Acute Autoimmune Hepatitis: Disguised by a Normal IgG Gammaglobulin Level and Negative Autoimmune Markers

Abstract

Purpose: We report a rare case of acute liver injury secondary to seronegative autoimmune hepatitis (AIH) with IgE hypergammaglobulinemia. The purpose of this report is to bring to light the complexity in diagnosing seronegative AIH and the importance of prompt diagnosis to prevent progression to liver failure. A 20-year-old African America female with a history of polycystic ovarian syndrome (PCOS) and new-onset type 2 diabetes mellitus (T2DM) was transferred to our facility after presenting to a local hospital with symptoms of malaise, nausea and vomiting. Laboratory studies revealed INR of 1.1, AST of 1108 U/L and ALT of 1031 U/L and total bilirubin of 8.2 mg/dL. She exhibited no signs of hepatic encephalopathy or ascites. Thorough history revealed no risk factors for viral hepatitis or alcohol/toxic exposures. Her medications - discontinued upon admission - included drospirenone/ethinyl estradiol oral contraceptive pills begun a year ago for the treatment of PCOS and metformin started 1 month prior for T2DM. Serologic studies for acute hepatitis A, B, C, E, CMV, HSV, HIV, and EBV were negative. Iron studies, serum ceruloplasmin and copper were all within normal limits. The anti-mitochondrial, antinuclear, alpha-1 antitrypsin, anti-smooth muscle, and anti liver/kidney microsomal antibodies were negative. The immunoglobulins (Ig) G, IgM, and IgA were normal. The IgE was elevated at 963 IU/mL. Doppler ultrasound of the liver revealed a normal appearing liver with patent hepatic vasculature with flow in the normal direction. A liver biopsy revealed no steatosis, moderate mixed inflammatory infiltrate of the portal tracts with mild interphase activity and moderate ductular reaction, pericholangitis with periportal and focal bridging fibrosis. Given the absence of typical IgG hypergammaglobulinemia and serologic markers for AIH, the presence of T2DM, and normal liver synthetic function, initiation of immunosuppression was deferred and laboratory studies reassessed frequently. Although liver enzymes initially declined after discontinuation of her medications, both AST and ALT stabilized at nearly 400 U/L. However, after 6 weeks, a slight rise in her INR to 1.4 was noted and prednisone therapy was promptly initiated. Within 2 weeks after initiation of prednisone therapy, liver enzymes decreased by >50% confirming a therapeutic response to immunosuppression and reaffirming a diagnosis of seronegative autoimmune hepatitis. In retrospect, based on the Revised Original Scoring System of the International Autoimmune Hepatitis Group, this patient's pretreatment aggregate score was > 15, making AIH a definite diagnosis in spite of the normal IgG and negative autoimmune markers.