LIVER FUNCTION

TEST

By Sheldon Miller &

Dominique Scott
Liver Disease- Overview
● Described as any abnormal state of hepatic
function characterized mainly by:
○ Hx- Abdominal pain, nausea, vomiting, diarrhea, dark
urine, changes in stool, weight changes, peripheral
edema, etc.
○ O/E- Abdominal mass/distension, jaundice, peripheral
edema, portosystemic shunting, ascites, hepatomegaly,
JVP, muscle wasting
○ Laboratory findings- Abnormal AST, ALT, ALP, GGT,
LDH, 5NT, bilirubin, PT, total protein, albumin levels
 Liver Screen
● A typical liver screen includes:
○ LFTs
○ Coagulation screen
○ Viral -Hepatitis A,B &C, EBV, CMV,
○ Autoimmune- Anti-mitochondrial antibody (AMA), Anti-smooth
muscle antibody (ASMA), Anti-liver/kidney microsomal antibodies
(Anti-LKM), Antinuclear antibody (ANA), p-ANCA
○ Immunoglobulins – IgM/IgG
○ Alpha-1 Antitrypsin – Alpha-1 Antitrypsin deficiency
○ Serum Copper – Wilson’s disease
○ Ceruloplasmin – Wilson’s disease
○ Ferritin – Haemochromatosis
Liver Function Test
● Defined as a group of tests used to evaluate the
current physiological state of the liver. They include:
○ Ductal/Excretory- Bilirubin (total, direct, indirect), Alkaline
phosphatase (ALP), Gamma-glutamyl transferase (GGT)
○ Cellular integrity/necroinflammatory indices -Aspartate
aminotransferase (AST), ALT, Alkaline phosphatase (ALP),
GGT, 5’-nucleotidase(5NT)
○ Synthetic
■ Total protein(including clotting factors, acute phase
reactants(i.e. CRP), AFP, albumin, prothrombin time
(PT), lipid profile
 ALT
● Mainly found in the liver
● Normal range:
○ Male: 29- 33 U/L
○ Female: 19-25 U/L
● ALT Ddx
○ Acute or chronic viral hepatitis, steatohepatitis, acute
Budd-Chiari syndrome, ischemic hepatitis,
hemochromatosis, medications/toxins, autoimmune,
alpha1-antitrypsin deficiency, wilson disease, celiac
disease
 AST
● Non-specific- found in the liver, heart, muscle, and
other places
● Normal Range:
○ Male: 10- 40 U/L
○ Female: 9-32 U/L
● AST Ddx
○ Ethanol-related, steatohepatitis, cirrhosis, non-hepatic
(hemolysis, myopathy, thyroid disease, exercise)
 Albumin
● Normal range
○ 40-60 g/L
○ Suggests an acute process in pathologies
○ Ddx: viral hepatitis, choledocolithiasis
● Low Albumin
○ <40 g/L
○ Suggests a chronic process
○ Ddx: cirrhosis, cancer, and other chronic liver disease
 Prothrombin Time
● Normal Range
○ 11.0-13.7 seconds
● Prolonged
○ > 13.7 seconds
○ Ddx: DIC, Lupus anticoagulant, warfarin therapy,
factor I, II, V, VII, or X deficiency, AND
■ Hepatic: Vit K deficiency due to malabsorption,
significant hepatocellular dysfunction
○ Failure of correction with Vit K administration suggests
severe hepatocellular injury
 ALP
● Indicates high bone turnover
● Ddx: Intrahepatic, or extrahepatic
● Workup: serum calcium, PTH, 25-hydroxy Vit
D, X-ray & bone scintigraphy
● Confirming hepatic origin
○ GGT or 5NT elevated if in hepatic origin
○ + elevated bilirubin may not require
confirmation
ALP Workup
ALP Workup
Bone Scintigraphy
 GGT
● Gamma-glutamyl transferase (GGT)- enzyme found mainly in
the liver and is a useful marker for detecting bile duct pathologies
● Isolated GGT
○ Indicates high bone turnover
○ Ddx: bone, placenta
○ Workup: serum calcium, PTH, 25-hydroxy Vit D, X-ray
