Chapter 58: Jaundice

Jaundice is a yellow discolouration of the skin and mucosal surfaces caused by the accumulation of excessive bilirubin.¹ It is a cardinal symptom of hepatobiliary disease and haemolysis. Important common causes include gallstones, hepatitis A, hepatitis B, hepatitis C, drugs, alcohol and Gilbert syndrome. The commonest clinical encounter with jaundice, especially physiological jaundice, is in the newborn. As for all patients, the history and examination are paramount, but investigations are essential to clinch the diagnosis of jaundice.

The three major categories of jaundice are (see FIG. 58.1):

• obstructive:

  • – extrahepatic

  • – intrahepatic

• hepatocellular

• haemolytic

A summary of the diagnostic strategy model is presented in TABLE 58.2.

Probability diagnosis

The answer depends on the age and social grouping of the patient, especially if the patient indulges in risk-taking behaviour or has travelled overseas.

Viral hepatitis A, B or C account for the majority of cases of jaundice.

In the middle-aged and elderly group, a common cause is obstruction from gallstones or cancer. It is common for older people to have painless obstructive jaundice; bear in mind that the chances of malignancy increase with age.

Alcoholic liver disease is common and may present as chronic alcoholic cirrhosis with liver failure or as acute alcoholic hepatitis. It is worth emphasising that such patients can make a dramatic recovery when they cease drinking alcohol.

In family practice we encounter many cases of drug-induced jaundice, especially in the elderly. These drugs are outlined later in the chapter, under ‘Seven masquerades checklist’.

Serious disorders not to be missed

Malignancy must always be suspected, especially in the elderly patient and those with a history of chronic active hepatitis (e.g. post hepatitis B or C infection). The former is more likely to have carcinoma of the head of the pancreas and the latter, hepatocellular carcinoma (hepatoma).

Metastatic cancer must be kept in mind, especially in those with a history of surgery, such as large bowel cancer, melanoma and stomach cancer. An enlarged, knobbly, hard liver is a feature.

Hepatic failure can be associated with severe systemic infection (e.g. septicaemia and pneumonia), and after surgery in critically ill patients. A patient who has the classic Charcot triad of upper abdominal pain, fever (and chills) and jaundice should be regarded as having ascending cholangitis until proved otherwise. Wilson syndrome, although rare, must be considered in all young patients with acute hepatitis. A history of neurological symptoms, such as a tremor or a clumsy gait, and a family history is important. If Wilson disease is suspected, an ocular slit lamp examination, serum ceruloplasmin levels (low in 95% of patients) and a liver biopsy should be performed. Early diagnosis and treatment mean a better prognosis.

Reye syndrome is a rare and severe complication of influenza and some other viral diseases, especially in children when given aspirin. There is rapid development of hepatic failure and encephalopathy.

Pitfalls

Gallstones, especially in the absence of upper abdominal pain, can be overlooked, so this possibility should be kept in mind in the elderly.

Gilbert syndrome is worth considering, especially as it is the commonest form of unconjugated hyperbilirubinaemia. It affects at least 3% of the population.

Cardiac failure can present as jaundice with widespread tenderness under the right costal margin. It can be insidious in onset or manifest with gross acute failure. It can be confused with acute cholecystitis. The biochemical abnormalities seen are very variable. Usually there is a moderate rise in bilirubin and alkaline phosphatase and sometimes, in acute failure, a marked elevation of transaminase may occur, suggesting some hepatocellular necrosis.

There are many other pitfalls for a family doctor, who may encounter the conditions very rarely, if at all. Such disorders include:

• inherited conjugated hyperbilirubinaemias (Dubin–Johnson and Rotor syndromes) caused by faulty excretion by liver cells

• haemochromatosis (associated pigmentation and diabetes)

• chronic active hepatitis

• primary biliary cirrhosis

• primary sclerosing cholangitis (associated with ulcerative colitis)

General pitfalls

• Excluding jaundice by examining the sclera in artificial light

• Not realising that the sclera in elderly patients often have an icteric appearance (without jaundice)

• Omitting to take a careful history, including illicit drugs

• A liver biopsy is essential in all patients with chronic hepatitis

Seven masquerades checklist

Of this group the haemolytic anaemias and drugs have to be considered.

