title: Serum hyaluronic acid with serum ferritin accurately predicts cirrhosis and reduces the need for liver biopsy in C282Y hemochromatosis.
abstract: Diagnosing the presence of cirrhosis is crucial for the management of patients with C282Y hereditary hemochromatosis (HH). HH patients with serum ferritin >1,000 microg/L are at risk of cirrhosis; however, the majority of these patients do not have cirrhosis. Noninvasive markers of hepatic fibrosis may assist in determining which patients with a serum ferritin >1,000 microg/L have cirrhosis and require liver biopsy. This study evaluated the utility of current diagnostic algorithms for detecting cirrhosis, including serum ferritin concentration, platelet counts, and aspartate aminotransferase (AST) levels, in combination with serum markers of fibrosis, hyaluronic acid and collagen type IV (CLIV), in predicting cirrhosis in HH patients. Stage of fibrosis, serum hyaluronic acid and CLIV levels, were measured in 56 patients with HH. No patient with a serum ferritin <1,000 microg/L had cirrhosis, but only 40% of patients with serum ferritin >1,000 microg/L were cirrhotic. A combination of platelet count (<200 x 10(9)/L), elevated AST, and serum ferritin >1,000 microg/L did not detect 30% of cirrhotic subjects. Serum hyaluronic acid was increased in HH compared with controls (42.0 +/- 9.8 ng/mL versus 19.3 +/- 1.8 ng/mL; P = 0.02). A hyaluronic acid concentration >46.5 ng/mL was 100% sensitive and 100% specific in identifying patients with cirrhosis. In patients with serum ferritin >1,000 microg/L, hyaluronic acid levels were significantly elevated in patients with cirrhosis versus those without cirrhosis (137 +/- 34.4 ng/mL versus 18.6 +/- 1.5 ng/mL, respectively; P = 0.006). CLIV >113 ng/mL was 100% sensitive but only 56% specific for cirrhosis (area under the curve = 0.78; P = 0.01).
  
  
  CONCLUSIONS
  In HH, the measurement of hyaluronic acid in patients with serum ferritin >1,000 microg/L is a noninvasive, accurate, and cost-effective method for the diagnosis of cirrhosis. (HEPATOLOGY 2009;49:418-425.).
authors.affiliation: School of Medicine, The University of Queensland, Greenslopes Private Hospital, Brisbane, Australia.
authors.forename: Darrell H G
authors.initials: DH
authors.lastname: Crawford
authors.forename: Therese L
authors.initials: TL
authors.lastname: Murphy
authors.forename: Louise E
authors.initials: LE
authors.lastname: Ramm
authors.forename: Linda M
authors.initials: LM
authors.lastname: Fletcher
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Clouston
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
authors.forename: V Nathan
authors.initials: VN
authors.lastname: Subramaniam
authors.forename: Lawrie W
authors.initials: LW
authors.lastname: Powell
authors.forename: Grant A
authors.initials: GA
authors.lastname: Ramm
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D005234:Fatty Liver / Q000453:epidemiology; D005260:Female; D005293:Ferritins / Q000097:blood*; D006432:Hemochromatosis / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010976:Platelet Count; D011237:Predictive Value of Tests; D012372:ROC Curve
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D006820:Hyaluronic Acid; D005293:Ferritins; D007501:Iron; D001219:Aspartate Aminotransferases