Multiple Factors Contribute to Positive Results for Hepatitis A Virus Immunoglobulin M Antibody

Abstract

Context.-In the United States, a successful vaccination program for hepatitis A virus (HAV) infection has decreased both its incidence and the true positive rate for diagnostic immunoglobulin M (IgM) antibody to HAV in acute hepatitis.Objective.-To survey positive results of HAV IgM tests and determine the effect of changing ordering options.Design 1 Since the introduction of a safe and effective vaccine and its widespread adoption, the actual number of cases has decreased to approximately 10% of the peak level.2 Of paramount importance, any bona fide new diagnosis of acute hepatitis A has public health implications. Cases are reported to the local health departments to identify a possible common source of infection and provide postexposure prophylaxis to contacts of the index patient.Testing for immunoglobulin (Ig) M antibodies against HAV (IgM anti-HAV) is the mainstay of the serologic diagnosis for acute hepatitis A infection and has been highly sensitive and specific.3-5 The presence of any detectable antibody (total anti-HAV) plus the absence of high-titer IgM-specific antibodies is used to differentiate between past and current infection. In the past few years, isolated reports have documented an increase in the number of positive results for IgM anti-HAV in patients whose illnesses were not consistent with the case definition of hepatitis A in conjunction with the decrease in true incidence. [6][7][8] We conducted a retrospective study to determine how commonly we may be encountering potential false-positive results after noticing the occurrence of positive IgM anti-HAV test results in the absence of clinical findings suggesting acute viral hepatitis. We explored possible underlying reasons and the effect of changing ordering options. MATERIALS AND METHODSAn institutional review board approved a retrospective medical record analysis for all patients with positive results for IgM anti-HAV antibodies between January 2007 and December 2010. Patients were identified by querying the laboratory information system (Cerner Millennium, Cerner Corporation, Kansas City, Missouri) to generate the list of samples and order type (individual test or group) associated with positive results. Results from internal and external quality control assessments were excluded. Data CollectionPatient demographics, clinical history, and laboratory data were obtained through review of electronic and paper medical records. Patient age, sex, and race/ethnicity were recorded for each patient. Laboratory data included test results for bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), all viral hepatitis serologic assays, rheumatoid factor, and human immunodeficiency virus antibody at the time of diagnosis. Test OrderingTest order information was obtained from the electronic medical record and from review of paper medical records. The ordering

A Rare Presentation of Hepatitis A Infection with Extrahepatic Manifestations

“…A positive test is considered false positive in a patient without clinical criteria, which can be varied from mild prodromal symptoms to fulminant hepatitis with or without extrahepatic manifestations [25]. False positive IgM tests have been reported with concomitant viral illnesses or a positive rheumatoid factor [26]. It may indicate hepatitis A virus exposure or dormant viral infection [25].…”

Immunoglobulin M for Acute Infection: True or False?

“…Of approximately 2,000 samples tested annually, only 5 or 6 have been IgM positive, and of these, only 40% have represented true cases of acute hepatitis A. The poor positive predictive value of HAV IgM reflects inappropriate testing of patients who do not have acute hepatitis and the low prevalence of HAV disease (21,22). The true positives represent values that are usually 9 to 10 times the cutoff in acute HAV.…”

False positive anti-hepatitis A virus immunoglobulin M in autoimmune hepatitis/primary biliary cholangitis overlap syndrome: A case report

“…The diagnosis of acute hepatitis A primarily involves serological testing of anti-HAV IgM, which is highly specific and sensitive without testing for the pathogen itself. However, other factors can result in anti-HAV IgM seropositivity in the clinical evaluation[ 7 ], potentially leading to an incorrect diagnosis of acute hepatitis A. A Hep A false-positive result might also be caused by the cross-reaction of antibodies in individuals with autoimmune diseases or chronic or acute infections.…”