title: Liver fibrosis in HIV-infected individuals on long-term antiretroviral therapy: associated with immune activation, immunodeficiency and prior use of didanosine.
abstract: It is unclear whether HIV infection is associated with liver fibrosis in the absence of chronic hepatitis B or C virus (HBV/HCV) coinfection. We compared prevalence of liver fibrosis, noninvasively assessed by the Fibrosis-4 (FIB-4) index, between HIV-infected patients and uninfected controls, and explored determinants of a higher FIB-4 score, indicative of more liver fibrosis.
  
  
  
  FIB-4 was assessed in HIV-uninfected and HIV-1-infected, predominantly virologically suppressed participants of the AGEhIV Cohort Study without HBV and/or HCV coinfection, and aged at least 45. Using multivariable regression, we investigated associations between FIB-4 and HIV-status, HIV-disease characteristics, antiretroviral drugs and markers of microbial translocation and immune activation.
  
  
  
  Prevalence of advanced liver fibrosis (FIB-4 ≥ 3.25) was low: 1.4% in HIV-infected and 1.0% in HIV-uninfected participants. After adjustment for age, sex, ethnicity, detectable anti-hepatitis B core/anti-HCV antibodies and excessive alcohol intake, HIV remained significantly associated with higher FIB-4 (+4.2%, P = 0.05). Prior exposure to didanosine, longer duration of a CD4 cell count below 500 cells/μl and a lower CD4 cell count at enrollment were each associated with a higher FIB-4. Markers of immune activation (soluble CD163, activated CD8 T-lymphocytes and regulatory T-lymphocytes) were associated with a higher FIB-4 in HIV-infected but not HIV-uninfected study participants.
  
  
  
  HIV infection was independently associated with higher FIB-4 scores, indicating more advanced liver fibrosis, though the difference in FIB-4 scores between HIV-infected and HIV-uninfected was small. Higher levels of immune activation were associated with liver fibrosis in HIV-infected, even in the absence of HBV or HCV infection, but not in HIV-uninfected individuals.
authors.affiliation: aDepartment of Global Health, Academic Medical Center and Amsterdam Institute for Global Health and Development bAcademic Medical Center, Division of Infectious Diseases and Center for Infection and Immunity Amsterdam cHIV Monitoring Foundation dDepartment of Neurology, Academic Medical Center eDepartment of Experimental Immunology, Academic Medical Center fDepartment of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Kooij
authors.forename: Ferdinand W N M
authors.initials: FW
authors.lastname: Wit
authors.forename: Rosan A
authors.initials: RA
authors.lastname: van Zoest
authors.forename: Judith
authors.initials: J
authors.lastname: Schouten
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: Michèle
authors.initials: M
authors.lastname: van Vugt
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Marc
authors.initials: M
authors.lastname: van der Valk
mesh_terms: D000368:Aged; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D016049:Didanosine / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence
chemical_list: D044966:Anti-Retroviral Agents; D016049:Didanosine