title: Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis.
abstract: Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression.
  
  
  
  We determined the incidence and predictors of advanced hepatic fibrosis measured by the Fibrosis-4 index (≥3.25) in a large diverse population of HIV-infected patients without significant liver disease at baseline (Fibrosis-4 score <1.45) in care between January 2000 and March 2014. We used Cox proportional hazards analysis to examine factors associated with progression to Fibrosis-4 score ≥3.25.
  
  
  
  Among 14,198 HIV-infected patients, hepatitis C virus (HCV) coinfection [adjusted hazard ratio (aHR) 1.9, 95% confidence interval (CI): 1.6 to 2.1], hepatitis B virus coinfection (aHR 1.5, 95% CI: 1.2 to 1.8), alcohol-use disorder (aHR 1.4, 95% CI: 1.2 to 1.6), and diabetes (aHR 1.9, 95% CI: 1.6 to 2.3) were associated with progression to advanced fibrosis in multivariable analysis. In addition, patients at each lower level of time-varying CD4 cell count had a significantly greater risk of progression, with ∼7-fold higher risk in those with CD4 <100 cells per cubic millimeter (aHR 6.9, 95% CI: 5.8 to 8.3) compared with CD4 ≥500 cells per cubic millimeter. An increasing gradient of risk was also observed among patients with higher time-varying HIV viral load (VL), with the greatest risk noted with VL ≥100,000 copies per milliliter (aHR 2.6, 95% CI: 2.2 to 3.1) compared with VL <500 copies per milliliter.
  
  
  
  Lower CD4 cell count and higher HIV VL were significantly associated with progression to advanced hepatic fibrosis in a dose-dependent manner, independent of the risk associated with traditional factors: hepatitis C virus or hepatitis B virus coinfection, alcohol, and diabetes. Our findings suggest that early treatment of HIV infection could mitigate liver disease.
authors.affiliation: Departments of *Medicine; †Epidemiology, University of Washington, Seattle, WA; ‡Department of Medicine, University of California-San Diego, San Diego, CA; §Department of Medicine, University of California-San Francisco, San Francisco, CA; ‖Department of Medicine, Harvard University, Fenway Health, Boston, MA; ¶Department of Medicine, Case Western University, Cleveland, OH; #Department of Medicine, University of North Carolina, Chapel Hill, NC; **Department of Medicine, University of Alabama, Birmingham, AL; and ††Department of Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: H Nina
authors.initials: HN
authors.lastname: Kim
authors.forename: Robin
authors.initials: R
authors.lastname: Nance
authors.forename: Stephen
authors.initials: S
authors.lastname: Van Rompaey
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Delaney
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Crane
authors.forename: Edward R
authors.initials: ER
authors.lastname: Cachay
authors.forename: Elvin
authors.initials: E
authors.lastname: Geng
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Boswell
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
authors.forename: Richard D
authors.initials: RD
authors.lastname: Moore
authors.forename: Mari M
authors.initials: MM
authors.lastname: Kitahata
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000150:complications; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D006526:Hepatitis C / Q000150:complications / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D019562:Viral Load