title: Long-term follow-up of hepatitis C infection in a large cohort of patients with inherited bleeding disorders.
abstract: OBJECTIVE
  Patients with inherited bleeding disorders are an interesting group to study the long-term course of chronic hepatitis C virus (HCV) infection, because of their uniform mode of infection and reliable follow-up. Our aim was to assess the long-term occurrence of adverse liver-related events in these patients.
  
  
  METHODS
  The occurrence and determinants of end-stage liver disease (ESLD) were assessed using retrospective data of 863 HCV infected patients with inherited bleeding disorders from the Netherlands and the UK.
  
  
  RESULTS
  Median follow-up since HCV infection was 31 years, while 30% of patients had >35 follow-up years. Nineteen percent of patients spontaneously cleared the virus and 81% developed chronic HCV infection. Of the 700 patients with chronic HCV, 90 (13%) developed ESLD. Hepatocellular carcinoma (HCC) was diagnosed in 3% of patients with chronic HCV, 41% of which occurred in the last six years. Determinants of ESLD development were age at infection (hazard ratio (HR) 1.09 per year increase), HIV co-infection (HR 10.85), history of alcohol abuse (HR 4.34) and successful antiviral treatment (HR 0.14). Of the 487 patients who were still alive at the end of follow-up, 49% did not undergo optimal conventional antiviral treatment.
  
  
  CONCLUSIONS
  After over 30 years of HCV infection, ESLD occurred in a significant proportion of patients with inherited bleeding disorders. HCC appears to be an increasing problem. There is a significant potential for both conventional and new antiviral treatment regimens to try and limit ESLD occurrence in the future.
authors: Van Creveldkliniek, Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: D.E.FransenvandePutte@umcutrecht.nl.
authors: Dietje Elisabeth
authors: DE
authors: Fransen van de Putte
authors: Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors: Michael
authors: M
authors: Makris
authors: Van Creveldkliniek, Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Kathelijn
authors: K
authors: Fischer
authors: Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, United Kingdom.
authors: Thynn Thynn
authors: TT
authors: Yee
authors: Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors: Lisa
authors: L
authors: Kirk
authors: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Karel Johannes
authors: KJ
authors: van Erpecum
authors: Department of Hepatology, Royal Free London NHS Foundation Trust, London, United Kingdom.
authors: David
authors: D
authors: Patch
authors: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Medical Microbiology and Public Health Research Institute (CAPHRI), Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Dirk
authors: D
authors: Posthouwer
authors: Van Creveldkliniek, Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Eveline Pauline
authors: EP
authors: Mauser-Bunschoten
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D002648:Child; D015331:Cohort Studies; D058625:End Stage Liver Disease / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged
keywords: AIDS; CI; ESLD; End-stage liver disease; HAART; HCC; HCV; HIV; HR; Hemophilia; Hepatitis C; Hepatocellular carcinoma; IFN; Inherited bleeding disorders; LSM; Long-term follow-up; PegIFN; SVR; UK; United Kingdom; acquired immunodeficiency syndrome; confidence interval; end-stage liver disease; hazard ratio; hepatitis C virus; hepatocellular carcinoma; highly active antiretroviral treatment; human immunodeficiency virus; interferon; liver stiffness measurement; pegylated interferon; sustained virological response