Ref 1-Assessment of Jaundice

Assessment
of jaundice
The right clinical information, right where it's needed
Last updated: May 02, 2018

Table of Contents
Summary 3
Overview 4
Aetiology 4
Emergencies 13
Urgent considerations 13
Red flags 14
Diagnosis 16
Step-by-step diagnostic approach 16
Differential diagnosis overview 20
Differential diagnosis 22
Online resources 47
References 48
Images 51
Disclaimer 53
Summary
◊ Jaundice (icterus) is the result of accumulation of bilirubin in the bloodstream and subsequent
deposition in the skin, sclera, and mucous membranes. The normal range for total bilirubin is 3.4 to
20 micromol/L (0.2-1.2 mg/dL). Jaundice may not be clinically evident until serum levels exceed 51
micromol/L (3 mg/dL).
The underlying aetiology of jaundice may be quite difficult to discern. A pointed history and physical
examination is of utmost importance. By using this approach, an accurate diagnosis is possible in
approximately 85% of patients.[1]
Assessment of jaundice Overview
Aetiology
Jaundice may be due to a large number of disorders and can be classified according to the site of bilirubin
metabolism dysfunction (prehepatic, intrahepatic, and extrahepatic) or according to type of bilirubin
OVERVIEW
accumulation (increased direct or indirect bilirubin levels). It is important to distinguish jaundice from
pseudo-jaundice, as this helps to avoid unnecessary investigations. Pseudo-jaundice is usually caused
by carotenaemia, a clinical condition characterised by yellow pigmentation of the skin and increased beta-
carotene levels in the blood. In most cases, the condition follows prolonged and excessive consumption of
carotene-rich foods, such as carrots, pumpkin, and sweet potatoes. The sclerae are always spared, which
readily distinguishes carotenaemia from jaundice.
Toxic and iatrogenic causes

Alcoholic liver disease
• Alcoholic liver disease is caused by chronic, heavy alcohol ingestion greater than approximately 40 to
80 g/day in men and 20 to 40 g/day in women for 10 to 12 years. The progression of fibrosis in patients
with alcoholic liver disease is faster in those who smoke. Alcohol produces liver damage through a
range of mechanisms.
• The liver is the main site of alcohol metabolism, which occurs by 2 main pathways: alcohol
dehydrogenase and cytochrome P-450 2E1. Liver damage occurs firstly because increased flux
through the alcohol dehydrogenase pathway alters the ratio of NAD to NADH, leading to inhibition of
gluconeogenesis, increased fatty acid oxidation, and, ultimately, increased fatty infiltration in the liver.
• The cytochrome P-450 2E1 pathway also metabolises alcohol and generates free radicals; oxidative
stress leads to hepatocyte necrosis and apoptosis.
• The alcohol metabolite acetaldehyde, when bound to cellular protein, produces antigenic adducts
and induces inflammation. Alcohol also affects the barrier function of intestinal mucosa, producing
endotoxaemia, which leads to hepatic inflammation.
Drug-induced hyperbilirubinaemia
• The reported incidence of drug-induced hepatitis ranges between 0.8% and 1.5% of patients admitted
to hospital for liver dysfunction.[2] [3] [4] [5] These seemingly small numbers of patients are deceiving
because the associated mortality is approximately 10%.[6] [7]
• Drugs may cause direct or indirect hyperbilirubinaemia.[8] Direct hyperbilirubinaemia is usually due
to an acute liver injury, which may involve hepatitis, cholestasis, mixed hepatitis and cholestasis, or,
rarely, steatosis.
• Paracetamol is the drug most commonly associated with drug-induced liver injury in the US and other
Western countries. Hepatotoxicity due to paracetamol poisoning is dose-dependent, with acute liver
failure more likely with doses in excess of 150 mg/kg.[9]
• In a retrospective analysis of the United Network for Organ Sharing liver transplant database from
1990 to 2002, 15.6% of patients undergoing transplant for acute hepatic necrosis were identified
as having drug-induced acute liver failure, of which paracetamol toxicity accounted for 46% of the
transplant recipients.[10]
• Antibiotics are the most common type of drug to be associated with non-paracetamol associated drug-
induced liver injury. Antiepileptics (e.g., phenytoin, carbamazepine, lamotrigine) and non-steroidal anti-
inflammatory drugs represent the next group of drugs commonly implicated.[11]
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 02, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
• Liver injury associated with herbal and dietary supplements is increasing in frequency worldwide. In
the Drug-Induced Liver Injury Network (DILIN) prospective study of drug-induced liver injury, herbal
and dietary supplements accounted for 16% of cases overall.[12] The most commonly reported
product was bodybuilding supplements, with a phenotype suggestive of injury from anabolic steroids.
OVERVIEW
Among the non-anabolic steroid-associated cases in the DILIN study, 16% were attributed to single or
multiple named herbal products (e.g., green tea, kava kava, kratom, black cohosh); 8% to traditional
botanical mixtures (e.g., Chinese herbs, Korean herbs, Ayruvedic medications); 7% to simple vitamin
and mineral supplements (e.g., niacin, levocarnitinine); and the remaining 68% to multi-ingredient
nutritional supplements.
• N-acetylcysteine is used to prevent or minimize liver damage due to paracetamol toxicity, and may
benefit non-paracetamol-induced drug injury in adults.[13]
• Autoimmune hepatitis should be considered in all cases of drug-induced liver injury.
Benign biliary obstruction

Choledocholithiasis
• Jaundice due to choledocholithiasis occurs as a result of either the primary formation of stones in the
common bile duct (CBD) or the passage of gallstones from the gallbladder through the cystic duct into
the CBD.
• Bile stasis, bactibilia, chemical imbalances, pH imbalances, increased bilirubin excretion, and the
formation of sludge are among the principal factors thought to lead to the formation of stones.
• Gallstones are differentiated by their chemical composition. Cholesterol stones are composed mainly
of cholesterol, black pigment stones are mainly pigment, and brown pigment stones are made up of a
mix of pigment and bile lipids.
• Obstruction of the CBD by gallstones leads to symptoms and complications that include pain, jaundice,
cholangitis, pancreatitis, and sepsis.
Postoperative stricture
• Iatrogenic biliary duct injury, most commonly caused by surgical injury during cholecystectomy, can
lead to benign strictures, which can, in turn, lead to obstruction.
Infection
The viral hepatitides A, B, C, D, and E all have the potential to cause jaundice.
Hepatitis A
• A single-stranded RNA picornavirus.

• The most common cause of acute viral hepatitis and is particularly common among children and
young adults. In some countries, >75% of adults have been exposed. It does not cause chronic liver
disease.
• It spreads primarily by faecal-oral contact and thus may occur in areas of poor hygiene. Waterborne
and food-borne epidemics occur, especially in developing countries. Eating contaminated raw shellfish
is sometimes the cause. Sporadic cases are also common, usually as a result of person-to-person
contact.
• Relative frequency as a cause of acute hepatitis has decreased in Western society. Improvements in
hygiene, public health policies, and sanitation have had the greatest impact on hepatitis A. Vaccination
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 02, 2018.
5
programmes and passive immunisation have successfully led to some reduction in illness in high-risk
groups.
Hepatitis B
OVERVIEW
• Hepatitis B virus (HBV) is the most common cause of chronic hepatitis worldwide. HBV is transmitted
hematogenously and sexually.
• The infectious particle consists of a viral core plus an outer surface coat. The core contains circular,
double-stranded DNA and DNA polymerase, and it replicates within the nuclei of infected hepatocytes.
• The outcome of this infection is a complicated virus-host interaction. Infection may result in a self-
limiting disease requiring no treatment, particularly in the immunocompetent, adult-acquired infection,
where the risk of chronicity is less than 4%. However, it may also result in a high rate of chronic
disease (50% to 90%) if it is acquired perinatally, or in early childhood.
• Chronic hepatitis B virus (HBV) infection can cause liver cirrhosis.
• HBV is often transmitted parenterally, typically by contaminated blood or blood products. Routine
screening of donor blood for hepatitis B surface antigen (HBsAg) has nearly eliminated the previously
common post-transfusion transmission, but transmission through needles shared by drug users
remains common. Vertical transmission from mother to infant is common.
• Antiviral therapy is effective in suppressing viral replication, as defined by undetectable HBV DNA in
approximately 95% of patients who are treated with oral antiviral therapy.
Hepatitis C
• Hepatitis C virus (HCV) is a single-stranded RNA flavivirus.

