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.

Keywords: Autoimmune hepatitis; Case report; Hepatitis A virus; Primary biliary cholangitis.

Figure 1

Time course of liver function tests and anti-hepatitis A virus immunoglobulin M, autoantibodies, immunoglobulin levels. Total bilirubin: Upper limit of normal (ULN) < 28 μmol/L, aspartate aminotransferase ULN < 40 IU/L, alanine aminotransferase ULN < 45 IU/L, γ-glutamyl transferase ULN < 50 IU/L, alkaline phosphatase ULN < 105 IU/L. ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; ANA: Antinuclear antibody; ASMA: Anti-smooth muscle antibodies; AST: Aspartate aminotransferase; GGT: γ-glutamyl transferase; HAV: Hepatitis A virus; IgG: Immunoglobulin G; IgM: Immunoglobulin M; LKM 1: Anti-liver kidney microsome type 1.

Figure 2

Hematoxylin-eosin staining. A: Liver biopsy tissue shows chronic hepatitis with moderate interface hepatitis accompanied by plasma cell infiltration (hematoxylin-eosin staining; magnification: × 200); B: Image of the box shown in A at 2 × magnification. Showing plasma cell infiltration (white arrow) and bile duct lesions (black arrow).