Hyperferritinemia and hypergammaglobulinemia predict the treatment response to standard therapy in autoimmune hepatitis

PLoS One. 2017 Jun 8;12(6):e0179074. doi: 10.1371/journal.pone.0179074. eCollection 2017.


Autoimmune hepatitis (AIH) is a chronic hepatitis with an increasing incidence. The majority of patients require life-long immunosuppression and incomplete treatment response is associated with a disease progression. An abnormal iron homeostasis or hyperferritinemia is associated with worse outcome in other chronic liver diseases and after liver transplantation. We assessed the capacity of baseline parameters including the iron status to predict the treatment response upon standard therapy in 109 patients with untreated AIH type 1 (AIH-1) in a retrospective single center study. Thereby, a hyperferritinemia (> 2.09 times upper limit of normal; Odds ratio (OR) = 8.82; 95% confidence interval (CI): 2.25-34.52) and lower immunoglobulins (<1.89 times upper limit of normal; OR = 6.78; CI: 1.87-24.59) at baseline were independently associated with the achievement of complete biochemical remission upon standard therapy. The predictive value increased when both variables were combined to a single treatment response score, when the cohort was randomly split into a training (area under the curve (AUC) = 0.749; CI 0.635-0.863) and internal validation cohort (AUC = 0.741; CI 0.558-0.924). Patients with a low treatment response score (<1) had significantly higher cumulative remission rates in the training (p<0.001) and the validation cohort (p = 0.024). The baseline hyperferritinemia was accompanied by a high serum iron, elevated transferrin saturations and mild hepatic iron depositions in the majority of patients. However, the abnormal iron status was quickly reversible under therapy. Mechanistically, the iron parameters were not stringently related to a hepatocellular damage. Ferritin rather seems deregulated from the master regulator hepcidin, which was down regulated, potentially mediated by the elevated hepatocyte growth factor. In conclusion, baseline levels of serum ferritin and immunoglobulins, which are part of the diagnostic work-up of AIH, can be used to predict the treatment response upon standard therapy in AIH-1, although confirmation from larger multicenter studies is pending.

MeSH terms

  • Adult
  • Animals
  • Area Under Curve
  • Cohort Studies
  • Ferritins / blood*
  • Hepatitis, Autoimmune / blood*
  • Hepatitis, Autoimmune / complications
  • Hepatitis, Autoimmune / therapy*
  • Hepatocyte Growth Factor / pharmacology
  • Hepcidins / metabolism
  • Homeostasis
  • Humans
  • Hypergammaglobulinemia / blood
  • Hypergammaglobulinemia / complications*
  • Iron
  • Mice
  • ROC Curve
  • Reference Standards
  • Remission Induction
  • Treatment Outcome


  • Hepcidins
  • Hepatocyte Growth Factor
  • Ferritins
  • Iron

Grants and funding

This work was supported by grants from the German Research Foundation (KFO250 project 7; SFB TR 127 project A4; HA6880/2-1). RT was supported by the Young Faculty program from the Hannover Medical School.