Drug-related jaundice

Drug-induced jaundice is common and many drugs are implicated. The patterns of drug-related liver damage include cholestasis, necrosis (‘hepatitis’), granulomas, chronic active hepatitis, cirrhosis, hepatocellular tumours and veno-occlusive disease.^4,5 Some drugs, such as methyldopa, can initiate haemolysis.

The important drugs to consider are presented in TABLE 58.3. Antibiotics, especially flucloxacillin, amoxycillin + clavulanate and erythromycin, are commonly implicated.

Haemolysis

The patient may present with the symptoms of underlying anaemia and jaundice with no noticeable change in the appearance of the urine and stool. The degree of haemolysis may vary from the lemon-yellow tinge of pernicious anaemia in an elderly patient to a severe haemolytic crisis precipitated by drugs or broad beans (favism) in a patient with an inherited red cell deficiency of glucose-6-phosphate dehydrogenase (G6PD). More common causes include the hereditary haemolytic anaemias, such as congenital spherocytosis and thalassaemia major. Acquired causes include incompatible blood transfusions, malignancies (such as lymphoma), severe sepsis and some drugs.

Splenomegaly occurs in most patients with haemolytic anaemia, and decreased red cell survival can be measured.

Psychogenic considerations

This is not really applicable for an organic problem such as jaundice. Nevertheless, the cause may be related to factors in the patient’s lifestyle, such as homosexuality, sexual promiscuity or intravenous drug abuse, and the patient may be reluctant to offer this information. Discreet, concerned probing will be necessary.

History

The history should include questioning about the following:

• any episodes of jaundice

• change in colour of faeces and urine

• anorexia, sore throat, weight loss, pruritus

• abdominal pain

• residence and members of household

• contact with patients with hepatitis or jaundice

• recent overseas travel

• exposure to blood or blood products

• needle-stick injuries or exposure to needles, such as acupuncture, tattooing and intravenous drugs

• dietary history—shellfish, drinking water

• sexual history—evidence of promiscuity

• drug history, including alcohol, paracetamol

• recent medical history, including surgery

• family history—family contacts who have had jaundice, haemolytic disease and other genetic liver diseases

• ethnic history—liable to haemolytic disease, contact with hepatitis B

• occupational history—exposure to hazards

Significance of various symptoms

• Pain in the right hypochondrium:

  • – gallstones

  • – acute hepatitis (a constant ache)

  • – cholecystitis

• Anorexia, dark urine, fever:

  • – viral hepatitis probable

  • – alcoholic liver disease possible

  • – drug-induced hepatitis possible

• Pruritus:

  • – cholestasis probable

  • – possible with all liver diseases

• Arthralgia, rash:

  • – viral hepatitis

  • – autoimmune hepatitis

Examination

The abdominal examination is very important. The liver should be palpated carefully for enlargement, consistency and tenderness under the right costal margin. Search for enlargement of the gall bladder and the spleen. The gall bladder lies in the transpyloric line. A palpable gall bladder indicates extrahepatic biliary obstruction, and splenomegaly may indicate haemolytic anaemia, portal hypertension or viral hepatitis. Test for ascites.

Skin excoriation may indicate pruritus, which is associated with cholestatic jaundice. Look for evidence of chronic liver disease, such as palmar erythema, easy bruising, spider naevi and muscle wasting, and testicular atrophy and gynaecomastia. Test for hepatic flap (asterixis) and fetor, which indicate liver failure. Search for lymphadenopathy, which may be indicative of malignancy.

The examination should include dipstick urine testing for bilirubin and urobilinogen.

A summary of the possible findings is presented in FIGURE 58.2.

Investigations

The main investigations are FBE and the standard LFTs and viral serology for the infective causes, particularly hepatitis A, B and C virus (also EBV and CMV).

A summary of the general findings for liver function tests is shown in TABLE 58.4. Consideration should be given to ordering fractionalisation of bilirubin to determine whether it is conjugated or unconjugated (important in diagnosis of Gilbert syndrome).

Diagnostic markers for hepatitis

• Hepatitis A: IgM antibody (HAV Ab)

• Hepatitis B: surface antigen (HBsAg)

• Hepatitis C: HCV antibody (HCV Ab)

Hepatobiliary imaging

Tests to identify causes such as malignancy or gallstones are now sophisticated and should be chosen with care.

• X-ray: a plain abdominal X-ray shows up to 15–20% of opaque gallstones

• Transabdominal ultrasound (US): the most useful investigation for detecting gallstones and dilatation of the common bile duct; also detects liver metastases and other diffuse liver diseases

• HIDA scintiscan: useful in diagnosis of acute cholecystitis

• CT scan: for diagnosis of enlargement of the head of the pancreas and other pathology; indicated if US unsatisfactory

• PTC: percutaneous transhepatic cholangiography: shows imaging of biliary tree

• ERCP: endoscopic retrograde cholangiopan-creatography; PTC and ERCP (best) determine the cause of the obstruction and relieves it by sphincterotomy and removal of CBD stones

• MRCP: magnetic resonance cholangiography provides non-invasive planning for obstructive jaundice

• Liver isotopic scan: useful for liver cirrhosis, especially of the left lobe

• Fibroscan (transient elastography) to measure liver fibrosis

Specific tests

Some specific tests include:

• auto-antibodies for autoimmune chronic active hepatitis and primary biliary cirrhosis

• carcinoembryonic antigen to detect liver secondaries, especially colorectal

• serum iron studies, especially transferrin saturation—elevated in haemochromatosis

• alpha-fetoprotein—elevated in hepatocellular carcinoma; mild elevation with acute or chronic liver disease (e.g. cirrhosis)

• serum ceruloplasmin level—low in Wilson disease

• liver biopsy

• EBV/cytomegalovirus serology (consider if hepatitis serology negative)

Jaundice in the newborn is clinically apparent in 50% of term babies and more than 80% of preterm.⁶ Icterus is therefore common and invariably physiologically benign. However, it is a cause for concern as there are many other causes and investigation is needed to determine whether the bilirubin is conjugated (always pathological) or unconjugated. If conjugated, consider the serious biliary atresia (stools are white); also a cyst obstructing the bile duct or neonatal hepatitis. Prompt referral is essential.

Jaundice occurring in the first 24 hours after birth is not due to immature liver function but is pathological and usually due to haemolysis consequent on blood group incompatibility. In primigravidas it is usually due to ABO incompatibility. Causes of pathological jaundice are presented in TABLE 58.5 Such causes demand referral.

Bilirubin encephalopathy

Unconjugated bilirubin can be regarded as a neurological poison. With increasing serum levels an encephalopathy (which may be transient) can develop, but if persistent can lead to the irreversible brain damage known as kernicterus. The level of bilirubin causing kernicterus is totally unpredictable, but a guideline as a cause for concern in babies with Rh disease is a serum unconjugated bilirubin of 340 μmol/L (20 mg/dL).

Guidelines for treatment for hyperbilirubinaemia (at 24–36 hours)—an example:

• >285 μmol/L—phototherapy

• >360 μmol/L—consider exchange transfusion

An example of a normogram is presented in FIGURE 58.3.

Physiological jaundice

This mild form of jaundice, which is very common in infants, is really a diagnosis of exclusion. In a term infant the serum bilirubin rises quickly after birth to reach a maximum by day 3–5, then declines rapidly over the next 2–3 days before fading more slowly for the next 1–2 weeks. Management includes phototherapy.

ABO blood group incompatibility

This is antibody-mediated haemolysis (Coomb test positive):

• Mother is O

• Child is A or B

Jaundice develops within first 24 hours.

Treatment

• Perform a direct Coomb test on infant.

• Phototherapy is required immediately.

• These children require follow-up developmental assessment including audiometry.

Breast milk jaundice

If the secondary causes of prolonged jaundice are excluded, the baby is well and breastfeeding, the likely cause of unconjugated elevated bilirubin is breast milk jaundice. It occurs in 2–4% of breastfed infants. It usually begins late in the first week and peaks at 2–3 weeks. Diagnosis is confirmed by suspending (not stopping) breastfeeding for 24–48 hours. The serum bilirubin falls and then breastfeeding can continue. The mother, who can express milk for this short period, must be reassured that there is nothing wrong with the milk and advised to resume. Some doctors recommend continuation of breastfeeding.

Viral infection is the commonest cause of jaundice in the older child, especially hepatitis A and hepatitis B. It is uncommon for viral hepatitis to become chronic in childhood.

