Liver, biliary system and exocrine pancreas

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Chapter 16 Liver, biliary system and exocrine pancreas

Common clinical problems from liver and biliary system disease 403
Pathological basis of hepatic signs and symptoms 403
Normal structure and function 404
Investigation of liver disease 407
Tumours of the liver 423

Liver cysts 425
Liver involvement by systemic disease 426
Transplantation and the liver 426

Normal structure and function 426
Congenital abnormalities 427
Normal structure and function 429
Investigation of pancreatic disease 429
Congenital abnormalities 430
Commonly confused conditions and entities relating to liver, biliary and pancreatic pathology 433



Pathological basis of hepatic signs and symptoms

Sign or symptom Pathological basis
Jaundice Haemolysis (increased formation of bilirubin), liver disease (impaired conjugation and/or excretion) or biliary obstruction
Dark urine Conjugated hyperbilirubinaemia (water-soluble)
Pale faeces Biliary obstruction causing lack of bile pigments
Spider naevi Secondary to hyperoestrogenism
Oedema Reduced plasma oncotic pressure due to hypoalbuminaemia
Xanthelasma Cutaneous lipid deposits due to hypercholesterolaemia in chronic biliary obstruction
Steatorrhoea Malabsorption of fat due to lack of bile (e.g. biliary obstruction)
Pruritus Biliary obstruction resulting in bile salt accumulation
Ascites Combination of hypoalbuminaemia, portal hypertension and secondary hyperaldosteronism
Bruising or bleeding Impaired hepatic synthesis of clotting factors
Hepatomegaly Increased size of liver due to inflammation (e.g. hepatitis), infiltration (e.g. amyloid, fat) or tumour (primary or secondary)
Haematemesis Ruptured oesophageal varices due to portal hypertension
Encephalopathy Failure of liver to remove exogenous or endogenous substances mimicking or altering balance of neurotransmitters



Forming the interface between the gastrointestinal tract and the rest of the body, the liver is of crucial importance in metabolising, storing or excreting the absorbed products of digestion. The liver has numerous other vital functions; therefore, the clinical consequences of liver disease are often wide-ranging and, if severe, life-threatening. However, considerable functional reserve and reparative capacity enables many patients to tolerate cellular injury or losses that, in other organs, would imperil their survival.

This wedge-shaped organ, weighing approximately 1.5 kg in the adult, is situated in the right hypochondrial region of the abdominal cavity. It has four lobes: the right is larger than the left; the smaller caudate lobe is situated posteriorly and the quadrate lobe is more anterior. The liver receives blood from two sources:

arterial blood from the right and left hepatic arteries, which are branches of the coeliac axis
venous blood from the hepatic portal vein, which drains much of the alimentary tract, from the stomach to the rectum, and the spleen.

Blood leaves the liver through the hepatic veins, which drain into the inferior vena cava.

Bile is formed in the liver and drains from it into the right and left hepatic ducts; these fuse to form the common bile duct to be joined by the cystic duct, which communicates with the gallbladder where the bile is stored and concentrated.

Most of the liver comprises liver cells (hepatocytes). These are arranged in plates one cell thick, bordering the vascular sinusoids through which flows hepatic arterial and portal venous blood. The blood flowing through the vascular sinusoids is separated from the liver cells by a thin fenestrated (porous) barrier of cells (endothelial cells and phagocytic Kupffer cells) and the space of Disse. Within the space of Disse the basement membrane is interrupted, thus allowing free exchange of molecules at the liver cell membrane. Blood flowing through the vascular sinusoids drains into hepatic vein branches (central veins or terminal hepatic venules). Bile formed by the liver cells is secreted from them into minute canaliculi which run along the centre of the liver cell plates to drain into the bile duct branches in the portal tracts. Close to the vascular sinusoids in the vicinity of the terminal hepatic venules are stellate cells called the perisinusoidal cells of Ito; these are involved in hepatic fibrosis by synthesising collagen.

The portal tracts each contain three tubular structures, which are branches of:

the bile duct
the hepatic artery
the portal vein.

These constitute the portal triad and are supported by collagen-rich connective tissue.

The microanatomy of the liver can be regarded conceptually as either acinar or lobular (Fig. 16.1):

Acini are centred on the axial vessels, arising from the hepatic artery and portal venous channels in the adjacent portal tract. Their periphery is demarcated by the surrounding hepatic veins.
Lobules are centred on terminal hepatic venules (‘central veins’). Their periphery is demarcated by imaginary lines joining each of the surrounding portal tracts.

Fig. 16.1 Comparison of acinar and lobular concepts of the microanatomical units of the liver. image The acinar concept explains better the pathophysiology of the liver. Cells in acinar zone 3, being the most remote from the vascular supply in the hilum of the acinus, are consequently the most vulnerable to injury. Death of liver cells in zone 3 results in the observed necrosis bridging between portal tracts and central veins in severe liver injury. image Lobular units are, however, often easier to perceive in histological sections.

Of the two microanatomical concepts—acinar or lobular—the ‘acinar concept’ is now considered to be more useful because it explains better many of the pathophysiological disturbances in liver disease. The zone of liver cells most remote from the axial vessels in the centre of the acinus (acinar zone 3) is the most susceptible to injury resulting from vascular insufficiency, as in circulatory shock or cardiac failure. As adjacent zones 3 are contiguous, liver cell death in this zone is often confluent.

The portal tracts are circumscribed by a boundary of liver cells, known as the limiting plate, which is breached in some forms of chronic liver inflammation; disruption of the limiting plate, when seen in biopsies, denotes that progression to cirrhosis is likely. The liver cells at the portal tract boundary can, in response to bile duct injury or obstruction, undergo a metaplastic change and proliferate to form new bile ductules.

Liver cells are rich in organelles, including numerous mitochondria, lysosomes, peroxisomes (microbodies), and rough and smooth endoplasmic reticulum, reflecting their wide range of metabolic functions. The cytoplasm is also laden with glycogen; this glycogen can be excessive in diabetes and in congenital deficiencies of glycogen debranching enzymes (the glycogenoses).

Liver cells synthesise albumin, clotting factors including fibrinogen, some complement components, alpha-1 antitrypsin, etc., and remove from the body many waste products and potentially toxic substances. Through the expression of specific receptors on the liver cells, the liver—the site of action of statins, the cholesterol-lowering drugs—has a major role in the uptake and metabolism of the low-density lipoproteins involved in atheroma (Ch. 13). Liver cells also metabolise or activate many other drugs. Extensive disease of the liver therefore affects many vital functions and has profound effects on the body.

Liver cells contain many enzymes, some of which are diagnostically important. Their release from damaged or dying liver cells into the blood, where their activity can be measured, indicates the presence and severity of liver disease (Table 16.1). These enzymes include:

aspartate aminotransferase (AST)
alanine aminotransferase (ALT)
gamma-glutamyltransferase (GGT).

Table 16.1 Diagnostic usefulness of serum analyses in liver disease

Test Deviation from normal Interpretation
AlbuminNormal 35–50 g/l Liver failure
Prothrombin timeNormal < 15 s Liver failure
Alanine aminotransferase (ALT)Normal < 40 IU/l Hepatocellular injury
Aspartate aminotransferase (AST)Normal < 40 IU/l Hepatocellular injury
Gamma-glutamyltransferase (GGT)Normal < 50 IU/l Hepatocellular injury (centrilobular)
Alkaline phosphataseNormal < 100 IU/l
Biliary obstruction
Hepatic metastases

BilirubinNormal 5–12 μmol/l↑

Hepatocellular injury
Biliary obstruction
Liver failure
Congenital hyperbilirubinaemia

IgM anti-HAV antibodyPresentHepatitis AHBsAgPresentHepatitis B or carrierHBeAgPresentActive hepatitis B infectionAnti-HCV antibodyPresentHepatitis C virus exposureHCV RNAPresentActive hepatitis C infectionCaeruloplasmin↓Wilson’s diseaseIgA↑Alcoholic cirrhosisIgG↑Autoimmune hepatitisIgM↑Primary biliary cirrhosisAnti-mitochondrial antibodyPresentPrimary biliary cirrhosisAnti-smooth muscle, antinuclear or anti-LKM antibodiesPresentAutoimmune hepatitisFerritin↑HaemochromatosisAlpha-1 antitrypsin↓Alpha-1 antitrypsin deficiencyAlpha-fetoprotein (AFP) (normally undetectable)↑Liver cell carcinoma

HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; LKM, liver and kidney microsomal antigen.

All cells in the liver are capable of regeneration. The liver cells are classified as stable—that is, they are not normally replicating but will do so if the liver is injured. This regenerative capacity is vital in the recovery of patients with liver damage due to viruses, drugs or trauma, but if the damage is persistent or occurs repeatedly, it can result in loss of the normal acinar or lobular structure and its replacement by regenerative liver cell nodules which are functionally inefficient. This is the condition called cirrhosis.

Some changes occur naturally in the liver with age. In the fetus, the liver is a relatively larger organ compared to the rest of the body. It is a major site of haemopoiesis and the adult liver can revert to this activity in some haematological disorders. The fetal liver synthesises alpha-fetoprotein, a fetal serum protein, and this is replaced by albumin towards the end of gestation. Alpha-fetoprotein synthesis by the adult liver usually denotes the presence of a primary liver cell carcinoma. With advancing age, the liver shrinks and becomes dark brown due to an increased amount of lipofuscin pigment in the liver cells (‘brown atrophy’).


The investigation of a patient with liver disease commonly includes:

analysis of serum concentrations of bilirubin, hepatic enzymes, albumin, clotting factors, etc.
immunological testing for auto-antibodies and for viral antigens and antibodies
imaging techniques
liver biopsy.

These investigations complement careful history-taking and a thorough clinical examination.



Bilirubin pigment is a breakdown product of the haem moiety of haemoglobin (Fig. 16.2). It is produced at sites of red cell destruction (e.g. spleen) and circulates in the blood in an unconjugated water-insoluble form bound to albumin. In the liver it is conjugated to glucuronic acid by the enzyme glucuronyl transferase. Conjugated bilirubin is water-soluble and can therefore appear in the urine if the outflow of bile from the liver is interrupted; the patient’s urine then becomes stained with conjugated bilirubin. Bilirubin is converted by bacteria in the intestine to faecal urobilinogen (stercobilinogen), some of which is absorbed and then excreted, mostly in the bile to complete its enterohepatic circulation or, in only trace amounts normally, by the kidneys to appear in the urine as urobilinogen. Stercobilinogen is oxidised to stercobilin (faecal urobilin), the principal faecal pigment.


Fig. 16.2 Simplified pathways of bilirubin metabolism. Excessive breakdown of haemoglobin, as in haemolytic anaemias, will lead to increased biliary excretion of bilirubin. Biliary obstruction will cause regurgitation of conjugated water-soluble bilirubin into the blood which is then excreted in the urine, causing it to darken. Liver cell damage in hepatitis will cause impaired biliary excretion of urobilinogen and conjugated bilirubin; these are excreted in the urine, causing it to darken. The enterohepatic circulation, which involves urobilinogen, also returns cholic acid and chenodeoxycholic acid to the liver; this enhances bile secretion.

In early or recovering viral hepatitis, impaired biliary excretion results in preformed stercobilinogen appearing in the urine in excess as urobilinogen; this is one sensitive marker of early liver injury. In well-established biliary obstruction, the urinary urobilinogen concentration falls, because the cessation of biliary excretion into the gut results in sustained absence of synthesis of faecal urobilinogen.


In liver cell injury, damage to the membranes of cells and their organelles allows intracellular enzymes to leak into the blood, where the elevated concentrations can be measured. Examples include ALT, AST and GGT. Their diagnostic usefulness is summarised in Table 16.1.

The enzyme alkaline phosphatase is normally present in bile. Obstruction to the flow of bile, by gallstones for example, causes regurgitation of alkaline phosphatase into the blood, resulting in increased serum concentrations.

Many of these enzymes are not exclusively specific to the liver; therefore the results of diagnostic serum assays need careful interpretation.


Albumin is a major serum protein synthesised by the liver cells. It has a relatively long half-life, compared to that of clotting factors (see below), so liver damage has to persist before decreased serum levels are found. In chronic liver disease, such as cirrhosis, a low serum albumin concentration is an important manifestation of liver failure, which results in peripheral oedema and contributes to the presence of ascites due to a reduction in plasma oncotic pressure.

Clotting factors

Liver cells synthesise the vitamin K-dependent clotting factors, deficiency of which results in a bleeding tendency. This can be detected in the laboratory by measuring the prothrombin time. A prolonged bleeding and prothrombin time is a further manifestation of liver failure and, because these clotting factors have a relatively short half-life, deficiency may be found quite early in the course of the illness. The prothrombin time should be measured before performing a liver biopsy or undertaking surgery on a patient with liver disease to avoid the risk of unexpected haemorrhage. These clotting factor deficiencies can be corrected by administration of high doses of vitamin K or of the clotting factors themselves.


Although insignificant amounts of immunoglobulins are synthesised in the liver, immunological abnormalities often accompany liver disease and are useful diagnostic markers. These abnormalities include the appearance in the patient’s blood of auto-antibodies to normal tissue antigens. The antibodies are not responsible for the tissue damage in the liver diseases with which they are associated. Examples include:

anti-mitochondrial antibodies in primary biliary cirrhosis
antinuclear antibodies and anti-smooth muscle antibodies in autoimmune hepatitis.

Polyclonal immunoglobulin elevations also occur:

raised IgG in autoimmune hepatitis
raised IgM in primary biliary cirrhosis
raised IgA in alcoholic cirrhosis.

Antibodies to hepatitis viruses are, in some instances (e.g. hepatitis A), clinically useful markers of these infections. Viral antigens or nucleic acids can also be tested for.


Techniques used to visualise the liver and detect lesions within it include:

cholangiography (often together with pancreatography), to visualise the biliary system
scintigraphy after the injection of 99mTc-labelled colloids, which are taken up by the phagocytic Kupffer cells
computed tomography (CT)
magnetic resonance imaging (MRI).


The two common types of liver biopsy are:

wedge biopsies, taken during an abdominal operation
needle biopsies, which are much more frequent and are done percutaneously.

Both procedures carry a small but significant risk of haemorrhage and biliary leakage from the biopsy site. Bile duct obstruction is a contraindication to liver biopsy because of the increased risk of biliary peritonitis from bile leakage from the biopsy site. The risk must be outweighed by the likely therapeutic benefit to the patient resulting from an accurate assessment of their liver disease.

Most liver diseases produce diffuse abnormalities in the organ; a biopsy from any part of it will therefore be representative. Focal lesions such as tumours may be missed, particularly by percutaneous needle sampling, but the biopsy needle can be guided to them by using imaging techniques such as ultrasonography.

Liver biopsies are examined by light microscopy after sectioning and staining. Unlike renal biopsies, little additional clinically useful information is obtained by examining liver biopsies with the electron microscope.


Jaundice (or icterus) is the name given to yellowing of the skin and mucosal surfaces due to the presence of bilirubin. Usually jaundice is observable when the serum bilirubin concentration exceeds 40 micromol/l. Note, however, that:

1. Many patients with significant liver disease, often severe, are not jaundiced.
2. Liver disease is not the only cause of jaundice.

The accumulation of bilirubin in the skin may cause some embarrassment to the patient and, often if due to biliary obstruction, discomfort due to pruritus.

Jaundice in infants

Physiological neonatal jaundice is relatively common, particularly in premature infants. Although it causes understandable parental anxiety, the jaundice is rarely severe and it fades as liver function matures. However, high bilirubin levels in infancy can be directly harmful. Because the neonatal blood–brain barrier is relatively permeable, unconjugated bilirubin can accumulate in the lipid-rich brain tissue, causing bilirubin encephalopathy or kernicterus; this can be avoided by phototherapy or, in severe cases, exchange transfusion.

Worsening jaundice may be one of the clinical features alerting to the presence of a congenital abnormality within the hepato-biliary system. Such abnormalities may be:


Structural congenital abnormalities include:

biliary atresia, characterised by failure of bile duct development during embryogenesis
biliary hypoplasia (Alagille’s syndrome), an autosomal dominant syndrome in which paucity of bile ducts is accompanied by dysmorphic facies, skeletal abnormalities and mental retardation
congenital hepatic fibrosis, an autosomal recessive disorder in which hepatic fibrosis is often associated with cystic kidneys
choledochal cysts, more common in Japan than in Western Europe, and in girls than boys.

Functional abnormalities include congenital metabolic defects involving the liver (see Ch. 7) and congenital hyperbilirubinaemias.

Classification of jaundice

Jaundice may be classified as pre-hepatic, intrahepatic or post-hepatic, depending on the site of the lesion, or conjugated and unconjugated, based on chemical analysis of the bilirubin in the blood or by deduction from the colour of the patient’s urine. Only conjugated bilirubin is sufficiently water soluble to be excreted in the urine.

Pre-hepatic jaundice

The main cause of pre-hepatic jaundice is haemolysis, due for example to hereditary spherocytosis or autoimmune red cell destruction (see Ch. 23). In these conditions there is excessive production of bilirubin from the haemoglobin released from lysed red cells. Because the excess bilirubin is unconjugated, it is not excretable in the urine; the urine colour is normal (hence the synonym ‘acholuric jaundice’). The bile, however, may contain so much bilirubin that there is a risk of pigment gallstone formation.

Intrahepatic jaundice

Hepatic disorders in which jaundice may be a feature include:

acute viral hepatitis
drug-induced liver injury
alcoholic hepatitis
decompensated cirrhosis
intrahepatic bile duct loss (e.g. primary biliary cirrhosis, sclerosing cholangitis, biliary hypoplasia)
in pregnancy, intrahepatic cholestasis and acute fatty liver.

In these conditions there is accumulation of bilirubin within the liver (intrahepatic cholestasis), often histologically evident in biopsies as plugs of bile pigment distending canaliculi. The excess bilirubin is predominantly conjugated, is therefore water soluble and is excreted in the urine, causing darkening; this is a simple but diagnostically useful observation.

Congenital hyperbilirubinaemia

Congenital metabolic defects in the intrahepatic conjugation, transport or excretion of bilirubin are relatively rare causes of jaundice. These include:

Gilbert’s syndrome (predominantly unconjugated)
Crigler–Najjar syndrome (predominantly unconjugated)
Dubin–Johnson syndrome (predominantly conjugated)
Rotor syndrome (predominantly conjugated).

Post-hepatic jaundice

Obstruction of the extrahepatic bile ducts is an important cause of jaundice necessitating urgent investigation and alleviation in order to prevent serious damage to the liver. Important causes are:

congenital biliary atresia—often accompanied by a reduction in the number of intrahepatic ducts
gallstones—usually associated with biliary colic and a non-distendable chronically inflamed gallbladder
strictures—often following previous biliary surgery
tumours—notably carcinoma of the head of the pancreas compressing the common bile duct.

As with intrahepatic causes, some of which also directly interfere with biliary drainage (e.g. primary biliary cirrhosis, sclerosing cholangitis), the excess bilirubin is conjugated and darkens the urine. Conversely, the patient’s faeces are pale. Pruritus is a common and troublesome symptom, probably due to bile salt accumulation.


image May present with acute onset of jaundice
image Causes include viruses, alcohol, drugs, bile duct obstruction
image Possible outcomes include complete recovery, chronic liver disease, or death from liver failure

Liver injury is conveniently divided into acute and chronic for the purposes of description and clinical management. However, in practice, the same cause may produce either an acute or a chronic illness, in the latter event not necessarily with any preceding clinically evident acute phase. For example, viral hepatitis is considered here under the heading of acute liver injury, but it can lead to chronic liver damage.


The major causes of acute liver injury are:

viral infections
high alcohol consumption
adverse drug reactions
biliary obstruction, commonly due to gallstones.

Direct physical injury to the liver, such as laceration in a road traffic accident, is another important form of acute liver injury, but the focal nature of the injury contrasts with the diffuse injury produced by the agents listed above. Recovery from acute liver injury, focal or diffuse, is attributable to the capacity of the organ for cellular regeneration.

Clinicopathological features

The clinical and laboratory manifestations of acute liver injury are:

raised serum bilirubin and transaminases
in severe cases, evidence of liver failure.

Most of the signs and symptoms of acute liver damage are predictable from the known functions of the liver. The best known is jaundice (or icterus) due to failure of the liver to secrete bile at the rate at which it is formed in the body from the destruction of red cells. Severe acute liver damage can lead to bruising and haemorrhage, due to clotting factor deficiency, and coma due to the accumulation of toxic metabolites that mimic neurotransmitters (‘false neurotransmitters’).

Laboratory investigations

Laboratory investigations will reveal evidence of liver cell damage, in that there will be elevated levels of serum enzymes, particularly the transaminases, and bilirubin. Liver cell damage results in some impairment of bilirubin conjugation, but also failure to excrete conjugated bilirubin and any stercobilinogen absorbed from the gut. Consequently, the urine is darkened by the presence of excess conjugated bilirubin and urobilin (derived by oxidation from urobilinogen) that cannot be excreted by the liver (Fig. 16.2). Eventually, as the liver damage persists, urobilinogen disappears from the urine because little or no bilirubin is being excreted by the liver. Jaundice due to bile duct obstruction—commonly by gallstones—also results in dark urine due to excess conjugated bilirubin that cannot be excreted by the liver; urobilinogen is usually absent, unless the obstruction is of very recent onset or intermittent, because no bilirubin reaches the intestine. Examination of urine and faeces (for colour) can therefore assist in the differential diagnosis of jaundice (Table 16.2).

Table 16.2Differential diagnosis of jaundice from bile abnormalities in urine and faeces, and from serum



In almost all cases of acute liver injury there will be liver cell degeneration or death and an inflammatory reaction. Superimposed on this uniform reaction to acute injury are, in many cases, diagnostic changes specific to the causative agent.

Also evident in liver biopsies will be the pattern of cell damage, from which the prognosis can be deduced (Fig. 16.3):

Death of individual liver cells (apoptosis) is the most frequent pattern in viral hepatitis and usually denotes certain recovery with no long-term sequelae.
Death of periportal hepatocytes at the limiting plate (interface hepatitis) or entire acinar zones, usually zone 3 (bridging necrosis), disrupts the hepatic architecture and leads to a risk of cirrhosis developing.
Liver cell death substantially affecting entire acini (panacinar necrosis) leads to liver failure and a significant risk of imminent death.

Fig. 16.3 Patterns of liver cell death and their clinicopathological significance. Death of the liver cells immediately surrounding central veins denotes cardiac failure, some other impediment to venous drainage, or some toxic cause (e.g. paracetamol overdose). Bridging necrosis (in acinar zone 3) is a feature of severe hepatitis. Interface hepatitis is death of liver cells at the margin of the portal tracts; this is a feature of chronic hepatitis due to a variety of causes. Apoptotic death of single cells is typical of acute viral hepatitis.

Viral hepatitis

image Common cause of acute liver injury
image Hepatitis viruses A, B, C and E, and delta agent
image Other viruses causing liver damage include Epstein–Barr virus, yellow fever virus, herpes simplex virus and cytomegalovirus

Hepatitis viruses

The main hepatitis viruses (Table 16.3) are:

hepatitis A virus (HAV)
hepatitis B virus (HBV)
hepatitis C virus (HCV)
hepatitis E virus (HEV)
delta agent, a defective virus requiring HBV for pathogenicity.