• HCV is the leading cause of chronic viral hepatitis in the Western world.
• Infection with HCV is self-limited in only a small minority of infected people. Chronic infection develops
in 70% to 80% of patients infected with HCV. Cirrhosis develops within 20 years of disease onset in
20% of people with chronic infection.
• Infection is most commonly transmitted through blood, primarily when parenteral drug users share
needles, but also through tattoos or body piercing. Sexual transmission and vertical transmission from
mother to infant are relatively rare. Transmission through blood transfusion has become very rare since
the advent of screening tests for donated blood.
• Advances in hepatitis C treatments, with various combinations of NS3/4 targeting protease inhibitors,
non-structural protein 5B (NS5B) polymerase inhibitors, and non-structural protein 5A (NS5A) targeting
agents that inhibit the viral replication cycle, have altered the hepatitis C landscape internationally.
Response rates of 90% to 99% are now possible with a shorter duration of treatment (8-12 weeks),
compared with previously available combination therapy with antiviral and interferon.
Hepatitis D
• A defective virus that needs the presence of hepatitis B to cause clinically recognisable disease.
Hepatitis E
• Hepatitis E virus (HEV) infection is a worldwide disease with different epidemiological and clinical
patterns of disease between the developing and developed countries.[14]
• In developing countries, outbreaks of acute HEV (HEV1 and HEV2) infection are often waterborne
and linked to faecal contamination of the water supply. It represents an acute, self-limiting illness that
usually requires either no treatment, or supportive treatment only. Jaundice occurs in about 40% of
patients.
• Increased mortality is seen in pregnant women, with mortality rates of 20% to 25% reported,
particularly during the third trimester.[15]
• In developed countries, HEV3 and HEV4 are transmitted zoonotically from animal reservoirs. Jaundice
occurs in about 75% of patients.
OVERVIEW
• Chronic infection is more common in the developed world, with rapid progression to cirrhosis in organ
transplant recipients, patients with haematological malignancy requiring chemotherapy, and individuals
with HIV.
• In addition to the classical hepatic manifestation, HEV has been associated with extrahepatic
manifestation of disease, ranging from neurological syndromes, renal injury, pancreatitis, and
haematological disorders.
Ascending cholangitis
• An infection of the biliary tree, most commonly caused by obstruction. The 2 most common underlying
causes are choledocholithiasis and strictures due to surgery, chronic pancreatitis, radiotherapy, or
chemotherapy.
• In its less severe form, there is biliary obstruction with inflammation and bacterial seeding and growth
in the biliary tree.
• In the more severe, life-threatening form, known as toxic cholangitis or cholangitis with sepsis, patients
have purulent biliary tree contents, as well as evidence of sepsis, hypotension, multi-organ failure, and
mental status changes.
• Obstruction of the common bile duct initially results in bacterial seeding of the biliary tree, possibly
via the portal vein. Sludge also forms, providing a growth medium for the bacteria. As the obstruction
progresses, the bile duct pressure increases. This forms a pressure gradient that promotes
extravasation of bacteria into the bloodstream and, ultimately, sepsis.
HIV infection
• Patients with known HIV disease represent a unique population with a multitude of possible aetiologies
for jaundice.[16] Co-infection with either HCV or HBV is not uncommon. Highly active antiretroviral
therapy (HAART) is a well-known aetiology of drug-induced hepatitis.
• A wide range of opportunistic infections and malignancy can cause hepatobiliary pathology in HIV-
infected patients. Frequently, there is co-infection with HBV or HCV, as well as complications related
to other viruses (cytomegalovirus [CMV], Epstein-Barr virus, or herpes simplex virus [HSV]). Autopsy
studies have shown a 33% to 78% rate of infection or malignancy in HIV-infected patients that range
from viral (CMV and HSV), to granulomatous ( Mycobacterium avium complex), to fungal.[16]
Parasitic infections
• Parasitic infections that cause jaundice include ascariasis (caused by Ascaris lumbricoides ),
hydatidosis (caused by Echinococcus granulosus ), Clonorchis sinensis , and Fasciola hepatica .
Metabolic causes
Primary non-alcoholic steatohepatitis
• The growing epidemic in the Western world is thought to be associated with increased obesity within
developed countries.
7
• Although the pathophysiology is not yet fully understood, the most widely held hypothesis implicates
insulin resistance as the key mechanism leading to the accumulation of excessive triglyceride in the
liver and subsequent development of hepatic steatosis.
• Age >45 years, obesity, diabetes mellitus, and elevated aspartate aminotransferase/alanine
OVERVIEW
aminotransferase all increase the risk of fibrosis.

Secondary non-alcoholic steatohepatitis
• Causes include drugs such as amiodarone, methotrexate, nifedipine, corticosteroids, tamoxifen,

parenteral nutrition, and short bowel syndrome.
• Rarer causes include metabolic diseases such as glycogen storage disease and homocysteinuria,
Wilson's disease, and coeliac disease.
Inflammatory and immune-mediated causes

Autoimmune hepatitis
• A chronic inflammatory disease of the liver of unknown aetiology. The pathogenesis is believed
to involve a complex interplay between a genetic predisposition, environmental triggers (several
viruses, drugs, or herbal agents have been proposed to be triggers), autoantigens, and dysfunction of
immunoregulatory mechanisms.
• Characterised by the presence of circulating autoantibodies with a high serum globulin concentration,
inflammatory changes on liver histology, and a favourable response to immunosuppressive treatment.
Primary biliary cirrhosis
• A chronic disease of the small intrahepatic bile ducts that is characterised by progressive bile duct
damage (and eventual loss) occurring in the context of chronic portal tract inflammation. Fibrosis
develops as a consequence of the original insult and the secondary effects of toxic bile salts retained
in the liver, resulting, ultimately, in cirrhosis.
• The almost universal presence of autoantibodies (classically antimitochondrial antibodies) has led to
the widely held view that the disease is autoimmune in aetiology.
Primary sclerosing cholangitis
• A chronic progressive cholestatic liver disease, characterised by inflammation and fibrosis of the
intrahepatic and/or extrahepatic bile ducts, resulting in diffuse, multifocal stricture formation.
• Often associated with inflammatory bowel disease (occurs in approximately 3% to 6% of patients with
ulcerative colitis and 1.2% of patients with Crohn's disease).[17] [18] Patients with ulcerative colitis or
Crohn's disease are also at increased risk for the development of cholangiocarcinoma, an additional
aetiology of jaundice.
• The aetiology is not well understood. It is believed to be an immune-mediated disorder initiated by an
as yet unidentified trigger. However, it is not a classic autoimmune disease, as it does not respond to
immunosuppressive treatment.
• Complications include dominant biliary stricture (a focal area of tight narrowing of the extrahepatic
biliary tree that develops in 40% to 50% of patients as a result of progressive stricturing) and end-
stage liver disease (due to chronic progressive biliary fibrosis).
IgG4 cholangiopathy
• Once associated with autoimmune pancreatitis, IgG4 cholangiopathy represents a myriad of systemic
inflammatory disorders that affect multiple organs and are associated with elevated serum IgG4 levels
or bile duct inflammation that includes IgG4-mediated plasma cells.
• Patients are typically men aged 50 to 60 years and more than 75% will present with common bile duct
OVERVIEW
obstruction and jaundice.[19]
• Corticosteroids are the initial treatment and may be needed for maintenance.
Neoplastic causes
Pancreatic cancer
• Refers to primary pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 85%
of all pancreatic neoplasms. Progression of pancreatic cancer has been shown to follow a linear
progression model from pre-invasive pancreatic intraepithelial neoplastic (PanIN) lesions to invasive
ductal adenocarcinoma.
• Carcinoma of the pancreas has had a markedly increased incidence during the past several decades
and ranks as the fourth leading cause of cancer death in the United States.
• Despite the high mortality rate associated with pancreatic cancer, its aetiology is poorly understood.
• Cancer of the exocrine pancreas is rarely curable and has an overall survival rate of <4%. The highest
cure rate occurs if the tumour is truly localised to the pancreas; however, this stage of the disease
accounts for <20% of cases.
• Carcinoma of the head of the pancreas results in obstruction of the distal common bile duct and the
development of obstructive jaundice. One systematic review found that 30% of people with pancreatic
cancer reported having jaundice.[20] Jaundice had a positive predictive value for pancreatic cancer of
4% in people over 40 years of age.[20]
Cholangiocarcinoma
• Cholangiocarcinoma is a tumour that arises from the intrahepatic or extrahepatic biliary epithelium.
More than 90% are adenocarcinomas, and the remainder are squamous cell tumours.
• The aetiology of most bile duct cancers remains undetermined; however, infections, primary sclerosing
cholangitis, and chemical exposure are implicated in its development. In Southeast Asia, chronic
infections with liver flukes, Clonorchis sinensis and Opisthorchis viverrini , have been causally related
to cholangiocarcinoma. Other parasites, such as Ascaris lumbricoides , have been implicated in the
pathogenesis of cholangiocarcinoma.
• A strong relationship exists between cholangiocarcinoma and primary sclerosing cholangitis.
Cholangiocarcinoma generally develops in patients with long-standing ulcerative colitis and primary
sclerosing cholangitis. The lifetime risk of developing this cancer in the setting of primary sclerosing
cholangitis is 10% to 20%.
• Patients with ulcerative colitis without symptomatic primary sclerosing cholangitis are also at increased
risk.
• Certain chemical exposures have been implicated in the development of bile duct cancers, primarily
in workers in the aircraft, rubber, and wood-finishing industries. Cholangiocarcinoma has occasionally
developed years after administration of the radiopaque medium thorium dioxide.
• Congenital diseases of the biliary tree, including choledochal cysts and Caroli's disease, have been
associated with cholangiocarcinoma. Other conditions rarely associated with cholangiocarcinoma
include bile duct adenomas, biliary papillomatosis, and alpha-1 antitrypsin deficiency.
9
Haematological causes
Hereditary haemolytic anaemias
• Haemolysis of red blood cells (RBCs) leads to elevation of serum bilirubin levels. Clinical jaundice is
OVERVIEW
seen once bilirubin levels rise above 34 to 68 micromol/L (2 to 4 mg/dL).

• Causes include RBC membrane defects (hereditary spherocytosis, elliptocytosis, pyropoikilocytosis),
enzyme deficiencies (glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency),
and abnormal haemoglobin production (sickle cell anaemia, thalassaemia).
Acquired haemolytic anaemias
• Haemolysis of RBCs leads to elevation of serum bilirubin levels. Clinical jaundice is seen once bilirubin
levels rise above 34 to 68 micromol/L (2 to 4 mg/dL).
• Autoimmune haemolytic anaemia occurs when RBCs are attacked by autoantibodies and targeted
for extravascular destruction. This usually occurs either as part of other autoimmune conditions
(e.g., systemic lupus erythematosus, rheumatoid arthritis, or scleroderma) or in relation to a
lymphoproliferative disorder (usually non-Hodgkin's lymphoma or chronic lymphocytic leukemia).
• Alloimmune haemolytic anaemia can be caused by transfusion reactions, usually due to ABO
incompatibility.
• Many drugs are associated with haemolysis, some through immune-mediated mechanisms, and
others through non-immune-mediated mechanisms.
• Infectious causes include cytomegalovirus, infectious mononucleosis, toxoplasmosis, and
leishmaniasis.
• Microangiopathic haemolytic anaemias: these are serious anaemias caused by disseminated
intravascular coagulation, thrombotic thrombocytopenia purpura, haemolytic uremic syndrome, and
eclampsia.
• Paroxysmal nocturnal haemoglobinuria is a rare disorder resulting in an acquired RBC membrane
defect and subsequent haemolysis.
Pregnancy
An evaluation of data from consecutive deliveries in a maternity department at one US hospital found that
397 pregnant women, out of a total of 80,857 (0.5%), had elevated bilirubin. The most common causes
were gallstones (25%), pre-eclampsia/eclampsia/HELLP (24%), and intrahepatic cholestasis of pregnancy
(13%).[21]
HELLP syndrome
• The HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome is a serious complication in
pregnancy characterised by haemolysis, elevated liver enzymes, and low platelet count.
• The aetiology is not clear. As the condition is considered to be a subtype of severe pre-eclampsia, the
causative factors, although still hypothetical, should be similar.
• The disease process is characterised by vasospasm and endothelial dysfunction with variable degrees
of hepatic ischaemic damage, microangiopathic haemolytic anaemia, and thrombocytopenia. Vascular
changes predominantly affect the liver, and decreased hepatic perfusion may be documented by
Doppler examination. The damage may lead to intraparenchymal haemorrhage and/or subcapsular
hepatic haematomas and, rarely, to hepatic infarction.
Cholestasis of pregnancy
• Mild jaundice is occasionally seen in cholestasis of pregnancy, although it is not a dominant feature.
The condition is caused by impaired bile flow, allowing bile salts to be deposited in the skin and the
placenta due to a combination of hormonal, genetic, and environmental factors.
OVERVIEW
Genetic causes
Hereditary haemochromatosis
• An adult-onset disorder characterised by inappropriately high iron absorption, resulting in progressive

