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Blood, 1 September 2002, Vol. 100, No. 5, pp. 1584-1589
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
End-stage liver disease in persons with hemophilia and
transfusion-associated infections
James J. Goedert,
M. Elaine Eyster,
Michael M. Lederman,
Titica Mandalaki,
Philippe de
Moerloose,
Gilbert C. White II,
Anne L. Angiolillo,
Naomi L. C. Luban,
Kenneth E. Sherman,
Marilyn Manco-Johnson,
Liliana Preiss,
Cindy Leissinger,
Craig M. Kessler,
Alan R. Cohen,
Donna DiMichele,
Margaret W. Hilgartner,
Louis M. Aledort,
Barbara L. Kroner,
Philip S. Rosenberg, and
Angelos Hatzakis for the Multicenter Hemophilia Cohort
Study
From the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, Rockville, MD; Milton S. Hershey
Medical Center, Pennsylvania State University School of Medicine; Case
Western Reserve University School of Medicine, Cleveland, OH;
Hemophilia Center, Second Regional Blood Transfusion Center, Laikon
General Hospital, Athens, Greece; Hôpital Cantonal Universitaire,
Geneva, Switzerland; Comprehensive Hemophilia Center, University of
North Carolina, Chapel Hill; Department of Hematology, Children's
Hospital National Medical Center, Washington, DC; Division of Digestive
Diseases, University of Cincinnati Medical Center, OH; Mountain States
Regional Hemophilia and Thrombosis Program, University of Colorado,
Aurora; Research Triangle Institute, Rockville, MD; Section of
Hematology/Oncology, Tulane University Medical School, New Orleans, LA;
Lombardi Cancer Research Center, Georgetown University Hospital,
Washington, DC; Department of Hematology, Children's Hospital of
Philadelphia, PA; Hemophilia Treatment Center, New York Presbyterian
Hospital, NY; Hemophilia Center, Mount Sinai Medical Center, New York,
NY; and National Retrovirus Reference Center, Athens University School
of Medicine, Athens, Greece. Other collaborators and institutions of
the Multicenter Hemophilia Cohort Study are listed in the appendix at
the end of this article.
Many persons with hemophilia were infected with hepatitis C
and B viruses (HCV, HBV) and HIV, but the consequences of these transfusion-acquired infections are poorly defined. We estimated the
risk of HCV-related end-stage liver disease (ESLD) and the associations
of age, HBV, and HIV with that risk. All 1816 HCV-seropositive hemophilic patients at 16 centers were followed for up to 16 years. Of
these, 624 were HIV and 1192 were HIV-coinfected; 135 had
persistent HBV surface antigenemia, 1374 had resolved HBV infection,
and 287 were HBV-uninfected. ESLD was defined as bleeding esophageal
varices, hepatic encephalopathy, persistent ascites, or death excluding
nonhepatic causes of these conditions. Competing risk models were used
to estimate the annual hazard rate and cumulative incidence of ESLD.
Proportional hazards models were used to estimate relative hazards of
ESLD with covariates. ESLD developed in 127 of the HCV/HIV-coinfected
participants, with an estimated 16-year cumulative incidence of 14.0%
(95% confidence interval [CI], 11.6%-16.4%). Without HIV, 10 HCV-infected participants developed ESLD, for a significantly lower
cumulative incidence of 2.6% (95% CI, 1.0%-4.3%,
P < .0001). ESLD risk increased steeply with age in both
groups. With HIV, ESLD risk was increased 8.1-fold (95% CI, 1.9-35.2)
with HBV surface antigenemia, 2.1-fold (95% CI, 1.3-3.3) with fewer
than 0.2 × 109/L (200/µL) CD4+
lymphocytes, and 1.04-fold (95% CI, 1.03-1.06) per year of age. Thus,
HIV is associated with a markedly increased risk of HCV-related ESLD
for persons with hemophilia, particularly with HBV infection, low
CD4+ lymphocytes, or older age.
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