External validation of the IAIHG autoimmune hepatitis response criteria in a multicentric real-world cohort

Background & aims: The goal of treatment in autoimmune hepatitis (AIH) is induction of remission to prevent the development of liver fibrosis, cirrhosis, and its related complications. Various definitions of treatment response and remission have been used. The International Autoimmune Hepatitis Group (IAIHG) recently defined consensus criteria for treatment response. We aimed to validate the IAIHG response criteria in our cohort and establish correlations with survival endpoints.

Methods: We performed a retrospective, multicentric cohort study in one tertiary and seven secondary care centres in Belgium. Eligible patients were at least 18 years of age at data collection and were diagnosed with AIH by a simplified IAIHG score of ≥6. Complete biochemical response (CBR) was defined according to the IAIHG consensus criteria as normalisation of transaminases and serum IgG within the first 6 months of treatment. The primary endpoint was liver-related survival - defined as freedom from liver-related death or liver transplantation. Secondary endpoints were overall mortality and transplant-free survival. Outcomes were compared between patients attaining CBR and those with insufficient response.

Results: Biochemical response status could be determined in 200 patients with AIH: CBR was achieved in 128 (64.0%) individuals. Patients not achieving CBR more frequently presented with cirrhosis on initial histology (22.2% vs. 10.9%, p = 0.036). Liver-related mortality or liver transplantation as a primary outcome occurred in 26 patients (13.0%). Patients achieving CBR exhibited superior liver-related (hazard ratio 0.118; 95% CI 0.052-0.267; p <0.0001) and overall (hazard ratio 0.253; 95% CI 0.111-0.572; p = 0.0003) survival.

Conclusions: We externally validated the IAIHG consensus criteria for CBR and confirmed their correlation with survival endpoints in a multicentric, real-world cohort. Patients with AIH achieving CBR as an intermediate endpoint have significantly superior liver-related and overall survival.

Impacts and implications: Corticosteroids remain the cornerstone of treatment to induce remission of disease activity in autoimmune hepatitis (AIH), and the majority of patients require long-term corticosteroid treatment to achieve sustained remission. Definitions of response to treatment have varied over the years, and consistently used intermediate endpoints are needed to facilitate advancements in non-corticosteroid treatment for autoimmune hepatitis. The International Autoimmune Hepatitis Group (IAIHG) defined consensus criteria on endpoints in the treatment of AIH, for which further external validation is needed. Here, we demonstrate the usefulness of the IAIHG consensus criteria and corroborate their correlation to primary endpoints, such as liver-related survival and native liver survival in a multicentric, real-world setting. The design of future studies can rely on the IAIHG consensus criteria as intermediate endpoints.