EASL clinical practice guidelines for HFE Hemochromatosis

Article in Press 9Clinical Practice GuidelinesTable 6. Data from studies addressing the penetrance of C282Y homozygotes.Authors Ref. Study type C282Yhomozygotes(females)Definition of penetrant disease AffectedindividualsPenetrance CommentsBurt et al. (1998) [10] Cross-sectional 5 (4) Hepatic iron index >1.9 upon liverbiopsyDistante et al. (1999) [13] Cross-sectional 2 (1) Iron removed >5 g or HII >1.9 orhistological iron grade >2+McDonnell et al. (1999) [127] Cross-sectional 4 (3) Iron removed >5 g or HII >1.9 orhistological iron grade >2+3 60% No liver biopsy in unaffected individuals because ofnormal serum iron parameters1 50% Unaffected patient had Pearl’s stain Grade 2 and HII of 1.73 75% One unaffected patient had elevated serum ironparametersOlynyk et al. (1999) [14] Cross-sectional 16 (9) HII >1.9 or histological iron grade >2 9 56.3% Two additional patients had serum ferritin of 1200 mg/Land 805 mg/L respectively, but did not undergo liverbiopsy. Cirrhosis was found in 1 patient, fibrosis in3 patients, and arthritis in 6 patientsDistante et al. (2000) [136] Cross-sectional& short termfollow upBulaj et al. (2000) [137] Cross-sectional –affectedindividualsCross-sectional –family membersCross-sectional –unselectedBarton et al. (1999) [138] Cross-sectional –family based14 (9) HII >1.9 or histological iron grade >2or congestive heart failure + markedand persistent hyperferritinemia andTS > 55%184 (48) At least one disease-relatedcondition (cirrhosis, fibrosis, elevatedALT or AST, arthropathy)3 21.4% Liver biopsy available only in 5 patients; a total of5 patients of whom 4 had no biopsy had persistenthyperferritinemia137 74.5%214 (101) 33 15.4%107 (41) 7 6.5%25 (n.d.) Cirrhosis or diabetes attributable toiron overload6–23 24–79% Ill-defined HC phenotype was present in a total of 23patientsBeutler et al. (2002) [21] Cross-sectional 152 (79) ‘liver problems’ (assessed in 124) 10 8.1% Signs and symptoms that would suggest a diagnosis of HCin only one patientWaalen et al. (2002) [139] Cross-sectional 141 (80) Only symptoms and serum ironparameters reportedDeugnier et al. (2002) [23] Cross-sectional 54 (44) At least one disease-relatedsymptom (fatigue, arthralgia,diabetes, increased ALT)Phatak et al. (2002) [26] Cross-sectional 12 (8) Iron removed >5 g for males and >3gfor females92 patients had elevated serum ferritin concentrations,disease-associated symptoms were equal in control groupand C282Y homozygotes35 64.8% 21 patients had increased serum iron parameters5 42% Increased serum ferritin in 50% of patientsPoullis et al. (2003) [98] Cross-sectional 12 (5) Histological iron grade >2 7 58% Increased serum ferritin in 11 out of 12 patients, butcoincidence of significant co-morbidities (HCV and iron in5 patients)Olynyk et al. (2004) [140] Longitudinal 10 (6) Hepatic iron >25 mmol/g 6 60% Gradual increase in TS over 10 year observation – nobiopsy in 4 patientscontinued on next pageClinical PracticeGuidelinesJournal of Hepatology 2010 | xxx–xxxxxPlease cite this article in press as:European Association for the Study of the Liver. EASL Clinical Practice Guidelines for HFE Hemochromatosis.J Hepatol (2010). doi: 10.1016/j.jhep.2010.03.001. © 2010 European Association for the Study of the Liver.