Multicenter Hemophilia Cohort Studies (MHCS-I and MHCS-II)
Clinical Trials URL:
Study Type: Epidemiology Study
Prepared on June 8, 2010
Last Updated on September 1, 2012
Study Dates: MHCS-I: 1982-1996 ; MHCS-II: 2001-2005
Consent: Unrestricted Consent
Commercial Use Restrictions: No
NHLBI Division: DBDR
Collection Type: Open BioLINCC Study - See bottom of this webpage for request information
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.
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.
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".
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.
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.
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