& bone scintigraphy
○ Confirming hepatic origin
■ GGT or 5NT elevated if in hepatic origin
■ + elevated bilirubin may not require confirmation
 Classification
● Abnormal LFTs may be classified according to pattern:
○ Hepatocellular
○ Cholestatic
○ Mixed
○ Isolated Hyperbilirubinemia
OR
● According to duration:
○ Acute(<6 wks)
○ Subacute (6 wks-6 mths)
○ Chronic(>6 mths)
 Hepatocellular
● Pattern:
○ Markedly elevated aminotransferases(> 10 fold)
vs elevated ALP levels (> 3 fold)
○ Bilirubin can be elevated
○ Synthetic function may be abnormal
● Ddx:
○ ALT pre-dominant, or AST-predominant
 Cholestatic
● Pattern:
○ Markedly elevated ALP(<10 fold) vs aminotransferases (<3 fold)
○ Bilirubin can be elevated
○ Synthetic function may be abnormal
● Ddx:
○ Hepatobiliary: Bile duct obstruction, primary biliary cirrhosis,
primary sclerosing cholangitis, medication-induced, infiltration
(sarcoidosis, amyloidosis, lymphoma, etc.), cystic fibrosis, liver
mets, cholestasis
○ Non-Hepatobiliary: Bone disease, pregnancy, chronic renal
failure, lymphoma or other malignancies, congestive heart failure,
childhood growth, infection or inflammation
 Isolated Hyperbilirubinemia
● Total- 0- 1.0 mg/dL or 0-17 µmol/L
● Fractionated:
○ Conjugated(direct)- 0-0.4 mg/dL or 0-7 µmol/L
■ Suggests decreased bile ductule excretion or
hepatocyte pigment leakage into the serum
○ Unconjugated(indirect)- 0.3- 1.0 mg/dL or 5-17
µmol/L
■ Suggests overproduction, impaired uptake, or
impaired conjugation of bilirubin
Ddx- Unconjugated
● Increased bilirubin production- extravascular hemolysis,
extravasation of blood into tissues, intravascular
hemolysis, dyserythropoiesis, wilson disease
● Impaired hepatic bilirubin uptake
○ CCF, portosystemic shunts, gilbert syndrome, rifampin,
probenecid, flavaspadic acid, bunamiodyl
● Impaired bilirubin conjugation
○ Crigler-Najjar syndrome I & II, gilbert syndrome,
neonates, hyperthyroidism, ethinyl estradiol, liver
diseases(chronic hepatitis, advanced cirrhosis)
 Ddx- Conjugated
● Canalicular organic anion transport- Dubin- Johnson syndrome
● Impaired sinusoidal bilirubin uptake
● Extrahepatic cholestasis
○ Choledocholithiasis, Intrinsic and extrinsic tumors(cholangiocarcinoma,
pancreatic cancer), Primary sclerosing cholangitis, AIDS cholangiopathy,
Acute/chronic pancreatitis, strictures, parasitic(i.e. ascaris, liver flukes)
● Intrahepatic cholestasis
○ Viral, alcoholic & chronic hepatitis, non-alcoholic steatohepatitis,primary
biliary cholangitis, drugs(alkylated steroids, chlorpromazine, herbal
supplements, arsenic), Sepsis(+other hypoperfusion states), total
parenteral nutrition, postoperative, organ transplant, sickle cell hepatic
crisis, pregnancy, end stage liver disease
Summary
 References
● Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme
results in asymptomatic patients. N Engl J Med 2000;
342:1266.
● Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline:
Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol
2017; 112:18.
● https://www.uptodate.com/contents/approach-to-the-patient-
with-abnormal-liver-biochemical-and-function-
tests?source=bookmarks_widget
● https://www.ncbi.nlm.nih.gov/books/NBK482489/
● https://www.ncbi.nlm.nih.gov/books/NBK302/
Thank
You