Interpretation of Liver

function Tests

BY :

PROF DR : ABDEL RAHMAN A. MOKHTAR

PROFESSOR INTERNIST - GASTROENTEROLOGIST
Mansoura University 2019
Interpretation of Liver function
Tests
The Liver does
TOO much for
any single test
or set of tests to
determine.
 Although it seems to be a
misleading term , yet , it is firmly
Liver function tests inserted in the medical vocabulary.

• Liver function tests (LFTs or LFs), are groups of laboratory blood

assays designed to give information about the state of a patient's 
liver.

The parameters measured include PT/INR, albumin, bilirubin (direct

and indirect) and liver enzymes ( SGPT , SGOT , Alk ph , GGT ).

• Some tests are associated with functionality (e.g. prothrombin &

albumin , bilirubin ); some with cellular integrity (e.g., 
transaminases) and some with conditions linked to the biliary tract
(gamma-glutamyl transferase and alkaline phosphatase).
Serum Glutamic-Pyruvic Transaminase ( SGPT ) / Alanine Transaminase ( ALT )

Serum Glutamic-Oxalacetic Transaminase ( SGOT ) / Aspartate Transaminase ( AST )

 Indications

 These tests can be used to

(1)Detect the presence of liver disease.
(2) Distinguish among different types of liver disorders.
(3) Gauge the extent of known liver damage, and
(4) Follow the response to treatment.
(5) Some or all of these measurements are also carried out
(usually about twice a year for routine cases) on those
individuals taking certain medications — anticonvulsants
are a notable example — in order to ensure that the
medications are not damaging the person's liver.
TOOLS
 Liver chemistry tests

Serum Glutamic-Pyruvic Transaminase ( SGPT ) / Alanine Transaminase ( ALT )

Serum Glutamic-Oxalacetic Transaminase ( SGOT ) / Aspartate Transaminase ( AST )
 Common serum liver chemistry tests
• AST- liver, heart skeletal 1. Liver enzymes are important
muscle, kidneys, brain, RBCs markers of liver injury but are
• In liver 20% activity is not……….Liver function .
cytosolic and 80% ……not… Accurate markers of
mitochondrial severity of liver disease.
• Clearance performed by
sinusoidal cells, half-life 17hrs

• ALT - more specific to liver, 2. Month to month variation is

v.low concentrations in kidney expected, minor changes in
and skeletal muscles.
levels have no prognostic
• In liver totally cytosolic.
significance
• Half-life 47hrs
 Alkaline
Phosphatase N.B : 5´-Nucleotidase

• Present in nearly all tissues - • Normal 0.3 to 3.2

isoenzymes Bodansky units
• Spectrum of
• Localised in the microvilli of
abnormality similar
the bile canalicus in the liver to that of SAP
• Also present in bone, • Specificity for
intestine, placenta, kidney hepatobiliary disease
and wbc. • May be used to
• Elevation may be confirm hepatic
origin of elevated
physiological or pathological
SAP.
  Lack of sensitivity (may be normal in cirrhosis
Limitations or HCC)
Lack of specificity (aminotransferase levels may
be elevated in musculoskeletal or cardiac
disease)
 Degree of elevation does not always correlate with
severity of liver disease
A group of tests is needed in order to ‘infer’
functional liver status. Probability of liver
disease is high when more than one test is
abnormal or the findings are persistently
abnormal on serial testing

 Mixed injury/obstruction patterns are common

in REAL LIFE !!

A normal does not mean normal :

DO NOT assume that a NORMAL test result
indicates absence of liver disease. (example: AST
& ALT can be normal in End Stage Cirrhosis.)
What is this ?????
And Now Our Featured Presentation…
General categories of tests
• Tests of the • Tests to detect
biosynthetic injury to
capacity of the hepatocytes
• Hepatocytes are
liver : damaged so they leak –
so these enzymes are
GPT(ALT) HIGH
Albumen
GOT (AST)
Prothrombin
LDH

Alkaline
phosphatase (ALP)
Gamma- Type 4 collagen,
glutamyltransferas Fibrotest etc.
e (GGT)
Bilirubin
• Markers of • Tests to
cholestasis / detect
obstruction : fibrosis in
the liver :
Road Map for Interpretation of LFTs
 Perform Diagnosis
History
Exam
Investigation

Classify the
Consider the
abnormality
HC or biliary ?
D.D :
Massive HC injury ?
Most common .
Evidence of functional
& Most treatable .
abnormality ?

