Patients with abnormal liver function test

.
Liver function tests (LFTs) liver biochemical tests1-2
2
1. (enzyme tests) markers liver injury
(hepatocellular injury)
serum aminotransferases alanine aminotransferase (ALT
serum glutamic-pyruvic transaminase SGPT) aspartate
aminotransferase (AST serum glutamic-oxaloacetic
transaminase SGOT)
1.2
cholestasis alkaline
phosphatase (ALP) gamma glutamyl transpeptidase (GGT)
2. (tests of liver function) serum albumin,
prothrombin time (PT) serum bilirubin
1.1

Markers hepatocellular injury

Markers hepatocellular injury necrosis serum aminotransferases1-2
ALT cytosol AST
cytosol ( 20) mitochondria ( 40) 3 AST
ALT 4
1-3 ALT AST
reticuloendothelial system half-life ALT 47
total AST 17 mitochondrial AST 87 3
range ALT AST mean 2 standard deviations
2.5 LFTs 4 upper
limit ALT AST 5-6
40 IU/L guideline ALT

30 IU/L 19 IU/L6 ALT

ALT AST
erythromycin para-aminosalicylic acid aminotransferase
colorimetric tests SMA-12/60
autoanalyser uremic toxin ALT AST 7
Crohn's disease ALT
Markers cholestasis
ALP GGT markers cholestasis ALP
ALP
hypermetabolic state ALP
intestinal ALP isoenzyme GGT ALP
1-3 ALP
ALP electrophoresis polyacrylamide gel
sepharose 5'-nucleotidase half-life ALP 5-7
clearance
serum ALP congenital hypophosphatasia, hypothyroidism,
pernicious anemia, fulminant Wilson's disease, zinc deficiency, congenital hypophosphatemia
progressive familial intrahepatic cholestasis1-2
GGT LFTs
3 drinks 2-3 GGT
half-life GGT 26 GGT 8 8
GGT marker
phenobarbital phenytoin (dilantin) GGT 2 9
Markers synthetic function
Albumin albumin 12
albumin compensate
albumin 2 2 3 albumin

extravascular, extracellular space half-life albumin

20 albumin plasma volume
albumin
albumin ascites hypoalbuminemia
serum globulin transient bacteremia LFTs
reverse albumin/globulin (A/G) ratio serum globulin
nonspecific autoimmune hepatitis serum IgG 10 primary biliary
cirrhosis (PBC) serum IgM 11
serum albumin LFTs
proteinuria, acute chronic inflammatory state burns,
trauma sepsis albumin active
rheumatic disorders, severe end-stage malnutrition 1-3
Coagulation factors coagulation factors ( factor
VIII von Willebrand factor (vWF) ) fibrinogen, vitamin
K-dependent factors (prothrombin, factors VII, IX, X) factor V factor VII
half-life factors X IX prothrombin time (PT)
prolonged PT
cholestatic liver disease 2
vitamin K 10 subcutaneous intravenous 3
cholestasis correct PT factor V
2 1-3 factor V vitamin K-dependent factor V
factor V
fulminant hepatic failure factor V 20 poor
prognosis liver transplantation
prolonged PT disseminated intravascular
coagulation, inherited deficiencies of coagulation factors antagonize
prothrombin complex international normalized ratio (INR)
coagulopathy PT standardized value
PT 12-14
Serum bilirubin heme
unconjugated bilirubin conjugated glucuronic acid

 conjugated bilirubin hyperbilirubinemia

overproduction uptake, conjugation, excretion
conjugated bilirubin conjugated bilirubin
dipstick test
isolated hyperbilirubinrmia unconjugated conjugated
bilirubin unconjugated hyperbilirubinemia overproduction hemolysis
inherited disorders spherocytosis, sickle cell anemia, pyruvate kinase glucose6-phosphate dehydrogenase deficiency acquired hemolytic disorders
microangiopathic hemolytic anemia, hemolytic-uremic syndrome, paroxysmal nocturnal
hemoglobinuria immune hemolysis serum total bilirubin 5 mg/dL
confirm reticulocyte count haptoglobin unconjugated
hyperbilirubinemia hepatic uptake/conjugation bilirubin
Gilbert's disease, Crigler-Najjar syndrome rifampicin probenecid 1-3
isolated conjugated hyperbilirubinemia 2 inherited conditions
Dubin-Johnson syndrome Rotor syndrome1-3 hepatocellular diseases
cholestasis serum bilirubin conjugated bilirubin
unconjugated bilirubin LFTs
approach abnormal LFTs
LFTs

