title: Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals.
abstract: BACKGROUND
  Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.
  
  
  METHODS
  Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.
  
  
  RESULTS
  LRD accounted for 145 of 670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively).
  
  
  CONCLUSIONS
  Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.
authors: aUCL, London, UK bCHIP, Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark cDepartment of Medicine I, University of Bonn, Bonn, Germany dBotkin Hospital of Infectious Diseases, St Petersburg eNovgorod Centre for AIDS, Novgorod, Russia fHospital Saint Antoine, Paris, France gBelarus State Medical University, Minsk, Belarus hSacco hospital, Milan, Italy iHospital de Sant Pau, Barcelona, Spain.
authors: Daniel
authors: D
authors: Grint
authors: Lars
authors: L
authors: Peters
authors: Juergen K
authors: JK
authors: Rockstroh
authors: Aza
authors: A
authors: Rakmanova
authors: Tatiana
authors: T
authors: Trofimova
authors: Karine
authors: K
authors: Lacombe
authors: Igor
authors: I
authors: Karpov
authors: Massimo
authors: M
authors: Galli
authors: Pere
authors: P
authors: Domingo
authors: Ole
authors: O
authors: Kirk
authors: Jens D
authors: JD
authors: Lundgren
authors: Amanda
authors: A
authors: Mocroft
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology*; D017093:Liver Failure / Q000453:epidemiology* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000998:Antiviral Agents