title: The effect of HIV infection, immunodeficiency, and antiretroviral therapy on the risk of hepatic dysfunction.
abstract: BACKGROUND
  Limited data exists regarding the effect of chronic HIV infection on the liver. We sought to characterize the hepatic risks of HIV infection, immunodeficiency, and cumulative use of antiretroviral therapy (ART).
  
  
  METHODS
  Adult HIV infected and 10:1 age-matched and sex-matched HIV-uninfected individuals were followed for incident hepatic dysfunction or hepatic dysfunction-related death. Multivariable Poisson regression models were used to obtain incident rate ratios, adjusting for multiple hepatic risk factors including alcohol/drug abuse, hepatitis B and C, and diabetes.
  
  
  RESULTS
  We identified 20,775 HIV-infected and 215,158 HIV-uninfected individuals. HIV-infected individuals had a significantly greater overall risk compared with HIV-uninfected individuals of both hepatic dysfunction and hepatic dysfunction-related death. The highest risk was seen in patients with low CD4 cell counts not on ART [adjusted rate ratio of hepatic dysfunction-related death 59.4; (95% confidence interval: 39.3 to 89.7), P < 0.001; hepatic dysfunction, adjusted rate ratio 15.7 (95% confidence interval: 11.4 to 21.6), P < 0.001]. In an HIV-infected only model, factors that increased risk included low CD4 cell count, high HIV RNA level, alcohol/drug abuse, hepatitis B or C coinfection, and diabetes. Longer cumulative exposure to ART did not increase risk, regardless of therapy class.
  
  
  CONCLUSIONS
  HIV-infected individuals have a higher risk of hepatic dysfunction and hepatic dysfunction-related death compared with HIV-uninfected individuals, even with adjustment for known hepatic risk factors. Hepatic outcomes were associated with lower CD4+ T-cell counts but not with longer cumulative ART exposure. These findings provide indirect evidence supporting early use of ART to reduce the risk for hepatic-related complications.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Kaiser Permanente, Los Angeles, CA 90027, USA. william.j.towner@kp.org
authors.forename: William J
authors.initials: WJ
authors.lastname: Towner
authors.forename: Lanfang
authors.initials: L
authors.lastname: Xu
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Leyden
authors.forename: Michael A
authors.initials: MA
authors.lastname: Horberg
authors.forename: Chun R
authors.initials: CR
authors.lastname: Chao
authors.forename: Beth
authors.initials: B
authors.lastname: Tang
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Klein
authors.forename: Leo B
authors.initials: LB
authors.lastname: Hurley
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Silverberg
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D015994:Incidence; D008107:Liver Diseases / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D008297:Male; D015999:Multivariate Analysis; D012044:Regression Analysis; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000150:complications; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents