Does the presence of Hepatitis A (HA) antibody Immunoglobulin M (IgM) determine immunity?

From the Guidelines

Hepatitis A antibody IgM does not determine immunity, but rather indicates a current or recent hepatitis A virus (HAV) infection. IgM antibodies appear early in the infection process, typically within 2-4 weeks after exposure, and generally disappear within 3-6 months 1. To determine immunity to hepatitis A, testing for hepatitis A total antibodies or specifically IgG antibodies is more appropriate. The presence of IgG antibodies indicates either past infection or successful vaccination, both of which confer long-term immunity against the virus 1.

Some key points to consider:

• IgM antibodies are used to diagnose acute infection, while IgG antibodies are used to confirm immunity status 1
• IgG anti-HAV, which appears early in the course of infection, remains detectable for the person's lifetime and provides lifelong protection against the disease 1
• Testing for total anti-HAV is used in epidemiologic studies to measure the prevalence of previous infection or by clinicians to determine whether a person with an indication for pre-exposure prophylaxis is already immune 1
• The decision to test for immunity should be based on the expected prevalence of immunity, the cost of vaccination compared with the cost of serologic testing, and the likelihood that testing will not interfere with initiation of vaccination 1

In clinical practice, distinguishing between IgM and IgG antibodies is crucial for making informed decisions about patient care and management. Finding IgM antibodies suggests active infection requiring monitoring and supportive care, while IgG antibodies without IgM indicate protective immunity without current infection. Healthcare providers use these different antibody tests for distinct purposes - IgM for diagnosing acute infection and IgG for confirming immunity status 1.

From the FDA Drug Label

The presence of antibodies to HAV confers protection against hepatitis A infection. However, the lowest titer needed to confer protection has not been determined.

The hepatitis A antibody IgM does not directly determine immunity. Immunity is conferred by the presence of antibodies to HAV, but the specific role of IgM in determining immunity is not explicitly stated in the drug label.

• The drug label does mention that antibodies to HAV confer protection, but it does not specify how IgM relates to this protection.
• It also mentions that the lowest titer needed to confer protection has not been determined, which suggests that the relationship between antibody levels and immunity is not fully understood 2.

From the Research

Hepatitis A Antibody IgM and Immunity

• The presence of hepatitis A IgM antibody (IgM anti-HAV) is an accepted marker of acute viral hepatitis A infection 3.
• However, the persistence of IgM anti-HAV can vary significantly among individuals, with some patients becoming seronegative early in the disease course while others remain positive for prolonged periods greater than 200 days 3.
• The diagnosis of acute hepatitis A virus (HAV) infection is based on the detection of HAV immunoglobulin M (IgM), but IgM could be detected due to nonspecific polyclonal activation of the immune system 4.
• An avidity test for anti-HAV IgG was developed to distinguish acute infection, where low-avidity antibodies are detected, from immune reactivation 4.
• The window period of anti-hepatitis A virus immunoglobulin M antibodies in diagnosing acute hepatitis A can lead to negative serology at initial presentation, complicating the diagnosis of hepatitis A 5.
• Repeat testing for anti-HAV IgM is recommended, particularly in patients with features of the initial phase of hepatitis and a high cutoff index (COI) value of anti-HAV IgM 5.
• The appearance and persistence of hepatitis A IgM antibody in acute clinical hepatitis A can vary, with levels peaking two to four weeks after onset and declining gradually thereafter 6.
• The probability of IgM anti-HAV positivity decreases over time, with 25% positivity at the end of the sixth month and 3.4% at the end of the ninth month after onset 6.

Factors Influencing IgM Anti-HAV Results

• Multiple factors can contribute to positive results for hepatitis A virus immunoglobulin M antibody, including recent, resolved, or indeterminate HAV infection 7.
• Current assays for IgM HAV antibodies may be overused in the absence of clinical acute hepatitis, and future clinical decision support may improve patterns of order entry 7.
• Dormant viral infection may be a continuing source of antigen, leading to positive IgM HAV antibody test results 7.

Clinical Implications

• Awareness of the marked variability in the persistence of IgM anti-HAV is important in the interpretation of IgM anti-HAV as a serologic marker of recent hepatitis A infection 3.
• The timing of the assay and the level of IgM anti-HAV should be considered in the etiological diagnosis of acute hepatitis 6.