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Home > Studies > Multicenter Hemophilia Cohort Studies (MHCS)

Multicenter Hemophilia Cohort Studies (MHCS)

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Accession Number
HLB00941221a

Study Type
Epidemiology Study

Collection Type
Open BioLINCC Study See bottom of this webpage for request information

Study Period
MHCS-I: 1982-1996 ; MHCS-II: 2001-2005

NHLBI Division
DBDR

Dataset(s) Last Updated
July 27, 2021

Clinical Trial URLs
https://clinicaltrials.gov/ct2/show/NCT00341705

Primary Publication URLs
N/A

Consent

Commercial Use Data Restrictions No

Data Restrictions Based On Area Of Research No

Commercial Use Specimen Restrictions No

Non-Genetic Use Specimen Restrictions Based On Area Of Use Yes

Genetic Use Of Specimens Allowed? Yes

Genetic Use Area Of Research Restrictions Yes

Specific Consent Restrictions
Consent for MHCS I specimens restricts their use to research related to hemophilia or its complications (which includes HIV, AIDS, hepatitis and other viruses). Consent for MHCS II specimens restricts their use to research related to HIV, HCV, other viruses, human genes (DNA), and future developments that are relevant to these viruses, hemophilia and their complications.

Objectives

The First Multicenter Hemophilia Cohort Study (MHCS-I) evaluated and prospectively followed patients with hemophilia or a related coagulation disorder. Initiated in 1982, this study particularly sought to understand the cause and natural history of HIV infection and AIDS in this population which was at high risk for development of AIDS.

The Second Multicenter Hemophilia Cohort Study (MHCS-II) evaluated and prospectively followed a cohort of subjects with hemophilia who were exposed to hepatitis C virus (HCV). The primary objectives were to quantify the rates of liver decompensation, hepatocellular carcinoma, and non-Hodgkin lymphoma and to evaluate candidate clinical, genetic, virologic, serologic and immunologic markers that are likely to be on the causal pathway for these conditions, identify predictive clinical and laboratory markers and follow the markers over time, identify host genes that confer susceptibility or resistance to HCV and HIV infections or to the diseases that result from these infections and to identify response and complication rates of various anti-HCV and anti-HIV regimens in the setting of comprehensive clinical care of persons with hemophilia.

Background

Treatment of hemophilia patients with contaminated plasma products before 1990 resulted in extraordinary prevalence rates of human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV, HCV). The first cases of acquired immunodeficiency syndrome (AIDS) were reported in the United States in 1981 and the first cases of AIDS in hemophilia patients were reported one year later. In contrast to HIV-1, HBV, HCV were present in the human population and HBV and HCV were almost certainly was always a contaminant of blood and plasma donated for transfusion prior to the development of diagnostic tests to screen blood donors.

Subjects

Adults and children who had a congenital coagulation disorder [hemophilia A or B (congenital factor VIII or IX deficiency)] von Willebrand's disease, or other were enrolled from 8 collaborating hemophilia centers in the US between 1982 and 1985. Four additional centers from the US and 4 centers from Europe joined the study between 1987 and 1990.

In MHCS-II, 52 collaborating hemophilia centers in North and South America and Europe, enrolled patients who had a congenital coagulation disorder [hemophilia A or B (congenital factor VIII or IX deficiency), von Willebrand's disease, or other], who had reached 13 years of age, and who had serological or molecular evidence of HCV or HIV-1 infection. The majority of subjects consisted of a "HCV cohort" of whom a portion was co-infected with HIV, the "HIV cohort".

Design

In MHCS-I, subjects were evaluated semiannually with a standardized physical examination, abstraction of medical records, and phlebotomy.

In MHCS-II, The natural time scale was used, beginning with the estimated date of HCV or HIV infection to an event of interest, death, or censoring. Time initiated on the estimated date of HCV infection (HCV cohort) or HIV infection (HIV cohort) but follow-up was defined as the date of the first blood sample collected for the MHCS-I or -II. The main outcomes were liver decompensation, hepatocellular carcinoma and non-Hodgkin lymphoma. Measures included HCV viral load, anti-HCV levels and other markers of the primary outcomes such as serum cholesterol and inflammatory cytokine levels; host genetic polymorphism.

Conclusions

Nearly one-third of the MHCS-II participants were infected with HIV-1, many of whom were infected in childhood and all of whom have survived with HIV-1 for more than 15 years. As survivors, relatively few of them had an AIDS-defining opportunistic infection or malignancy (17%) or laboratory-defined AIDS. In contrast to use of HAART for HIV-1 infection, only a minority of MHCS-II participants had been treated for their HCV infection. In the MHCS-II cohort of HCV-seropositive people with hemophilia and related coagulation disorders, the prevalence rates of ascites, hepatomegaly, splenomegaly and persistent jaundice were 2- to 3-fold higher with HIV-1, when adjusted for age and most could not be ascribed to HAART or other anti-HIV-1 regimens.

