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Published on: May 29, 2020
Markedly Elevated CA 19-9 in ANA/ASMA-Negative IgG4-Related Autoimmune Hepatitis With Concomitant Pancreatitis: A
1Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA, clevelandclinic.org.
Background:
IgG4-related disease (IgG4-RD) can involve the liver and pancreas and may present without conventional autoimmune hepatitis (AIH) autoantibodies, creating diagnostic delay unless IgG4 testing and tissue immunostaining are pursued. We describe an older man with acute hepatocellular injury and marked hyperbilirubinemia who was negative for antinuclear (ANA) and antismooth muscle (ASMA) antibodies but had markedly elevated serum IgG4 and IgG4-positive plasma cell infiltration on liver biopsy, consistent with IgG4-related autoimmune hepatitis (IgG4-AIH).
Case Presentation:
A man in his 80s presented with abdominal pain followed by progressive jaundice and pruritus, with acute hepatocellular injury and hyperbilirubinemia. Evaluation showed negative ANA and ASMA, elevated total IgG (2166 mg/dL) and IgG4 (442.5 mg/dL), CA 19-9 1268 U/mL, and CT/MRCP findings consistent with pancreatitis without biliary obstruction or mass. HFE analysis showed compound heterozygosity. Liver biopsy demonstrated interface hepatitis with plasma cell-rich inflammation and increased IgG4-positive plasma cells (up to 58 per high-power field), supporting IgG4-AIH. Minimal iron deposition on biopsy favored inflammation-related iron study abnormalities rather than primary hemochromatosis. The pancreatic findings were most consistent with probable Type 1 autoimmune pancreatitis. Prednisone 40 mg daily led to improvement, with normalization of transaminases and total bilirubin by Day 57 (approximately 8 weeks) in available follow-up testing.
Conclusion:
IgG4-AIH is diagnostically challenging, particularly in seronegative presentations. Unexpectedly high CA 19-9 may be seen in IgG4-RD, which may mimic malignancy. In atypical presentations such as those occurring in older adults without conventional antibody positivity or with concurrent pancreatitis on imaging, clinicians should promptly consider early biopsy with immunostaining to avoid diagnostic delay and enable timely steroid treatment.
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