Incidence of liver disease in people with HFE mutations

Background—Most patients with haemo-chromatosis have mutations of the HFE gene. However, the risk to people with HFE mutations of developing disease manifestations of haemochromatosis is not known. Aims—To determine the risk of develop-ing cirrhosis and liver cancer in individu-als with HFE mutations in a population where few people were being treated 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 from the biopsy specimens and exons 2 and 4 of the HFE gene were amplified using polymerase chain reaction. The products were analysed for the C282Y (845A) and H63D (187G) mutations. Results—Three (8.8%) patients from the liver cancer group were homozygous for the C282Y mutation. Five (2.6%) patients from the cirrhosis group were homo-zygous for the C282Y mutation. One case fell in both the liver cancer and cirrhosis groups. C282Y homozygosity was thus sig-nificantly more frequent in both groups than in the normal population. These 215 cases are representative of a population of about 250 000 over 20 years. During this period we estimate that about 260 births or deaths of C282Y homozygous individu-als occurred within this population. Conclusions—A diagnosis of liver cancer or cirrhosis is rare in the lifetime of indi-viduals from this population who are homozygous for the C282Y mutation (2.5%; upper 95 % confidence interval (CI) = 8%). Similarly liver disease is rare among C282Y/H63D compound heterozy-gotes (1%; upper 95 % CI = 3.5%)