Diagnostic Significance Of Distinct Iron Deposition Profiles In Different Liver Zones

As a common pathological feature,determination of hepatic iron deposition is crucial in diagnosing the occurrence and progression of many liver-and iron-related diseases.However,the heterogeneities in architecture,function and hepatocyte differentiation of the liver lead to uncertain understanding on the iron distribution pattern across the liver,which is important for diagnosis and target treatment.Thus far,little is known on the profiles of iron deposition in different liver zones,particularly under conditions with disordered iron homeostasis.Here,we uncovered the uneven iron distribution pattern in the livers of patients with hereditary hemochromatosis?HH?,showing the region with the highest iron concentration near the entrance site of the portal vein and hepatic artery in contrast to the sites with the lowest iron concentration close to the distal edge of the livers.Distinct iron distribution profiles were also found throughout liver zones in wild-type mice and various mouse models with iron metabolism disorders,including hemochromatosis(Hfe^-/-),iron deficiency and inflammation.Of note,similar findings observed in HH patients were further demonstrated in Hfe^-/-mice.Moreover,the zones with greater iron accumulation appear to be more sensitive to iron changes,e.g.iron increase upon iron overload and iron loss in response to iron deficiency.Mechanistic investigation manifested that these differential iron changes in liver zones were subjected to the regulation by the hepcidin-ferroportin axis,the master regulator of iron homeostasis.Additionally,our data corroborated the reliability of magnetic resonance imaging?MRI?in recognizing the differential iron deposition profiles among liver zones.Our study would thus open a new path to seek the precise evaluation of iron-associated liver diseases.