Immunoglobulin G and liver stiffness in autoimmune hepatitis: Timing matters more than biochemical correction

OBJECTIVES: Transient elastography may overestimate fibrosis in autoimmune hepatitis (AIH) because hepatic inflammation independently increases liver stiffness measurement (LSM). We aimed to determine which inflammation markers confound LSM in AIH, whether algebraic correction improves accuracy, and when LSM becomes reliable for fibrosis staging. METHODS: Single-center retrospective cohort of adults with AIH, paired diagnostic Metavir biopsy, and at least one FibroScan visit with same-visit alanine aminotransferase (ALT) and immunoglobulin G (IgG). Mixed-effects linear regression modeled LSM on biopsy stage, ALT, IgG, and time since diagnosis with a patient-level random intercept. An inflammation-adjusted LSM was computed by subtracting estimated ALT and IgG contributions. Spearman correlation and DeLong-tested AUROC for advanced fibrosis (F3-F4) compared measured and adjusted LSM, stratified by inflammation state and treatment timing. RESULTS: We analyzed 208 FibroScan observations from 119 AIH patients (49 with advanced fibrosis). IgG was independently associated with LSM (β = +0.003 kPa per mg/dL, p < 0.001) while ALT was not (β ≈ 0, p = 0.68). The IgG-LSM relationship varied by treatment timing (IgG × 0-6 months interaction p = 0.001; IgG × 12-24 months p = 0.004). Algebraic correction did not improve discrimination (full-cohort AUROC measured 0.76 vs adjusted 0.72, DeLong p = 0.18). LSM accuracy for advanced fibrosis varied by timing: AUROC 0.71 pretreatment (n = 35), 0.64 at 12-24 months (n = 22), and 0.83 beyond 24 months (n = 72). CONCLUSIONS: In AIH, IgG-not ALT-independently inflates LSM, with a time-dependent effect strongest early after diagnosis. Algebraic correction did not improve fibrosis discrimination, but LSM accuracy improved substantially beyond 24 months after AIH diagnosis. Timing rather than algebraic correction is the more actionable clinical strategy for FibroScan interpretation in AIH.