In the MHCS-II, 74% of the HIV-1-positive and 51% of the HIV-1-negative participants had evidence of current or previous HBV infection. In MHCS-I, the risk of decompensated end stage liver disease was increased 8.1-fold for carriers of hepatitis B surface antigen (HBsAg) and 3.4-fold for the much larger group of hemophiliacs who had cleared HBsAg.

Publications

Melendez-Morales L, Konkle BA, Preiss L, Zhang M, Mathew P, Eyster ME, Goedert JJ. Chronic hepatitis B and other correlates of spontaneous clearance of hepatitis C virus among HIV-infected people with hemophilia. AIDS. 2007; 21(12):1631-6.


Goedert JJ; Second Multicenter Hemophilia Cohort Study. Prevalence of conditions associated with human immunodeficiency and hepatitis virus infections among persons with haemophilia, 2001-2003. Haemophilia. 2005; 11(5):516-28.


Engels EA, Frisch M, Lubin JH, Gail MH, Biggar RJ, Goedert JJ. Prevalence of hepatitis C virus infection and risk for hepatocellular carcinoma and non-Hodgkin lymphoma in AIDS. J Acquir Immune Defic Syndr. 2002; 31(5):536-41.


Goedert JJ, Eyster ME, Lederman MM, Mandalaki T, De Moerloose P, White GC 2nd, Angiolillo AL, Luban NL, Sherman KE, Manco-Johnson M, Preiss L, Leissinger C, Kessler CM, Cohen AR, DiMichele D, Hilgartner MW, Aledort LM, Kroner BL, Rosenberg PS, Hatzakis A. End-stage liver disease in persons with hemophilia and transfusion-associated infections. Blood. 2002; 100(5):1584-9.


O'Brien TR, Blattner WA, Waters D, Eyster E, Hilgartner MW, Cohen AR, Luban N, Hatzakis A, Aledort LM, Rosenberg PS, Miley WJ, Kroner BL, Goedert JJ. Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. JAMA. 1996; 276(2):105-10.


Ehmann WC, Eyster ME, Wilson SE, Andes WA, Goedert JJ. Relationship of CD4 lymphocyte counts to survival in a cohort of hemophiliacs infected with HIV. Multicenter Hemophilia Cohort Study. J Acquir Immune Defic Syndr. 1994;7(10):1095-8.


Goedert JJ, Cohen AR, Kessler CM, Eichinger S, Seremetis SV, Rabkin CS, Yellin FJ, Rosenberg PS, Aledort LM. Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate. Multicenter Hemophilia Cohort Study. Lancet. 1994; 344(8925):791-2. Erratum in: Lancet 1994; 344(8931):1238.


Eyster ME, Fried MW, Di Bisceglie AM, Goedert JJ. Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood. 1994; 84(4):1020-3.


Goedert JJ, Kessler CM, Aledort LM, Biggar RJ, Andes WA, White GC 2nd, Drummond JE, Vaidya K, Mann DL, Eyster ME, et al. A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. N Engl J Med.1989; 321(17):1141-8.


Lozier JN, Rosenberg PS, Goedert JJ, Menashe I. (2011), A case–control study reveals immunoregulatory gene haplotypes that influence inhibitor risk in severe haemophilia A. Haemophilia, 17: no. doi: 10.1111/j.1365-2516.2010.02473.x

Additional Details

Study Population

Subjects:

MHCS-I: 2061

MHCS-II: 2570

*There are 405 subjects enrolled in MHCS-I and MHCS-II

Age:

MHCS-I:

 

Frequency

Percent

Cumulative
Frequency

Cumulative
Percent

Unknown

896

43.47

896

43.47

<1

11

0.53

907

44.01

1-10

134

6.50

1041

50.51

11-20

270

13.10

1311

63.61

21-30

331

16.06

1642

79.67

31-40

249

12.08

1891

91.75

41-50

95

4.61

1986

96.36

51-60

47

2.28

2033

98.64

61-70

25

1.21

2058

99.85

71-80

3

0.15

2061

100.00

 

MHCS-II:

 

