Z Gastroenterol 2011; 49 - P2_26
DOI: 10.1055/s-0030-1269543

Iron metabolism in patients with ALD

I Ganzleben 1, G Millonig 1, T Longerich 2, P Schirmacher 3, HK Seitz 1, HK Seitz 1, S Mueller 1
  • 1Alkoholforschungslabor und Medizinische Klinik, Salem Krankenhaus, Heidelberg, Heidelberg
  • 2Institut für Pathologie, Heidelberg, Heidelberg
  • 3Institut für Pathologie, Universitätsklinik Heidelberg, Heidelberg

Aims:

Alcoholic liver disease (ALD) is the major liver disease in the developed world that is characterized by pathological hepatic iron deposits. This non-HFE-related iron overload is considered a key mechanism of rapid disease progression towards liver cirrhosis and hepatocellular carcinoma. We here performed a systematic histological, protein and mRNA expression analysis on liver biopsies from patients with well characterized ALD.

Methods: 100 with histologically confirmed ALD were included. Clinical parameters, liver biopsies and serum iron parameters were collected. Histology and iron content were assessed by H&E and Prussian Blue staining. We then selected 30 liver biopsies (10 without and 20 with iron overload) for quantitative real time PCR analysis for iron metabolism genes (among them hepcidin, transferrin receptor 1, ferroportin, transferrin, ferritin light and heavy chain, HO-1). In addition liver sections were stained immunohistochemically for ferritin, ferroportin, transferrin receptor 1 and 2 and HO-1.

Results: In our cohort 50% of patients had iron overload in liver biopsy. Iron overload was mild to moderate and of a mixed type. Although serum ferritin rapidly decreases during alcohol detoxification the initial serum-ferritin concentration showed a significant difference between those patients with and without iron overload (p=0.02). Despite the difference in liver iron content and serum-ferritin among the two groups of ALD-patients, there was no significant regulation in iron metabolism associated genes at the RNA-level. Immunohistochemistry revealed distinct and individual staining patterns for ferritin, ferroportin, TfR1 and TfR2. The intensity, however, did not correlate with Prussian Blue staining.

Conclusion: Serum-ferritin is an indicator of iron overload in ALD despite its rapid decrease during alcohol withdrawal. However, absolute and spatial expression of key iron-related proteins are not correlated to iron deposits.

alcoholic steatohepatitis - ferritin - ferroportin - heme oxygenase 1 - hepcidin - transferrin receptor