Liver fibrosis and accelerated immune dysfunction (immunosenescence) among HIV-infected Russians with heavy alcohol consumption - an observational cross-sectional study.
Por:
So-Armah K, Freiberg M, Cheng D, Lim JK, Gnatienko N, Patts G, Doyle M, Fuster D, Lioznov D, Krupitsky E and Samet J
Publicada:
31 dic 2019
Ahead of Print:
31 dic 2019
Resumen:
BACKGROUND: The multifactorial mechanisms driving negative health outcomes among risky drinkers with HIV may include immunosenescence. Immunosenescence, aging of the immune system, may be accentuated in HIV and leads to poor outcomes. The liver regulates innate immunity and adaptive immune tolerance. HIV-infected people have high prevalence of liver-related comorbidities. We hypothesize that advanced liver fibrosis/cirrhosis is associated with alterations in T-cell subsets consistent with immunosenescence. METHODS: ART-naïve people with HIV with a recent history of heavy drinking were recruited into a clinical trial of zinc supplementation. Flow cytometry was used to characterize T-cell subsets. The two primary dependent variables were CD8+ and CD4+ T-cells expressing CD28-CD57+ (senescent cell phenotype). Secondary dependent variables were CD8+ and CD4+ T-cells expressing CD45RO + CD45RA- (memory phenotype), CD45RO-CD45RA+ (naïve phenotype), and the naïve phenotype to memory phenotype T-cell ratio (lower ratios associated with immunosenescence). Advanced liver fibrosis/cirrhosis was defined as FIB-4 > 3.25, APRI=1.5, or Fibroscan measurement =10.5 kPa. Analyses were conducted using multiple linear regression adjusted for potential confounders. RESULTS: Mean age was 34 years; 25% female; 88% hepatitis C. Those with advanced liver fibrosis/cirrhosis (N = 25) had higher HIV-1 RNA and more hepatitis C. Advanced liver fibrosis/cirrhosis was not significantly associated with primary or secondary outcomes in adjusted analyses. CONCLUSIONS: Advanced liver fibrosis/cirrhosis was not significantly associated with these senescent T-cell phenotypes in this exploratory study of recent drinkers with HIV. Future studies should assess whether liver fibrosis among those with HIV viral suppression and more advanced, longstanding liver disease is associated with changes in these and other potentially senescent T-cell subsets.
Filiaciones:
So-Armah K:
Department of Medicine, Boston University School of Medicine, 801 Massachusetts Avenue, Crosstown Building, 2nd Floor, Boston, MA, 02118, USA.
Freiberg M:
Department of Medicine, Vanderbilt University School of Medicine
Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA.
Cheng D:
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
Lim JK:
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
Gnatienko N:
Department of Medicine, Boston Medical Center, Boston, MA, USA
Patts G:
Department of Biostatistics and Data Coordinating Center, Boston University School of Public Health, Boston, MA, USA
Doyle M:
Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA
:
Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
Lioznov D:
Department of Infectious Diseases and Epidemiology, Smorodintsev Research Institute of Influenza, First Pavlov State Medical University, St. Petersburg, Russia
Krupitsky E:
First Pavlov State Medical University, V. M. Bekhterev National Research Medical Center for Psychiatry and Neurology, St. Petersburg, Russia
Samet J:
Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
gold, Green Published
|