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

Abstract

BACKGROUND Autoimmune hepatitis (AIH) is an immune-mediated liver disease affecting all age groups. Associations between hepatitis A virus (HAV) and AIH have been described for many years. Herein, we report a case of an AIH/primary biliary cholangitis (PBC) overlap syndrome with anti-HAV immunoglobulin M (IgM) false positivity. CASE SUMMARY A 55-year-old man was admitted with manifestations of anorexia and jaundice along with weakness. He had marked transaminitis and hyperbilirubinemia. Viral serology was positive for HAV IgM and negative for others. Autoantibody screening was positive for anti-mitochondria antibody but negative for others. Abdominal ultrasound imaging was normal. He was diagnosed with acute hepatitis A. After symptomatic treatment, liver function tests gradually recovered. Several months later, his anti-HAV IgM positivity persisted and transaminase and bilirubin levels were also more than 10 times above of the upper limit of normal. Liver histology was prominent, and HAV RNA was negative. Therefore, AIH/primary biliary cholangitis (PBC) overlap syndrome diagnosis was made based on the “Paris Criteria”. The patient was successfully treated by immunosuppression. CONCLUSION This case highlights that autoimmune diseases or chronic or acute infections, may cause a false-positive anti-HAV IgM result because of cross-reacting antibodies. Therefore, the detection of IgM should not be the only method for the diagnosis of acute HAV infection. HAV nucleic acid amplification tests should be employed to confirm the diagnosis.

Hepatitis A: Viral Structure, Classification, Life Cycle, Clinical Symptoms, Diagnosis Error, and Vaccination

“…Therefore, detecting acute HAV infection exclusively by anti-HAV IgM is insufficient. HAV nucleic acid studies could be conducted more widely, especially in individuals with lower cutoff values for anti-HAV IgM [ 91 ].…”

Recent advances in hepatitis A virus research and clinical practice guidelines for hepatitis A virus infection in Japan

“…50 It should be noted that autoimmune diseases or infectious diseases may lead to a false positive anti-HAV IgM result because of cross-reacting antibodies. 70 A specific and sensitive automated chemiluminescent immunoassay or chemiluminescent enzyme immunoassay for anti-HAV IgM is available in Japan. 8,71 Detection of HAV RNA in feces and sera As HAV is an RNA virus, detection of HAV RNA in feces and sera from patients with hepatitis A by reverse transcription polymerase chain reaction (RT-PCR) methods is useful for early diagnosis and a better understanding of its pathogenesis.…”

“…80 Measurement of HAV RNA is an important tool in certain cases. 70,[82][83][84] Determination of HAV genotype At least six genotypes (I to VI) exist, although there is only one serotype of HAV. [85][86][87] HAV genotypes I, II, and III infect humans, and at least six subgenotypes (IA, IB, IIA, IIB, IIIA, and IIIB) exist.…”

“…Therefore, when hepatitis A is suspected with a negative result for anti‐HAV IgM, anti‐HAV IgM antibodies should be repeatedly examined at >7 days after the first examination to rule out the possibility of a seronegative window of HAV infection 50 . It should be noted that autoimmune diseases or infectious diseases may lead to a false positive anti‐HAV IgM result because of cross‐reacting antibodies 70 . A specific and sensitive automated chemiluminescent immunoassay or chemiluminescent enzyme immunoassay for anti‐HAV IgM is available in Japan 8,71 …”

(Seltene) infektiöse Hepatitiden als wichtige Differenzialdiagnose der unklaren Hepatopathie

“…Ein Fallbericht aus China zeigte, dass wohl kreuzreagierende Antikörper im Rahmen eines Overlapsyndroms von Autoimmunhepatitis und primär biliärer Cholangitis in seltenen Fällen für einen falsch positiven Nachweis von Anti-HAV-IgM verantwortlich sein können, sodass ggf. dann doch die parallel vorliegende Leberbiopsie wichtige Hinweise zur Ätiologie liefern kann [ 33 ], wobei bei Plasmazellreichtum histologisch auch die Differenzialdiagnose einer Autoimmunhepatitis in Betracht kommen kann.…”