Revisiting Ferritin‐ IgG Score to Predict Complete Biochemical Response in Autoimmune Hepatitis

BACKGROUND: Predictive tools in autoimmune hepatitis (AIH) are scarce. A study proposed low ferritin and high IgG as prognostic markers for complete biochemical response (CBR). AIMS: We aimed to externally validate the prognostic role of ferritin-IgG score and its individual components in an independent multicentre AIH cohort. METHODS: This multicentre study included 487 patients from the Hannover cohort (n = 166) and the Spanish ColHai registry (n = 321). Patients with ferritin < 2.09×ULN received 1 point and those with IgG > 1.89×ULN received 1 point, yielding a score of 0-2. Because baseline characteristics differed between cohorts, the score was additionally evaluated after inverse probability of treatment weighting (IPTW) propensity score. RESULTS: At baseline, Hannover patients were younger (p = 0.005) and had higher transaminases, bilirubin (p < 0.001), ferritin (p = 0.006) and IgG (p = 0.006). Overall, 79.7% achieved CBR; CBR rates were higher in ColHai at 6 (50.2% vs. 34.6%, p = 0.001) and 12 months (67.6% vs. 51.9%, p = 0.001). The score was associated with response in the Hannover cohort but showed no predictive capacity in ColHai (C-statistic 0.51 [95% CI 0.45-0.56] at 6 months; 0.51 [0.45-0.57] at 12 months; 0.54 [0.47-0.61] at any time during the follow-up). After IPTW, the score was not associated with CBR in the ColHai cohort (HR 0.86, 95% CI 0.67-1.10), whereas IgG retained its predictive value, with baseline levels < 1.89×ULN associated with a higher probability of achieving CBR. CONCLUSIONS: The ferritin-IgG score failed external validation in an independent multicentre cohort. Ferritin showed no prognostic value, whereas the predefined IgG threshold retained its ability to predict treatment response.