IgG4‐Associated Autoimmune Hepatitis: a Systematic Review

BACKGROUND: IgG4-associated autoimmune hepatitis (IgG4-AIH) is an emerging entity characterized by overlapping features of classical autoimmune hepatitis (AIH) and IgG4-related disease (IgG4-RD). However, significant heterogeneity in diagnostic criteria has obscured its true prevalence and clinical significance. This systematic review aimed to characterize the clinical, serological, and histopathological features of IgG4-AIH. METHODS: Following PRISMA guidelines, a systematic search was conducted across PubMed, Embase, and Web of Science. Study selection, data extraction, and quality assessment using Joanna Briggs Institute (JBI) tools were performed independently by two reviewers. A narrative synthesis was conducted. RESULTS: A total of 43 studies (11 cohort studies, 32 case reports and series) describing 185 patients were included. The cohort was predominantly of Asian origin and showed a female predominance. The most common autoantibody was antinuclear antibody (73%-78%), while serum IgG4 levels were highly variable but exceeded the 135-mg/dL threshold in all cases. Histopathologically, interface hepatitis and plasma cell infiltration were frequent features, and advanced fibrosis (Stages 3-4) was noted in approximately half the patients. Concurrent IgG4-RD was significantly more prevalent in case-based studies versus cohort studies (58% vs. 8.2%, respectively). Glucocorticoid therapy demonstrated high efficacy, with over 70% of patients achieving biochemical remission within three months. CONCLUSION: This systematic review characterizes IgG4-AIH as a distinct clinical entity bridging classical AIH and IgG4-RD. Its unique clinical and pathological profile underscores the need for consensus diagnostic criteria and prospective studies to determine optimal management strategies and long-term outcomes.