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.

Changing epidemiology of hepatitis B in a U.S. community.

Despite a reduction in newly acquired hepatitis B virus (HBV) infections since the mid-1980s, HBV remains an important cause of liver disease in the U.S. We report the prevalence of chronic HBV infection in a U.S. community and describe demographic and clinical characteristics. The Rochester Epidemiology Project records healthcare encounters of residents of Olmsted County, Minnesota. For all cases with a potential diagnosis of hepatitis B in this database, complete medical records were reviewed to identify subjects who met the inclusion criteria, i.e., a clinician diagnosis of chronic HBV infection and a laboratory record of positive hepatitis B surface antigen (HBsAg). There were 191 residents with chronic HBV infection in the community, consisting of 53% Asian, 29% African, 13% Caucasian, and 5% other or unknown race. The overall age- and sex-adjusted prevalence of HBV in this community was 0.15% in 2000. The race-specific prevalence was highest among Asians (2.1%), followed by African Americans (1.9%). The prevalence among Caucasians was 0.02%. Overall, 86% were born outside the U.S., 98% of whom were non-Caucasian. A total of 131 residents were tested for HBV replicative status, of whom 27% had viral replication. Of those tested for aminotransferases (n = 184), 28% had an abnormal value at least once. In a multivariable regression analysis, replicative status was the most influential (odds ratio [OR] = 5.98, P <.01) factor associated with abnormal aminotransferase values, followed by male gender (OR = 3.69) and age greater than 40 years (OR = 2.32 per decade). In conclusion, in this Midwestern community, chronic HBV infection was predominantly seen in immigrants from endemic parts of the world.

Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community.

BACKGROUND & AIMS: The epidemiology of primary sclerosing cholangitis (PSC) in the United States is unknown. We report the incidence, clinical spectrum, and outcomes of PSC in Olmsted County, Minnesota. METHODS: Using the Rochester Epidemiology Project, a medical records linkage system in Olmsted County, Minnesota, we identified county residents with PSC, and the diagnosis was confirmed according to clinical, biochemical, radiographic, and histologic criteria. RESULTS: Twenty-two patients met diagnostic criteria for PSC in 1976-2000. The age-adjusted (to 2000 U.S. whites) incidence of PSC in men was 1.25 per 100,000 person-years (95% CI, 0.70 to 2.06) compared with 0.54 per 100,000 person-years (95% CI, 0.22 to 1.12) in women. The prevalence of PSC in 2000 was 20.9 per 100,000 men (95% CI, 9.5 to 32.4) and only 6.3 per 100,000 women (95% CI, 0.1 to 12.5). Seventy-three percent of cases had inflammatory bowel disease, the majority with ulcerative colitis. Survival among PSC patients was significantly less than expected for the Minnesota white population of similar age and gender (P < 0.001). CONCLUSIONS: These data represent the first population-based estimates of the incidence and prevalence of PSC in the United States. The incidence and prevalence of PSC were approximately one third of those previously described for primary biliary cirrhosis in the same population. Our data suggest that the prevalence of PSC in the United States, with its attendant medical burdens, is significantly greater than previously estimated.