Adams, et al., 1991²⁵

Specialty clinic
Canada
Retrospective case series

n = 85

Probands: 48

Discovered family members: 37

Men: 53

Arthritis: 40

Diabetes: 18

Diagnosed between 1958 and 1989

Diagnosis was based on clinical history, physical examination, SF levels, and TS and was confirmed through liver biopsy

Patients with iron-loading anemias, transfusional iron overload, and dietary iron overload were excluded

Survival was compared against provincial life-table data matched for age and sex

Mean: 8.1 (SD, 6.8) y

Analysis was censored at 20 y because only 5 patients were followed for >20 y

500 mL blood/wk until SF level <30 µg/L or patient became anemic

Mean number of treatments: 43 (SD, 51)

Treatment resumed if SF levels became elevated

Deaths: 17

Cumulative survival:
5 y: 87%
10 y: 81%
20 y: 71%

Expected survival: significantly decreased survival at all times except 1 y and >14 y

No significant difference between noncirrhotic patients and hypothetical cohort of age- and sex-matched patients

Adjusted RR for death:
Cirrhosis: 5.54
Arthritis: 0.24

NR

Fair

Bomford and Williams, 1976⁵⁹

Specialty clinic
United Kingdom
Case series

n = 111

Patients diagnosed through routine clinical practice who received treatment

Treated: 85

Untreated controls: 26

Excluded persons with secondary iron overload. Diagnosis made "by clinical, biochemical and where possible histological criteria"

26 untreated historical controls who were not comparable to treated patients

1937 to approximately 1975

600 mL was removed weekly until hemoglobin < 10 g/dL and serum iron level decreased to <10 µmol/L

Biopsy usually repeated after completion of treatment. Treatment resumed if chelatable body iron levels increased to >1000 µg/kg body weight

79 of 85 completed full course

Diabetes: 56
Improved: 16 of 56
Worsened: 7 of 56
New cases: 3

Liver histology: 75
Improved: 5 of 75
No definite change: 68 of 75
Worsened: 2 of 75

NR

Fair

Niederau, et al., 1996⁶⁰

Diagnosed patients from primary care clinics
Germany
Retrospective case series

n = 251

Mean age: 45.7 (SD, 10.8) y

Men: 224

Noncirrhotic: 109
Asymptomatic: 41
Family screening: 15

Cirrhotic: 142
Asymptomatic: 7

Diabetic: 120

2 lost to followup

Diagnosed between 1947 and 1991

Patients were diagnosed on basis of clinical features and biochemical test results: liver function, serum iron, TS, and SF. Confirmed by liver biopsy

Expected deaths were calculated for a German normal population that was age- and sex-matched for time period of observation

Mean: 14.1 (SD, 6.8) y

From 1979 on, patients were treated 1-2 times/wk by TP (500 mL) until SF levels were normal

185 patients with documented iron depletion received mean of 84.8 (SD, 4.4) treatments to achieve depletion

All patients underwent 4-12 TPs per y after depletion

Cumulative survival:
5 y: 93%
10 y: 77%
20 y: 55%
30 y: 20%

Significantly reduced compared with expected survival in matched population

Select Table 9a for details of liver iron concentration at diagnosis per fibrosis stage.

Select Tables 9b and 9c for details of changes in fibrosis stage after iron depletion and symptoms.

NR

Fair-poor

McDonnell, et al., 1999⁵⁵

Population-based mailings to all known patients with HC and organizations with access to patients with HC in United States, Canada, Australia, and northern Europe

Patients from >17 countries, including United States (84%), Australia (6%), United Kingdom (6%), and Canada (4%)

Retrospective cross-sectional study

n = 2851 patients (80% of all surveys mailed)

White: 99%

Men: 62%

Diagnosis made 1990 or later: 70%

Diagnosis made before 1980: 6%

Led to diagnosis: 35% from symptoms related to hereditary HC, 45% from routine or ancillary laboratory test, 20% from diagnosis of family member

56% diagnosed by primary care physician

67% initially diagnosed with alternate condition to explain symptoms

Mean age at symptom onset: 41 (SD, 14) y

Mean age when sought treatment: 43 (SD, 14) y

Mean age at diagnosis: 50 (SD, 13) y

None

NA

Location at which patient had TP: physician's office/hospital (73%), blood bank (25%), home (0.1%)

Some or all symptoms improved with therapy: 86%

Mean time for improvement: 39 (SD, 67) wk

New symptoms developed despite treatment: 33%

Select Table 9d for details.

Compared with NHANES II and III, similar proportion of patients reported arthritis, liver or gallbladder disease, and extreme fatigue as general population

65% of patients with symptoms said the benefit of treatment outweighed difficulties

20% found the process routine and expressed indifference

12% expressed a negative attitude toward TP that they attributed to poor venous access, time involved, dissatisfaction that the removed blood was discarded

Fair

Powell, et al., 2006⁵⁸

First-degree relatives of C282Y homozygotes with clinical HC or screened population with elevated serum iron measures

Australia

Prospective cross-sectional study

n = 672,401 from family screening; 271 from primary care screening

Underwent biopsy after TP: 25

Patients were those with "uncertainty about cirrhosis or persistently abnormal liver enzyme levels"

White: predominantly

Men: 53%

Homozygotes identified from family or primary care screening

Those with high alcohol intake were not analyzed for changes in cirrhosis/fibrosis (n = 5)

None

Up to 24 years

TP until TS <0.15 or SF level <20 µg/L

NR because of high alcohol intake: 5 of 25 (20%)

Improved fibrosis score: 19 of 20 (95%)

No change in cirrhosis: 1 of 20 (5%)

NR

Fair