Beutler et al., 2002a³²; Beutler, et al., 2002b⁴⁸, Beutler, et al., 2000⁴⁹, Waalen, et al., 2002⁵⁰

KP San Diego
n = 41,038
Mean age, 57 y
Non-Hispanic white persons: 77%
140 C282YY homozygotes from KP San Diego screening study

152 of 41,038
3.7/1000

>0.50: men, 75%; women, 40%
Elevated overall: 57%
After exclusion of frequent blood donors: 76% men, 41% women

>250 µg/L: men, 76%
>200 µg/L: women, 54%
Elevated overall: 65%
After exclusion of frequent blood donors: men; 77%; women, 56%

NR
102 eligible (not previously treated)
54 completed treatment
13 of 54 (24%) had > 5 g iron removed

C282YY: 5.6%
Non-C282YY: 8.4%

AST level > 40 U/L
C282YY: 8.2%
Non-C282YY: 3.8%

NR

Good—excellent controls. Excluded previously identified C282Y homozygotes in determining prevalence of genotype and disease expression.

Deugnier, et al., 2002⁵¹

Brittany, France
n = 9396
35.8% men (deliberately weighted to include younger men)

54 of 9396
5.7/1000

>0.55: men, 80%
>0.50: women, 41%
Elevated overall: 48%

>280 µg/L: men, 70%
>130 µg/L: women, 33%
Elevated overall: 40%

NR

Men
C282YY: 0%
Non-C282YY: 0.8%

Women
C282YY: 2.3%
Non-C282YY: 0.9%

Men
ALT level > 70 U/L
C282YY: 10%
Non-C282YY: 5%

Women
ALT level > 35 U/L
C282YY: 5%
Non-C282YY: 5%

Fair—not strictly population-based because overselected. Inclusion of younger men could minimize disease expression.

Olynyk, et al., 1999⁵²

Busselton, Australia
n = 3011, randomly selected
50% men
Predominately white persons
Age, 20-79 y

16 of 3011
5.3/1000
4 of 16 previously diagnosed
12 new
C282YY (5.3/1000)

>0.45: 93.8%
2nd measurement
> 0.45: 93.8%

>300 µg/L: 50%
>300 µg/L in untreated persons: 58.3%

Liver biopsy: 7 of 12 (58%)
HII > 1.9: 4 of 7 (57.1%) of those having biopsy
33% of C282YY homozygotes
HIC > 20 µmol/g dry: 100% of those biopsied (7/7)
58% C282YY

NR

NR

Fibrosis: 29% of persons having biopsy (2 of 7)
Cirrhosis: 14% of persons having biopsy (1 of 7) (also had history of alcohol intake >60 g/d)
No controls

Good—considered confounders for liver disease. Excluded previously identified C282Y homozygotes.

Burt, et al., 1998⁵³

n = 1064 voters in New Zealand
39.8% men
Mean age: 50 y

5 of 1064
4.7/1000

>0.55: 100%

Second measurement:
>300 µg/L: men, 100%
>160 µg/L: women, 50%
Elevated overall: 60%

Liver biopsy: 60%
HII > 1.9:
3 of 3 (100%) selected C282YY homozygotes
3 of 5 (60%) all C282YY homozygotes

NR

NR

NR

Fair—did not exclude previously identified C282Y homozygotes, so estimates of screening prevalence are less accurate. Did not consider confounders for liver disease.

Distante, et al., 1999⁵⁴

n = 505 hospital employees in Oslo, Norway
79% women
Mean age: 38 y

2 of 505
4/1000

>0.50: 100%

>200 µg/L: 100%

TP in 50%: 5.2 g of iron removed
1 of 1 with IO by TP
HIC: 47 µmol/g
Biopsy: 0 of 1
IO: 50% selected C282YY homozygotes
Total IO: 100%

NR

NR

NR

Good

McDonnell, et al., 1999⁵⁵

n = 1450 HMO employees in Springfield, Missouri
83% women
98% white
Mean age: 41 y

6 of 1450
4.1/1000

>0.50: women, 2
>0.60: men, 2
Elevated overall: 67% of C282YY homozygotes

>95th percentile for age and sex:
50% of C282YY homozygotes

HII = 2.2:
1 of 1 by biopsy
1 of 2 by TP
2 of 3 (67%) of selected C282YY homozygotes
2 of 6 (33%) of all C282YY homozygotes

NR

NR

Fibrosis: 0 of 1 (0%)

Fair/good—some inconsistencies between data reported in text and figures/tables. Did not consider confounders for liver disease.

Delatycki, et al., 2005⁵⁶

n = 11,307 workplace employees in Australia
47% men
63% northern European

51 of 11,307
4 previously diagnosed
4.5/1000
47 new C282YY homozygotes

Criteria for elevation not given; 65% had "elevated" values

NR

6 recommended for testing; 4 had biopsy

NR

NR

Fibrosis:
2 of 4 had biopsy
50% of selected C282YY homozygotes
4.3% (2 of 47) of all C282YY homozygotes

Fair—did not exclude previously identified C282Y homozygotes, so estimates of screening prevalence are less accurate. Did not consider confounders for liver disease. Unclear criteria for iron overload.

Barton, et al., 1999⁵⁷

n = 150 relatives of 61 probands in Alabama
52% women
100% white
Mean age: 46 y
1 patient <18 y was C282YY homozygote

25/149
161/1000

> 0.50: women, 2
> 0.60: men, 2
Overall: 87.5%

300 µg/L (men)

200 µg/L (women)
Elevated overall: 96%

NR

16%

NR

2/25 (8%)

Fair—unable to determine how many tested family members were spouses.

Powell et al., 2006⁵⁸

401 C282YY first-degree relatives of 259 probands with proven C282YY-associated HC
50% female
Mean age:
Men, 38 y;
Women, 44 y

ND

Men: Mean, 72% (range, 12%-100%)
Women: Mean, 64% (range, 7%-100%)

Men: Median, 700 µg/L
Women: Median, 300 µg/L

Hepatic stain > 3+:

Men
Selected C282YY homozygotes: 82 of 111 (74%)
All C282YY homozygotes: 82 of 200 (41%)

Women
Selected C282YY homozygotes: 46 of 74 (62%)
All C282YY homozygotes: 46 of 201 (23%)

Men: 4 of 200 (2%)
Women: 7 of 201 (3%)

Men: 24%
Women: 7%

Fibrosis or cirrhosis:

Men
Selected C282YY homozygotes: 32 of 111 (29%)
All C282YY homozygotes: 32 of 200 (16%)

Women
Selected C282YY homozygotes: 5 of 74 (7%)
All C282YY homozygotes: 5 of 201 (2%)

Fair—large sample with reasonably well-specified diagnostic and case criteria. Sample clearly was selected, but no information provided to judge how selective. May fairly represent family screening-detected, but no information given on number tested or whether some were omitted. Did not represent "asymptomatic" general population screening because all persons who underwent genotyping had some initial elevation in serum iron levels. Very selective group for treatment responsiveness; all those with alcohol intake were omitted.