iron overload. The organs involved are the liver, heart, pancreas, pituitary, joints, and skin.
• The most common autosomal recessive genetic disorder.
• The gene responsible for the disease is called HFE and is located on chromosome 6. It is mutated in
most individuals with hereditary haemochromatosis. Findings suggestive of increased iron transport at
the basolateral membrane of enterocytes in haemochromatosis have emerged.
Alpha-1 antitripysin (alpha 1-AT) deficiency
• A common inherited disorder associated with retention of the liver-produced protein alpha 1-AT in
the liver and low levels of alpha 1-AT in the serum. Pulmonary and hepatic manifestations include
emphysema and cirrhosis.
• In the most severe form of alpha 1-AT deficiency, the clinical features consist of early-onset
emphysema, neonatal hepatitis, chronic hepatitis, cirrhosis, and hepatocellular carcinoma. However,
phenotypic expression throughout life is extremely variable.
• The gene for alpha 1-AT is located on chromosome 14, and mutations at the protease inhibitor (PI)
locus lead to a single amino acid substitution (glutamic acid for lysine 342) that impairs secretion of the
mutant gene product, leading to retention of alpha 1-AT in the hepatocyte and low levels of alpha 1-AT
in the serum.
Wilson's disease
• A rare autosomal recessive inherited disorder of copper metabolism characterised by excessive

deposition of copper in the liver, brain, and other tissues.
• The genetic defect, localised to chromosome arm 13q, has been shown to affect the copper-
transporting adenosine triphosphatase (ATPase) gene (ATP7B) in the liver.
• Patients usually present with liver disease during the first decade of life or with neuropsychiatric illness
during the third decade.
• The diagnosis is confirmed by measurement of serum ceruloplasmin, urinary copper excretion, and
hepatic copper content, as well as the detection of Kayser-Fleischer rings.
Gilbert's syndrome
• An autosomal recessive condition characterised by intermittent jaundice in the absence of haemolysis

or underlying liver disease.
• It may be precipitated by dehydration, fasting, menstrual periods, or stress, such as an intercurrent
illness or vigorous exercise.
• Patients may report vague abdominal discomfort and general fatigue for which no cause is found.
These episodes resolve spontaneously, and no treatment is required, except supportive care.
• With the exception of unconjugated hyperbilirubinaemia, standard liver function test results are normal.
No further investigations are required.
11
Crigler-Najjar syndrome
• A rare, autosomal recessive disorder of bilirubin metabolism caused by glucuronosyltransferase

deficiency, which causes congenital non-haemolytic jaundice. It is divided into 2 distinct forms (types 1
OVERVIEW
and 2) based on the severity of the disease.

• Type 1 disease results in severe jaundice and bilirubin encephalopathy, leading to neurological
impairment, which can cause permanent neurological deficits.
• Type 2 disease is milder, with less marked hyperbilirubinaemia, and neurological impairment does not
occur.
Assessment of jaundice Emergencies
Urgent considerations
(See Differential diagnosis for more details)
Patients with ascending cholangitis can be identified by the application of Charcot’s triad. This includes
the presence of fever, jaundice, and right upper quadrant pain. Management in these patients requires
early administration of appropriate antibiotics. The organism is usually a gram-negative bacillus.
Gentamicin is recommended provided renal function is stable. Intravenous fluid resuscitation is
required. An early ultrasound should be performed to confirm the presence of an obstructed biliary
tree, followed by decompression of the obstructed biliary system, usually by endoscopic retrograde
cholangiopancreatography.
Haemolysis
Massive haemolysis as a cause of jaundice should be considered in the presence of falling haemoglobin and
EMERGENCIES
absence of overt blood loss. Immune haemolytic anaemias generally have characteristic clinical findings,
including rapid onset and progression, dark urine, and jaundice, with or without splenomegaly. Laboratory
findings (e.g., increased LDH and indirect bilirubin, and decreased haptoglobin) are important in confirming
a haemolytic process and in establishing an immunological aetiology (e.g., antiglobulin test results). Early
haematological input would be advocated with consideration of high-dose intravenous corticosteroids or
intravenous immunoglobulins.
HELLP syndrome
The HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome is a serious complication in
pregnancy characterised by haemolysis, elevated liver enzymes, and low platelet count, occurring in 0.5%
to 0.9% of all pregnancies and in 10% to 20% of cases with severe pre-eclampsia. Typical clinical symptoms
are right upper abdominal quadrant or epigastric pain, nausea, and vomiting. The upper abdominal pain may
be a fluctuating pain similar to colic.
The first step is to evaluate the patient. The clinical maternal status, gestational age (ultrasound determined),
presence of labour, and cervical Bishop score should be determined. The laboratory examination must
include full blood count (of which the platelet count is key for diagnosis), coagulation parameters, aspartate
aminotransferase, LDH, and haptoglobin and urine examination. Blood pressure measurement, ultrasound
examination, and fetal assessment tests (cardiotocography and Doppler examination) are important. The
next step is to stabilise the maternal clinical condition with intravenous fluids, antihypertensive drugs (e.g.,
labetalol or nifedipine), and magnesium sulphate to prevent convulsions.
The timing of delivery requires careful consideration. The use of corticosteroids to stabilise the maternal
condition and assist fetal lung development is advocated by some groups. The use of platelet transfusions
prior to caesarean section is also beneficial.
It is useful to note that about 30% of the HELLP syndromes develop after birth, the majority within the first 48
hours. As early post-partum administration of high-dose corticosteroids might accelerate recovery, its routine
administration is highly recommended (10 mg of dexamethasone every 12 hours).
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Acute alcoholic hepatitis

Alcoholic hepatitis (AH) is a syndrome of progressive inflammatory liver injury associated with heavy ethanol
intake. Mild alcoholic hepatitis is a benign disorder with negligible short-term mortality. However, when
alcoholic hepatitis is of sufficient severity to cause jaundice, hepatic encephalopathy, or coagulopathy,
mortality can be substantial. Patients who are severely affected present with sub-acute onset of fever,
hepatomegaly, leukocytosis, marked impairment of liver function (e.g., jaundice, coagulopathy), and
manifestations of portal hypertension (e.g., ascites, hepatic encephalopathy, variceal haemorrhage).
Rapid assessment is essential. Identifying sources of infection, excluding bacterial peritonitis and
gastrointestinal bleeding, evaluating fluid status, and excluding electrolyte abnormalities, as well as
recognising malnutrition, are important issues to consider during initial assessment and management. The
application of the Glasgow Alcoholic Hepatitis Score or Maddrey’s Discriminant Function index allows the
identification of patients with severe alcoholic hepatitis.
The management centres on providing nutritional support, maintaining adequate protein and caloric intake,
treating co-existing infections, and correcting electrolyte abnormalities.
EMERGENCIES
Infection may be both the precipitant for decompensation and a leading factor of poor outcome in alcoholic
hepatitis. Urine and blood cultures, as well as chest radiography, should be included in the initial work-up of
patients.
Patients with AH who receive less than 21 kcal/kg/day have been shown to have a lower survival. It is
essential therefore to address nutritional support and supplementation early.[22]
In the absence of infection, corticosteroids may be beneficial in patients with severe alcoholic hepatitis in the
short term. The Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial failed to show any difference
in medium or long-term survival.[23] If glucocorticoids are used initially, response should be assessed using
Lille criteria, and glucocorticoids discontinued if there is no objective response.[24] [25] Finally, careful
management of fluid status and monitoring for the development of hepatorenal syndrome is necessary. If
hepatorenal syndrome occurs, the combination of human albumin infusions, terlipressin, and antibiotics
should be administered. In the long term, prolonged abstinence from alcohol is necessary to prevent further
deterioration in hepatic function and to improve mortality.
Red flags
• Alcoholic liver disease
• Hepatitis B
• Drug-induced direct hyperbilirubinaemia
• Ascending cholangitis
• Autoimmune hepatitis
• Pancreatic carcinoma
• Cholangiocarcinoma
• Pregnancy
EMERGENCIES
15
Assessment of jaundice Diagnosis
Step-by-step diagnostic approach

