Hepatitis A virus (HAV)

Hepatitis A virus (HAV) was originally called “infectious hepatitis” or “short-incubation hepatitis,” and has an incubation period of 3-4 weeks (range, 2-6.5 weeks). HAV is highly contagious. During active infection it is excreted in the stool and is usually transmitted via fecal contamination of water or food. However, infection by fecal contamination can also spread from person to person. Although urine and saliva are less infectious than stool, they can transmit HAV infection. The greatest quantity of virus excretion in stool occurs before clinical symptoms develop, although much lower levels of excretion may occur for a few days after onset of clinical illness. Clinical illness is usually not severe, and fatality is rare. However, cases of severe HAV hepatitis with a high fatality rate have been reported. There usually is complete recovery in 1-3 weeks and no carrier state. Occasional patients may have more prolonged illness, lasting as long as a year. One report indicates that 8%-10% of cases have a fluctuating clinical and laboratory test course, sometimes for as long as 12-15 months.

There is increased incidence of HAV infection in children, and epidemics occur within institutions for mentally retarded children, day-care centers, and orphanages. These children frequently infect institution staff, and day-care patients infect parents and other household contacts. Occasional epidemics are confined to adults, usually associated with eating contaminated food or shellfish from contaminated water. About 40%-50% (range, 30%-60%) of adults in the United States who have been tested have antibody against HAV; in some “third world” countries, this may be as high as 90%-100%. More than 50% of acute HAV infections are subclinical (“anicteric hepatitis”), including almost all infants, 75% of children less than 2 years old, and 60% of those 4-6 years old. In adults, only about 10% are asymptomatic (range, 0-60%).

Tests for HAV infection

At present, serologic tests are not available to detect HAV antigen. Electron microscopy (EM) can detect HAV virus in stool as early as 1-2 weeks after exposure; this period ends about 1-4 days after onset of symptoms (range, 1 week before to 2 weeks after symptoms). Virus in stool is not detectable on admission in 40%-65% of patients. Presence of HAV in blood terminates just before or at the beginning of symptoms, too late to be detected in most patients.

Antibody testing currently is the best method for diagnosis. Both RIA and ELISA methods have been used. Tests for HAV antigen are not yet commercially available. When they do become available, the major problem will be the disappearance of antigen before or shortly after onset of clinical symptoms. Two types of antibody to HAV antigen are produced. One is a macroglobulin (IgM), which appears about 3-4 weeks after exposure (range, 15-60 days), or just before the beginning of the AST increase (range, 10 days before to 7 days after the beginning of the AST increase). Peak values are reached approximately 1 week after the rise begins, with return to normal (nondetectable) in about 2 months (range, 1-5 months or 1-2 weeks after clinical symptoms subside to about 4 months after symptoms subside). However, in a few cases detectable IgM antibody has remained as long as 12-14 months. The second type of antibody is IgG, which appears about 2 weeks after the beginning of the IgM increase (between the middle stages of clinical symptoms and early convalescence), reaches a peak about 1-2 months after it begins to rise, and then slowly falls to lower titer levels, remaining detectable for more than 10 years (Fig. 17-2).

Serologic tests in HAV infection

Fig. 17-2 Serologic tests in HAV infection.

If the IgM antibody is elevated but the IgG antibody is not, this proves acute HAV infection. If the IgM antibody is nondetectable and the IgG antibody is elevated, this could mean residual elevation from old HAV infection or a recent infection in the convalescent stage. If clinical symptoms began less than 1 week before the specimen was obtained, an old HAV infection is more likely. If the test for IgM antibody is not done and the IgG antibody is elevated, this could mean either a recent infection or residual elevation from a previous infection. A rising titer is necessary to diagnose recent infection using the IgG antibody alone. If the test for IgM antibody is not done and the IgG test is nonreactive, it could mean either no infection by HAV or that the specimen was drawn before the IgG antibody titer began to rise. Whether another specimen should be drawn 2 weeks later to rule out a rising titer depends on the length of time that elapsed since clinical symptoms began or ended. Therefore, interpretation of HAV antibody test results depends on when the specimen was obtained relative to onset of clinical symptoms and which antibody or antibodies are being assayed.

HAV Antibodies

HAV-IgM ANTIBODY
Appearance

About the same time as clinical symptoms (3-4 weeks after exposure, range 14-60 days), or just before beginning of AST/ALT elevation (range, 10 days before 7 days after)

Peak

About 3-4 weeks after onset of symptoms (1-6 weeks)

Becomes nondetectable

3-4 months after onset of symptoms (1–6 months). In a few cases HAV-IgM antibody can persist as long as 12-14 months.

HAV-TOTAL ANTIBODY

Appearance

About 3 weeks after IgM becomes detectable (therefore, about the middle of clinical symptom period to early convalescence)

Peak

About 1-2 months after onset

Becomes nondetectable

Remains elevated for life, but can slowly fall somewhat

Summary
HEPATITIS A ANTIGEN AND ANTIBODIES

HAV-Ag by EM (in stool)

Shows presence of virus in stool early in infection

HAV-Ab (IgM)

Current or recent HAV infection

HAV-Ab (total)

Convalescent or old HAV infection

Summary: Diagnosis of HAV Infection

Best all-purpose test(s) to diagnose acute HAV infection = HAV-Ab (IgM)
Best all-purpose test(s) to demonstrate past HAV infection/immunity = HAV-Ab (Total)
(see also the box)