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More safeguards may be needed in liver transplantation, after the discovery of a new mutation in a recipient sparking iron overload. This seemingly rare event questions the supposed suitability of donor livers heterozygous for the C282Y gene—the commonest type transplanted.
The case centred on iron overload detected in a liver biopsy specimen taken from a recipient four years after transplantation during a hernia repair. Hepatic iron concentration (HIC) was way above normal and hepatic iron index (HII) indicated hereditary haemochromatosis. Yet the recipient did not have the condition before transplantation and was negative for HFE mutations C282Y and H63D. The donor was heterozygous for the C282Y gene and had only mild iron stores in the liver.
Sequencing of the HFE gene disclosed single base heterozygosity in exon 1 g.189G→C, causing serine substitution at codon 6 (R6S) in the recipient, and C282Y heterozygosity in the donor. Two thirds of the recipient’s living relatives were heterozygous for R6S but not C282Y or H63D mutation; none showed iron overload. Thirty five European controls without hereditary haemochromatosis tested negative for the R6G mutation. The authors propose an interaction between R6S and C282Y mutations to explain the events.
The donor was a 46 year old woman with HIC and HII values within the normal range and the recipient a 34 year old man with cirrhosis of the liver from alcohol misuse Both were Caucasian.
Transplantation of livers heterozygous for C282Y is widespread, but this discovery casts doubt on safety.