • Intrahepatic
• Hepatitis cholestasis of
• Cirrhosis pregnancy
• Medications/Toxins • Benign recurrent
• Primary biliary cholestasis
cirrhosis • Vanishing bile duct
• Primary sclerosing syndromes
cholangitis • Dubin-Johnson
• Sepsis syndrome
• Total parenteral • Rotor syndrome
nutrition
 Diagnostic approach in elevated serum bilirubin

elevated bilirubin

History and PE

unconjugated bilirubin conjugated bilirubin

normal ALP, ALT, AST 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 conjugated bilirubin

normal ALP, ALT, AST normal ALP, ALT, AST abnormal ALP, ALT, AST
Rotor’s syndrome AST, ALT ALP
Dubin-Johnson syndrome predominate predominate
/ /
hemolysis studies, as elevated
review medications ALT evaluation U/S

present absent

ERCP as elevated ALT evaluation

review medications
AMA, ERCP, liver biopsy
 Case 11
ผู ป ้ ่ 3 วันก่อน
้ ่ วยชายอายุ 30 ปี มาด้วยจุกแน่ นลินปี
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 ในผู ป ้ ่ วยรายนี ้
 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 Pathologic
• >60 yr. • intrahepatic
• child and adolescent • extrahepatic
• pregnancy
• blood group O
• post meal (fatty meal)
 Alkaline phosphatase
Intrahepatic Extrahepatic
viral alcohol intraluminal obstruction :
drug pregnancy gall stones, ascariasis,
PBC PSC hemobilia
TPN sepsis disease of BD :
vanishing bile duct syndrome PSC, choledochal cyst,
benign recurrent cholestasis cholangioCA,
benign post-op. cholestasis AIDS cholangiopathy
paraneoplastic syndrome external compression :
venoocclusive disease LN, GB CA, Mirizzi’s syndrome,
GVHD 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
modest (up to 3x) rise in aminotransferase,
and up to 20x rise in ALP, bilirubin N-5x

• 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
• Anabolic steroid • Gold salts
• Allopurinol • Imipramine
• Amoxicillin-clavuronic acid • Indinavir
• Captopril • Iprindole
• Carbamazepine • Nevirapine
• Chlorpropamide • Methytestosterone
• Cyproheptadine • Methylenedioxymethamphetam
• Diltiazem ine
• Erythromycin • Oxaprozin
• Estrogens • Pizotyline
• Floxuridine • Quinidine
• Flucloxacillin • Tolbutamide
• Fluphenazine • 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

yes no
negative positive

not hepatobiliary U/S ERCP AMA

review medication
AMA negative
no duct dilatation
liver biopsy observation
> 6 months

as elevated ALT evaluation, liver

biopsy, ERCP
 Case 12
ผู ป
้ ่ 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 และบอกสาเหตุของความผิดปกติดงั กล่าว
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
 Case 12
ผู ป
้ ่ วยหญิงอายุ 40 ปี มาตรวจสุขภาพประจาปี กินคุมกาเนิ ดอยู ่
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 และบอกสาเหตุของความผิดปกติดงั กล่าว
 Summary
Hepatocellular necrosis Biliary obstruction Infiltration

toxin/ viral alcohol complete partial

ischemia
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, increase, normal

unresponsive to vit K responsive to vit K
albumin increase in subacute/chronic usually normal, normal
decrease in advance
 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
Thank You