Severe acute cytolytic hepatitis revealing IgG4-related liver disease in a young woman

IgG4-related disease is a systemic immune-mediated fibroinflammatory condition that can involve multiple organs, with hepatobiliary manifestations being increasingly recognized. While IgG4-related sclerosing cholangitis represents the most frequent hepatic presentation, primary parenchymal liver involvement, known as IgG4-related hepatitis, remains rare and poorly characterized. Its presentation may mimic other causes of acute hepatitis, posing significant diagnostic challenges. We report the case of a 37-year-old woman with no past medical history who presented with generalized asthenia and episodes of lipothymia, without jaundice, pruritus, fever, or abdominal pain. Physical examination was unremarkable. Laboratory investigations revealed progressive and severe isolated hepatocellular injury, with alanine aminotransferase levels peaking at 1294 U/L and aspartate aminotransferase at 803 U/L, while cholestatic enzymes and bilirubin remained near normal. An extensive etiological workup excluded viral hepatitis, including hepatitis A, B, C, and E, as well as Epstein–Barr virus infection. Autoimmune liver disease antibodies were negative, and abdominal ultrasound showed no abnormalities. Given the absence of an identifiable cause, serum IgG4 levels were assessed and found to be markedly elevated at 3.751 g/L, approximately four times the upper limit of normal. Corticosteroid therapy was initiated, resulting in a rapid and dramatic biochemical response with near-complete normalization of liver enzymes. Owing to this favorable evolution, liver biopsy was not performed. Azathioprine was subsequently introduced as maintenance therapy during steroid tapering. This case highlights IgG4-related hepatitis as a rare but important cause of severe acute cytolytic hepatitis, even in the absence of biliary involvement or histological confirmation. Markedly elevated serum IgG4 levels combined with a striking response to corticosteroids can strongly support the diagnosis after careful exclusion of alternative etiologies.