1A and 1B. In these figures, it is demonstrated that many C282Y homozygotes have normal ALT levels, but also that patients with an elevated ALT level are unlikely to be C282Y homozygotes. The correlation between ALT and ferritin was stronger in C282Y homozygotes than in nonhomozygotes, which is consistent with an inflammatory cause of the hyperferritinemia in nonhomozygotes. Daporinad datasheet The proportion of male C282Y homozygotes with ALT and AST levels <40 IU/L was 71% and 87%, respectively. The proportion of female C282Y homozygotes with ALT and AST levels <40 IU/L was 87%

and 95%, respectively. The decreasing probability of being a C282Y homozygote across groups in men and women with increasing ALT levels is shown in Fig. 2. Similar results were determined for AST. P values for chi-square tests for trends in proportions for ALT were 0.036 for men and 0.00017 for women. Mantel-Haenszel chi-square adjusted for gender was <0.0001. An unanticipated observation was that the probability of being a C282Y homozygote decreased as serum ALT and AST levels increased. The results of the subgroup analysis limited to Caucasians were similar. It is widely believed that the probability of diagnosing many liver diseases increases as serum transaminases increase. In the present study of subjects with

hyperferritinemia, the probability of being a C282Y homozygote decreased with increasing ALT and AST levels. This probably occurs

because the deposition of excessive iron alone in hepatocytes of persons with hemochromatosis is not inflammatory. “Silent” hepatic fibrosis PD 332991 occurs in some subjects with hemochromatosis and normal serum transaminases.6, 7 On the other hand, some patients with hemochromatosis and HFE C282Y homozygosity have both hepatic iron overload and an inflammatory liver condition. For example, approximately 15% of C282Y homozygotes diagnosed in medical care 上海皓元医药股份有限公司 have severe hepatic steatosis proven by liver biopsy. These patients had higher median serum ALT and ferritin levels than C282Y homozygotes without hepatic steatosis or other inflammatory liver disorder.8 In contrast, patients referred for evaluation of elevated serum ferritin levels usually have hyperferritinemia resulting from inflammatory liver disease, rather than iron overload resulting from HFE hemochromatosis.9 In prospective analyses of subjects with chronic elevation of serum transaminases, hepatic steatosis associated with or without excessive ethanol consumption was the predominant cause of elevated serum transaminases.10-13 Hemochromatosis was rare in these case series.9 In the present study, there was a potential bias wherein HEIRS Study non-C282Y homozygous participants were deliberately selected for postscreening clinical examinations because they had elevated serum transferrin saturation and ferritin measures.