Evaluating Associations Between Cumulative Use of Chronic Liver Injury-Inducing Antiretroviral Therapy and Hepatocellular Carcinoma, By Chronic Liver Disease Status
8 affiliations
- 1Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- 2Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- 3VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT
- 4Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ
- 5Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
- 6Department of Medicine, Yale School of Medicine, New Haven, CT
- 7Department of Biostatistics and Epidemiology, School of Public Health, Rutgers University, New Brunswick, NJ
- 8Division of Infectious Diseases, Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ
Abstract
BACKGROUND: Prolonged exposure to hepatotoxic antiretroviral therapy (ART) could lead to chronic liver injury, which might increase risk of hepatocellular carcinoma (HCC). We used causal inference methods to evaluate if cumulative exposure to ART with known mechanisms of chronic liver injury is associated with HCC among people with HIV (PWH), by chronic liver disease (CLD) status. METHODS: We conducted a cohort study of antiretroviral-naive PWH with and without diagnosed CLD who initiated ART in the Veterans Affairs between 1999 and 2023. Exposure to ART with known mechanism of chronic liver injury (mitochondrial toxicity or accumulation of toxic intermediates) was determined monthly through prescription fills. Incident HCC was identified by Veterans Affairs National Cancer Registry and/or recorded diagnoses. Marginal structural models estimated odds ratios (ORs) with 95% confidence intervals (CIs) of HCC associated with cumulative exposure to chronic liver injury-inducing ART compared with ART without chronic liver injury mechanisms, by CLD status. RESULTS: Among 11,854 PWH without CLD and 6771 PWH with CLD, we observed 112 and 378 HCC events, respectively. Among PWH without CLD, ≥4 years of exposure to chronic liver injury-inducing ART was associated with HCC when compared with ≥4 years of use of ART without chronic liver injury mechanisms (OR = 4.02 [95% CI: 1.00-16.24]). Among PWH with CLD, ≥4 years of exposure to chronic liver injury-inducing ART was not associated with HCC (OR = 1.36; 95% CI: 0.68-2.72). CONCLUSION: Four or more years of ART with a chronic liver injury mechanism was associated with HCC among PWH without CLD, but not those with CLD.
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BibTeX
@article{torgersen2026evaluating,
title = {{Evaluating Associations Between Cumulative Use of Chronic Liver Injury-Inducing Antiretroviral Therapy and Hepatocellular Carcinoma, By Chronic Liver Disease Status}},
author = {Jessie Torgersen and Craig W. Newcomb and Dean M. Carbonari and Christopher T. Rentsch and Tamar H. Taddei and Amy C. Justice and Jason A. Roy and Vincent Lo Re},
journal = {Journal of acquired immune deficiency syndromes (1999)},
year = {2026},
month = nov,
doi = {10.1097/qai.0000000000003923},
url = {https://doi.org/10.1097/qai.0000000000003923},
note = {CC BY},
}
RIS
TY - JOUR
TI - Evaluating Associations Between Cumulative Use of Chronic Liver Injury-Inducing Antiretroviral Therapy and Hepatocellular Carcinoma, By Chronic Liver Disease Status
AU - Jessie Torgersen
AU - Craig W. Newcomb
AU - Dean M. Carbonari
AU - Christopher T. Rentsch
AU - Tamar H. Taddei
AU - Amy C. Justice
AU - Jason A. Roy
AU - Vincent Lo Re
PY - 2026
DA - 2026/11/01
JO - Journal of acquired immune deficiency syndromes (1999)
DO - 10.1097/qai.0000000000003923
UR - https://doi.org/10.1097/qai.0000000000003923
AB - BACKGROUND: Prolonged exposure to hepatotoxic antiretroviral therapy (ART) could lead to chronic liver injury, which might increase risk of hepatocellular carcinoma (HCC). We used causal inference methods to evaluate if cumulative exposure to ART with known mechanisms of chronic liver injury is associated with HCC among people with HIV (PWH), by chronic liver disease (CLD) status. METHODS: We conducted a cohort study of antiretroviral-naive PWH with and without diagnosed CLD who initiated ART in the Veterans Affairs between 1999 and 2023. Exposure to ART with known mechanism of chronic liver injury (mitochondrial toxicity or accumulation of toxic intermediates) was determined monthly through prescription fills. Incident HCC was identified by Veterans Affairs National Cancer Registry and/or recorded diagnoses. Marginal structural models estimated odds ratios (ORs) with 95% confidence intervals (CIs) of HCC associated with cumulative exposure to chronic liver injury-inducing ART compared with ART without chronic liver injury mechanisms, by CLD status. RESULTS: Among 11,854 PWH without CLD and 6771 PWH with CLD, we observed 112 and 378 HCC events, respectively. Among PWH without CLD, ≥4 years of exposure to chronic liver injury-inducing ART was associated with HCC when compared with ≥4 years of use of ART without chronic liver injury mechanisms (OR = 4.02 [95% CI: 1.00-16.24]). Among PWH with CLD, ≥4 years of exposure to chronic liver injury-inducing ART was not associated with HCC (OR = 1.36; 95% CI: 0.68-2.72). CONCLUSION: Four or more years of ART with a chronic liver injury mechanism was associated with HCC among PWH without CLD, but not those with CLD.
SN - 1525-4135
SN - 1944-7884
ER -