If an elderly person presents with jaundice the usual causes and investigations have to be considered. Obstructive jaundice is the commonest form of jaundice in the elderly and may be caused by gallstones blocking the common bile duct (may be painless) and carcinoma of the head of the pancreas, the biliary tract itself, the stomach or multiple secondaries for other sites. While it is not uncommon for a gallstone to produce marked obstructive jaundice and yet be painless, it is appropriate to adhere to the old adage that painless obstructive jaundice is due to neoplasm—particularly if the gall bladder is palpable (Courvoisier’s law).

Alcoholic liver disease, although most frequently affecting patients between 40 and 60 years, can present for the first time over age 60 years. The commonest cause of hepatocellular jaundice in the elderly is probably alcoholic cirrhosis; hepatitis A is still relatively uncommon in old persons.

Drugs do not cause jaundice in the elderly as frequently as they once did, particularly as phenothiazines, especially chlorpromazine, are not prescribed as often as previously. However, drugs should be considered as a potential cause and a careful check of the drug history is important.

A generation ago hepatitis A (infectious hepatitis or yellow jaundice) was the commonest recognised form of viral hepatitis, presenting usually with an abrupt onset of fever, anorexia, nausea and vomiting. It usually occurred in epidemics and hence was common in overcrowded institutions and camps. Now hepatitis B and C are the most commonly reported types of viral hepatitis with an onset that is more insidious and with a longer incubation period.^4,7 Symptoms include malaise, anorexia, nausea and polyarthritis. Acute hepatitis C is often subclinical.

The various forms of hepatitis are summarised in TABLE 58.6. All forms of hepatitis are common in developing countries and travellers are at risk of contracting these infections: hepatitis A and E from faeco-oral transmission; and hepatitis B, C, D and G from intravenous drugs and bodily fluids (from sexual transmission, in particular, for hepatitis B).

Evidence points to more viruses causing non-ABC hepatitis.⁸ Hepatitis F virus has been claimed to be transmitted enterically while the newly designated hepatitis G virus (HGV) is transmitted parenterally. It does not appear to cause a severe illness in recipients. It can be predicted that the hepatitis alphabet will continue to expand.

In hepatitis A, liver damage is directly due to the virus, but in hepatitis B and C it is due to an immunologic reaction to the virus.

Other infections that can present with jaundice as part of a systemic disease are malaria, Epstein–Barr mononucleosis, cytomegalovirus, Q fever, toxoplasmosis, leptospirosis and, rarely, measles, varicella, yellow fever, rubella, herpes simplex, dengue fever, Lassa fever and Marburg and Ebola virus.

Hepatitis A

Hepatitis A is becoming relatively less prevalent in developed countries. It is enterically transmitted and arises from the ingestion of contaminated food, such as shellfish, or water. There is no carrier state and it does not cause chronic liver disease. Hepatitis A most often causes a subclinical or self-limited clinical illness.

Clinical features

Pre-icteric (prodromal) phase:

• anorexia, nausea ± vomiting

• malaise

• headache

• distaste for cigarettes in smokers

• mild fever

• ± diarrhoea

• ± upper abdominal discomfort

Icteric phase (many patients do not develop jaundice):

• dark urine

• pale stools

• hepatomegaly

• splenomegaly (palpable in 10%)

Recovery usually in 3–6 weeks.

Fulminant hepatitis with liver coma and death may occur but is rare.

Investigations

LFTs and viral markers confirm the diagnosis. The antibodies to HAV are IgM, which indicates active infection, and IgG antibodies, which means past infection and lifelong immunity and which is common in the general population. Ultrasound is useful to exclude bile duct obstruction, especially in an older patient.

Outcome and treatment

Hepatitis A has an excellent prognosis with most patients making a complete recovery, and patients should be reassured. The mortality is less than 0.5%. Admission to hospital is not usually necessary. There is no specific treatment, so management is as follows.

• Provide appropriate reassurance and patient education.

• Rest as appropriate.

• Follow a fat-free diet.

• Avoid alcohol, smoking and hepatotoxic drugs (until recovery).

• Advise on hygiene at home to prevent spread to close contacts and family members. Recent evidence indicates that it can be spread sexually and by IV drugs.

• Wash hands carefully after using the toilet and disinfect them with antiseptic.

• Do not handle food for others with your fingers.

• Do not share cutlery and crockery during meals.

