HOW TO WORK-UP A PATIENT WITH JAUNDICE

ESTABLISH THE PRESENCE OF JAUNDICE

Jaundice refers to elevated levels of bilirubin in the circulating
blood, with consequent deposition in tissues. In mild cases, the
jaundice is only apparent in the sclerae, where even a small amount
of the yellow color stands out against the white conjunctivae. In
more severe cases, the skin takes on a yellow to orange color.
Rarely excess carotene can give a deceptive yellow color to the
sclerae. In people of color where deeper pigmentation may make
detecting jaundice more difficult, it is often helpful to examine the
palmar and plantar surfaces, as well as the mucosa of the oral
cavity, as well as the conjunctiva of the eyes. Although the liver
converts the breakdown pigments of hemoglobin to water-soluble
bilirubin which is excreted into the gastrointestinal tract as bile, the
pigment is not usually visible in the liver. When bile is seen in the
liver biopsy, the process is called cholestasis. The normal level of
total bilirubin in the serum is 0.2 to 1.0 mg/dl.
DECIDE WHETHER THE JAUNDICE IS HEPATIC IN ORIGIN
Jaundice is not always hepatic in origin. The pigment in jaundice
comes mainly from the breakdown of red blood cells. With severe
hemolysis the excess pigment load can exceed the ability of a
normal liver to keep up with excretion. A mild but clinically
recognizable jaundice can result. The percentage of bilirubin which
is indirect (water insoluble) is characteristically high. The
reticulocyte count will be elevated. The elevated reticulocyte count
is helpful in distinguishing the jaundice related to hemolysis (a
problem of overproduction) from Gilberts syndrome (a problem of
defective plasma clearance). This is another cause of mild jaundice
with a high percentage of indirect reacting bilirubin. This
syndrome, which is quite common, is familial in nature; other tests
(transaminase, alkaline phosphatase) are normal. Another familial
cause of low-grade jaundice with little effect on overall liver
junction is the Dubin-Johnson syndrome; this syndrome is

uncommon. Here the mild jaundice is characterized by a higher

percentage of direct (water-soluble) bilirubin (normal direct
bilirubin is <0.2 mg/dl).
DECIDE WHETHER JAUNDICE IS DUE TO DAMAGE TO
THE BILIARY TREE OR TO LIVER CELLS
BILIARY TREE
The serum alkaline phosphatase (alk phos) and gamma glutamyl
transpeptidase (GGT) are more associated with damage to the
biliary tree (additionally the GTT is helpful in determining if the
Increased alk phos is of biliary tract or bone origin). The serum
aminotransferases (AST and ALT) more reflect damage to the
hepatocytes. In jaundice due to biliary problems the percentage of
total bilirubin that is direct (conjugated) is increased. In complete
obstruction, no bile reaches the gastrointestinal tract and the feces
become pale or clay colored. If there is crampy right upper
quadrant pain associated with the onset of jaundice, the likely
cause is a stone lodged in the common bile duct. When obstruction
of the common bile duct is due to tumor, the jaundice is usually
painless. In someone with jaundice due to biliary tree disease
(elevated bilirubin, high direct fraction, elevated alk phos and
GGT) the first step is usually to visualize the biliary tree.
Ultrasound is frequently used as the first step. An increased
diameter of the common bile duct is often seen if there is
obstruction, stones may also be visualized. CT or MRCP (magnetic
resonance cholangiopancreatography) scans (more expensive than
ultrasound) give more detailed information. If these imaging
methods produce equivocal results, more direct visualization can
be done via ERCP (endoscopic retrograde
cholangiopancreatography). In this more expensive procedure, the
papilla of Vater is visualized through an endoscope. A catheter is
placed into the ampulla of Vater, and dye can be injected into the
common bile duct or the pancreatic duct. This can detect even
small subtle lesions. Sometimes small stones can be removed

