P146 High prevalence of aetiological cofactors in patients with haemochromatosis undergoing liver transplantation: a UK wide retrospective analysis

<h3>Introduction</h3> Haemochromatosis causes excess iron deposition in the liver thereby increasing the risk of cirrhosis and hepatocellular carcinoma (HCC). Patients who develop cirrhosis and/or HCC who meet specific criteria are eligible for liver transplantation. Approximately 1% of all liver transplants identify haemochromatosis as an indication. The risk of cirrhosis is further increased in the presence of cofactors such as alcohol excess and diabetes mellitus. We aimed to assess the prevalence of aetiological cofactors in patients with haemochromatosis who have undergone liver transplantation in the United Kingdom (UK). <h3>Methodology</h3> We included all patients who underwent liver transplantation in the UK from 1st April 2008 to 31st March 2023. Cases were identified from the UK Transplant Registry (UKTR) held by NHS Blood &amp; Transplant where haemochromatosis was recorded as the primary, secondary or tertiary indication for transplantation. Each of the 7 UK liver transplant units retrospectively reviewed electronic patient data to identify patient demographics, investigations, medical history and mortality. <h3>Results</h3> A total of 123 patients (Male 86.2%) were identified as being transplanted with a diagnosis of haemochromatosis representing 1.08% of liver transplants during the study period. Genotypic data showed that 56 patients were C282Y homozygotes with the remaining being compound heterozygotes (n=19), non-HFE genotypes (n=2), genotype unknown (n=30) and other low risk HFE genotypes (n=16) (e.g. C282Y heterozygotes). Considering the recorded indications for liver transplantation, in addition to case note review, 82/123 (66.7%) patients transplanted with haemochromatosis had additional aetiological risk factors for cirrhosis, including previous harmful alcohol (in 47.2%), metabolic dysfunction-associated steatotic liver disease (in 26.0%) and viral hepatitis (in 6.5%). Among C282Y homozygotes, 53.6% (30/56) had additional cofactors, compared with 91.4% (32/35) of those with compound heterozygosity and other lower risk genotype (p&lt;0.01, Fisher’s exact test). HCC was present in 56.1% (69/123) of patients. Amongst these, 39 (31.7%) were C282Y homozygotes and 9 (7.3%) were compound heterozygotes/other low risk genotypes. By comparison, according to the UKTR, among all patients listed for liver transplantation in UK during the same period, 2618/11409 (22.4%) had HCC. <h3>Conclusion</h3> Additional aetiological cofactors are very common in patients with haemochromatosis who require liver transplantation. This is particularly evident among patients with genotypes associated with less severe iron overload. This highlights the importance of actively monitoring and treating cofactors in patients with haemochromatosis.