• Do not use tea-towels to dry dishes.

Prevention

Simple health measures such as good sanitation, effective garbage disposal and hand washing are probably responsible for the major decrease in the disease. Immune serum globulin (0.03–0.06 mL/kg IM) confers satisfactory passive immunity for close contacts (within 2 weeks of contact) and for travellers to endemic areas for up to 3 months. An active vaccine consisting of a two-dose primary course is the best means of prevention.

Hepatitis B

Hepatitis B has protean clinical manifestations. Transmission is by blood spread, percutaneous, sexual transmission, perinatal spread or by close prolonged family contact. Infection may be subclinical or self-limited acute hepatitis. Fulminant hepatitis is rare. Five per cent of subjects go on to become chronic carriers of the virus. Most are ‘healthy carriers’ but some may develop chronic active hepatitis, cirrhosis and hepatoma. The serology of hepatitis B involves antibody responses to the four main antigens of the virus (core, DNA polymerase, protein X and surface antigens). Passive and active vaccines are available, and should be used freely in groups at risk, including babies of infected mothers. High-risk groups are presented in TABLE 58.7. The clinical features are the same as those found in hepatitis A infection but may be less abrupt in onset but more severe in the long term.⁷ A serum sickness-like immunological syndrome may be seen with transient rashes (e.g. urticaria or a maculopapular rash), and polyarthritis affecting small joints in up to 25% of cases in the prodromal period.

Investigations^5,9,10

The main viral investigation for HBV is HBsAg (surface antigen), which is searched for routinely. If detected, indicating hepatitis B positive or carrier, a full viral profile is then formed.

HBsAg may disappear or persist. Its presence indicates a current or chronic infection as well as a carrier state (see FIG. 58.4). Chronic hepatitis B (carriage) is defined as the presence of HBsAg for at least 6 months.

HBeAg is a soluble protein from the pre-core and core. Antibodies develop to both HBsAg and HBeAg.

Monitoring and outcome^9,10

The possible course of events is shown in FIGURE 58.5. The majority of patients recover completely with the outcome depending on several factors, including the virulence of the virus and the immune state and age of the patient. Some will develop chronic hepatitis, some will develop a fulminant course, and others will become asymptomatic carriers and present a health risk to others.

Monitor progress with 6–12 monthly LFTs, HBeAg and HBV DNA.

• Negative HBsAg and HBV DNA (with anti-HBe) = resolving, with anti-HBs = full recovery.

• Positive HBsAg and HBV DNA = replicating and infective—refer.

• Monitor LFTs every 6 months. Refer if ALT elevated.

Treatment⁵

There is no specific treatment initially—being similar to hepatitis A, appropriate reassurance and patient education are necessary. Advise avoidance of alcohol. Avoid certain drugs, e.g. sedatives, NSAIDs, OCP, until recovery (normal LFTs). Advise about prevention of transmission, especially safe sex and sharing needles. Refer to a liver transplantation centre if encephalopathy or severe coagulopathy develop. Treatment of chronic hepatitis B infection (abnormal LFTs) is with the immunomodulatory and antiviral agents—pegylated interferon alpha and entecavir, tenofovir or other agents. This is expensive but it achieves permanent remission in 25% of patients, and temporary remission in a further 25%.⁷ Liver transplantation has been performed, but is often followed by recurrence of hepatitis B in the grafted liver. Follow up with regular LFTs and alpha-fetoprotein screening. It is appropriate to refer any HBsAg positive patient with an abnormal ALT and/or signs of chronic liver disease to a specialist since the evaluation of chronic hepatitis B can be complex.⁴

Prevention

Active immunisation through hepatitis B vaccination has been a major breakthrough in the management of this serious illness. There is a course of three injections. If there is a negative antibody response after 3 months, revaccinate with a double dose. If the response is positive, consider a test in 5 years with a view to a booster injection.

For non-immune patients at risk (e.g. after a needle-stick injury), hepatitis B immunoglobin (HBIg), which contains a high level of HBV surface antibody, is appropriate.

Prenatal screening of pregnant women and appropriate use of HBIg and HB vaccine is useful in preventing perinatal vertical transmission of HBV.

Hepatitis C^5,9,11,12

Hepatitis C virus is responsible for most cases of viral hepatitis in Australia. It is primarily contracted from intravenous drug use or tattooing. It does not seem to be spread very readily by sexual contact although there is a small risk during heterosexual and homosexual intercourse. It is also not readily spread perinatally.

Clinical symptoms of hepatitis C are usually minimal (often asymptomatic), and the diagnosis is often made after LFTs are found to be abnormal. An important feature is that there are at least six major genotypes of HCV and treatment decisions are based on the genotype; thus, patients with acute hepatitis C should have HCV genotype testing.

Hepatitis C infection may be self-limiting, but more commonly (in about 70% of cases) causes a slow, relentless progression to chronic hepatitis, cirrhosis (20%) and also hepatoma.⁷ See FIGURE 58.6. The severity of hepatic fibrosis can be assessed by liver biopsy or, preferably, by a non-invasive device called a FibroScan that assesses ‘hardness or stiffness’ of the liver via the technique of transient elastography. A raised ALT level that is tested three times over the next 6 months implies disease activity. HCV RNA (a PCR test) is present when the ALT becomes abnormal while the anti-HCV rises more slowly and may not be detectable for several weeks. If the PCR test is negative, the hepatitis C infection has resolved.

Diagnosis and progress

This is by serology:

• HCV Ab (anti-HCV) +ve = exposure (current or past)

• $HCV-RNA+ve=chronic viraemia−ve=spontaneous clearance$

• CD₄/HCV = viral load

• ALTs on LFTs indicate disease activity (tested 3 times over next 6 months)

  ALT persistently normal = good prognosis

  ALT ↑ ↑ = requires referral for treatment

• If PCR +ve + significant viral load + ALT ↑ perform HCV genotype—determines treatment

• PCR −ve, ALT −ve = infection clear

Treatment^5,12

The current standard treatment for chronic hepatitis C is direct-acting antivirals (DAAs) taken daily by mouth. These agents are now supplanting interferonbased therapy. The determination of genotype and viral load, as well as hepatic status, will identify those most likely to respond to therapy.

Examples of DAAs are:

• protease inhibitors, e.g. simeprevir

• nucleotide polymerase inhibitors, e.g. sofosbuvir

• non-nucleotide inhibitors, e.g. dasabuvir

• NS5A inhibitors, e.g. daclatasvir, ledipasvir

These agents are given in combination according to the genotype. Cure rates are in the order of 95%. Treatment can be managed within general practice, in collaboration with a specialist gastroenterologist.¹³

The recommended steps for pretreatment assessment are:^13,14

1. Confirm the diagnosis of chronic HCV infection.

2. Test for hepatitis C virus genotype and viral load.

3. Document the HCV treatment history.

4. Evaluate comorbidity and liver status, especially cirrhosis (refer if present), FBE, APRI, LFTs, blood glucose, creatinine U and E, HIV, HBV.

5. Discuss contraception and pregnancy (if applicable).

6. Consider concomitant medication.

7. Assess adherence to treatment.

8. Select treatment regimen (8 or 12 weeks) and review potential drug interactions.

9. Consult with a specialist.

10. Treat and monitor.

Cure is defined as undetectable plasma HCV RNA at least 12 months after treatment.

Those at increased risk of having hepatitis B and C

• Blood transfusion recipients (prior to HBV and HCV testing)

• Intravenous drug users (past or present)

• MSM who have practised unsafe sex

• Kidney dialysis patients

• Sex industry workers

• Those with abnormal LFTs with no obvious cause

• Tattooed people/body piercing

Prevention of transmission of hepatitis B and C viruses

Advice to those who are positive for HCV:

• Do not donate blood or any body organs or tissues.

• Do not share needles.

• Advise health care workers, including your dentist.

• Do not share intimate equipment such as toothbrushes, razors, nail files and nail scissors.

• Wipe up blood spills in the home with household bleach.

• Cover up cuts or wounds with an adequate dressing.

• Dispose of bloodstained tissues, sanitary napkins and other dressings safely.

• Use safe sex practices such as condoms.

• Avoid tattooing.

Hepatitis D

Hepatitis D is a small defective virus that lacks a surface coat. This is provided by hepatitis B virus, and so hepatitis D infection occurs only in patients with concomitant hepatitis B.

