Elghezewi A, Mohamed M. Autoimmune hepatitis in the context of systemic lupus erythematosus: A narrative review of overlap syndrome and lupus-associated hepatitis. World J Hepatol 2026; 18(10): 124793 [DOI: 10.4254/wjh.124793]
Corresponding Author of This Article
Abdelwahap Elghezewi, MD, Academic Fellow, FACG, FACP, Section of Gastroenterology, Marshall University, 249 15th Street, Huntington, WV 25701, United States. elghezewia@marshall.edu
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Gastroenterology & Hepatology
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review-article
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Elghezewi A, Mohamed M. Autoimmune hepatitis in the context of systemic lupus erythematosus: A narrative review of overlap syndrome and lupus-associated hepatitis. World J Hepatol 2026; 18(10): 124793 [DOI: 10.4254/wjh.124793]
World J Hepatol. Oct 27, 2026; 18(10): 124793 Published online Oct 27, 2026. doi: 10.4254/wjh.124793
Autoimmune hepatitis in the context of systemic lupus erythematosus: A narrative review of overlap syndrome and lupus-associated hepatitis
Abdelwahap Elghezewi, Mujtaba Mohamed
Abdelwahap Elghezewi, Mujtaba Mohamed, Section of Gastroenterology, Marshall University, Huntington, WV 25701, United States
Author contributions: Elghezewi A conceived and designed the review, performed the literature search, and wrote the original draft; Mohamed M critically revised the manuscript for important intellectual content and supervised the work; and all authors have read and approved the final version of the manuscript.
AI contribution statement: The AI tool Claude (Anthropic) was used to assist with drafting and editing portions of this manuscript, specifically for language polishing and editing of the Main Text and for assistance with literature synthesis during drafting. No portion of the Main Text was generated de novo by the AI tool without subsequent author rewriting and verification. The AI tool did not participate in the design of the study, the interpretation of its results, or the selection of the literature to be cited, and no images in the manuscript were generated by AI. All content was critically reviewed and verified by the named authors, who take full responsibility for the work.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Abdelwahap Elghezewi, MD, Academic Fellow, FACG, FACP, Section of Gastroenterology, Marshall University, 249 15th Street, Huntington, WV 25701, United States. elghezewia@marshall.edu
Received: June 24, 2026 Revised: August 5, 2026 Accepted: September 17, 2026 Published online: October 27, 2026 Processing time: 119 Days and 9.1 Hours
Abstract
Liver enzyme abnormalities of any etiology occur in 25%-60% of patients with systemic lupus erythematosus, a figure reflecting overall hepatic involvement rather than lupus hepatitis specifically, which accounts for only a minority of these cases. Hepatic manifestations remain absent from all major classification criteria, and true autoimmune hepatitis (AIH) co-exists with systemic lupus erythematosus in an estimated 0.6%-5% of cohorts. This overlap carries risk of progressive fibrosis, cirrhosis, and liver failure - outcomes essentially absent in lupus hepatitis alone - yet no validated diagnostic criteria or prospective trials exist. This narrative review synthesizes evidence on epidemiology, genetics, immunopathogenesis, diagnosis, management, and outcomes. The two entities are mechanistically distinct: AIH is a cell-mediated, organ-directed process targeting hepatocyte autoantigens, whereas lupus hepatitis is driven by humoral immune complex deposition with complement consumption. Key discriminators include anti-smooth muscle antibody, anti-soluble liver antigen/liver-pancreas, anti-ribosomal P antibodies, serum complement levels, and liver biopsy with C1q immunofluorescence. Infectious mimics warrant exclusion before escalating immunosuppression. Management follows standard AIH principles, with mycophenolate mofetil an attractive dual-purpose agent. The evidence base remains predominantly low quality; prospective registries, overlap-specific diagnostic algorithms, and trials of dual-purpose agents are the highest research priorities.
Core Tip: Liver enzyme abnormalities affect up to 60% of patients with systemic lupus erythematosus, yet true autoimmune hepatitis (AIH)-systemic lupus erythematosus overlap is rare and often over-diagnosed because antinuclear antibodies and hypergammaglobulinemia inflate International AIH Group scores. AIH is cell-mediated and can progress to cirrhosis, whereas lupus hepatitis is immune complex-mediated with complement consumption and an excellent prognosis. Liver biopsy with C1q immunofluorescence, anti-smooth muscle and anti-soluble liver antigen/liver-pancreas antibodies, and complement levels are key discriminators. Mycophenolate mofetil is the preferred dual-purpose agent; validated overlap-specific criteria remain needed.