Look at pattern of Look at tests of

Think of Non - function
hepatic causes abnormality :
cholestatic vs
hepatocellular .
Think of Non - Step 1
hepatic causes

Bilirubin elevation: the source may be RBCs (e.g., with haemolysis,

intra-abdominal bleeds, or haematomas).

• AST: the source may be skeletal or cardiac muscle.

• Alk phos: the source may be bone, placenta, kidney, or intestines.
• Gamma-GT: the source may be the heart or RBCs.
. Look at pattern
of abnormality : Step 2
cholestatic vs
hepatocellular .

ALT is more strongly

inhibited by vit B6 def.
common in alcoholics,
Also,alcohol causes
mitochondrial damage
releasing more AST.
Look at tests Step 3
of function

Albumen : Prothrombin Time / INR

Depends on nutrition,
Hormonal factors.
Catabolism.
Loss in stool and urine
Not specific for liver disease

I
 Step 3 ……..continue

Prothrombin Time / INR

In presence of adequate vitamin K
The liver synthesizes coagulation factors except FVIII.
Clotting abnormality indicates impairment in ability of liver to synthesize the CF.

In vit K deficiency, vit K 10 mg SC decreases prolonged PT >30% within 24 hrs

IN ACUTE

IN CIRRHOSIS :
 Step 3
……..continue
Modified Child-Turcotte-Pugh score for grading
severity of liver disease
Classify the
Step 4
abnormality
HC or biliary ?
Massive HC injury ?
Evidence of functional
abnormality ?
Consider the D.D : Step 5
Most common .
& Most treatable .

D.D: of Hepatocellular Damage.

D.D of Cholestatic pattern.

 Step 5 ……. continue

D.D: of Hepatocellular Damage

A Autoimmune
hepatitis
B Hepatitis B
C Hepatitis C
D Drugs or toxins
E Ethanol / Hep E
(Pregnancy)
F Fatty liver
G Growths (i.e.,
tumors)
H Hemodynamic
disorder
(Hepatic venous outflow
obstruction – BCS - or “shock
liver”)
I Inborn errors - iron
(hemochromatosis),
copper (Wilson's
disease) or alpha1-
antitrypsin deficiency
 Step 5 …….
D.D considering the continue
Pattern & magnitude of alteration
• DD of severe elevations
of ALT, AST (> 15 times
ULN)
Elevations in the• Relatively ltd
• Indicate
intermediate range - marked
less useful for hepatocellular injury or
limiting the DD,
necrosis
caused by diseases
• Drug induced -
of both categories
acetaminophen
• Occupational/environm
ental toxins - toluene,
CCl4
• Ischemic hepatitis
• Viral hepatitis - A, B, D,
E, Herpes
 Step 5 …….
continue
D.D of Cholestatic pattern.

Markers of Cholestasis/Obstruction

 Alkaline phosphatase (ALP)

• Isolated
• Associated with hyperbilirubinemia (cholestatic disorders)
• May be sole abnormality in many cholestatic or infiltrative diseases
• To be interpreted in the clinical setting of history and physical examination if
sole abnormality

 Gamma-glutamyltransferase (GGT)
 Bilirubin
Step 5 …….
continue
Physiologically ALP
increase in :
In tissues undergoing
metabolic stimulation
Third trimester of
pregnancy
Adolescence.
 Step 5 …….
continue
When SAP elevation is detected
 Repeat the test.
 Confirm the hepatic origin :
Serum GGT.
AP elevation up to 3 times ULN
5`- Nucleotidase.
Non – specific
AP isoenzymes. Occurs in all types
 If medications suspected, discontinue of liver disorders.
them and repeat test

> 3 times ULN

• Persistently elevated SAP - evaluate for
Cholestatic liver disease Cholestatic disorders
Infiltrative liver disease Infiltrative disorders
Biliary obstruction
Metastases
Step 5 ……. continue
 Step 5 …….
continue
Gammaglutamyl transferase (γ-glutamyl transpeptidase)

• Found in hepatocytes and biliary

epithelial cells
• Sensitive for hepatobiliary disease
but ltd by lack of specificity
• With other enzyme abnormalities,
raised GGT would support a
hepatobiliary cause
• Can confirm hepatic source for a
raised AP
• Raised GGT and raised transaminases
with ratio of AST to ALT 2:1 or more
suggestive of ALD
• Medications can cause mild rise
• Normal range 0 to 30 IU/L
 Step 5 ……. Continue

