Incidence of liver disease in people with HFE mutations

Background-Most patients with haemochromatosis have mutations of the HFE ge ne. However, the risk to people with HFE mutations of developing disease ma nifestations of haemochromatosis is not known. Aims-To determine the risk of developing cirrhosis and Liver cancer in indi viduals with HFE mutations in a population where few people were being trea ted for haemochromatosis. Methods-215 archive biopsy specimens of liver cancer (n=34) and cirrhosis ( n=190) were retrieved from histology archives. Blood samples from 1000 indi viduals from the normal population were also collected. DNA was extracted f rom the biopsy specimens and exons 2 and 4 of the HFE gene were amplified u sing polymerase chain reaction. The products were analysed for the C282Y (8 45A) and H63D (187G) mutations. Results-Three (8.8%) patients from the liver cancer group were homozygous f or the C282Y mutation. Five (2.6%) patients from the cirrhosis group were h omozygous for the C282Y mutation. One case fell in both the liver cancer an d cirrhosis groups. C282Y homozygosity was thus significantly more frequent in both groups than in the normal population. These 215 cases are represen tative of a population of about 250 000 over 20 years. During this period w e estimate that about 260 births or deaths of C282Y homozygous individuals occurred within this population. Conclusions-A diagnosis of liver cancer or cirrhosis is rare in the lifetim e of individuals from this population who are homozygous for the C282Y muta tion (2.5%; upper 95% confidence interval (CI) 8%). Similarly Liver disease is rare among C282Y/H63D compound heterozygotes (1%; upper 95% CI = 3.5%).