Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis.
BACKGROUND
DNA-based HFE gene testing can confirm hereditary hemochromatosis in most people of Northern European descent. However, liver biopsy is important to detect cirrhosis.


OBJECTIVE
To develop noninvasive criteria to predict the presence or absence of advanced hepatic fibrosis or cirrhosis in Americans with hemochromatosis.


METHODS
Cross-sectional study.


METHODS
Six tertiary care referral clinics.


METHODS
182 patients with phenotypically defined hemochromatosis.


METHODS
Liver histopathology and serum ferritin, aspartate aminotransferase, and alanine aminotransferase levels. Multivariate logistic regression analysis was used to examine factors associated with cirrhosis (defined as bridging fibrosis or unequivocal cirrhosis on biopsy).


RESULTS
Cirrhosis was present in 40 of 182 (22%) patients in the overall group and in 35 of 147 (24%) of C282Y homozygotes. Only 1 of 93 patients with a serum ferritin level less than 1000 microg/L had cirrhosis compared with 39 of 89 patients with serum ferritin levels greater than 1000 microg/L (P < 0.001). No C282Y homozygotes or C282Y/H63D compound heterozygotes with serum ferritin levels less than 1000 microg/L had cirrhosis. Elevated serum aminotransferase levels (P = 0.001) and serum ferritin levels greater than 1000 microg/L (P = 0.001), but not age older than 40 years (P = 0.2), were independently associated with cirrhosis. In a multivariate model, the probability of cirrhosis was 7.4% among patients with serum ferritin levels less than 1000 microg/L compared with 72% among patients with serum ferritin levels greater than 1000 microg/L after adjustment for age and elevated serum liver enzyme levels.


CONCLUSIONS
Patients with hemochromatosis and serum ferritin levels less than 1000 microg/L are unlikely to have cirrhosis. Liver biopsy to screen for cirrhosis may be unnecessary in such patients, regardless of age or serum liver enzyme levels.
Morrison
Elizabeth D
ED
University of Washington, Seattle, Washington 98195, USA.
Brandhagen
David J
DJ
Phatak
Pradyumna D
PD
Barton
James C
JC
Krawitt
Edward L
EL
El-Serag
Hashem B
HB
Gordon
Stuart C
SC
Galan
Mark V
MV
Tung
Bruce Y
BY
Ioannou
George N
GN
Kowdley
Kris V
KV
D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D003430:Cross-Sectional Studies; D005293:Ferritins / Q000097:blood*; D006432:Hemochromatosis / Q000150:complications*; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000209:etiology; D008111:Liver Function Tests; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012372:ROC Curve; D012044:Regression Analysis; D014481:United States
D005293:Ferritins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase