Testing for haemochromatosis in a liver clinic population: relationship between ethnic origin, HFE gene mutations, liver histology and serum iron markers
Bibliographic record
Abstract
OBJECTIVE: To identify the most appropriate testing strategy for genetic haemochromatosis in a liver clinic population by determining the ethnic distribution of the HFE mutations and the relationship between serum iron markers, hepatic siderosis and HFE genotype. DESIGN AND SETTING: Observational study of 427 patients being investigated for abnormal liver function tests between 1997 and 2000 attending a liver clinic at a teaching district general hospital in south London, UK. METHODS: All patients were tested for H63D and C282Y gene mutations, and the ethnic origin was determined. Data were available for most patients for non-fasting serum iron, ferritin and transferrin saturation on presentation and fibrosis and siderosis scores from liver biopsy. RESULTS: The C282Y mutation was not detected in any patients of Asian or Afro-Caribbean origin but was found almost exclusively in northern Europeans, especially those classified as Celtic, one in seven of whom were heterozygous for this mutation. Three per cent of all the patients tested were C282Y homozygotes. The H63D mutation was distributed more widely. An elevated serum transferrin saturation was both a more sensitive and a more specific test for genetic haemochromatosis than either serum ferritin or iron. Significantly raised mean siderosis scores were found on liver biopsy in C282Y homozygote and C282Y/H63D compound heterozygote groups but not in wild-type, simple heterozygote, or H63D homozygote groups. Forty-five per cent of the C282Y homozygotes detected already had cirrhosis. CONCLUSIONS: In a multiracial liver clinic population, previously undiagnosed C282Y homozygosity was found to be common (3% in our study) but restricted to those of northern European heritage, particularly those with Celtic ancestry. A serum transferrin saturation proved a better initial test to select patients for genotyping than serum iron or ferritin. Laboratory costs can be minimized with no loss of diagnostic sensitivity by selecting patients for genotyping based on northern European ethnic origin and raised serum transferrin saturation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".