Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis

J Acquir Immune Defic Syndr. 2016 Aug 1;72(4):437-43. doi: 10.1097/QAI.0000000000000992.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Coinfection / complications
  • Disease Progression
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology
  • Hepatitis C / complications
  • Hepatitis C / physiopathology
  • Humans
  • Incidence
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / physiopathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • United States / epidemiology
  • Viral Load