Association between hepatic iron deposition, and serum bilirulin levels, mutations of UGT1A1 and HFE gene in patients with hereditary unconjugated hyperbilirubinemia

Histological findings of liver in patients with hereditary unconjugated hyperbilirubinemia (HUH) are generally mild. But Iron deposition in liver shown in some patients may indicate iron overload which can be contributing factor to additional complications. Mechanism of increased iron deposition is unclear. We studied the features of pathological changes, bilirubin levels, mutations of UGT1A1 and HFE gene among patients with iron deposition and compared with patients without iron deposition. Liver biopsies from 59 patients with HUH were stained with HE, Masson's trichrome, Reticulin and Perls' Prussian blue. Ishak and Deugnier scoring systems were used to assess inflammatory activity, the extent of fibrosis and distribution of iron deposition, respectively. Serum were used for evaluation of bilirubin levels, DNA amplification and sequencing were performed to detect mutations of genes. Of the 59 patients, 20 patients (33.9%) had iron deposition in the liver. The pattern of iron deposition is similar to the HFE-related hereditary hemochromatosis (HH), mainly in periportal hepatocytes, and the Deugnier score of parenchymal iron deposition was significantly higher than mesenchymal score (P<0.001). Total serum bilirubin levels (P=0.009), unconjugated bilirubin levels (P=0.024) and the frequency of heterozygous mutations in UGT1A1 gene (P=0.001) were also significantly higher in patients with iron deposition. Ten of the twelve patients (83.3%) with iron deposition who underwent HFE testing had an intronic variant in intron 2 (IVS2+4T -> C). Iron deposition in liver biopsies of patients with HUH is related to increased bilirubin levels and mutations of UGT1A1 gene and HFE gene.