title: The natural history of HCV in a cohort of haemophilic patients infected between 1961 and 1985.
abstract: OBJECTIVE
  This study describes the long term follow up of haemophilic patients infected with hepatitis C virus (HCV) between 1961 and 1985.
  
  
  METHODS
  Clinical and treatment records from 310 patients with inherited coagulation disorders treated with blood product before 1985 were reviewed. Standard survival analysis methods were used to model progression to liver failure and death.
  
  
  RESULTS
  A total of 298/305 (98%) patients tested were anti-HCV positive. Twenty seven (9%) individuals consistently HCV polymerase chain reaction negative were considered to have cleared the virus. By 1 September 1999, 223/310 (72%) were alive, 26 (8%) had died a liver related death, and 61 (20%) had died from other, predominantly human immunodeficiency virus (HIV) related, causes. Kaplan-Meier progression rates to death from any cause and liver related deaths 25 years after exposure to HCV were 47% (95% confidence intervals (CI) 34-60) and 19% (95% CI 10-27), respectively. After 13.3 years from 1985, by which time all patients had seroconverted to HIV, progression rates to death from any cause and liver related deaths were, respectively, 8% (95% CI 4-13) and 3% (95% CI 0.4-6) for those HIV negative, and 57% (95% CI 48-66) and 21% (95% CI 13-31) for those HIV positive (p=0.0001). Using Cox proportional hazard models, the adjusted relative hazard of death for individuals coinfected with HIV compared with those infected with HCV alone was 19.47 (95% CI 9.22-41.10), 0.99 (95% CI 0.39-2.53), 3.47 (95% CI 1.40-8.63), and 9.74 (95% CI 3.91-24.26) for the age groups at infection 10-19 years, 20-29 years, and >30 years, respectively, compared with the age group <10 years. The adjusted relative hazard for genotype 1 compared with other genotypes was 2.7 (95% CI 1.36-5.15).
  
  
  CONCLUSIONS
  While 25 year follow up of 310 haemophilic patients has shown the potentially lethal combination of HIV and HCV coinfection, HCV singly infected individuals show slow progression of liver disease.
authors.affiliation: Haemophilia Centre and Haemostasis Unit, Royal Free Hospital, London, UK.
authors.forename: T T
authors.initials: TT
authors.lastname: Yee
authors.forename: A
authors.initials: A
authors.lastname: Griffioen
authors.forename: C A
authors.initials: CA
authors.lastname: Sabin
authors.forename: G
authors.initials: G
authors.lastname: Dusheiko
authors.forename: C A
authors.initials: CA
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000150:complications* / Q000276:immunology / Q000401:mortality; D006526:Hepatitis C / Q000150:complications* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D008875:Middle Aged; D016016:Proportional Hazards Models