The diagnosis of jaundice is usually easy to establish based on history and observation of yellow
discoloration of the sclerae, skin, and mucous membranes. It should be distinguished from pseudo-jaundice
due to carotenaemia, in which the sclerae are spared.
[Fig-1]
[Fig-2]
History
Risk factors leading to the development of jaundice should be sought, such as alcohol use, intravenous drug
use, relevant occupational history, travel history to endemic regions, and sexual activity (number of partners;
type of intercourse; known intercourse with hepatitis B virus-, hepatitis C virus-, or HIV-infected patients).
The CAGE score is highly specific for detecting alcohol abuse. It consists of 4 questions, and 2 positive
answers require further investigation into alcoholism. These questions address efforts to cut down drinking,
criticism about one's drinking, guilt, and need to drink upon waking in the morning. [CAGE and CAGE-AID
questionnaires] [26]
The possibility of pregnancy should be explored. The past medical history should include specific questioning
identifying inflammatory bowel disease, pancreatic disorders, history of blood transfusions, anaemia,
or the presence of an inherited haemoglobinopathy such as thalassaemia or sickle cell disease. Past
surgical history should focus on procedures involving the hepatobiliary tract and the pancreas. A review of
prescription and over-the-counter medication and herbal supplement use, both current and recent past, is
recommended. Family history should inquire about symptoms of inherited anaemias, haemoglobinopathies,
and liver disorders.
Of note, clinical manifestations range from completely asymptomatic to severely ill. The presenting symptoms
tend to be non-specific, such as fatigue, malaise, pruritus, weight loss, anorexia, pale stool, and dark urine.
Pain may occur but is not universal; it may suggest ascending cholangitis or a biliary stone.
DIAGNOSIS
Examination
The physical examination should focus on the liver and complications associated with cirrhosis. In those
with known or presumed liver disease, a careful skin examination may reveal track marks on the extremities,
evidence of ecchymosis or petechiae, and, in some, the presence of spider angioma and palmar erythema.
Muscle wasting may be present in patients with chronic liver disease. Temporal wasting and loss of the
thenar eminence may be observed. The presence of parotid gland enlargement, gynaecomastia, and a
Dupuytren's contracture is highly suggestive of chronic alcohol abuse.
The abdominal examination should include close inspection for collateral veins (caput medusa) and ascites.
The liver and spleen should be palpated and percussed during both inspiration and expiration, checking for
enlargement, pain, and nodularity. A nodular liver with decreased size suggests cirrhosis, and the presence
of collateral vessels suggests portal hypertension. Confusion or frank somnolence on continued questioning,
asterixis, or altered deep tendon reflexes may be indicative of hepatic encephalopathy. Lung examination
may reveal evidence of pleural effusion (hepatic hydrothorax). Cardiovascular examination may point towards
liver dysfunction due to congestion from right heart failure. Rectal examination may reveal evidence of
gastrointestinal bleeding. The presence or absence of a palpable gallbladder should be noted as well.
Courvoisier's law states that enlargement of the gallbladder with jaundice is likely to result from carcinoma of
the head of the pancreas rather than a stone in the common duct. With a common duct stone, the gallbladder
is usually scarred from infection and does not distend.
Laboratory tests
Initial laboratory testing for all patients should include liver function tests with fractionation of the bilirubin
(direct and indirect), prothrombin time (PT) and international normalised ratio (INR), and full blood count
(FBC). A low platelet count is suggestive of portal hypertension or alcohol abuse. Anaemia is a prominent
feature in liver disease patients, prompting iron studies. An increased PT and INR when coupled with a low
albumin is indicative of synthetic liver dysfunction and suggestive of cirrhosis or acute liver failure. In acute
alcoholic hepatitis, application of the Glasgow Alcoholic Hepatitis Score and the MELD score are useful
in the determination of the severity of disease and are of prognostic significance.[27] [22] The Maddrey
Discriminant Function index is a useful guide to rationalise the use of corticosteroids in severe disease: a
score greater than 32 reflects severe disease.[28] Elevation can be seen in cholestasis without synthetic liver
dysfunction, due to malabsorption of vitamin K.
Two patterns of liver function derangement have been described: cholestatic or hepatocellular. The
cholestatic pattern consists of predominant elevation of bilirubin, alkaline phosphatase, and gamma-GT,
and the hepatocellular pattern consists of elevations of bilirubin, aspartate aminotransferase, and alanine
aminotransferase. These patterns are non-specific and can significantly overlap.
For specific cases additional tests are needed.
• Autoimmune hepatitis should be excluded in all patients. Aminotransferase levels are usually more
strikingly elevated than those of bilirubin and alkaline phosphatase. Erythrocyte sedimentation rate,
antinuclear antibody, antismooth muscle antibody, anti-LKM-1 antibody, elevated gamma globulins,
and anti-soluble liver antigen antibody should be measured to exclude the diagnosis. Confirmatory
diagnosis is with liver biopsy.
• IgG4 cholangiopathy diagnosis usually requires a combination of supporting clinical, laboratory,
radiological, and histological data. Measured serum IgG4 ≥1.35 g/L (≥135 mg/dL) is 80%
specific for the disease.[29] Elevated gamma-GT, alkaline phosphatase, and modest elevation
DIAGNOSIS
of aminotransaminase levels support the diagnosis. Radiological appearances of simultaneous
stricture of intra-pancreatic portion of the common bile duct and of the hepatic hilum with associated
pancreatitis is more likely in IgG4 cholangiopathy.
• Viral hepatitis: in patients with suspected exposure to or symptoms of hepatitis A, B, C, D, and E,
the following laboratory tests are warranted: hepatitis A antibody IgM, hepatitis B serology or viral
load, hepatitis B virus DNA, hepatitis C serology or viral load, hepatitis C virus genotyping/RNA, and
hepatitis D and E serologies/polymerase chain reaction.
• Haemolysis or haemolytic anaemia: in patients with pallor, weakness, shortness of breath, or dark-
coloured urine, tests should include haptoglobin, LDH, a reticulocyte count, and a peripheral blood
smear. If a transfusion reaction is suspected, a direct antiglobulin test is also indicated. Some patients
may need work-up for sickle cell anaemia.
• Haemochromatosis: patients suspected of haemochromatosis should receive a transferrin saturation
test, iron studies, a genetic test to determine the haemochromatosis gene mutation (confirmatory),
and a liver biopsy. These patients tend to have joint pain, fatigue, lack of energy, abdominal pain, and
cardiac problems.
• Primary biliary cirrhosis: this may be the cause of jaundice in patients with fatty subcutaneous
deposits, fluid retention, and dry eyes and mouth. Tests should include a liver biopsy and a blood test
to identify the antimitochondrial antibody.
17
• Alpha-1 antitrypsin deficiency: serum level and genotype looking for the Z or M (Malton) alleles are
warranted with a suspicious family history (liver or lung disease in those younger than 40 years of age)
and symptoms of alpha-1 antitrypsin deficiency (e.g., emphysema), and when other diagnoses are
ruled out.
• Wilson's disease: a genetic test is indicated if signs and symptoms are suspicious (tremor, Kayser-
Fleischer rings, ascites, hepatitis by 20s), and other diagnoses have been ruled out. A liver biopsy with
copper concentration, serum ceruloplasmin, and urinary copper excretion measurements is needed.
• Crigler-Najjar syndrome (type 1 or 2): if suspected, a further work-up is recommended. Patients may
have a family history of Crigler-Najjar and worsening jaundice of the skin and sclerae with an onset on
the second or third day of life and persisting beyond 2 weeks. Unconjugated and total bilirubin levels
tend to be elevated, whereas conjugated bilirubin would be low. A liver biopsy or enzyme assay should
be completed to look for low or absent glucuronyl transferase. The phenobarbital test can be used to
distinguish type 1 and type 2. In type 1, there is no resulting change in bilirubin, and in type 2, bilirubin
levels are decreased. Finally, a chromatographic analysis of bile helps distinguish type 1 and type 2.
• Parasitic disease: patients with recent foreign travel to endemic regions may have parasitic
disease causing jaundice. A stool study, analysing ova and parasites, is needed. Ultrasound and
cholangiography are also helpful in identifying parasites.
• AIDS cholangiopathy: the diagnosis is one of exclusion in a patient with known HIV infection. The
cholangiopathy may be related to highly active antiretroviral therapy (HAART), HIV itself, or comorbid
and opportunistic infections. Endoscopic retrograde cholangiopancreatography can provide therapy in
the form of biliary sphincterotomy, dilation, and/or stenting of the biliary strictures.
Imaging modality: estimating the pre-test probability of biliary

obstruction
Once the initial clinical assessment and laboratory tests are complete, the pre-test probability of biliary
obstruction should be estimated in order to guide the choice of imaging. Most patients require some form of
imaging so that mechanical obstruction can be definitively excluded and clues to hepatic and post-hepatic
causes identified. The American College of Radiology Appropriateness Criteria for jaundice define the
following major categories:[30]
DIAGNOSIS
• High likelihood of benign biliary obstruction: patients present with jaundice and acute abdominal pain
• High likelihood of malignant biliary obstruction: patients typically present with insidious development of
jaundice and associated constitutional symptoms (weight loss, fatigue, etc.)
• Low likelihood of mechanical obstruction: history, clinical features, and initial laboratory tests
consistent with specific hepatic and post-hepatic causes (e.g., history of alcohol use or exposure to
infectious agent, painless jaundice without constitutional symptoms, hepatocellular pattern of liver
function tests)
• Indeterminate likelihood of obstruction: confusing clinical presentation.
High likelihood of benign biliary obstruction

Ultrasound is the preferred initial modality of investigation, as it is accurate, inexpensive, readily available,
and non-invasive (sensitivity of 55% to 95% and specificity of 71% to 96%). It is limited by its decreased
sensitivity for detecting biliary ductal calculi and the inability to visualise the distal common bile duct if
obscured by overlying bowel gas.[30]
In patients with acute biliary obstruction and suspected complicating conditions such as cholangitis,
cholecystitis, or pancreatitis not well evaluated by sonography, a pre-intravenous and post-intravenous
contrast-enhanced abdominal CT study is useful in defining the level of obstruction, likely cause, and co-
existent complications. CT can detect partially calcified biliary calculi but is relatively insensitive for detecting
bilirubinate or cholesterol calculi.[30]
If patients have suspected sclerosing cholangitis or biliary stricture, magnetic resonance

cholangiopancreatography is useful to assist in delineating the biliary tree and guiding the need for
endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography
(PTC) to achieve drainage. This approach decreases the risk of development of a suppurative cholangitis,
which may occur with a failed ERCP in a dilated biliary system.[30]
High likelihood of malignant biliary obstruction

Ultrasound is used to confirm the presence of biliary obstruction, but patients require further imaging to
confirm the diagnosis.[30] Malignant obstruction is most commonly due to pancreatic carcinoma but may be
secondary to cholangiocarcinoma of either the proximal or distal duct or to periductal nodal compression.
A contrast-enhanced multipass CT examination with multi-planar reformation has high sensitivity for lesion
detection and 70% accuracy in discriminating resectable and unresectable disease. It has a sensitivity of
74% to 96% and specificity of 90% to 94% for detecting biliary obstruction. Important information in tumour
staging includes tumour contiguity or invasion of the superior mesenteric and portal veins, peri-pancreatic
tumour extension, regional adenopathy, and hepatic metastases.
In cases where CT and sonography are equivocal, endoscopic retrograde cholangiopancreatography (ERCP)
and endoscopic ultrasound may provide imaging and allow a cytological diagnosis to be made using fine
needle aspiration or brushing. The role of fluorodeoxyglucose-positron emission tomography/CT in this
clinical scenario has been endorsed in the UK National Institute for Health and Care Excellence guideline on
pancreatic cancer.[31]
Low likelihood of mechanical obstruction

Ultrasound is the preferred imaging modality to exclude mechanical obstruction. Magnetic resonance
DIAGNOSIS
cholangiopancreatography may also be considered. In patients with decompensated chronic liver disease
with jaundice and ascites, the addition of portal tract Doppler studies at the time of ultrasonography and
subsequent triphasic CT imaging of the liver would be useful to exclude portal vein occlusion.[30]
Indeterminate likelihood of obstruction