It is usually spread parenterally and if chronic is usually associated with progressive disease with a poor prognosis. Treatment with interferon has a variable success rate. Antibodies to the delta virus, both anti-HDV and anti-HDV IgM (indicating a recent infection) as well as HDV Ag can be measured.¹⁵ Referral to a specialist is recommended.

Hepatitis E

Hepatitis E is an enterically transmitted virus that occurs in outbreaks in certain countries with a poor water supply, such as some Asian subcontinent countries. Epidemiologically, HEV behaves like HAV, with well-documented water-borne epidemics in areas of poor sanitation. There is a high case fatality rate in endemic areas (10–20%) and in pregnant females.

Hepatitis F

Researchers claim to have identified HGF virus, which is spread enterically.¹⁶ Treatment can be comfortably managed within general practice.

Hepatitis G

HGV has been identified as a transfusion-spread virus. It has subsequently been found to be prevalent among Queensland blood donors.^10,17

Cholestatic jaundice

Cholestasis refers to the syndrome of biliary obstructive jaundice whereby there is obstruction to the flow of bile from the hepatocyte to the duodenum, thus causing bilirubin to accumulate in the blood. It is classified into two main groups:

• intrahepatic cholestasis—at the hepatocyte or intrahepatic biliary tree level

• extrahepatic cholestasis—obstruction in the large bile ducts by stones or bile sludge

The significant causes are listed in TABLE 58.8.

Symptoms

• Jaundice (greenish tinge)

• Dark urine and pale stools

• Pruritus—worse on palms and soles

• Pain varies from nil to severe

Gallstones and jaundice

Gallstones can be found in the following (see FIG. 58.7):

• gall bladder (asymptomatic up to 75%)—the majority remain here

• neck of gall bladder (biliary ‘colic’ or acute cholecystitis)

• cystic duct (biliary ‘colic’ or acute cholecystitis)

• common bile duct—may cause severe biliary ‘colic’, cholestatic jaundice or cholangitis

Acute cholecystitis is accompanied by mild jaundice in 25% of cases, due to accompanying common duct stones.¹⁵

Common bile duct stones may be asymptomatic or may present with any one or all of the triad of abdominal pain, jaundice and fever. The jaundice varies, depending on the amount of obstruction. The liver is moderately enlarged if the obstruction lasts for more than a few hours.

The investigations of choice for cholestatic jaundice are ultrasound and ERCP.

Acute cholangitis

This is due to bacterial infection of the bile ducts secondary to abnormalities of the bile duct, especially gallstones in the common duct. Other causes are neoplasms and biliary strictures.

Charcot triad (present in 70%) is shown in the diagnosis box.

Older patients can present with circulatory collapse and Gram-negative septicaemia. Urgent referral is necessary.

Carcinoma of head of the pancreas

Pancreatic cancer is the fourth commonest cause of cancer death in the UK and US.¹⁵

Clinical features

• M > F

• Mainly >60 years of age

• Obstructive jaundice

• Pain (over 75%)—epigastric and back

• Enlarged gall bladder (50–75%)

• Weight loss, malaise, diarrhoea

• Migratory thrombophlebitis

• Palpable hard, fixed mass

• Metastases (e.g. left supraclavicular gland of Virchow—Troisier sign)

• Occult blood in stool

• Glycosuria

Diagnosis

• Scanning by ultrasound or CT scan may show mass

• ERCP

Prognosis

Prognosis is very poor: 5-year survival is 5%.

Cirrhosis of the liver

Cirrhosis is accompanied by jaundice as a late and serious manifestation with the exception of primary biliary cirrhosis, where jaundice appears before advanced liver failure. The development of jaundice usually indicates that there is minimal hepatic reserve and is therefore found in conjunction with other signs of liver failure (see FIG. 58.8).

Causes

Common:

• alcohol excess

• chronic viral hepatitis (esp. HBV, HCV)

  Others:

• autoimmune chronic active hepatitis

• primary biliary cirrhosis (autoimmune)

• haemochromatosis

• Wilson disease

• drugs (e.g. methotrexate)

• cryptogenic (no cause found)

Clinical features

• Anorexia, nausea ± vomiting

• Swelling of legs

• Abdominal distension

• Bleeding tendency

• Drowsiness, confusion or coma (if liver failure)

Signs

• Spider naevi (distribution of superior vena cava)

• Palmar erythema of hands

• Peripheral oedema and ascites

• Jaundice (obstructive or hepatocellular)

