Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (sd 118) ng/ml [208 (sd 122) ng/ml in wild-type and 225 (sd 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (sd 36) ng/ml in haemochromatosis patients, and 159 (sd 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes.

The main Fe storage organ in the body is the liver. In patients with chronic liver disease, secondary Fe overload is common. Phlebotomy, often used in the West to reduce Fe overload to improve the efficacy of interferon therapy, is not socially acceptable in India. We assessed the efficacy of a low-Fe diet in reducing serum Fe levels. Nineteen patients with hepatitis B- and C-related chronic liver disease, ten with normal (< 25 μmol/l) baseline serum Fe levels (group A) and nine with high (> 25 μmol/l) serum Fe levels (group B) were included. All the subjects were advised to eat a low-Fe diet. The daily Fe intake was reduced approximately 50 % by consumption of the rice-based diet. Haemoglobin, serum Fe, transferrin saturation index (TSI), ferritin and alanine transaminase (EC 2.6.1.2) levels were studied at 1 and 4 months. Dietary Fe intake and body weight were closely monitored. All patients complied with the dietary regimen and at 4 months significant (P < 0·001) reductions from baseline were seen in serum Fe (20 (SD 3) V. 12 (sd 4) μmol/l group A; 30 (sd 3) v. 19 (sd 7) μmol/l group B) and TSI (38 (sd 8) v. 23 (sd 9) % group A; 53 (sd 15) v. 34 (sd 13) %, group B) in both the groups, albeit earlier in group B subjects. Serum ferritin levels, however, reduced only in group A (112 (sd 62) v. 43 (sd 25) ng/ml, P < 0·05) and not in group B. Non-significant reductions in haemoglobin levels were seen in both groups. Alanine transaminase levels reduced significantly (P < 0·05) in both the groups (95 (sd 49) v. 44 (sd 25) IU/l, group A; 82 (sd 16) v. 51 (sd 14) IU/l group B). Thus, a low-Fe diet results in significant reductions in serum Fe and TSI levels, irrespective of baseline Fe levels. This diet should be evaluated to improve the efficacy of interferon therapy in patients with hepatitis B- and C-related chronic liver disease.