Corticosteroid Exposure in Autoimmune Hepatitis: Early Toxicity, Cumulative Burden and Associations With Long-Term Patient-Reported Outcomes

Autoimmune hepatitis (AIH) requires corticosteroid-based induction therapy, but prolonged exposure is common in practice.

This study quantified corticosteroid utilization patterns and associations with adverse outcomes from a patient perspective.

A cross-sectional patient-reported survey recruited AIHA network members with physician-confirmed AIH (N = 563). Corticosteroid exposure was quantified using annual duration thresholds (≥ 90 days/year at ≥ 5 mg/day prednisone-equivalent). Early side effects (within 6 months; n = 491) and long-term metabolic complications (≥ 2 years disease duration; n = 385) were assessed using multivariable logistic regression adjusting for age, sex and disease duration.

Among 563 participants (median age 53 years; 87.4% female), all participants received a corticosteroid at diagnosis (77.6% prednisone; 11.4% budesonide). Side effects within 6 months were near-universal (96.6%; median 5 symptoms) and greater with predniso(lo)ne than budesonide (5.82 vs. 3.55 symptoms; p < 0.001); 51.2% of predniso(lo)ne-initiated patients developed a new metabolic condition within 6 months. Long-term complications affected 75.9% of the chronically exposed cohort, including weight gain > 5% (47.0%), osteoporosis (30.4%) and hypertension (18.1%). Each additional cumulative year of extensive exposure was independently associated with the composite adverse outcome (adjusted OR 1.11, 95% CI 1.02-1.22; p = 0.014), osteoporosis, Type 2 diabetes, weight gain and cataracts, with significant dose-response gradients (p-trend ≤ 0.008). Patients with > 5 cumulative years had 4-fold higher odds of the composite outcome versus patients in the None exposure group (OR 4.21, 95% CI 1.51-11.71).

Corticosteroid exposure in AIH is associated with dose-dependent toxicity from the first months of treatment. Reduced induction dosing and budesonide represent potential steroid-minimization strategies in appropriate patients, warranting prospective evaluation.