International Journal of Clinical Science and Medical Research

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.

IgG4-related disease, IgG4-related hepatitis, acute hepatitis, hepatocellular injury, corticosteroids

1. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Modern Pathology. sept 2012;25(9):1181‑92. 
2. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. The Lancet. avr 2015;385(9976):1460‑71. 
3. Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH. IgG4-Related Disease. Annu Rev Pathol Mech Dis. 24 janv 2014;9(1):315‑47. 
4. Tanaka A, Tazuma S, Okazaki K, Nakazawa T, Inui K, Chiba T, et al. Clinical Features, Response to Treatment, and Outcomes of IgG4-Related Sclerosing Cholangitis. Clinical Gastroenterology and Hepatology. juin 2017;15(6):920-926.e3. 
5. Zen Y, Kawakami H, Kim JH. IgG4-related sclerosing cholangitis: all we need to know. J Gastroenterol. avr 2016;51(4):295‑312. 
6. Zen Y, Nakanuma Y. IgG4 Cholangiopathy. International Journal of Hepatology. 2012;2012:1‑6. 
7. Lee HE, Zhang L. Immunoglobulin G4-related hepatobiliary disease. Seminars in Diagnostic Pathology. nov 2019;36(6):423‑33. 
8. Nakanuma Y, Ishizu Y, Zen Y, Harada K, Umemura T. Histopathology of IgG4-Related Autoimmune Hepatitis and IgG4-Related Hepatopathy in IgG4-Related Disease. Semin Liver Dis. 28 juill 2016;36(03):229‑41. 
9. Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4‐Related Disease. Arthritis & Rheumatology. juill 2015;67(7):1688‑99. 
10. Stone JH. IgG4-related disease: pathophysiologic insights drive emerging treatment approaches.