The effect of the metabolic syndrome, hepatic steatosis and steatohepatitis on liver fibrosis in hereditary hemochromatosis.

OBJECTIVES: The variability in phenotypic expression of hereditary hemochromatosis (HH) is not fully understood. We sought to examine whether the metabolic syndrome, hepatic steatosis or steatohepatitis influenced hepatic fibrosis among patients with HH and iron overload. METHODS: We identified 86 patients with C282Y/C282Y or C282Y/H63D HH and iron overload (hepatic iron concentration (HIC) >2,200 microg/g for males, >1,600 microg/g for females). Features of the metabolic syndrome were assessed at the time of liver biopsy. Biopsies were scored by a blinded pathologist. Significant fibrosis was defined as peri-portal fibrosis or greater. RESULTS: The mean (+/-SD) age of the study population was 53+/-12 years and 68 (79%) were male. The median (range) values of ferritin and HIC were 1,125 (253-9,530) microg/l and 9963 (1926-50 887) microg/g, respectively. The metabolic syndrome was present in 23 (27%), hepatic steatosis in 43 (50%), steatohepatitis in 18 (21%) and significant fibrosis in 38 (44%). Overall, neither the metabolic syndrome nor any of its components were associated with significant fibrosis or a higher mean fibrosis stage. Hepatic steatosis but not steatohepatitis was associated with a lower fibrosis stage. C282Y/H63D compound heterozygous individuals who had glucose intolerance had more severe fibrosis compared with those without glucose intolerance (1.0+/-1.0 vs. 0.1+/-0.3, P=0.01). CONCLUSIONS: Overall, the metabolic syndrome and fatty liver were not associated with hepatic fibrosis among individuals with HH and iron overload. However, glucose intolerance may be important risk factor for the development of hepatic fibrosis in subjects with the C282Y/H63D HFE genotype.