LFTs 15
LFTs hemolysis
serum bilirubin AST
ALP (placenta) 17-18
LFTs
1-2


autoimmune diseases
stigmata spider nevi, palmar erythema, gynecomastia, caput medusae, parotid
gland enlargement, testicular atrophy, Dupuytren's contractures
LFTs
19

LFTs 3
1 pattern LFTs (hepatocellular, cholestasis mixed)
2
3 (prognosis)
1 pattern LFTs
Patterns hepatocellular parenchymatous disease ALT AST
patterns cholestatic liver disease ALP GGT
3 1 ( 1)
1 LFTs (x upper limit of normal)1
Enzyme Measured

Aspartate or alanine aminotransferase

<2-3

2-3 to 20

>20

Alkaline phosphatase

<1.5-2

1.5-2 to 5

>5

Gamma glutamyl transpeptidase

<2-3

2-3 to 10

>10

2 patterns marker
ALT ( upper limit of normal) ALP (
upper limit of normal) parenchymatous disease 5, mixed pattern
2-5 cholestatic liver disease 2 20
1 ALT ( upper limit of normal) ALP (
upper limit of normal) parenchymatous disease, mixed pattern
cholestatic liver disease

 ALT 800 U/L (upper normal limit 40 U/L)

ALP 160 (upper normal limit 80 U/L) ALT 800/40
ALP 160/80 10 LFTs parenchymatous disease 2
ALT 1200 U/L ALP 800 U/L ALT 1200/40 ALP 800/80
3 ( 2 5) LFTs mixed hepatocellular
cholestasis 3 ALT 120 U/L ALP 400 U/L
ALT 120/40 ALP 400/80 0.6 ( 2) cholestatic liver
disease

2
Parenchymatous disease
ALT 20
1000 U/L acute viral hepatitis anti-HAV IgM
acute viral hepatitis A, anti-HBc IgM HBsAg acute viral hepatitis B HBV
reactivation acute viral hepatitis C anti-HCV 2
HCV PCR
toxins 2 predictable unpredictable
(idiosyncratic) predictable (dose-dependent)

 acetaminophen hepatotoxicity paracetamol overdose idiosyncratic

antituberculosis drugs
NSAIDs21 toxins vinyl chloride, herbal preparations
pyrrolizidine alkaloids (Jamaica bush tea) Amanita phalloides verna
ischemic hepatitis (shock liver) hypoxic hepatitis 22-23 cardiac arrest
severe heart failure lactate dehydrogenase (LDH)
hemodynamic
LFTs autoimmune hepatitis
fulminant hepatitis poor prognosis24 acute liver
failure AST/ALT 4 ALP/bilirubin 2 fulminant
Wilsonian hepatitis25-26
ALT AST acute viral hepatitis
chronic hepatitis 6 ( 2)
coinfection aminotransferase
HBsAg-positive HBeAg anti-HBe
HBV DNA viral load HBeAg positive chronic hepatitis B (CHB)
HBV DNA 105 copies/mL 20,000 IU/mL HBeAg negative CHB
HBV DNA 104 copies/mL 2,000 IU/mL liver biopsy
HBeAg negative CHB27 anti-HCV-positive HCV
RNA viral load HCV genotype liver biopsy genotype 128
alcoholic hepatitis AST ALT 2 AST
500 IU/L ALT 300 IU/L1-3 chronic hepatitis non-virus nonalcohol nonalcoholic fatty liver disease (NAFLD)
metabolic syndrome exclude ALT/AST 129
hepatitis ALT AST Wilsons disease
40
Kayser-Fleischer (KF) ring serum ceruloplasmin 24-hour
urine copper 100 mcg/day liver biopsy
quantitative copper 250 mcg/gm dry weight 30-31 autoimmune hepatitis
(AIH) immunoglobulin G (IgG) autoantibodies

