S5648 A Clinical Conundrum: Seronegative Primary Autoimmune Hepatitis

Introduction: Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease characterized by immune-mediated hepatocellular injury. It is theorized to result from a loss of tolerance to hepatocyte-specific antigens in genetically susceptible individuals. Here we report an atypical case of seronegative AIH. Case Description/Methods: A 41-year-old woman with no significant medical history presented with week-long generalized fatigue followed by new-onset jaundice and vomiting. She denied previous history of intravenous drug use, alcohol use, or international travel. Initial labs were significant for total bilirubin 3.6 mg/dL, conjugated bilirubin 2.4 mg/dL, aspartate aminotransferase 1082 U/L, alanine aminotransferase 2093 U/L and acute hepatic panel was negative. On physical exam, skin was mildly jaundiced and the upper abdomen was diffusely tender. Initial computed tomography (CT) abdomen and pelvis showed no evidence of primary sclerosing cholangitis. Further hepatitis workup was negative for ceruloplasmin, acute ɑ-1 antitrypsin, alpha-fetoprotein, EBV/CMV viral panel, anti-nuclear, anti-mitochondrial and anti-smooth muscle antibodies. Follow-up liver magnetic resonance imaging was negative for evidence of iron overload. Percutaneous liver biopsy revealed severe lobular and portal acute hepatitis consistent with autoimmune hepatitis thus patient was started on extended 10-week prednisone taper. Two-week post-hospitalization follow-up showed improved liver function tests and bilirubin, mycophenolate was added for disease control. Outpatient follow-up found no evidence for anti-liver kidney microsomal or soluble liver antigen antibodies. Discussion: AIH is classified into either Type 1, characterized by either anti-nuclear (ANA) and anti-smooth muscle (SMA) antibodies, or Type 2, characterized by anti-liver kidney microsomal type-1 (LKM1) antibodies.1 It has a broad clinical presentation ranging from asymptomatic elevations in liver enzymes to fulminant hepatic failure. When recognized early, AIH carries a favorable prognosis with most patients achieving remission on corticosteroid therapy followed by azathioprine or mycophenolate. This case underscores the diagnostic challenge posed by autoimmune hepatitis, particularly in patients who lack detectable antibodies thus reinforcing the need for vigilance in evaluating unexplained liver inflammation. Reference 1. Czaja, Albert J., and Michael P. Manns. “The validity and importance of subtypes in autoimmune hepatitis: a point of view.” American Journal of Gastroenterology (Springer Nature) 90.8 (1995). PMID: 7639216.