title: Is there evidence for an increase in the death rate from liver-related disease in patients with HIV?
abstract: BACKGROUND
  Increases in deaths due to liver-related disease (LRD) among HIV-infected individuals have been reported although the influence of combination antiretroviral therapy (cART) on LRD is controversial.
  
  
  OBJECTIVE
  To determine changes over time in the death rate from LRD and if longer exposure to cART was associated with an increased death rate from LRD in 10 937 patients from EuroSIDA, an observational longitudinal cohort study.
  
  
  RESULTS
  A total of 184 (1.7%) died from LRD during 52 236 person-years of follow-up (PYFU). The death rate from LRD declined from 6.9 per 1000 PYFU before 1995 [95% confidence interval (CI), 3.9-9.9] to 2.6 at/after 2004 (95% CI, 1.6-4.0). When the current CD4 cell count and other factors were taken into account, there was a 13% increase in the death rate from LRD per year (95% CI, 5-20%, P = 0.0008). In patients who had started cART, there was a 12% increase in the death rate from LRD per additional year exposure to cART (95% CI, 4-20%, P = 0.022) after adjustment for current CD4 cell count and other factors.
  
  
  CONCLUSIONS
  Death rates from LRD appeared to decrease across Europe. However after adjustment for the current CD4 cell count, and therefore increases in CD4 cell counts in patients taking cART, there was a significant increase over time in death rates from LRD. In patients with similar CD4 cell counts, longer exposure to cART was associated with an increased death rate from LRD. This may be due to direct liver toxicity of antiretrovirals, progression of liver disease due to hepatitis B virus or hepatitis C virus over time as patients survive longer, or some other factor.
authors.affiliation: Royal Free Centre for HIV Medicine and Dept Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK. a.mocroft@pcps.ucl.ac.uk
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Jurgen
authors.initials: J
authors.lastname: Rockstroh
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.forename: Stephane
authors.initials: S
authors.lastname: de Wit
authors.forename: Jose
authors.initials: J
authors.lastname: Gatell
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D019694:Hepatitis B, Chronic / Q000401:mortality*; D019698:Hepatitis C, Chronic / Q000401:mortality*; D006801:Humans; D015994:Incidence; D008297:Male; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D004338:Drug Combinations