title: End-stage liver disease in persons with hemophilia and transfusion-associated infections.
abstract: 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 x 10(9)/L (200/microL) 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. goedertj@mail.nih.gov
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: M Elaine
authors.initials: ME
authors.lastname: Eyster
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Titica
authors.initials: T
authors.lastname: Mandalaki
authors.forename: Philippe
authors.initials: P
authors.lastname: De Moerloose
authors.forename: Gilbert C
authors.initials: GC
authors.lastname: White
authors.forename: Anne L
authors.initials: AL
authors.lastname: Angiolillo
authors.forename: Naomi L C
authors.initials: NL
authors.lastname: Luban
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Marilyn
authors.initials: M
authors.lastname: Manco-Johnson
authors.forename: Liliana
authors.initials: L
authors.lastname: Preiss
authors.forename: Cindy
authors.initials: C
authors.lastname: Leissinger
authors.forename: Craig M
authors.initials: CM
authors.lastname: Kessler
authors.forename: Alan R
authors.initials: AR
authors.lastname: Cohen
authors.forename: Donna
authors.initials: D
authors.lastname: DiMichele
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Hilgartner
authors.forename: Louis M
authors.initials: LM
authors.lastname: Aledort
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Kroner
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Angelos
authors.initials: A
authors.lastname: Hatzakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000209:etiology / Q000503:physiopathology; D006467:Hemophilia A / Q000628:therapy*; D006509:Hepatitis B / Q000209:etiology / Q000503:physiopathology; D006526:Hepatitis C / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D007223:Infant; D017114:Liver Failure, Acute / Q000209:etiology* / Q000821:virology; D008297:Male; D011446:Prospective Studies; D065227:Transfusion Reaction