The imaging work-up is frequently geared to the dominant clinical symptom. Ultrasound is certainly
appropriate if the sole question is whether obstruction exists. In cases in which most of the abdominal organs
need to be assessed, either CT or MRI can be used, although CT more reliably displays all abdominal
anatomy.[30]
19
Differential diagnosis overview
Common
Alcoholic liver disease
Choledocholithiasis
Hepatitis E
Hepatitis A
Hepatitis B
Hepatitis C
Non-alcoholic steatohepatitis
Drug-induced direct hyperbilirubinaemia
Autoimmune hepatitis
Pancreatic carcinoma
Haemochromatosis
DIAGNOSIS
Pregnancy
Post-operative stricture
Drug-induced indirect hyperbilirubinaemia
Haemolytic anaemia
Gilbert's syndrome
Carotenaemia
Uncommon
Hepatitis D
IgG4 cholangiopathy
Uncommon
Cholangiocarcinoma
Primary biliary cirrhosis
Primary sclerosing cholangitis
Wilson's disease
Alpha-1 antitrypsin deficiency
Parasitic infections
AIDS cholangiopathy
Crigler-Najjar syndrome, types 1 and 2
DIAGNOSIS
21
Differential diagnosis
Common
◊ Alcoholic liver disease
History Exam 1st Test Other tests
5 to 10 years of alcohol parotid gland »serum liver »upper endoscopy:

abuse (>50 to 60 g/ enlargement, function varices
day for men and 20 to Dupuytren's tests: aspartate Urgent upper
30 g/day for women), contracture, aminotransferase gastrointestinal
abdominal pain, generalised wasting, and alanine
pruritus, generalised gynaecomastia, altered aminotransferase rarely endoscopy is indicated
malaise, weight loss, sensorium, asterixis or >200 U/L; raised serum to evaluate and treat
fatigue, anorexia, altered deep tendon bilirubin; low albumin varices if patient
cachexia, pale stool, reflexes, track marks Bilirubin >250 mmol/L presents with melaena
dark urine, melaena, or (if concomitant drug has a worse prognosis
haematemesis use), ecchymosis or haematemesis.
or petechiae, spider than bilirubin <125
angioma, thenar mmol/L when the
eminence loss, palmar Glasgow Alcoholic
erythema, caput Hepatitis Score
medusa, ascites,
hepatosplenomegaly (GAHS) or Maddrey’s
or small liver, pleural Discriminant Function is
effusion, right heart applied.[28] [27]
failure, positive rectal
examination (blood) Increased prothrombin
time and international
normalised ratio
when coupled
with low albumin
DIAGNOSIS
indicates synthetic
liver dysfunction and
suggests cirrhosis or
acute liver failure.[32]
»prothrombin time
(PT)/international
normalised ratio
(INR): elevated
Applying the GAHS, PT
>2.0 is associated with
a worse prognosis than
PT <1.5.[27]
Increased PT and
INR when coupled
with low albumin
indicates synthetic
Common

acute liver failure.
»full blood count:

low platelet count; high
white blood cell (WBC)
count
A low platelet count is
suggestive of portal
hypertension or alcohol
abuse.
A WBC count
>15x10^9/L has a
worse prognosis than a
WBC count <15x10^9/
L.
»urea: elevated
Applying the GAHS, a
urea of >5 mmol/L is
associated with a worse
prognosis.[27]
»CAGE score: >2

This test has a 91%
DIAGNOSIS
specificity for detecting
alcohol abuse.
[CAGE and CAGE-
AID questionnaires]
[26] It consists of 4
questions; 2 positive
answers require further
investigation into
alcoholism. These
questions address
efforts to cut down
drinking, criticism about
one's drinking, guilt,
and need to drink upon
waking in the morning.
»abdominal
ultrasound: usually
hyperechoic, may
23
Common

describe mixed
echogenicity in cirrhotic
patients
Also useful in
determining the
presence of ascites and
portal vein flow.
◊ Choledocholithiasis
right upper quadrant RUQ abdominal »serum liver »serum cholesterol:

(RUQ) pain, aggravated tenderness, fever function tests: high may be increased
by meals, fever direct bilirubin, gamma- »magnetic
GT, and alkaline resonance
phosphatase cholangiopancreatography:
»prothrombin stone(s) in the bile duct
time/international Used to detect the
normalised ratio: presence of stones in
usually normal
the biliary tree not seen
»full blood count:
on ultrasound.
elevated white blood
cell count »endoscopic
»abdominal ultrasound: stone(s)
ultrasound: intra- and in the bile duct
DIAGNOSIS
extrahepatic biliary tree Has the highest

dilation with/without sensitivity for detection
stone(s) in the common
bile duct of small stones in the
Sensitivity for biliary common bile duct.
dilation is high and
»endoscopic
for bile duct stone(s) retrograde
detection is low. cholangiopancreatography:
stone(s) in the bile duct
Should be reserved
for therapeutic
intervention. This
test has therapeutic
capabilities to extract
the stone(s) or facilitate
bile drainage through
stenting.
Common
◊ Hepatitis E
may be hx of risk may be normal; »serum liver »serum anti-

factors (e.g., travel abdominal function tests: hepatitis E virus IgM
to Southeast Asia, tenderness, tender high direct antibodies: positive
northern and central hepatosplenomegaly, bilirubin, aspartate Identifies acute
Africa, India, and lymphadenopathy, aminotransferase, infection with hepatitis
Central America), jaundice, ascites, signs alanine
exposure to pigs or of encephalopathy aminotransferase, E virus.
undercooked pork; (e.g., memory, alkaline phosphatase,
»hepatitis E virus
more common in attention, and and gamma-GT
polymerase chain
middle-aged/older concentration deficits, »prothrombin reaction: positive
men; anorexia, confusion, asterixis, time/international
nausea and vomiting, nystagmus, clonus, normalised ratio:
diarrhoea, abdominal rigidity, coma) may be increased
pain, pruritus,
myalgia, neurological »abdominal
symptoms (5% of ultrasound:
patients); pregnancy is nonspecific
associated with more
florid disease; patients
with pre-exsiting liver
disease have a high
risk of decompensation
and a 70% mortality
◊ Hepatitis A
DIAGNOSIS
may be hx of risk abdominal »serum liver »serum IgM anti-
factors (e.g., travel to tenderness, tender function tests: hepatitis A virus:
endemic part of the hepatosplenomegaly, high direct positive
world, close contact lymphadenopathy, bilirubin, aspartate Identifies acute
with known infected jaundice; fulminant aminotransferase, infection with hepatitis
person, known food- infection: worsening alanine
borne outbreak), jaundice, ascites, signs aminotransferase, A virus.
anorexia, nausea, of encephalopathy alkaline phosphatase,
vomiting, diarrhoea, (e.g., memory, and gamma-GT
abdominal pain, weight attention, and »prothrombin time
loss concentration deficits, (PT)/international
confusion, asterixis, normalised ratio
nystagmus, clonus, (INR): may be
rigidity, coma) increased
Increased PT and
INR when coupled
with low albumin
indicates synthetic
25
Common
◊ Hepatitis A

»full blood count: low

or normal platelet count
hypertension.
»abdominal
ultrasound:
nonspecific
◊ Hepatitis B
may be hx of risk acute infection: usually »serum liver »serum hepatitis

factor (e.g., travel to normal, but may function tests: B core antigen
endemic part of the have jaundice, tender high direct (HBcAg): positive
world, high-risk sexual hepatomegaly, and bilirubin, aspartate An intracellular antigen
hx, intravenous drug if severe: signs of aminotransferase, that is found in infected
use), may have minimal encephalopathy (e.g., alanine
or no symptoms, memory, attention, aminotransferase, hepatocytes.
may have lethargy, and concentration alkaline phosphatase,
»serum hepatitis B
nausea, vomiting, deficits, confusion, and gamma-GT
e antigen (HBeAg):
abdominal pain; asterixis, nystagmus, »prothrombin time positive
DIAGNOSIS
acute presentation clonus, rigidity, coma); (PT)/international Patients with a positive

(uncommon): chronic infection: normalised ratio
worsening jaundice may have jaundice, result are considered
(INR): may be
and lethargy, muscle wasting, highly infective for
increased
confusion; chronic gynaecomastia, palmar
Increased PT and hepatitis B.
infection with late erythema, spider
complications: pruritus, angiomata, petechiae, INR when coupled
»hepatitis B virus
abdominal swelling, ascites, distended with low albumin DNA: elevated
haematemesis, abdominal veins, indicates synthetic Can be measured
melaena, confusion, hepatosplenomegaly,
liver dysfunction and with either qualitative
lethargy, weight loss, signs of
weakness, bruising encephalopathy suggests cirrhosis or or quantitative
acute liver failure. assays. Levels are
generally measured
or normal platelet count by polymerase chain
A low platelet count is reaction amplification
suggestive of portal assay. Used to confirm
hypertension. active viral replication
and guide treatment.
Common
◊ Hepatitis B

»abdominal
ultrasound:
nonspecific
»serum hepatitis
B surface antigen
(HBsAg): positive
Positive result appears
in serum 1 to 10 weeks
after an acute exposure
and disappears when
infection abates.
There is an inherent
risk of developing
hepatocellular
carcinoma with chronic
hepatitis B infection.
◊ Hepatitis C
may be hx of risk early disease: normal »serum liver »serum hepatitis C

factors, (e.g., exam; late disease function tests: virus genotype/RNA:
intravenous drug use, with chronic infection: high direct positive
blood transfusion may be jaundice, bilirubin, aspartate With the introduction
DIAGNOSIS
before 1992 in the US, muscle wasting, aminotransferase, of newer agents
high-risk sexual hx); gynaecomastia, palmar alanine
acute infection: usually erythema, spider aminotransferase, for hepatitis C, the
asymptomatic, may angiomata, petechiae, alkaline phosphatase, duration for treatment
be fatigue, jaundice; ascites, distended and gamma-GT has decreased to
chronic infection: may abdominal veins, »prothrombin time 12 weeks, with a
be asymptomatic, but hepatosplenomegaly, (PT)/international shorter duration in
possible symptoms signs of normalised ratio
related to cirrhosis encephalopathy (e.g., special circumstances.
(INR): may be
and its complications, memory, attention, and Genotyping would
increased
such as pruritus, concentration deficits, still be useful to plan
Increased PT and
abdominal swelling, confusion, asterixis,
haematemesis, nystagmus, clonus, INR when coupled treatment using
melaena, confusion, rigidity, coma) with low albumin traditional therapy and
lethargy, weight loss, indicates synthetic for epidemiological
weakness, bruising data.

