Saturday, 2 November 2019

Hepatitis A

Hepatitis A

Hepatitis A is a highly infectious disease with worldwide distribution, which therefore spreads easily among children. Many cases are subclinical; others cause moderate morbidity. Overall mortality is less than 0.1%, but about 1% of hospital admissions with hepatitis A suffer severe or life-threatening disease.


In conditions of poor hygiene and sanitation, most infections occur in childhood and are mild or asymptomatic. Immunity is lifelong and outbreaks in adults are uncommon. In high-income countries, infection in children is less usual and infection occurs more commonly in adults, in whom it is more likely to be symptomatic. Three patterns of disease are then seen:

• sporadic infections among adult travellers to endemic countries;
• epidemics affecting mainly school-age children; and
• explosive common-source outbreaks.

Epidemics of hepatitis A tend to evolve slowly, last for several months and affect large geographical areas. Spread is from person to person, mainly by the faecal-oral route, occurring within households, nurseries, schools and other institutions.
Common-source outbreaks are usually associated with food contaminated by an infected handler, or with undercooked shellfish harvested from contaminated waters. Soft fruits have been associated with outbreaks, and water-borne outbreaks occur occasionally.

Virology and pathogenesis of hepatitis A

Hepatitis A virus (HAV) is a hepadnavirus in the family Picornaviridae. It is a small RNA virus, 27 nm in diameter with a single-stranded, approximately 7.5 kb genome of positive-sense RNA. A single polypeptide is synthesized and cleaved by viral proteases. The virus particle is more stable to heat, detergents and proteases than the other picornaviruses and this may explain the ease with which it is transmitted. The virus particle consists of four capsid polypeptides VP1–4. There are only one major serotype and four subtypes defined on the basis of the sequence of the VP1/2 junction.

The virus appears not to be cytopathic. Hepatic damage occurs after the feverish stage of illness and is probably immunologically mediated. Neutralizing antibodies are directed against groups of closely clustered epitopes on the virus surface. Humans are the only natural host, but the virus has been adapted by serial passage to grow in a wide range of primate cells.

Clinical features

The incubation period of 15–45 days is followed by malaise, nausea, lassitude, myalgia, arthralgia and variable fever. The intestinal mucosa is inflamed at this stage: sugar absorption tests are abnormal and children, particularly, may have loose stools. Viruses are excreted in the stools and urine. Features of hepatitis gradually appear after 2–7 days. The urine darkens as bilirubinuria increases, and the stools may be noticeably pale. Jaundice is first seen in the sclerae and later in the skin.

Fever resolves and virus excretion ceases as jaundice develops. Patients are now no longer infectious, and most patients feel better. After 7–10 days the appetite returns and jaundice begins to resolve. During the prodrome, the white cell count is normal, with a few atypical mononuclear cells. As the prodrome ends, rising plasma transaminases indicate hepatocellular damage, and conjugated bilirubin appears in blood and urine. The early transaminase levels are often 2000–7000 IU but these falls rapidly in most cases and are often below 100 IU after 7–10 days.

Cholestasis, with a rise in alkaline phosphatase to 250– 400 IU, is common during convalescence. Abnormality of bile-salt excretion may then cause itching. Occasion- ally cholestasis is severe and prolonged, with deepening jaundice and severe pruritus, persisting for months if untreated. This is a post-infectious event, not associated with viral replication.


The history of malaise followed by jaundice, and the absence of risk factors for blood-borne hepatitides is highly suggestive. Prolonged vomiting in an otherwise well child can occur in anicteric hepatitis. Laboratory investigations should include tests to exclude hepatitis B and C, and E where appropriate (see pp. 207–214).

Glucose-6-phosphate dehydrogenase deficiency can cause haemolysis and clinical jaundice, often following a viral infection, ingestion of proprietary antipyretic drugs or eating beans (favism). Spherocytosis, sickling conditions, and ovalocytosis may also cause haemolytic episodes. In travellers, malaria is a common cause of haemolysis, usually accompanied by significant fever.

Haemolytic jaundice is acholuric (not accompanied by bilirubinuria); urinalysis, therefore, shows normal bilirubin levels and raised urobilinogen. Persisting fever in viral hepatitis is unusual once jaundice has developed. In febrile hepatitis, Epstein–Barr virus (EBV) infection, or leptospirosis, may need to be excluded. Malaria must be excluded from tropical travellers. Acute cholecystitis presents with fever, right hypochondrial pain and often jaundice (see below). Gallstones may cause pain and obstructive jaundice. Painless cholestatic jaundice is a common feature of biliary or pancreatic carcinoma, which should be considered in all middleaged or elderly patients. Elevated alkaline phosphatase is a useful warning sign of obstructive or cholestatic pathology. Some drugs cause hepatocellular damage. Alcohol is the most common, but paracetamol toxicity is important. History of paracetamol ingestion should be sought in jaundiced patients.

Differential diagnosis of viral hepatitis

1 Other infections: Epstein–Barr virus infections, cytomegalovirus, leptospirosis.
2 Infections of the biliary system: acute cholecystitis, acute cholangitis, acute pancreatitis.
3 Obstructive jaundice: gallstones, tumours of the pancreaticobiliary system.
4 Haemolysis, e.g. glucose-6-phosphate dehydrogenase deficiency, malaria.
5 Drug jaundice, e.g. alcohol and paracetamol (hepatocellular), phenothiazines (cholestatic).



There is no specific antiviral treatment. Symptomatic treatment with mild analgesics and antiemetics improves prodromal symptoms. Antipruritic drugs may be helpful in convalescence, but cholestyramine is more effective for severe pruritus, as it interrupts enterohepatic recirculation of bile salts. There is little evidence that bed rest shortens the illness or prevents complications.

Prolonged severe cholestasis after hepatitis A responds to corticosteroid treatment. Initial dosage with prednisolone 30–40 mg/day can be reduced over 2–4 weeks depending on the clinical and biochemical response.



Liver failure is the most common complication. It may be fulminant and early, presenting with altered consciousness before jaundice develops, or subacute and progressive, with inexorable deterioration in liver function and deepening of jaundice. The prognosis is best in patients suffering rapid-onset liver failure and worst in those with insidious onsets.

Clinical indicators of liver failure are persistent vomiting, disturbed behaviour, flapping tremor of the outstretched hands and increasing drowsiness. The poor cerebral function is classically demonstrated by showing the patient’s inability to copy a drawing of a five-pointed star, although able to copy a square (constructional apraxia).

Biochemical warning signs are the disappearance of blood constituents synthesized by the liver: glucose, clotting factors and urea (albumin has a longer half-life and declines later). Transaminase levels may not accurately reflect hepatocellular damage as they decline with extensive cell death; initial levels above 7000 IU/l may predict severe hepatocellular damage. In a hepatic coma, the electroencephalogram shows characteristic 3/s slow-wave patterns. A blood pH of <7.3 or prothrombin time of >100 s is an indication for urgent referral to consider early liver transplantation.

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