SeminarHepatitis A
Section snippets
Virology
The hepatitis A virus (HAV) is a small, non-enveloped, spherical particle with cubic symmetry (panel). The virus is thermostable and acid-resistant. For some time after its identification, HAV was thought to be an enterovirus; in 1991, it was subclassified into its own unique genus (hepatovirus).1 Only one human HAV serotype has been identified. The four human genotypes that have been identified are stable2 and can be used to trace transmission. HAV vaccine prepared from any human HAV genotype
Epidemiology
The incubation period of hepatitis A is 15–50 days, with a mean of about 30 days. HAV is excreted in the faeces for 1–2 weeks before the onset of illness, and for at least 1 week afterwards. Viral shedding is greatest at the onset of symptoms and then declines rapidly. Faecal excretion for several months has been reported in a few infected neonates and adults, measured by highly sensitive techniques,9 but the epidemiological importance of this finding remains uncertain. HAV RNA can also be
Immunopathogenesis and immunity
As is the case for most of the identified human hepatitis viruses, a direct cytopathic effect for HAV is unknown. HAV replication and hepatocyte injury seem to be dissociated. Although circulating immune complexes are commonly found in hepatitis A,21 there is no direct evidence that they play a part in the induction of hepatocyte necrosis or in viral clearance. Cell-mediated immune mechanisms are thought to bring about the necroinflammatory lesions of hepatitis A; CD8 T lymphocytes and natural
Serological diagnosis
Hepatitis A is differentiated from the other forms of acute viral hepatitis by serological testing. Diagnosis depends on finding IgM antibody to HAV during the acute phase of the illness. IgM antibody persists for 3–6 months afterwards, and is seldom found after vaccination. Patients with asymptomatic hepatitis A may have detectable IgM anti-HAV for a shorter period than patients with symptomatic disease. Positive serum tests for anti-HAV without IgM anti-HAV indicate the presence of IgG
Clinical and laboratory features
Hepatitis A may begin with the abrupt onset of nonspecific prodromal constitutional and gastrointestinal symptoms. These include variable combinations of fever, malaise, weakness, anorexia, nausea and vomiting, arthralgias, and myalgias. Flu-like symptoms of pharyngitis, cough, coryza, photophobia, and headache may be present in children with symptomatic infection. Prodromal symptoms tend to abate with onset of jaundice, although the anorexia, malaise, and weakness may persist or increase
Treatment
Most patients can be treated at home, unless persistent vomiting or severe anorexia lead to dehydration. There are no specific dietary recommendations with the exception of a prohibition of alcohol during the acute phase. Vigorous or prolonged physical activity is best avoided. The need for rest is best determined by the patient's own perception of the severity of fatigue or malaise. Most patients show complete clinical and biochemical recovery within 3–6 months of the onset of illness.
Acute liver failure
Acute liver failure is heralded by worsening liver chemistry, change in mental state, and striking coagulopathy. Early signs include lethargy or irritability, accompanied by lengthening of the prothrombin time. Pronounced increases in serum bilirubin and aminotransferases are common, but the latter may decline towards normal despite disease progression. Cerebral oedema (usually without papilloedema) and multiple organ failure lead to death in 70–95% of patients. Survival rates of 65% or greater
Prophylaxis with immunoglobulin
Passive immunisation with human immunoglobulin containing IgG anti-HAV had been the mainstay of prophylaxis for about 50 years, well before the protective antibody could be serologically identified and before HAV vaccines were available. Immunoglobulin and HAV vaccines are compared in table 1. Low blood concentrations of anti-HAV produced by intramuscular injection of immunoglobulin provide pre-exposure protection against clinical disease in a substantial proportion of recipients.
Live, attenuated HAV vaccine
An inexpensive, live, attenuated vaccine would be especially useful in economically developing countries. Such vaccines have been produced in China, and millions of Chinese may have been immunised. Little information is currently available about these preparations. The H2-strain vaccine does not induce seroconversion if given orally, but nearly all of the individuals given the vaccine subcutaneously developed antibodies.25 Seronegative contacts of individuals who were subcutaneously vaccinated
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