 antinuclear antibody (ANA), antismooth muscle antibody (ASMA)

type 1 AIH liver biopsy type 2 type 3 AIH
antiliver-kidney microsomal antibody (antiLKM-1) antibodies against soluble liver
antigen (anti-SLA) 32-33
hereditary hemochromatosis (HHC)
(arthropathy) (skin bronzing hyperpigmentation)
(dilated cardiomyopathy)
serum transferrin saturation total serum iron serum iron ferritin
100 45% serum ferritin concentration 400
ng/mL 300 ng/mL
liver biopsy hepatic iron index (hepatic iron concentration (micromoles/gram dry
weight) ) homozygous HHC 1.9 genetic study
screening 34 HHC
secondary hemochromatosis thalassemia, hemolysis,

ALT chronic viral
nonviral hepatitis early cirrhosis AST ALT
Cholestatic liver disease
ALP confirm ALP GGT
extrahepatic intrahepatic cholestasis (space
occupying lesion) / invasion small, intrahepatic bile ducts
hepatocellular carcinoma, peripheral type cholangiocarcinoma metastasis
CA benign tumor hemangioma, hepatic adenoma, focal nodular
hyperplasia ALP ( 1,000 U/ L 6 )
infiltrative lesions granulomatous diseases, amyloidosis, sarcoidosis, infiltrating
tumors fungal infections3 malignant infiltration LDH
extrahepatic cholestasis acute biliary tract
obstruction 24-48 serum aminotransferase ( 300 IU/L)
serum ALP biliribin 35 ALP

 bile duct epithelium cholestasis ALP

ALP serum aminotransferase (cholangiocarcinoma)
periampullar cancers pancreatic cancer, gallbladder cancer duodenal cancer
ampullary cancer malignancy porta hepatits
focal
intrahepatic ductal obstruction partial extrahepatic duct obstruction primary
sclerosing cholangitis (PSC) ascending
cholangitis perinuclear antineutrophil cytoplasmic antibodies (p-ANCA)
endoscopic retrograde cholangiography (ERCP) magnetic resonance
cholangiography (MRCP) intra- extrahepatic bile-duct strictures dilations (beadlike appearance) biliary dilatation secondary sclerosing cholangitis

intrahepatic causes anabolic contraceptive steroids,

chlorpromazine, imipramine, tolbutamide, sulindac, cimetidine, erythromycin estolate,
trimethoprim-sulfamethoxazole, penicillin based antibiotics
, sepsis, parenteral nutrition
(hypercholesterolemia) serum
globulin IgM primary biliary cirrhosis (PBC)
antimitochondrial antibodies (AMA)
ALP GGT U/S upper abdomen ( 2)
CT MRI abdomen U/S
upper abdomen intrahepatic ducts dilatation ERCP
CT abdomen severe biliary
obstruction stent drainage percutaneous
2-3 serum bilirubin
slow phase deltabilirubin serum albumin (half-life 20 ) clearance bilirubin-glucuronide
delta-bilirubin phenomenon U/S intrahepatic
ducts dilatation intrahepatic cholestasis infiltrative lesion
partial extrahepatic duct obstruction

 2 approach ALP 1

ALP
ALP ALP Regan ALP
isoenzyme hepatic ALP isoenzyme Hodgkin's disease
renal cell carcinoma hepatic ALP isoenzyme
nonspecific hepatitis bystander phenomenon1
LFTs

 LFTs ( 2)

2 (Nonhepatic causes) LFTs 36

Test

albumin

Protein-losing enteropathy Serum globulins, alpha1-antitrypsin

clearance

AST
ALP

Bilirubin

Discriminating tests

Nephrotic syndrome

Urinalysis, 24-hr urinary collection for

protein

Congestive heart failure

Cardiac examination, two-dimensional

echocardiogram

Myocardial infarction

CK-MB, troponin, ECG

Muscle disorders

CK, ESR

Bone disease

GGT, serum leucine aminopeptidase, 59nucleotidase

Pregnancy

GGT, 59-nucleotidase, hCG in serum and

urine

Malignant tumor

Alkaline phosphatase electrophoresis

Hemolysis

Reticulocyte count, peripheral smear, LDH,

haptoglobin

Sepsis

Clinical setting, blood cultures

Ineffective erythropoiesis Peripheral smear, urine bilirubin,

hemoglobin electrophoresis, bone marrow
aspiration and biopsy
Shunt hyperbilirubinemia Clinical setting
PT