Serum bilirubin

glucuronic acid
globin

1 2 3 Into
heme
bile
bilirubin Free conjugated
Senescent
bilirubin bilirubin
red cell
iron

phagocyte albumin
hepatocyte

1. Uptake
Hyperbilirubinemia (Jaundice) 2. Conjugation
3. Excretion (rate limiting)
 Step 5 ……. Continue

Hyperbilirubinemia (Jaundice)

Hepatic Posthepatic
Prehepatic
Genetic defects, Bile Duct Obstruction
(Hemolysis)
primary liver disease Pancreatic Head CA

Unconjugate Mixed Conjugated Bilirubin

d Bilirubin

33
Consider the D.D : Step 5 …….
Continue
Most common .
& Most treatable .
Step 5 …….
Continue
Perform Diagnosis Step 6
History
Exam
Investigation

• History ……. Asymptomatic vs Symptomatic.

• Examination :
Hepatocellular versus cholestatic.
Compensated vs decompensated.
• Further invstigations :
As the situation needed.
 Step …… 6
History& Exam continue
……. Asymptomatic vs Symptomatic.
………Risk for liver disease.
…….. Hepatocellular vs cholestatic
History& Exam Step …… 6
……. Asymptomaticcontinue
vs Symptomatic.
………Risk for liver disease.
…….. Hepatocellular vs cholestatic
 Step …… 6
continue
History & Exam
…. Asymptomatic vs Symptomatic.
………Risk for liver disease.
…….. Hepatocellular vs cholestatic
Liver disease Reduced bile in intestine
• Cirrhosis causing malabsorption
• Portal hypertension • Vitamin A-night blindness
• D-osteomalacia
Accumulation of bile • E- neuromyelopathy
constituents • K-bleeding tendency
• Bilirubin- jaundice • Calcium-
• Bile acids ostemalacia/osteoporosis
• Pruritogens- pruritus • Fat- steatorrhea, FTT
• Lipids-zanthomata
• Copper-KF ring rare
 Step …… 6
continue
Further testing
as needed?
Can you read this ?

To Conclude :
Interpretation of
LFTs is more than
simple reading.
Thanks A lot
PROF DR : ABDEL RAHMAN A. MOKHTAR
 Case Presentation
49 y/o female comes to establish care after moving to your
area
Pertinent history
Hypertension
Obesity
Fibromyalgia
Symptomatology :
Weight gain of 45 pounds over the last year
Diffuse arthralgias and myalgias
No history of liver disease, denies alcohol use
Prior physician had a “concern” about lupus
 Case Presentation
• Medications
– Gabapentin,
– duloxetine,
– lisinopril,
– acetaminophen/hydrocodone PRN
• Exam
– BMI 39, BP 145/90
– No significant findings on exam
 Selected Laboratory data
Current Labs One year ago

• AST – 75 • AST 50
• ALT – 105 • ALT – 80
• AP – 98 • AP – 105
• T. bilirubin – 0.4 • T. bilirubin – 0.5
• Albumin 4.2 • Albumin 4.0
• Total protein – 6.5 • Total protein – 6.9
• ANA (+) 1:160
 Initial Step
Exclude common treatable liver
Our Patient’s Results
diseases
• Chronic viral hepatitis • HBsAg (-)
– HBsAG, anti-HCV
• Anti-HCV (-)
• Iron 59
• Hemochromatosis • TIBC 350
_ Serum iron, TIBC and • Transferin saturation 17%
ferritin.
• Ferritin 650 ng/ml

• Autimmune hepatitis :
 Could this be Hemochromatosis?
Our Patient’s Results
– Common – 1/400 whites, penetrance
of ~30%
Iron 59 – Presents with mild (<4x ULN)
TIBC 350 transaminase elevations
Transferrin – End-organ damage in middle age
saturation 17% – Best screening test – transferrin
Ferritin 650 ng/ml saturation >45%
• Elevated ferritin may indicate
inflammation
– Genetic testing available to establish
the diagnosis
• C282Y homozygote