Frequency

Percent

Cumulative
Frequency

Cumulative
Percent

Unknown

5

0.19

5

0.19

11-20

351

13.66

356

13.85

21-30

654

25.45

1010

39.30

31-40

623

24.24

1633

63.54

41-50

500

19.46

2133

83.00

51-60

281

10.93

2414

93.93

61-70

109

4.24

2523

98.17

71-80

39

1.52

2562

99.69

>80

8

0.31

2570

100.00

 
 
Sex:

MHCS-I:

 

Frequency

Percent

Cumulative
Frequency

Cumulative
Percent

Unknown

24

1.16

24

1.16

Male

1976

95.88

2000

97.04

Female

61

2.96

2061

100.00

 

MHCS-II:
 

Frequency

Percent

Cumulative
Frequency

Cumulative
Percent

Unknown

5

0.19

5

0.19

Male

2431

94.59

2436

94.79

Female

134

5.21

2570

100.00

 
Race:

MHCS-I:

 

Frequency

Percent

Cumulative
Frequency

Cumulative
Percent

Unknown

24

1.16

24

1.16

White

1670

81.03

1694

82.19

Black

225

10.92

1919

93.11

Other

142

6.89

2061

100.00

 

MHCS-II:

 

Frequency

Percent

Cumulative
Frequency

Cumulative
Percent

Unknown

5

0.19

5

0.19

White

2056

80.00

2061

80.19

Black

214

8.33

2275

88.52

Other

295

11.48

2570

100.00

 

Available Biospecimens

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3 of the BioLINCC handbook describes the components of the review process

Visits (Vials):

04/28/2022

  Serum Plasma Red Blood Cells DNA PBMC Total
Subjects with 1 visit 1,198 7,969 1,232 7,222 3,976 21,597
Subjects with 2 visits 1,824 16,874 2,424 2,641 9,306 33,069
Subjects with 3 visits 1,747 26,854 2,241 317 15,426 46,585
Subjects with 4 visits 1,693 25,527 657 27 12,772 40,676
Subjects with 5-10 visits 5,646 55,923 10 39 20,683 82,301
Subjects with 11+ visits 13,638 68,569 0 0 22,392 104,599
Subjects with no visit date 9 109 0 3 8 129

 
Visits (Subjects):

04/28/2022

  Serum
Total number of subjects Average volume (ml) per subject
Subjects with 1 visit 309 1.44
Subjects with 2 visits 241 2.95
Subjects with 3 visits 169 4.34
Subjects with 4 visits 125 5.58
Subjects with 5-10 visits 265 8.24
Subjects with 11+ visits 211 23.90
Subjects with no visit date 5 0.84
 
  Plasma
Total number of subjects Average volume (ml) per subject
Subjects with 1 visit 747 4.97
Subjects with 2 visits 767 10.40
Subjects with 3 visits 789 16.28
Subjects with 4 visits 557 22.27
Subjects with 5-10 visits 726 39.66
Subjects with 11+ visits 396 97.17
Subjects with no visit date 24 2.64
 
  PBMC
Total number of subjects Average vials per subject
Subjects with 1 visit 724 5.49
Subjects with 2 visits 794 11.72
Subjects with 3 visits 813 18.97
Subjects with 4 visits 526 24.28
Subjects with 5-10 visits 647 31.97
Subjects with 11+ visits 301 74.39
Subjects with no visit date 1 8.00
 
  Red Blood Cells
Total number of subjects Average vials per subject
Subjects with 1 visit 625 1.97
Subjects with 2 visits 608 3.99
Subjects with 3 visits 374 5.99
Subjects with 4 visits 82 8.01
Subjects with 5-10 visits 1 10.00
 
  DNA
Total number of subjects Average mass (µg) per subject Average vials per subject
Subjects with 1 visit 1,814 13.37 3.98
Subjects with 2 visits 425 17.59 6.21
Subjects with 3 visits 45 16.14 7.04
Subjects with 4 visits 3 25.18 9.00
Subjects with 5-10 visits 2 11.70 19.50
Subjects with no visit date 1 2.32 3.00

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Resources Available

Specimens and Study Datasets

Study Catalog

Study Publications (5)

Materials Available

  • DNA
  • Peripheral Blood Mononuclear Cells
  • Plasma
  • Red Blood Cells
  • Serum
  • More Details

Study Documents

  • PDF Data Dictionary (PDF - 4.8 MB)
  • PDF MHCS-I protocol (PDF - 456.5 KB)
  • PDF MHCS-II protocol (PDF - 114.5 KB)
  • Forms

Persons using assistive technology may not be able to fully access information in the study documents. For assistance, Contact BioLINCC and include the web address and/or publication title in your message. If you need help accessing information in different file formats such as PDF, XLS, DOC, see Instructions for Downloading Viewers and Players.

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