27
Common
◊ Hepatitis C

hypertension.
»hepatitis C
antibody: positive
Suggests previous
exposure to hepatitis
C, and raises the
possibility of hepatitis C
as a potential cause of
cirrhosis and jaundice.
»abdominal
ultrasound:
nonspecific
◊ Non-alcoholic steatohepatitis
often asymptomatic, advanced disease: »serum liver »liver biopsy: fat

obesity, diabetes, hepatosplenomegaly, function tests: droplets, inflammatory
hypertension, high ascites, spider high direct cells, absent Mallory
triglyceride level, angioma, oesophageal bilirubin, aspartate hyaline, fibrosis
low HDL cholesterol, or intestinal varices aminotransferase, staging, and presence
DIAGNOSIS
fatigue, malaise, dull alanine of cirrhotic change

ache in right upper aminotransferase, and »MRI: T1-weighted
quadrant, pruritus alkaline phosphatase images: areas of
»prothrombin time fatty infiltration with
(PT)/international increased signal
normalised ratio intensity
(INR): normal If the correct diagnosis
PT/INR increases if is in question, an MRI
cirrhosis or liver failure helps differentiate focal
develops. fatty areas from tumour
processes. Helps
»full blood count:
normal identify fatty infiltration
Thrombocytopenia but cannot determine
often occurs with inflammation.
cirrhosis.
Fibroscan is used as a
»fasting blood non-invasive marker of
glucose: may be fibrosis.
elevated
Common
◊ Non-alcoholic steatohepatitis

Elevated fasting blood
glucose, elevated
serum triglycerides, and
high blood pressure
help identify patients
at risk of the metabolic
syndrome and guide
treatment.
»serum
triglycerides: may be
elevated
Elevated fasting blood
glucose, elevated
serum triglycerides, and
high blood pressure
help identify patients
at risk of the metabolic
syndrome and guide
treatment.
»abdominal
ultrasound:
hypoechoic areas
(ovoid, round, or linear)
within a hyperechoic
DIAGNOSIS
liver
Helps identify
fatty infiltration but
cannot determine
inflammation.
»CT with contrast:

no mass effect or
contour deformation,
intrahepatic vessels
follow normal course
through the fatty
lesions, without
deformity
Most reliable test to
identify fatty infiltration
but cannot determine
inflammation.
29
Common
◊ Drug-induced direct hyperbilirubinaemia
paracetamol overuse tender »serum liver »serum indirect

or overdose, use hepatosplenomegaly, function tests: high antiglobulin test
of highly active lymphadenopathy total bilirubin, alanine (Coombs' test): may
antiretroviral therapy aminotransferase, detect autoantibodies
(HAART) for HIV, and aspartate
isoniazid, ethambutol, aminotransferase
amiodarone, non- »prothrombin time
steroidal anti- (PT)/international
inflammatories, herbal normalised ratio
preparations (kava, (INR): increased
ma-huang, comfrey,
Increased PT and
black cohosh, cascara),
antibiotics (especially INR when coupled
amoxicillin-clavulanate, with low albumin
gentamicin, indicates synthetic
erythromycin,
novobiocin,
rifampin), calcium- suggests cirrhosis or
channel blockers, acute liver failure.
ACE inhibitors,
chlorpromazine, »full blood count:
halothane, oestrogenic low or normal platelet
or anabolic steroids, count, high white blood
statins, oral cell count
contraceptives, »abdominal
ascorbic acid, ultrasound: non-
theophylline, specific findings
methyldopa,
phenelzine, »serum paracetamol:
DIAGNOSIS
isoproterenol, elevated if overdose,

aminophenol, may be normal in
epinephrine staggered overdose
(adrenaline), right
upper quadrant pain,
pruritus, generalised
malaise, weight loss,
fatigue, anorexia, pale
stool, dark urine
◊ Ascending cholangitis
chills, pain, pale stools, Charcot's triad: fever, »serum liver »magnetic
dark urine, pruritus, right upper quadrant function tests: high resonance
generalised malaise, tenderness, jaundice direct bilirubin, gamma- cholangiopancreatography:
weight loss, fatigue, GT, and alkaline stone(s) in the bile duct
anorexia phosphatase This test has a high
sensitivity for detection
Common
◊ Ascending cholangitis

Shows a cholestatic of bile duct dilation and
pattern primarily. stones.
»prothrombin »endoscopic
time/international ultrasound: stone(s)
normalised ratio: in the bile duct
may be increased There is a high
»full blood count: sensitivity for detection
elevated white blood of bile duct dilation and
cell count
stones, but availability
»abdominal limits its use.
ultrasound: biliary
dilation and stone(s) in »endoscopic
bile duct retrograde
Sensitivity for biliary cholangiopancreatography:
dilation is high, but bile duct obstruction;
sensitivity for bile duct pus draining from the
biliary tree
stone detection is poor.
This test has
therapeutic capabilities
to provide biliary
drainage.
◊ Autoimmune hepatitis
DIAGNOSIS
fatigue, abdominal pain, advanced disease: »serum liver »serum IgG: usually
arthralgias, pruritus, ascites, hepatomegaly, function tests: increased
nausea and vomiting, cirrhosis, spider fluctuating transaminitis Used to track treatment
pale stool, dark urine; angioma, mental but may be markedly response. With
may have associated confusion elevated in the acute
haemolytic anaemia, setting, high direct successful treatment,
thyroiditis, ulcerative bilirubin, alkaline serum IgG levels
colitis, diabetes, and/or phosphatase high, decline to near-normal
Sjogren's syndrome albumin may be low to normal levels.
High levels of alanine
aminotransferase »abdominal
(ALT) indicate ultrasound:
heterogeneous texture
liver inflammation.
Not diagnostic;
Treatment typically
however, suggests
continues for 1 year
active disease or
after ALT normalisation.
necrosis. Test helps
Low albumin, deranged
rule out hepatocellular
clotting indices,
31
Common
◊ Autoimmune hepatitis

and raised bilirubin carcinoma, a rare
indicate severe hepatic complication.
synthetic dysfunction in
»abdominal CT
either active disease or
scan: abnormal
cirrhosis. contrast enhancement,
irregular nodular liver
»full blood count: low (cirrhosis)
white blood cell count Not diagnostic;
and platelets
however, suggests
»erythrocyte
active disease or
sedimentation rate:
elevated necrosis. Test helps
Non-specific indicator rule out hepatocellular
of inflammatory activity. carcinoma, a possible
complication.
»antinuclear
antibody: positive »liver biopsy:
This autoantibody interface hepatitis,
identifies type 1 bridging necrosis,
fibrosis, lobular
disease.
collapse
»anti-smooth muscle May be performed
antibodies: positive percutaneously,
Identifies type 1 with ultrasound
disease. guidance, or via the
transjugular route. The
»anti-
DIAGNOSIS
transjugular route is
LKM-1antibody:
positive preferred with severe
Anti-liver-kidney thrombocytopenia,
microsome coagulopathy, or
autoantibody identifies ascites.
type 2 disease.
»anti-SLA antibody:
positive
Anti-soluble-liver
antigen autoantibody
identifies type 3
disease.
Common
◊ Pancreatic carcinoma
often asymptomatic positive Courvoisier's »serum liver »CT: pancreatic mass

until late disease, sign, palpable function tests: high and dilated bile duct
depression, weight gallbladder, ill- direct bilirubin, alkaline The CT should be
loss, early satiety, appearing, cachectic phosphatase, and completed with the
new-onset diabetes, gamma-GT
abdominal pain, pancreatic protocol
»prothrombin
pruritus, generalised (IV contrast, thin cuts
time/international
malaise, fatigue, through the pancreas,
normalised ratio:
anorexia, pale stool, and 3-phase).
may be increased
dark urine
»full blood count:
»fluorodeox yglucose-
low or normal platelet
positron emission
count, Hb, and
tomography/CT
haematocrit
(FDG#PET/CT):
»abdominal increased FDG activity
ultrasound: of pancreatic lesion
pancreatic mass and If the diagnosis is
dilated common bile
still unclear after
duct ± pancreatic duct
dilation CT in people with
obstructive jaundice
when pancreatic
cancer is suspected,
the UK National
Institute for Health
and Care Excellence
recommends that a
DIAGNOSIS
FDG-PET/CT scan
is offered, and/or
endoscopic ultrasound
(EUS) with EUS-guided
tissue sampling.[31]
»linear endoscopic
ultrasound:
pancreatic mass
The most sensitive test
for detecting pancreatic
mass. Fine needle
aspiration can be
done to secure tissue
diagnosis.
»endoscopic
retrograde
cholangiopancreatography
(ERCP): bile duct
33
Common
◊ Pancreatic carcinoma

and pancreatic duct
strictures
In patients with
obstructive jaundice,
ERCP is being used
to relieve the biliary
obstruction and assist
in tissue acquisition, if
not available.
◊ Haemochromatosis
usually asymptomatic usually normal; »serum liver »genetic test for

or found after screening gynaecomastia, function tests: high haemochromatosis:
in patients with ascites, altered direct bilirubin, alkaline positive
a positive FHx, sensorium, cachectic; phosphatase, and haemochromatosis
jaundice occurs in in decompensated gamma-GT gene mutation
decompensated disease signs of »prothrombin »liver biopsy:
disease with chronic liver disease time/international increased iron stores
established cirrhosis; plus associated normalised ratio: Used in patients >65
rarely patients present arthropathy may be increased years of age or those
with symptoms of
diabetes »full blood count: low presenting with a
serum ferritin >1000
DIAGNOSIS

mg/L or when there is
uncertainty regarding
hypertension.
the diagnosis.
»serum iron, serum
total iron-binding
capacity (TIBC),
serum ferritin: high
iron, low TIBC, high
ferritin
»serum transferrin
saturation test: >45%
»abdominal
ultrasound: non-
specific
Common
◊ Pregnancy
pregnant or recently elevated blood pressure »serum liver

delivered, pruritus, (pre-eclampsia and function tests:
hyperemesis eclampsia), tender intrahepatic cholestasis
gravidarum (first hepatomegaly, of pregnancy: high
trimester), HELLP splenomegaly, direct bilirubin,
syndrome (haemolysis, lymphadenopathy alkaline phosphatase,
elevated liver enzymes, and gamma-GT;
low platelets) in second HELLP, hyperemesis
and third trimesters gravidarum or
and post-partum, acute fatty liver of
abdominal pain, pregnancy: high direct
pruritus, generalised bilirubin, alanine
malaise, weight loss, aminotransferase,
fatigue, anorexia, pale and aspartate
stool, dark urine aminotransferase
The pattern varies for
different disorders. A
cholestatic pattern is
seen in intrahepatic
cholestasis of
pregnancy; and
hepatocellular damage
is expressed in
HELLP, hyperemesis
gravidarum, and acute
fatty liver of pregnancy.
DIAGNOSIS
»prothrombin time
(PT)/international
normalised ratio:
may be increased
PT may be prolonged
in rare cases when
vitamin K has been
depleted from liver
dysfunction.

