Adverse effects of antiretroviral therapy on liver hepatocytes and endothelium in HIV patients: An ultrastructural perspective |
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| Authors: | Sarah Chwiki Maria Mercedes Campos Mary E. McLaughlin David E. Kleiner Joseph A. Kovacs Caryn G. Morse |
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| Affiliation: | 1. Section of Histopathology, National Eye Institute, NIH, Bethesda, MD, USA;2. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA;3. Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD, USA;4. Critical Care Medicine Department, AIDS Section, Clinical Center, NIH, Bethesda, MD, USA |
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| Abstract: | Human immunodeficiency virus and antiretroviral therapy (ART) together can be far more detrimental to liver cells than either of the two unaided. However, ultrastructural aspects of the synergistic effects of HIV and ART have been understudied. In a patient cohort receiving ART, this study characterizes ultrastructurally sinusoidal degeneration, hepatocytic aberrations, mitochondrial dysfunction, accumulation of bulky lipid droplets (steatosis), and occlusion of sinusoidal lumina. Mitochondrial dysfunction causes the accumulation of acetyl-CoA which leads to insulin upregulation and resistance, lipid synthesis, and steatosis. Lipid droplets deposited in the sinusoids could be the source of the blood’s lipid profile alterations in HIV patients on ART. |
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| Keywords: | Antiretroviral therapy endothelium hepatotoxicity HIV liver mitochondria sinusoid steatosis |
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