• Enlarged tender liver (small liver in long-term cirrhosis)

• Ascites

• Gynaecomastia

• ± Splenomegaly (portal hypertension)

Complications

• Ascites

• Portal hypertension and GIT haemorrhage

• Portosystemic encephalopathy

• Hepatoma

• Kidney failure

Autoimmune chronic active hepatitis (ACAH)⁵

Also termed idiopathic ACAH, this usually affects young females (10–40 years) who present insidiously with progressive fatigue, anorexia and jaundice. Diagnosis is made by abnormal LFTs (which should raise suspicion), positive smooth muscle antibodies, a variety of other autoantibodies and a typical liver biopsy. If untreated, most patients die within 3–5 years. Treatment is with prednisolone orally, monitored according to serum alanine aminotransferase levels, and supplemented with azathioprine or mercaptopurine. About 80% respond, while 20% develop chronic liver disease. Specialist referral is advisable.

Primary sclerosing cholangitis⁵

This uncommon inflammatory disorder of the biliary tract presents with progressive jaundice and other features of cholestasis such as pruritus. It is often associated with ulcerative colitis. Diagnosis is based on characteristic cholangiopancreatography findings. There is no specific therapy, but refer for possible ERCP. Ursodeoxycholic acid may benefit some patients. Patients have an increased risk of colorectal cancer.

Primary biliary cirrhosis⁵

This is an uncommon cause of chronic liver disease that often presents with pruritis, malaise and an obstructive pattern of liver biochemistry. Found mainly in women. Treatment is with ursodeoxycholic acid orally.

Alcoholic liver disease

The main effects of alcohol excess on the liver are:

• acute alcoholic liver disease

• fatty liver

• alcoholic hepatitis (progresses to cirrhosis if alcohol consumption continues)

• alcoholic cirrhosis

If diagnosed, patients are advised to stop drinking alcohol for life except for fatty liver when small amounts can be drunk later.

Fatty liver

Alcohol can cause hepatic steatosis (fatty liver), which is almost universal in obese alcoholics. Non-alcoholic causes include obesity, diabetes mellitus, hypertriglyceridaemia and corticosteroids. A significant number with this very common condition (one in five Australians) will develop cirrhosis. Fatty liver is usually asymptomatic but some complain of malaise and tiredness. Serology is unhelpful. Diagnosis is by liver biopsy and perhaps CT scan. The treatment is weight loss through diet, which improves liver function and reduces fatty deposits.

Haemochromatosis

See CHAPTER 18.

The returned overseas traveller

The overseas traveller presenting with jaundice may have been infected by any one of the viruses—hepatitis A, B, C, D or E. All are prevalent in developing countries, especially in south-eastern and eastern Asia, some Pacific islands and Africa.

Other causes to consider are malaria, ascending cholangitis and drug-induced hepatic damage due to, for example, the antimalarials, including mefloquine (Lariam) and Fansidar. Refer to CHAPTERS 14 and 15.

The pregnant patient

Important hepatic disorders in pregnancy leading to jaundice are intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy and severe pre-eclampsia. Delivery is advisable at 37–38 weeks.

Postoperative jaundice

There are many possible causes of postoperative jaundice either in the immediate or the long-term postoperative phase. Hypoxia associated with shock in a severely ill patient or in a patient with cardiopulmonary disease may lead to transient abnormalities in liver function. Other causes include:

• post-transfusion hepatitis

• coincident viral hepatitis

• drugs, including anaesthetics

• transfusion overload (haemolysis)

• sepsis

• unmasked chronic liver disease and biliary tract disease

• cholestasis: post major abdominal surgery

Neonates of HBeAg positive mothers

The neonates should have the following (see CHAPTER 109):

• hepatitis B immunoglobulin IM within 24 hours of birth

• hepatitis B vaccine at birth, 1 month and 6 months

This is not 100% effective because some infants can be infected in utero.

• All patients with fulminant hepatitis

• All patients with chronic liver disease

• Painless obstructive jaundice

• Evidence of malignancy

• Symptomatic gallstones

• Patients with cirrhosis

• Acute fatty liver of pregnancy (very urgent)

• Suspected rare conditions (e.g. Wilson syndrome)

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• Gallstones

• Hepatitis A

• Hepatitis B

• Hepatitis C