ArticleBiomolecules2019
Alcohol Metabolism Potentiates HIV-Induced Hepatotoxicity: Contribution to End-Stage Liver Disease.
Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 31 citations in OpenAlex.
- Hepatocyte-Derived Apoptotic Bodies as Pathological Intercellular Messengers in the Liver.Biomolecules · 2026Review
- Pioglitazone Reverses Alcohol-induced Human Immunodeficiency Virus (HIV) Replication and IL-1β Expression in Alveolar Macrophages.American journal of respiratory cell and molecular biology · 2025Article
- Alcohol, Anti-HIV Drugs, and/or Hippuric Acid Deteriorate Cellular Stresses in Senescent Hepatocytes and Aging Murine Liver.Journal of addiction & prevention · 2025Article
- Drug induced liver injury in HIV patients on dolutegravir based antiretroviral therapy regimens in Wolaita Sodo comprehensive specialized hospital.Scientific reports · 2025Article
- Metabolic dysfunction-associated steatotic liver disease in people with HIV.Current opinion in HIV and AIDS · 2025Review
- Design and rationale for a randomized clinical trial testing the efficacy of a lifestyle physical activity intervention for people with HIV and engaged in unhealthy drinking.Contemporary clinical trials · 2024Article
- Review
- Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.International journal of molecular sciences · 2023Review
- Nutritional and Lifestyle Therapy for NAFLD in People with HIV.Nutrients · 2023Review
- Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol.International journal of molecular sciences · 2023Article
- A Pathogenic Role of Non-Parenchymal Liver Cells in Alcohol-Associated Liver Disease of Infectious and Non-Infectious Origin.Biology · 2023Review
- Increased liver stiffness promotes hepatitis B progression by impairing innate immunity in CCl4-induced fibrotic HBVFrontiers in immunology · 2023Article
- Alcohol and HIV-Derived Hepatocyte Apoptotic Bodies Induce Hepatic Stellate Cell Activation.Biology · 2022Article
- Alcohol: basic and translational research; 15th annual Charles Lieber &1st Samuel French satellite symposium.Experimental and molecular pathology · 2022Review
- A review of alcohol-pathogen interactions: New insights into combined disease pathomechanisms.Alcoholism, clinical and experimental research · 2022Review
- Cell-to-Cell Communications in Alcohol-Associated Liver Disease.Frontiers in physiology · 2022Article
- The Correlated Risk Factors for Severe Liver Damage Among HIV-Positive Inpatients With Abnormal Liver Tests.Frontiers in medicine · 2022Article
- Alcohol-Induced Lysosomal Damage and Suppression of Lysosome Biogenesis Contribute to Hepatotoxicity in HIV-Exposed Liver Cells.Biomolecules · 2021Article
- Review
- Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
In an era of improved survival due to modern antiretroviral therapy, liver disease has become a major cause of morbidity and mortality, resulting in death in 15-17% of human immunodeficiency virus (HIV)-infected patients. Alcohol enhances HIV-mediated liver damage and promotes the progression to advanced fibrosis and cirrhosis. However, the mechanisms behind these events are uncertain. Here, we hypothesize that ethanol metabolism potentiates accumulation of HIV in hepatocytes, causing oxidative stress and intensive apoptotic cell death. Engulfment of HIV-containing apoptotic hepatocytes by non-parenchymal cells (NPCs) triggers their activation and liver injury progression. This study was performed on primary human hepatocytes and Huh7.5-CYP cells infected with HIV-1ADA, and major findings were confirmed by pilot data obtained on ethanol-fed HIV-injected chimeric mice with humanized livers. We demonstrated that ethanol exposure potentiates HIV accumulation in hepatocytes by suppressing HIV degradation by lysosomes and proteasomes. This leads to increased oxidative stress and hepatocyte apoptosis. Exposure of HIV-infected apoptotic hepatocytes to NPCs activates the inflammasome in macrophages and pro-fibrotic genes in hepatic stellate cells. We conclude that while HIV and ethanol metabolism-triggered apoptosis clears up HIV-infected hepatocytes, continued generation of HIV-expressing apoptotic bodies may be detrimental for progression of liver inflammation and fibrosis due to constant activation of NPCs.
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Registered trials
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