Antibiotic use,
anticoagulant use,
steatorrhea, dietary

Response to vitamin K

deficiency
CK, creatine kinase; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; hCG, human
chorionic gonadotropin; LDH, lactate dehydrogenase
3 (prognosis)


Modified Child-Turcotte-Pugh prognostic classification ( 3)
5 parameters encephalopathy, ascites, bilirubin, albumin prothrombin time
3 A ( 5-6), B ( 7-9) C ( 10-15)
3 Modified Child-Turcotte-Pugh prognostic classification
parameters

points
1

Encephalopathy (grade)

1-2

3-4

Ascites

None

Slight

Moderate

Bilirubin (mg/dL)

1-2

2-3

>3

Albumin (g/dL)

>3.5

2.8-3.5

<2.8

Prolonged prothrombin time (sec)

INR

1-4
< 1.7

5-6
1.7-2.3

>6
> 2.3

Model for
End-stage Liver Disease. (MELD)37-39
Model for End-stage Liver Disease (MELD) Scoring Equation[*]
MELD score for TIPS = 0.957 loge(creatinine [mg/dL]) + 0.378 loge(bilirubin [mg/dL]) +

1.120 loge(INR) + .643 (cause of liver disease)[]

MELD score for liver transplantation[] = 0.957 loge(creatinine [mg/dL]) + 0.378
loge(bilirubin [mg/dL]) + 1.120 loge(INR) + .643
INR, international normalized ratio; TIPS, transjugular intrahepatic portosystemic shunt.
* Laboratory values less than 1.0 are set at 1.0. The maximum serum creatinine level considered
in the MELD score equation is 4.0 mg/dL.
0 if cholestatic or alcoholic liver disease, and 1 if other liver disease.
Multiply by 10 and round to the nearest whole number.
http://www.unos.org/resources/MeldPeldCalculator.asp?index=98
liver
transplantation
Direct quantitative testing hepatocyte function
parameters LFTs
organic anions
endogenous exogenous substances
bile acids caffeine lidocaine metabolites
clearance tests bromsulphalein (BSP) indocyanine green (ICG)
( 4)40

(biosynthetic capacity) serum lipoproteins, ceruloplasmin, ferritin alpha
1-antitrypsin
4 Quantitative liver function tests40
Quantitative liver
function test
Caffeine kelim

Type of test
metabolism

Blood-flow
Dependent
no

Sensitive to Diet or Measurement

Medication
yes

blood

Quantitative liver
function test

Type of test

Blood-flow
Dependent

Sensitive to Diet or Measurement

Medication

Antipyrine kelim

metabolism

no

yes

breath test

Antipyrine Cl

metabolism

no

yes

breath test

MEGX15min

metabolism

no

yes

blood

MEGX30min

metabolism

no

yes

blood

Erythromycin

metabolism

no

yes

breath test

Indocyananine green

extraction

yes

minimal

blood

Cholate kelim

extraction

yes

minimal

blood

Cholate Cliv

extraction

yes

minimal

blood

Cholate Cloral

extraction

yes

minimal

blood

Cholate shunt

extraction

yes

minimal

blood

Galactose elimination
capacity

consumption

yes

minimal

blood

Methionine breath test consumption

yes

minimal

breath test

Perfused hepatic mass

yes

minimal

scan

extraction

Cl, clearance; MEGX15min, monoethylglycinexylidide at 15 min; MEGX30min,

monoethylglycinexylidide at 30 min.

Liver function tests serum
aminotransferases ALT AST cholestasis
ALP GGT syntetic function serum albumin prothrombin time (PT)
(detoxify) organic anions
serum bilirubin abnormal LFTs 2
hepatocellular injury ALT AST ALP GGT cholestasis

 infiltrative diseases LFTs

liver biopsy

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