hypertension and is
found in HELLP.
»abdominal
ultrasound: normal
35
Common
◊ Pregnancy

This test is performed
to exclude alternative
causes for jaundice,
such as gallstones.
◊ Post-operative stricture
gallbladder or bile duct often normal »serum liver »endoscopic

surgery, abdominal examination function tests: high retrograde
pain, pruritus, fatigue, direct bilirubin, alkaline cholangiopancreatography:
anorexia, pale stool, phosphatase, and biliary stricture
dark urine gamma-GT Invasive, but allows for
»prothrombin sampling and stenting
time/international of the stricture.
normalised ratio:
may be increased
»full blood count:
count, Hb, and
haematocrit
»abdominal
ultrasound: non-
specific
DIAGNOSIS
»magnetic
resonance
cholangiopancreatography:
biliary stricture
Non-invasive.
◊ Drug-induced indirect hyperbilirubinaemia
paracetamol overuse tender »serum liver »serum indirect

or overdose, use hepatosplenomegaly, function tests: high antiglobulin test
of highly active lymphadenopathy total bilirubin, alanine (Coombs' test): may
antiretroviral therapy aminotransferase, detect autoantibodies
(HAART) for HIV, and aspartate
isoniazid, ethambutol, aminotransferase
amiodarone, non- »prothrombin time
steroidal anti- (PT)/international
inflammatories, herbal normalised ratio
preparations (kava, (INR): increased
ma-huang, comfrey,
Common
◊ Drug-induced indirect hyperbilirubinaemia

black cohosh, cascara), Increased PT and
antibiotics (especially INR when coupled
amoxicillin-clavulanate,
erythromycin, with low albumin
gentamicin, novobiocin, indicates synthetic
rifampin), calcium- liver dysfunction and
channel blockers, suggests cirrhosis or
ACE inhibitors,
chlorpromazine, acute liver failure.
halothane, oestrogenic
or anabolic steroids, »full blood count:
statins, oral
count, high white blood
contraceptives,
cell count
ascorbic acid,
theophylline, »abdominal
methyldopa, ultrasound: non-
phenelzine, specific
isoproterenol, »serum amoxicillin:
aminophenol, positive if ingested
epinephrine
(adrenaline), right »serum paracetamol:
upper quadrant pain, elevated if overdose
pruritus, generalised »serum amiodarone:
malaise, weight loss, positive if ingested
fatigue, anorexia, pale
stool, dark urine »serum
erythromycin: positive
if ingested
»serum angiotensin-
DIAGNOSIS
converting enzyme
inhibitor: positive if
ingested
»serum
chlorproma zine:
positive if ingested
»serum ascorbic
acid: positive if
ingested
»serum theophylline:
positive if ingested
»plasma
catecholamines:
elevated if ingested
37
Common
◊ Haemolytic anaemia
fever or chills, FHx of new onset of pallor, »serum liver »LDH: elevated
haemolytic disorders, splenomegaly function tests: high A non-specific test.
abdominal pain, indirect bilirubin with
pruritus, generalised normal or minimally »haptoglobin:
malaise, weight loss, elevated aspartate decreased
fatigue, anorexia, dark aminotransferase, The level decreases
urine alanine
only with massive
aminotransferase,
alkaline phosphatase haemolysis.
»full blood count: low »peripheral blood

Hb smear: sickle cells,
»abdominal schistocytes, or target
ultrasound: non- cells
specific May point towards
specific disorders
such as sickle cell
disease (sickle
cells), thrombotic
thrombocytopenic
purpura (schistocytes),
thalassaemia (target
cells).
»reticulocyte count:
elevated
»serum direct
DIAGNOSIS
antiglobulin test
(Coombs' test):
positive
Used if a transfusion
reaction is suspected.
»serum indirect
antiglobulin test
(Coombs' test): may
detect drug-induced
autoantibodies
◊ Gilbert's syndrome
young adult age, more normal other than »serum liver »blood smear: normal
common in males, icterus function tests: high »reticulocyte count:
often asymptomatic or indirect bilirubin; normal normal
non-specific symptoms alkaline phosphatase
Common
◊ Gilbert's syndrome

(abdominal cramps, If liver function tests »fasting bilirubin
fatigue, malaise) remain normal for 12 test: two- to threefold
rise in unconjugated
to 18 months, except bilirubin
for bilirubin, a definitive Within 48 hours of
diagnosis can be made. a fast, levels rise
significantly, then
»prothrombin
time/international return to normal within
normalised ratio: 24 hours of eating a
normal normal diet.
»full blood count:
normal »phenobarbital test:
normalised bilirubin
Upon administration
of phenobarbital,
bilirubin levels return
to normal with Gilbert's
syndrome.
◊ Carotenaemia
associated with jaundice affects only »none: clinical

prolonged and the skin, with sparing of diagnosis
DIAGNOSIS
excessive consumption the sclera
of carotene-rich foods,
such as carrots,
pumpkin, and sweet
potatoes
Uncommon
◊ Hepatitis D
may be hx of risk usually normal, »serum liver »serum IgM anti-

factors (e.g., infection but if severe acute function tests: hepatitis A virus:
with hepatitis B virus, infection may be high direct positive
high-risk sexual jaundice, tender bilirubin, aspartate Identifies acute
hx, intravenous hepatomegaly, signs of aminotransferase, infection with hepatitis
drug use), minimal encephalopathy (e.g., alanine
or no symptoms; memory, attention, aminotransferase, A virus.
acute presentation and concentration alkaline phosphatase,
(uncommon): deficits, confusion, and gamma-GT
39
Uncommon
◊ Hepatitis D

jaundice, lethargy, asterixis, nystagmus, »prothrombin time »serum total (IgM
confusion; chronic clonus, rigidity, coma); (PT)/international and IgG) anti-
infection with late chronic, late infection: normalised ratio hepatitis D virus
complications: itching, may be jaundice, (INR): may be antibodies: positive
abdominal swelling, muscle wasting, increased Performed by
haematemesis, gynaecomastia, palmar Increased PT and enzyme-linked or
melaena, confusion, erythema, spider INR when coupled
lethargy, weight loss, angiomata, petechiae, radioimmunoassay.
weakness, bruising ascites, distended with low albumin Hepatitis D is a
abdominal veins, indicates synthetic defective virus and can
hepatosplenomegaly, liver dysfunction and only replicate in the
signs of suggests cirrhosis or
encephalopathy presence of co-infection
acute liver failure. or super-infection with
hepatitis B virus.
»serum hepatitis
A low platelet count is B surface antigen
suggestive of portal (HBsAg): positive
hypertension. Positive result appears
in serum 1 to 10 weeks
»abdominal
after an acute exposure
ultrasound:
nonspecific and disappears when
infection abates.
There is an inherent
risk of developing
hepatocellular
DIAGNOSIS
carcinoma with chronic

hepatitis B infection.
»serum hepatitis
B core antigen
(HBcAg): positive
An intracellular antigen
that is found in infected
hepatocytes.
»serum hepatitis B
e antigen (HBeAg):
positive
Patients with a positive
result are considered
highly infective for
hepatitis B.
Uncommon
◊ IgG4 cholangiopathy
epigastric and epigastric tenderness, »serum liver »magnetic

abdominal pain, jaundice; may have function tests: high resonance
jaundice, weight loss; lymphadenopathy, direct bilirubin, gamma- cholangiopancreatography:
typically men aged 50 bibasal crepitation GT, and alkaline simultaneous strictures
to 60 years; may give related to multisystemic phosphatase; mildly and radiological
history of new onset manifestation elevated aspartate evidence of associated
diabetes mellitus or aminotransferase pancreatitis
diarrhoea associated and alanine This test has a high
with pancreatic aminotransferase sensitivity for detection
insufficiency »serum IgG4 level: of bile duct dilation and
≥1.35 g/L (≥135 mg/dL)
stones.
»abdominal
ultrasound or CT »endoscopic
scan: biliary dilation ultrasound: useful
with simultaneous intra- in obtaining tissue for
and extrahepatic duct histology; may reveal
dilation vascular involvement of
the splenic, portal, and
superior mesenteric
veins
»endoscopic
retrograde
bile duct obstruction;
pus draining from the
biliary tree
This test has
DIAGNOSIS
therapeutic capabilities
to provide biliary
drainage.
◊ Cholangiocarcinoma
pruritus, generalised usually normal; »serum liver »magnetic

malaise, weight loss, cachectic function tests: high resonance
fatigue, anorexia, pale direct bilirubin, alkaline cholangiopancreatography:
stool, dark urine phosphatase, and biliary stricture
gamma-GT Non-invasive test.
»prothrombin
time/international »endoscopic
normalised ratio: retrograde
may be increased cholangiopancreatography:
biliary stricture
»full blood count: Allows sampling of the
stricture and palliation
41
Uncommon
◊ Cholangiocarcinoma

count, Hb, and of jaundice with biliary
haematocrit stent.
»abdominal
ultrasound: non-
specific
◊ Primary biliary cirrhosis
female, pruritus, xanthelasma, »serum liver

fatigue, abdominal pain, hepatosplenomegaly, function tests: high
generalised malaise, right upper direct bilirubin, alkaline
weight loss, anorexia, quadrant pain, fatty phosphatase, and
pale stool, dark urine, subcutaneous deposits gamma-GT
keratoconjunctivitis, »prothrombin
xerostomia time/international
normalised ratio:
may be increased
hypertension.
»serum
DIAGNOSIS
antimitochondrial
antibody: positive
Positive in 95% of
patients with primary
biliary cirrhosis.
»liver biopsy: florid

bile duct lesion with
granuloma formation
◊ Primary sclerosing cholangitis
often asymptomatic, hx usually normal, skin »serum liver »magnetic

