Abstract
Although autoimmune hepatitis (AIH) can be treated with corticosteroid-based first-line therapy, incomplete remission is associated with progressive liver fibrosis. So far accepted predictors of the subsequent treatment response of AIH patients are lacking. Therefore, we analysed baseline parameters, including iron homeostasis and cytokine levels, in 60 children with paediatric AIH (pAIH). In contrast to adults, elevated serum markers indicating iron overload were not commonly found in children. Therefore, ferritin was not predictive of the treatment response in pAIH. Although baseline immunoglobulins were lower in pAIH children with subsequent complete biochemical remission (BR) upon standard first-line therapy, only lower AIH scores (≤16 points) could predict BR upon standard therapy in our training and validation cohorts. Additionally, higher baseline IL-2 and MCP-1/CCL2 levels were associated with BR in a sub-cohort. A combined score of IL-2 level and a simplified AIH score predicted treatment response more precisely than both parameter alone in this sub-cohort. In conclusion, the baseline AIH score could be validated as a predictor of treatment response in pAIH. Additionally, low baseline IL-2 may help identify children who need salvage therapy. This could be important because the use of low-dose IL-2 therapies is being tested in various autoimmune diseases.
Highlights
Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that manifests in all age groups and with an increasing incidence[1]
When the treatment response upon standard therapy was considered and children with iron deficiency anaemia were excluded, we found no significant differences in baseline iron parameters between biochemical remission (BR) and incomplete treatment response patients (IR + Ltx) (Fig. 1b, Table 1)
Altered iron homeostasis with elevated serum ferritin, transferrin saturation and serum iron is found in multiple liver diseases beyond haemochromatosis[19]
Summary
Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that manifests in all age groups and with an increasing incidence[1]. Once the diagnosis of active AIH is determined, an immunosuppressive medication that consists of predniso(lo)ne, or alternatively budesonide in non-cirrhotic patients[7,8], with or without azathioprine, is recommended[9]. Higher predniso(lo)ne doses per body weight are needed to achieve a sufficient treatment response to induction therapy for pAIH compared to adult AIH9. Since persistent inflammatory activity is associated with histological disease progression and reduced survival in AIH5,10–12, the early identification of patients with an insufficient response to standard therapy is clinically important. We identified dysregulated iron homeostasis and lower immunoglobulin G (IgG) titres as predictors of a good treatment response in adult AIH (aAIH) type 113. Since pAIH differs from aAIH in many clinical aspects, our aim was to identify prognostic baseline markers for the subsequent achievement of BR upon corticosteroid and azathioprine-based first-line therapy in pAIH. Iron metabolism was systematically assessed at diagnosis and during ongoing therapy and serum cytokines were measured as further immunological markers
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