during this procedure. Other expensive specialized biliary tract

imaging tests are the HIDA scan (hepatic iminodiacetic acid scan)
and PTC (percutaneous transhepatic cholangiogram). If there is no
mechanical obstruction and the process still appears to be biliary
(elevated alk phos and GGT) the disease is probably one affecting
the intrahepatic biliary tree. There are two such diseases frequently
encountered. Primary biliary cirrhosis (PBC) typically affects
middle-aged women; the key laboratory test is the
antimitochondrial antibody titer (elevated titers are nearly specific
for PBC). The other process is primary sclerosing cholangitis
(PSC), which has a moderate male predominance. Most patients
with PSC have ulcerative colitis. The ERCP has a characteristic
appearance in PSC.
DAMAGED HEPATOCYTES
Most cases of jaundice are due to diseases that damage the
hepatocytes. The transaminase (AST and ALT) are more elevated
than the alk phos or GGT. Jaundice may appear during the acute
phase or during the chronic phase (decompensated cirrhosis).
Alcohol related liver disease is a common cause of jaundice. A
history of prolonged significant use of alcohol is critical. The
transaminases are often only mildly elevated; an AST to ALT ratio
greater than 2 is very helpful. Viral hepatitis can cause jaundice as
an acute or chronic disease. A history of parenteral exposure
(commonly IV drug abuse) is suggestive. The transaminases are
significantly higher than in alcohol; the AST/ALT ratio is usually
less than 1. It cannot be emphasized too strongly how important
historical information is in evaluating liver disease. Adverse drug
reactions are recognized by noting the temporal relationship of the
start of drug use and the appearance of liver disease. Family
history may be very important (e.g., hemochromatosis or Wilsons
disease). A decrease in the serum albumin is suggestive of severe
chronic liver disease; albumin is synthesized in the liver, and the
serum level will drop with the loss of hepatic mass. Likewise a
coagulopathy (manifested by a prolonged prothrombin time) may

develop in severe liver disease since some of the coagulation

factors are synthesized in the liver.
LABORATORY TESTS FOR VIRAL HEPATITIS
FIRST-LINE DIAGNOSTIC TESTS
Hepatitis A antibody IgM (screens for acute hepatitis A)
Hepatitis B core antibody IgM (screens for acute Hepatitis B)
Hepatitis B surface antigen (screens for acute or chronic hepatitis
B; false negatives may occur in acute)
Hepatitis C antibody (has low sensitivity, especially in the acute
phase)
OTHER DIAGNOSTIC TESTS
Hepatitis A antibody IgM + IgG. (measures total antibody and
cannot distinguish acute from past infection)
Hepatitis B viral DNA (also called NAT) (this is a third line screen
for Hepatitis B; also used by some blood banks to screen donors)
Hepatitis B surface antibody (used as a screen for past infection or
immunization)
Hepatitis C RNA test (second line screen for Hepatitis C; also is
used to monitor response to therapy).
Hepatitis D and E tests
TESTS FOR PROGNOSIS AND/OR RESPONSE TO THERAPY
Hepatitis Be antigen and antibody
Hepatitis B viral DNA quantitative assay
Hepatitis B Lamivudine resistance
Hepatitis C RNA test
Hepatitis C viral genotyping
LABORATORY TESTS FOR OTHER LIVER DISEASES
AUTOIMMUNE HEPATITIS
Anti-nuclear antibody (ANA)

Smooth muscle antibody (ASMA)

HEMOCHROMATOSIS
Iron Studies
Genetic testing
ALPHA 1 ANTITRYPSIN DEFICIENCY
A1AT levels
Genetic testing
WILSONS DISEASE
Ceruloplasmin
PBC
Mitochondrial antibody (AMA)
PSC
UC-ANCA (can also be pos. in Autoimmune Hepatitis)
THE BIOPSY IN EVALUATING LIVER DISEASE
The biopsy is a sensitive and specific means of evaluating liver
disease and allows one to stage the process (how much fibrosis is
present). It is relatively safe except in individuals with coagulation
disorders and malignancy in the liver. It is imperative to check the
prothrombin time prior to biopsy. If it is elevated, it must be
corrected. If it cannot be corrected and a biopsy is deemed
necessary, a transjugular approach can be used. A few
characteristic findings are as follow:
Alcohol related liver disease fatty change, central vein and
sinusoidal fibrosis, Mallory bodies, neutrophils.
Non-alcoholic steatohepatitis(NASH) fatty change (usually more
than in alcohol), glycogenated nuclei, central vein and sinusoidal

fibrosis, usually fewer Mallory bodies and neutrophils than in

alcohol.
Chronic viral hepatitis portal lymphoid infiltrate, piecemeal
necrosis.
PBC granulomas around damaged ducts; loss of intrahepatic
ducts.
PSC concentric fibrosis and neutrophils around damaged ducts;
loss of intrahepatic ducts.
Hemochromatosis excess iron in the liver; fibrosis.
Antitrypsin deficiency PAS positive inclusions.
Wilsons disease excess copper in the liver.
F. Mitros, November 15, 1999 (tests and procedures updated Jan,
2011, L. Guerin and F Dee)