Table 1.
Data of untreated AIH-1 patients according to subsequent treatment response upon standard therapy.
Fig 1.
Hyperferritinemia and hypergammaglobulinemia were associated with the subsequent treatment response upon standard therapy in untreated AIH-1.
(A) Left panel: Serum ferritin (SF) in untreated AIH-1 patients with subsequent biochemical remission (BR; N = 83) and incomplete biochemical response (IR; N = 26). Right panel: Histological treatment response with complete remission (CR: N = 16), BR with incomplete histological response (BR/IHR: N = 7) and IR (N = 26). (B) The same analysis for immunoglobulin G (IgG). (C) The AUROC analysis for the prediction of IR before the treatment initiation for SF (dashed line), IgG (dotted line) and their combined treatment response score (black solid line) in the retrospective trainings cohort (N = 76). (D) Rates of BR according to the treatment duration for the treatment response score<1 (solid line) and score≥1 (dashed line) for the training and (E) validation cohort. (* p<0.05; not significant, p≥0.05)
Table 2.
AUROC and univariate analysis for the prediction of incomplete biochemical remission upon standard therapy in untreated AIH-1 in the training cohort.
Table 3.
Diagnostic performance of the treatment response score to predict incomplete treatment response in untreated AIH-1.
Table 4.
Enrichment for incomplete biochemical remission upon standard therapy with an increasing treatment response score in the total cohort.
Fig 2.
Reversible hyperferritinemia and mild iron deposition in untreated AIH-1.
(A) Intrahepatic iron deposition (blue granula) in untreated AIH-1 in (left) hepatocytes, (middle) portal fields and (right) the sinusoidal compartment (white arrow). (B) The semi-quantitative histopathological iron deposition score (left) in untreated AIH-1 with subsequent biochemical remission (BR: N = 47) or incomplete response (IR: N = 10) and (right) under therapy (Tx; N = 24) compared to baseline at diagnosis (Dx; N = 61). (C) Longitudinal course (mean and standard deviation) under therapy (M = month; Y = year) in BR (black) and IR (grey). (* p<0.05; ** p<0.01; *** p<0.001; ULN = upper limit of normal).
Fig 3.
Iron homeostasis is potentially deregulated by HGF driven suppression of hepcidin-25 in untreated AIH-1.
(A) Spearman rank correlation (SR) analysis of serum ferritin in AIH-1 with alanine aminotransferase (ALT) at diagnosis (Dx) in patients with subsequent biochemical remission (BR, left panel, N = 24) and incomplete biochemical response (IR, right panel, N = 24) matched for ALT, gender and age as far as possible. (B) SR analysis of serum ferritin and hepcidin-25 in patients with IR (N = 8; left panel) and with BR (N = 21; right panel) upon standard therapy and (C) in patients with achieved BR after 6–12 months of therapy (M 6–12; right; N = 7). (D) The hepatocyte growth factor (HGF, red; autofluorescence in green and blue) is expressed in (top) the portal tracts, endothelium and (bottom) liver sinusoids in a representative liver biopsy of untreated AIH-1. White bars represent 100 μm. (E) SR analysis of HGF and hepcidin-25 in untreated AIH-1 (N = 12) with subsequent BR and high ferritin (>2,09x ULN). (F) HGF in patients with high (hSF, N = 30) and low serum ferritin (lSF, N = 37). (* p<0.05; ** p<0.01; *** p<0.001; not significant, p≥0.05; ULN = upper limit of normal)