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Iron overload in cirrhosis-HFE genotypes and outcome after liver transplantation
D J Brandhagen1, W Alvarez, T M Therneau
1Mayo Clinic and Foundation, Rochester, MN, USA.
Insights
Liver transplant recipients with iron overload have significantly lower survival rates, mainly due to increased fatal infections. HFE gene mutations were uncommon in these patients.
Area of Science:
- Hepatology
- Transplantation Immunology
- Medical Genetics
Background:
- Hepatic iron deposition is common in liver transplant (LTx) recipients.
- A subset of LTx patients exhibit iron overload similar to hereditary hemochromatosis (HHC).
Purpose of the Study:
- To compare clinical outcomes in LTx patients with and without iron overload.
- To determine the prevalence of HFE mutations in LTx patients with iron overload.
Main Methods:
- Retrospective analysis of 456 liver transplant cases.
- Comparison of 41 explants with hepatic iron index (HII) > 1.9 to 41 matched controls without iron excess.
- Monitoring of posttransplantation complications, patient, and graft survival.
- HFE gene testing using DNA-based techniques.
Main Results:
- Five-year patient survival was significantly lower in LTx patients with iron overload (48% vs. 77%; P =.045).
- Fatal infections, particularly fungal, were more frequent in the iron overload group (24% vs. 7%; P =.03).
- HFE C282Y homozygosity was uncommon (4/41) in patients with severe hepatic iron overload.
Conclusions:
- Severe hepatic iron overload in LTx recipients is associated with reduced patient survival.
- Increased susceptibility to fatal bacterial and fungal infections contributes to decreased survival.
- HFE gene mutations are infrequent in LTx patients with hepatic iron overload.
Abstract:
Previously, we found appreciable hepatic iron deposition in one third of our patients undergoing liver transplantation (LTx) with approximately 10% of cases having quantifiable iron in the range of that seen in hereditary hemochromatosis (HHC). The aim of this study was to compare clinical outcome in liver transplant patients with and without iron overload. We also sought to determine the prevalence of HFE mutations in liver transplant patients with iron overload. Of 456 consecutive liver transplants, 41 explants had an hepatic iron index (HII) greater than 1.9, and these cases were compared to 41 matched liver transplant recipients without increased hepatic iron. Posttransplantation complications, along with patient and graft survival were monitored. HFE gene testing was performed using DNA-based techniques. Kaplan-Meier 5-year patient survival after LTx was significantly lower in cases with hepatic iron overload compared to matched controls without iron excess (48% vs. 77%; P =.045). Fatal infections (especially fungal) were more common in patients with iron overload (24% vs. 7%; P =.03). Of the 41 patients with a liver explant HII greater than 1.9, only 4 were C282Y homozygotes. Patients with severe hepatic explant iron overload undergoing LTx have a reduced survival compared to liver transplant recipients without explant iron excess. The reduced survival was attributable mainly to fatal bacterial and fungal infections. Despite the iron overload, HFE gene mutations were uncommon in patients with hepatic explant hemosiderosis.
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