Table 16.3Hepatitis viruses: their characteristics and associated diseases (delta agent, a defective virus, is not included)


These hepatitis viruses are immunologically distinct. Infection usually confers life-long immunity to the infecting virus but not to the others.

The clinical features range from a trivial illness without jaundice (anicteric hepatitis) which may escape detection (this is a common result of HAV infection) to a more significant illness with jaundice and other clinical evidence of disturbed liver function. Sometimes the illness is dominated by jaundice, with little elevation of serum transaminases (cholestatic hepatitis). Severe infection leads to overt liver failure.

Yellow fever, caused by a group B arbovirus, shares many clinical and histological features with the illness usually designated viral hepatitis, but it is not normally included within this group for the purposes of description, mainly because its geographical distribution is very restricted.

The liver may also become infected by many other viruses, but these are not regarded as ‘hepatitis viruses’ because the infection is not confined to the liver. Examples include:

infectious mononucleosis due to Epstein–Barr virus
herpes simplex virus 1

Hepatitis A virus

The main characteristics of hepatitis A are:

‘faecal–oral’ spread
relatively short incubation period
sporadic or epidemic
directly cytopathic virus
no carrier state
mild illness, full recovery usual.

Infection by HAV used to be called ‘infectious hepatitis’ because of its common occurrence in epidemics, though it also occurs sporadically. In most countries, infection by the virus is common, usually in youth; the resulting illness is often very mild and jaundice absent or so slight that it escapes notice. Overt jaundice and clinical recognition of the infection is less common. Hepatitis sufficiently severe to warrant hospital admission is unusual, and long-term sequelae or death are exceptional rarities. It is therefore a relatively benign infection.

HAV passes from one individual to another by ‘faecal– oral’ transmission—usually indirectly, such as by the contamination of food and drinking water with sewage. Because the virus is excreted in the faeces before jaundice appears, thus leading to the recognition of the illness and isolation of the patient, many other individuals can be rapidly exposed to the hazard of infection. The incubation period is relatively short. HAV produces liver cell damage by a direct cytopathic effect.

Specific diagnosis is made by seeking an IgM-class antibody to HAV in the patient’s serum; this indicates recent infection. A carrier state does not exist.

Hepatitis B virus

The main characteristics of hepatitis B are:

spread by blood, blood-contaminated instruments, blood products and venereally
relatively long incubation period
liver damage by antiviral immune reaction
carrier state exists
relatively serious infection.

Infection by HBV used to be called ‘serum hepatitis’ because it was known to be transmitted by blood and blood products. This is because infected, but apparently healthy, individuals can carry the virus in their blood and pass it on to others by the transfusion of blood or its products. This mode of transmission is much less common now that blood donors are screened by testing for the presence of the virus. However, the term ‘serum hepatitis’ has been abandoned because it misleadingly excludes transmission of the virus by other methods, notably venereally; the disease is often transmitted between homosexual males. HBV can also be transmitted by contaminated needles, such as may be used for tattooing or by drug addicts. There is a relatively high incidence of the carrier state in underdeveloped countries and the virus can be transmitted vertically from mother to child—in utero, during delivery or through intimate post-natal contact.

Specific diagnosis is made by seeking the hepatitis B surface antigen (HBsAg, formerly known as ‘Australia antigen’ because it was first detected in the serum of an Australian aborigine). The presence of the ‘e’ antigen (HBeAg) in the patient’s serum indicates active viral replication.

HBV produces liver cell damage not by a direct cytopathic effect but by causing viral antigens to appear on the cell surface (HBsAg); these are then recognised by the body’s immune system and the infected liver cells are destroyed (Fig. 16.4). Thus, if immunity is generally impaired or there is specific tolerance to the antigen, the virus can survive in the liver cells without causing damage; such patients become asymptomatic carriers of the virus and their body fluids are a hazard to other individuals. Liver biopsies of HBV-infected carriers show that the liver cells have a ground-glass texture to their cytoplasm due to the abundance of virus particles.


Fig. 16.4 Comparison of the pathogenesis of HAV and HBV hepatitis.

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