Hepcidin is a key mediator of anemia of inflammation in Crohn's disease.

UNLABELLED: Anemia often complicates the course of Inflammatory Bowel Disease (IBD). Hepcidin, a liver-produced peptide hormone, is a key mediator of anemia of chronic disease (ACD). We hypothesized that hepcidin is significantly elevated in anemic CD patients and that hepcidin may cause iron restriction and, therefore, mediate ACD. METHODS: We enrolled 17 patients with CD and ACD recruited from the Cedars-Sinai IBD Center. Routine blood tests included hemoglobin (Hgb), hematocrit, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Anemia was defined as hemoglobin <12g/dL and <13.5g/dL, in men and women, respectively. ACD was diagnosed on the basis of a combination of the following: a) normal or elevated ferritin b) lowered serum iron and total iron binding capacity and c) normal percent iron saturation. Serum and urine hepcidin, as well as IL-6 levels were also measured. Patients with documented iron-deficiency anemia were excluded. RESULTS: There was an excellent correlation between urine (expressed as ng/mg of creatinine) and serum hepcidin levels expressed as ng/ml (r=0.853, p<0.001). We also found a strong positive correlation between serum hepcidin and ferritin levels (r=0.723, p=0.0015). There was a positive correlation between serum hepcidin and IL-6 levels (r=0.546, p=0.023). We found a strong negative correlation between serum hepcidin concentrations and Hgb levels (r=0.528, p=0.029). CONCLUSION: We demonstrate that ACD in CD is characterized by high serum IL-6 and hepcidin levels, which negatively correlate with Hgb levels. Our data support the hypothesis that IL-6-driven hepcidin production mediates ACD in patients with CD.

Colorectal cancer screening and surveillance in Crohn's colitis.

AIMS: To assess colonoscopic screening and surveillance for detecting neoplasia in patients with long-standing colonic Crohn's disease (CD). PATIENTS AND METHODS: Colonoscopy and biopsy records from patients with colonic CD were evaluated at the Cedars-Sinai Inflammatory Bowel Disease Center during a 17-year period (1992-2009). RESULTS: Overall, 904 screening and surveillance examinations were performed on 411 patients with Crohn's colitis (mean 2.2 examinations per patient). The screening and surveillance examinations detected neoplasia in 5.6% of the patient population; 2.7% had low-grade dysplasia (LGD) (n=11), 0.7% had high-grade dysplasia (HGD) (n=3), and 2.2% had carcinoma (anal carcinoma n=3; rectal carcinoma n=6). Mean age of CD diagnosis was 25.6±0.8 years in those with normal examinations, compared to 17.7±2.7 years (p<0.001) in those with HGD, 36.85±1.43 in those with LGD (p=0.021) and 28.32±3.24 years in those with any dysplasia/cancer (p=0.034). Disease duration in patients with normal examinations was 19.1±0.5 years, compared to 36.8±4.4 years (p<0.001) in HGD, 16.88±2.59 in those with LGD (p=0.253) and 30.68±4.03 years in those with any dysplasia/cancer (p=0.152). The mean interval between examinations was higher in HGD (31.5±9.4 months) compared to those with normal colonoscopies (12.92±1.250 months; p=0.002). CONCLUSIONS: We detected cancer or dysplasia in 5.6% of patients with long-standing Crohn's colitis enrolled in a screening and surveillance program. Younger age at diagnosis of CD, longer disease course, and greater interval between exams were risk factors for the development of dysplasia.