Jessie Torgersen1,2, Michael J Kallan2, Dena M Carbonari2, Lesley S Park3, Rajni L Mehta4,5, Kathryn D'Addeo4,5, Janet P Tate4,5, Joseph K Lim4,5, Matthew Bidwell Goetz6, Maria C Rodriguez-Barradas7, Cynthia L Gibert8, Norbert Bräu9, Sheldon T Brown9, Jason A Roy10, Tamar H Taddei4,5, Amy C Justice4,5, Vincent Lo Re1,2. 1. Division of Infectious Diseases, Department of Medicine. 2. Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training. 3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Population Health Sciences, Stanford University School of Medicine, Stanford, CA. 4. VA Connecticut Healthcare System, West Haven, CT. 5. Yale University School of Medicine, New Haven, CT. 6. VA Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles, CA. 7. Infectious Diseases Section, Michael E. DeBakey VA Medical Center and Department of Medicine, Baylor College of Medicine, Houston, TX. 8. Washington DC VA Medical Center and George Washington University Medical Center, Washington, DC. 9. James J. Peters VA Medical Center, Bronx, NY, and Icahn School of Medicine at Mount Sinai, New York, NY. 10. Department of Biostatistics, Rutgers University School of Public Health, New Brunswick, NJ.
Abstract
BACKGROUND: Despite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infected patients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC. METHODS: We conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015). HCC was ascertained using Veterans Health Administration cancer registries and electronic records. Cox regression was used to determine hazard ratios (HR, 95% confidence interval [CI]) of HCC associated with higher current HIV RNA, longer duration of detectable HIV viremia (≥500 copies/mL), and current CD4+ cell percentage less than 14%, adjusting for traditional HCC risk factors. Analyses were stratified by previously validated diagnoses of cirrhosis prior to start of follow-up. RESULTS: Among 35 659 HIV-infected patients, 302 (0.8%) developed HCC over 281 441 person-years (incidence rate = 107.3 per 100 000 person-years). Among patients without baseline cirrhosis, higher HIV RNA (HR = 1.25, 95% CI = 1.12 to 1.40, per 1.0 log10 copies/mL) and 12 or more months of detectable HIV (HR = 1.47, 95% CI = 1.02 to 2.11) were independently associated with higher risk of HCC. CD4+ percentage less than 14% was not associated with HCC in any model. Hepatitis C coinfection was a statistically significant predictor of HCC regardless of baseline cirrhosis status. CONCLUSION: Among HIV-infected patients without baseline cirrhosis, higher HIV RNA and longer duration of HIV viremia increased risk of HCC, independent of traditional HCC risk factors. This is the strongest evidence to date that HIV viremia contributes to risk of HCC in this group.
BACKGROUND: Despite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infectedpatients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC. METHODS: We conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015). HCC was ascertained using Veterans Health Administration cancer registries and electronic records. Cox regression was used to determine hazard ratios (HR, 95% confidence interval [CI]) of HCC associated with higher current HIV RNA, longer duration of detectable HIV viremia (≥500 copies/mL), and current CD4+ cell percentage less than 14%, adjusting for traditional HCC risk factors. Analyses were stratified by previously validated diagnoses of cirrhosis prior to start of follow-up. RESULTS: Among 35 659 HIV-infectedpatients, 302 (0.8%) developed HCC over 281 441 person-years (incidence rate = 107.3 per 100 000 person-years). Among patients without baseline cirrhosis, higher HIV RNA (HR = 1.25, 95% CI = 1.12 to 1.40, per 1.0 log10 copies/mL) and 12 or more months of detectable HIV (HR = 1.47, 95% CI = 1.02 to 2.11) were independently associated with higher risk of HCC. CD4+ percentage less than 14% was not associated with HCC in any model. Hepatitis C coinfection was a statistically significant predictor of HCC regardless of baseline cirrhosis status. CONCLUSION: Among HIV-infectedpatients without baseline cirrhosis, higher HIV RNA and longer duration of HIV viremia increased risk of HCC, independent of traditional HCC risk factors. This is the strongest evidence to date that HIV viremia contributes to risk of HCC in this group.
Authors: Kaku A Armah; Kathleen McGinnis; Jason Baker; Cynthia Gibert; Adeel A Butt; Kendall J Bryant; Matthew Goetz; Russell Tracy; Krisann K Oursler; David Rimland; Kristina Crothers; Maria Rodriguez-Barradas; Steve Crystal; Adam Gordon; Kevin Kraemer; Sheldon Brown; Mariana Gerschenson; David A Leaf; Steven G Deeks; Charles Rinaldo; Lewis H Kuller; Amy Justice; Matthew Freiberg Journal: Clin Infect Dis Date: 2012-04-24 Impact factor: 9.079
Authors: Lesley S Park; Janet P Tate; Maria C Rodriguez-Barradas; David Rimland; Matthew Bidwell Goetz; Cynthia Gibert; Sheldon T Brown; Michael J Kelley; Amy C Justice; Robert Dubrow Journal: J AIDS Clin Res Date: 2014-07
Authors: Sahil Mittal; Hashem B El-Serag; Yvonne H Sada; Fasiha Kanwal; Zhigang Duan; Sarah Temple; Sarah B May; Jennifer R Kramer; Peter A Richardson; Jessica A Davila Journal: Clin Gastroenterol Hepatol Date: 2015-07-18 Impact factor: 11.382
Authors: Shawn L Fultz; Melissa Skanderson; Larry A Mole; Neel Gandhi; Kendall Bryant; Stephen Crystal; Amy C Justice Journal: Med Care Date: 2006-08 Impact factor: 2.983
Authors: Ashwin Balagopal; Frances H Philp; Jacquie Astemborski; Timothy M Block; Anand Mehta; Ronald Long; Gregory D Kirk; Shruti H Mehta; Andrea L Cox; David L Thomas; Stuart C Ray Journal: Gastroenterology Date: 2008-03-29 Impact factor: 22.682
Authors: Nicolás Merchante; Esperanza Merino; José López-Aldeguer; Francisco Jover; Marcial Delgado-Fernández; Maria José Galindo; Enrique Ortega; Antonio Rivero; Carlos Mínguez; Alberto Romero-Palacios; Sergio Padilla; Manuel Márquez-Solero; Concepción Amador; Maria José Ríos-Villegas; Francisco Téllez; Joaquín Portilla; Juan A Pineda Journal: Clin Infect Dis Date: 2012-09-05 Impact factor: 9.079
Authors: Marc A Kowalkowski; Rena S Day; Xianglin L Du; Wenyaw Chan; Elizabeth Y Chiao Journal: J Acquir Immune Defic Syndr Date: 2014-10-01 Impact factor: 3.731
Authors: H Nina Kim; Craig W Newcomb; Dena M Carbonari; Jason A Roy; Jessie Torgersen; Keri N Althoff; Mari M Kitahata; K Rajender Reddy; Joseph K Lim; Michael J Silverberg; Angel M Mayor; Michael A Horberg; Edward R Cachay; Gregory D Kirk; Jing Sun; Mark Hull; M John Gill; Timothy R Sterling; Jay R Kostman; Marion G Peters; Richard D Moore; Marina B Klein; Vincent Lo Re Journal: Hepatology Date: 2021-06-22 Impact factor: 17.298
Authors: Lisa R C Saud; Aline L Chagas; Claudia Maccali; Paulo V A Pinto; Natally Horvat; Regiane S S M Alencar; Claudia M Tani; Edson Abdala; Flair J Carrilho Journal: Eur J Gastroenterol Hepatol Date: 2021-04-01 Impact factor: 2.586
Authors: Allison R Webel; Julie Schexnayder; Patricia A Cioe; Julie A Zuñiga Journal: J Assoc Nurses AIDS Care Date: 2021 May-Jun 01 Impact factor: 1.809
Authors: Olof Elvstam; Gaetano Marrone; Patrik Medstrand; Carl Johan Treutiger; Veronica Svedhem; Magnus Gisslén; Per Björkman Journal: Open Forum Infect Dis Date: 2021-03-17 Impact factor: 3.835