Adams PC, Barton JC. Lancet 2007;370:1855-60

 Could this be Autoimmune
Hepatitis?
Our Patient’s Results

AST – 75
– Treatable, fatal if untreated
ALT – 105 – Typical presentation
AP – 98 • Significant ALT elevation (>5x ULN)
T. bilirubin – 0.4 • Elevated total protein, gamma
Albumin 4.2 globulin, IgG levels
Total protein – 6.5 • Increased bilirubin is common
ANA (+) 1:160 – Autoimmune markers
IgG level - normal
• ANA (+) in ~ 67%
• F-actin Smooth Muscle antibody
(+) in ~87%
– Liver biopsy with typical but not
diagnostic findings

Krawitt EL. NEJM 2006;354-366

 Could this be alcoholic liver
Our Patient’s Results
disease?
AST – 75 • History unreliable
ALT – 105
AP – 98 • Typical liver enzyme
T. bilirubin – 0.4 pattern
Albumin 4.2
– AST:ALT ratio >2 or 3
Total protein – 6.5
– Levels usually <200 U/dl
• Diagnosis
– Exclude other causes of liver
disease

Levitsky J, Mailliard ME. Sem Liv Dis 2004;24:233-247

 What about Celiac Disease?
• Affects 1% of the US population
Our Patient’s Results

AST – 75 • Elevated liver enzymes

ALT – 105 – Most common hepatic
AP – 98 presentation of celiac disease
T. bilirubin – 0.4 – 40% adults and 54% of children
Albumin 4.2
with Celiac disease
Total protein – 6.5
• Up to 9% of patients with
unexplained elevated liver
enzymes have celiac disease
• Diagnostic testing
– TTG IgA antibodies

Rubio-Tapia A, Murray JA. Hepatology 2007;46:1650-1658

COMMON LIVER DISEASES TO ALWAYS
EXCLUDE
Chronic viral hepatitis
► anti-HCV, HBsAg
Hemochromatosis
► iron, TIBC, ferritin
Autoimmune hepatitis
► typical presentation, elevated IgG, typical
liver biopsy
Non-alcoholic fatty liver disease
(NAFLD)

Krier M, Ahmed A. Clin Liver Dis 2009;13:167-177

 Most common cause of elevated
liver enzymes
Fatty liver disease
The hepatic(NAFLD)
manifestation of the
metabolic syndrome
Hamaguchi M, et al. Ann Intern Med 2005;143:722-728
 The Metabolic Syndrome
1. Abdominal obesity
Our Patient’s Results √
AST – 75
2. Hypertension
√
ALT – 105 3. Elevated triglycerides
√
AP – 98
T. bilirubin – 0.4 4. Low HDL√
Albumin 4.2
Cholesterol - 295 5. Fasting BS >100 mg/dL
LDL – 175
HDL – 32
Triglycerides – 350
FBS – 99 mg/dL

Cusi K. Clin Liv Dis 2009;13:545-563

Approach to Elevated Liver Tests
Look
Lookfor
forcommon
commontreatable
treatablediseases
diseases
a)a)viral
viralhepatitis,
hepatitis, b)
b)hemochromatosis
hemochromatosisc)c)alcohol
alcoholabuse
abuse

Consider
Considerimportant
importanttreatable
treatablediseases
diseases
Celiac
Celiacsprue
sprue
Autoimmune
Autoimmunehepatitis
hepatitis
Medication
Medicationhepatotoxicity
hepatotoxicity

Features
Featuresof
ofthe
themetabolic
metabolicsyndrome
syndromepresent?
present?
yes no

NAFLD
NAFLDlikely,
likely,look
lookfor
forevidence
evidenceof
of Referral
Referralfor
forexpert
expertevaluation
evaluation
advanced
advancedfibrosis,
fibrosis,consider
considerbiopsy
biopsy liver
liverbiopsy
biopsy
 What Will the Specialist Look For?
• Wilson’s disease
• Alpha-1 anti-trypsin deficiency
• Occult hepatitis B infection
• Seronegative autoimmune hepatitis
• NAFLD without metabolic syndrome
• Others
 To Summarize
1. Liver enzymes are important markers of liver
dysfunction but are not
Liver function tests
2. Every patient with elevated ALT deserves an
evaluation to detect treatable conditions
3. Month to month variation is expected, minor
changes in levels have no prognostic
significance
 To Summarize

• Patients with primarily elevation of alkaline

phosphatase are unique
– Evaluation consists of
• Liver imaging, AMA testing and possible biliary imaging
– Differential diagnosis is different
• Biliary obstruction
• Liver mass lesions
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Medication toxicity
• Granulomatous liver disease
Thanks