of ulcerative colitis or excoriations may be function tests: high resonance
Crohn's disease may present direct bilirubin, alkaline cholangiopancreatography:
be present; chills, night phosphatase, and biliary strictures
sweats, abdominal gamma-GT Preferred test with
pain suggest infection; the typical pattern of
pruritus, generalised
Uncommon
◊ Primary sclerosing cholangitis

malaise, weight loss, »prothrombin beading of the biliary
fatigue, anorexia, pale time/international tract apparent.
stool, dark urine normalised ratio:
may be increased »endoscopic
»full blood count: low retrograde
or normal platelet count cholangiopancreatography:
A low platelet count is biliary strictures
suggestive of portal Usually used when a
hypertension. therapeutic intervention
is planned with regard
»abdominal to acquiring brushing,
ultrasound: non-
biopsy, and stenting of
specific
dominant strictures.
◊ Wilson's disease
adolescence and Kayser-Fleischer rings, »serum liver »serum

early adulthood parkinsonian-like function tests: ceruloplasmin:
onset, tremor, clumsy tremor, rigidity, clumsy high direct decreased
gait, slurred speech, gait, poor balance, bilirubin, aspartate This test has low
abdominal pain, impaired co-ordination, aminotransferase, sensitivity and
pruritus, generalised abnormal postures, and alanine
malaise and weakness, repetitive movements, aminotransferase; specificity.
weight loss, anorexia, bradykinesia alkaline phosphatase
»urinary copper
DIAGNOSIS
pale stool, dark urine, (tongue, lips, and normal
excretion: increased
irritability, depression, jaw), dysarthria, »prothrombin
dementia, psychosis, dysphonia (hoarse »liver biopsy
time/international
easy bruising voice), inappropriate with copper
normalised ratio:
and uncontrollable concentration:
may be increased
grinning (risus increased copper
sardonicus), drooling, »full blood count: low The histological
generalised wasting, or normal platelet count
findings are non-
gynaecomastia, A low platelet count is
ascites, altered specific.
sensorium,
hypertension. »Wilson's disease
hepatosplenomegaly,
genetic test: positive
hypermelanotic »abdominal (pattern of di- and
pigmentation, bruises ultrasound: non- trinucleotide repeats
specific around ATP7B)
43
Uncommon
◊ Alpha-1 antitrypsin deficiency
FHx of liver disease, necrotising panniculitis, »serum liver »alpha-1 antitrypsin

abdominal pain, generalised wasting, function tests: serum level:
pruritus, generalised gynaecomastia, high direct decreased
malaise, weight loss, ascites, altered bilirubin, aspartate
fatigue, anorexia, sensorium, cachectic, aminotransferase,
pale stool, dark urine, ill-appearing and alanine
emphysema aminotransferase;
alkaline phosphatase
normal
»prothrombin
time/international
normalised ratio:
may be increased
hypertension.
»genotype: presence
of the Z or M (Malton)
alleles
»abdominal
ultrasound: non-
specific
◊ Parasitic infections
DIAGNOSIS
travel to endemic cachexia, muscle »stool for ova and »cholangiography:

areas, abdominal pain, wasting, tender parasites: positive Clonorchis sinensis
pruritus, generalised abdomen, Ascaris lumbricoides : multiple saccular
malaise, weight loss, hepatomegaly , Echinococcus dilations of intrahepatic
fatigue, anorexia, pale bile ducts; periportal
stool, dark urine granulosus , fibrosis
Clonorchis sinensis ,
»magnetic
Fasciola hepatica . resonance
»serum liver parasite visualised in
function tests: high the bile duct
direct bilirubin, alkaline
phosphatase, and »endoscopic
gamma-GT retrograde
»prothrombin parasite visualised in
time/international the bile duct
Uncommon
◊ Parasitic infections

normalised ratio: This procedure allows
may be increased for removal of the
»full blood count: low parasite from the biliary
tree.
»abdominal
ultrasound: Ascaris
lumbricoides : long,
linear, echogenic
structures; 4 lines sign
or non-shadowing
echogenic strips with
central tube
◊ AIDS cholangiopathy
abdominal pain, cachexia, right upper »serum liver »endoscopic

pruritus, generalised quadrant and epigastric function tests: high retrograde
malaise, weight loss, pain, fever direct bilirubin, alkaline cholangiopancreatography
fatigue, anorexia, phosphatase, and (ERCP): papillary
pale stool, dark gamma-GT stenosis and/or biliary
urine, high-risk strictures
»prothrombin
sexual activity (many The diagnosis of
time/international
partners, unprotected AIDS cholangiopathy
normalised ratio:
intercourse, intercourse may be increased is one of exclusion.
with HIV-infected), HIV-
DIAGNOSIS
positive, diarrhoea ERCP can provide
or normal platelet count therapy in the form of
»abdominal biliary sphincterotomy,
ultrasound: non- dilation, and/or stenting
specific
of the biliary strictures.
◊ Crigler-Najjar syndrome, types 1 and 2
severe jaundice kernicterus (type 1), »serum liver »phenobarbital test:

within first few days encephalopathy (type function tests: type 1: no change
after birth (type 1), 1, rare in type 2), high indirect bilirubin; in bilirubin; type 2:
abdominal pain, oculomotor palsy normal aspartate decreased bilirubin
pruritus, generalised aminotransferase The test may help
malaise, weight loss, and alanine distinguish Crigler-
fatigue, anorexia, pale aminotransferase
stool (normal in type 1), Najjar type 1 from type
dark urine 2.
45
Uncommon
◊ Crigler-Najjar syndrome, types 1 and 2

Bilirubin levels tend »chromatographic
to be higher in type 1 analysis of bile: type
1: absent conjugated
syndrome. bilirubin; type 2: large
amount of conjugated
»prothrombin bilirubin
time/international
Bile collected from the
normalised ratio:
may be increased duodenum through a
»full blood count: low duodenal catheter or
or normal platelet count upper gastrointestinal
»abdominal endoscope is useful in
ultrasound: non- differentiating type 1
specific and type 2.
DIAGNOSIS
Assessment of jaundice Online resources
Online resources
1. CAGE and CAGE-AID questionnaires (external link)
ONLINE RESOURCES
47
Assessment of jaundice References
Key articles
• Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and
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Assessment of jaundice Images
Images
Figure 1: Adult patient with jaundice
IMAGES
From: Owen PJD, Baghomian A, Lazarus JH, Godkin AJ. BMJ. 2007;335:773-774
Figure 2: Yellow-orange discoloration of the palms and soles of a 1-year-old boy with carotenaemia
contrasted with the mother’s normal skin colour
51
Assessment of jaundice Images
From: Anjay MA, Panaviel V, Nirmal S. BMJ Case Reports. 2009; doi:10.1136/bcr.2008.139014
IMAGES
Assessment of jaundice Disclaimer
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53
Contributors:
// Authors:
Rene Ramnarace, FRCP(Edin)

Consultant Gastroenterologist and Associate Lecturer in Medicine
University of the West Indies, Department of Medicine, San Fernando General Hospital, San Fernando,
Trinidad, West Indies
DISCLOSURES: RR declares that he has no competing interests.
// Acknowledgements:
Dr Rene Ramnarace would like to gratefully acknowledge Dr Harry R. Dalton, Dr Peter Draganov, and Dr
Grant F. Hutchins, previous contributors to this monograph. HRD, PD and GFH declare that they have no
competing interests.
// Peer Reviewers:
Jeffrey S. Upperman, MD, FACS, FAAP

Associate Professor of Surgery
Division of General Pediatric Surgery; Director of the Trauma Program, Childrens Hospital, Los Angeles, CA
DISCLOSURES: JSU declares that he has no competing interests.
Grant Sanders, MBBS

Consultant
Laparoscopic Upper Gastrointestinal Surgeon, Derriford Hospital, Plymouth, UK
DISCLOSURES: GS declares that he has no competing interests.

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Assessment

The right clinical information, right where it's needed

Last updated: May 02, 2018

Toxic and iatrogenic causes

Benign biliary obstruction

• A single-stranded RNA picornavirus.

• Hepatitis C virus (HCV) is a single-stranded RNA flavivirus.

aminotransferase all increase the risk of fibrosis.

• Causes include drugs such as amiodarone, methotrexate, nifedipine, corticosteroids, tamoxifen,

Inflammatory and immune-mediated causes

seen once bilirubin levels rise above 34 to 68 micromol/L (2 to 4 mg/dL).

• An adult-onset disorder characterised by inappropriately high iron absorption, resulting in progressive

• A rare autosomal recessive inherited disorder of copper metabolism characterised by excessive

• An autosomal recessive condition characterised by intermittent jaundice in the absence of haemolysis

• A rare, autosomal recessive disorder of bilirubin metabolism caused by glucuronosyltransferase

and 2) based on the severity of the disease.

Acute alcoholic hepatitis

• Drug-induced direct hyperbilirubinaemia

Step-by-step diagnostic approach

For specific cases additional tests are needed.

Imaging modality: estimating the pre-test probability of biliary

High likelihood of benign biliary obstruction

If patients have suspected sclerosing cholangitis or biliary stricture, magnetic resonance

High likelihood of malignant biliary obstruction

Low likelihood of mechanical obstruction

Indeterminate likelihood of obstruction

Differential diagnosis overview

Alcoholic liver disease

Drug-induced direct hyperbilirubinaemia

Drug-induced indirect hyperbilirubinaemia

Primary biliary cirrhosis

Primary sclerosing cholangitis

Alpha-1 antitrypsin deficiency

Crigler-Najjar syndrome, types 1 and 2

◊ Alcoholic liver disease

History Exam 1st Test Other tests

5 to 10 years of alcohol parotid gland »serum liver »upper endoscopy:

◊ Alcoholic liver disease

History Exam 1st Test Other tests

»full blood count:

»CAGE score: >2

◊ Alcoholic liver disease

History Exam 1st Test Other tests

History Exam 1st Test Other tests

right upper quadrant RUQ abdominal »serum liver »serum cholesterol:

extrahepatic biliary tree Has the highest

History Exam 1st Test Other tests

may be hx of risk may be normal; »serum liver »serum anti-

History Exam 1st Test Other tests

History Exam 1st Test Other tests

»full blood count: low

History Exam 1st Test Other tests

may be hx of risk acute infection: usually »serum liver »serum hepatitis

acute presentation clonus, rigidity, coma); (PT)/international Patients with a positive

History Exam 1st Test Other tests

History Exam 1st Test Other tests

may be hx of risk early disease: normal »serum liver »serum hepatitis C

»full blood count: low