title: Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study.
abstract: BACKGROUND
  An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases.
  
  
  METHODS
  We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death.
  
  
  RESULTS
  There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for <50 vs > or =500/microL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02).
  
  
  CONCLUSIONS
  Liver-related death was the most frequent cause of non-AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, CH-809a Zurich, Switzerland. infweb@usz.unizh.ch
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Nina
authors.initials: N
authors.lastname: Friis-Møller
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Wafaa M
authors.initials: WM
authors.lastname: El-Sadr
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.forename: Francois
authors.initials: F
authors.lastname: Dabis
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Law
authors.forename: Christian
authors.initials: C
authors.lastname: Pradier
authors.forename: Stephane
authors.initials: S
authors.lastname: De Wit
authors.forename: Börje
authors.initials: B
authors.lastname: Akerlund
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Calvo
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
authors.forename: Martin
authors.initials: M
authors.lastname: Rickenbach
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D008107:Liver Diseases / Q000150:complications / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents