Multicenter Hemophilia Cohort Studies (MHCS) - Catalog

Name

Multicenter Hemophilia Cohort Studies (MHCS)

Accession Number

HLB00941221a

Acronym

MHCS

Related studies

BSI Study IDs

HEB

HEM

Is public use dataset

False

Keywords

Has Study Datasets

True

Has Specimens

True

Specimen ID Type

Coded

Study Website

The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.

False

Study type

Epidemiology Study

Collection Type

Open BioLINCC Study

Cohort type

Both

Interventions

Study Open Date (Data)

2012-09-04

Study Open Date (Specimens)

2010-09-24

Date materials available

2010-06-08

Last updated

2012-09-01

Study period

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

Study Contacts
NHLBI Division

DBDR

Classification

Blood Disease

HIV study classification

HIV

COVID study classification

non-COVID

Pre-Website # of Specimens Shipped

22

# of Returned Specimens

0

Primary Publication URLs
N/A
Conditions

Hepatocellular Carcinoma
Liver Failure
Non-Hodgkin Lymphoma

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.

Participants

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.

Disease classification

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

Mat types

DNA
Peripheral Blood Mononuclear Cells
Plasma
Red Blood Cells
Serum

Network

The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.

  • Subjects

    MHCS-I: 2061

    MHCS-II: 2570

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


    Last Modified: Nov. 17, 2023, 12:44 p.m.
  • Age

     

    MHCS-I

    MHCS-II

    Total Subjects

    Unknown

    896

    5

    901

    < 1

    11

    .

    11

    1-18

    307

    117

    424

    18-29

    392

    698

    1,090

    30-39

    273

    505

    778

    40-49

    104

    435

    539

    50-59

    47

    240

    287

    60-69

    27

    119

    146

    70-79

    4

    35

    39

    80-89

    .

    11

    11


    Last Modified: July 3, 2024, 8:32 a.m.
  • Sex

     

    MHCS-I

    MHCS-II

    Total Subjects

    Unknown

    21

    5

    26

    Male

    1,979

    2,032

    4,011

    Female

    61

    128

    189


    Last Modified: July 3, 2024, 8:32 a.m.
  • Race

     

    MHCS-I

    MHCS-II

    Total Subjects

    Unknown

    21

    5

    26

    White

    1,672

    1,768

    3,440

    Black

    225

    149

    374

    Other

    143

    243

    386


    Last Modified: July 3, 2024, 8:32 a.m.

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

  • Material Types
  • General Freeze/Thaw Status
  • Visits (Vials)

    07/03/2024

     

    Serum

    Plasma

    DNA

    PERIPHERAL BL MONO CELLS

    Total Vials

    Subjects with 1 visit

    1,164

    8,113

    7,170

    3,912

    20,359

    Subjects with 2 visits

    1,829

    16,689

    2,603

    9,192

    30,313

    Subjects with 3 visits

    1,740

    27,163

    317

    15,342

    44,562

    Subjects with 4 visits

    1,701

    24,543

    39

    12,618

    38,901

    Subjects with 5-10 visits

    5,625

    55,190

    21

    20,575

    81,411

    Subjects with 11+ visits

    13,632

    69,386

    .

    22,483

    105,501

    Subjects with no visit date

    .

    .

    3

    .

    3


    Last Modified: July 3, 2024, 8:32 a.m.
  • Visits (Subjects)

    07/03/2024

     

    Serum

    Total number of subjects

    Average volume (mL) per subject

    Subjects with 1 visit

    299

    1.45

    Subjects with 2 visits

    241

    2.97

    Subjects with 3 visits

    168

    4.35

    Subjects with 4 visits

    126

    5.56

    Subjects with 5-10 visits

    263

    8.28

    Subjects with 11+ visits

    211

    23.89

     

     

    Plasma

    Total number of subjects

    Average volume (mL) per subject

    Subjects with 1 visit

    722

    5.18

    Subjects with 2 visits

    751

    10.50

    Subjects with 3 visits

    798

    16.25

    Subjects with 4 visits

    535

    22.36

    Subjects with 5-10 visits

    713

    39.85

    Subjects with 11+ visits

    396

    97.82

     

     

    DNA

    Total number of subjects

    Average mass (ug) per subject

    Subjects with no visit date

    1

    3.00

    Subjects with 1 visit

    1,788

    4.01

    Subjects with 2 visits

    420

    6.20

    Subjects with 3 visits

    45

    7.04

    Subjects with 4 visits

    4

    9.75

    Subjects with 5-10 visits

    1

    21.00

     

     

    PERIPHERAL BL MONO CELLS

    Total number of subjects

    Average volume (mL) per subject

    Subjects with 1 visit

    709

    5.52

    Subjects with 2 visits

    792

    11.61

    Subjects with 3 visits

    814

    18.85

    Subjects with 4 visits

    525

    24.03

    Subjects with 5-10 visits

    646

    31.85

    Subjects with 11+ visits

    298

    75.45


    Last Modified: July 3, 2024, 8:34 a.m.