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Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015.
JAMA Netw Open. 2021 02 01; 4(2):e2037512.JN

Abstract

Importance

People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era.

Objective

To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era.

Design, Setting, and Participants

This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020.

Exposures

HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation.

Main Outcomes and Measures

HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage.

Results

Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection.

Conclusions and Relevance

HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.

Authors+Show Affiliations

Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.Kaiser Permanente Mid-Atlantic States, Mid-Atlantic Permanente Research Institute, Rockville, Maryland.Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.Department of Medicine, University of Calgary, Calgary, Alberta, Canada.Department of Medicine, Yale University, West Haven, Connecticut.National Cancer Institute, Bethesda, Maryland.National Cancer Institute, Bethesda, Maryland.Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.Department of Medicine, University of California, San Diego, San Diego.Center for Population Health Sciences, Stanford University School of Medicine, Stanford, California.Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.Department of Medicine, University of Washington, Seattle.Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia. Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia. Perelman School of Medicine, Department of Medicine, University of Pennsylvania, Philadelphia.Department of Medicine, Johns Hopkins University, Baltimore, Maryland.Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.Department of Medicine, University of California, San Francisco, San Francisco.Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois.Kaiser Permanente Northern California, Oakland.Department of Medicine, Johns Hopkins University, Baltimore, Maryland.Retrovirus Research Center, Department of Medicine, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico.Department of Medicine, University of Washington School of Medicine, Seattle.Department of Medicine, University of Washington School of Medicine, Seattle.Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada. Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada.Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. Department of Medicine, Johns Hopkins University, Baltimore, Maryland.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

33595662

Citation

Sun, Jing, et al. "Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015." JAMA Network Open, vol. 4, no. 2, 2021, pp. e2037512.
Sun J, Althoff KN, Jing Y, et al. Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015. JAMA Netw Open. 2021;4(2):e2037512.
Sun, J., Althoff, K. N., Jing, Y., Horberg, M. A., Buchacz, K., Gill, M. J., Justice, A. C., Rabkin, C. S., Goedert, J. J., Sigel, K., Cachay, E., Park, L., Lim, J. K., Kim, H. N., Lo Re, V., Moore, R., Sterling, T., Peters, M. G., Achenbach, C. J., ... Kirk, G. D. (2021). Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015. JAMA Network Open, 4(2), e2037512. https://doi.org/10.1001/jamanetworkopen.2020.37512
Sun J, et al. Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015. JAMA Netw Open. 2021 02 1;4(2):e2037512. PubMed PMID: 33595662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015. AU - Sun,Jing, AU - Althoff,Keri N, AU - Jing,Yuezhou, AU - Horberg,Michael A, AU - Buchacz,Kate, AU - Gill,M John, AU - Justice,Amy C, AU - Rabkin,Charles S, AU - Goedert,James J, AU - Sigel,Keith, AU - Cachay,Edward, AU - Park,Lesley, AU - Lim,Joseph K, AU - Kim,H Nina, AU - Lo Re,Vincent,3rd AU - Moore,Richard, AU - Sterling,Timothy, AU - Peters,Marion G, AU - Achenbach,Chad J, AU - Silverberg,Michael, AU - Thorne,Jennifer E, AU - Mayor,Angel M, AU - Crane,Heidi M, AU - Kitahata,Mari M, AU - Klein,Marina, AU - Kirk,Gregory D, AU - ,, Y1 - 2021/02/01/ PY - 2021/2/17/entrez PY - 2021/2/18/pubmed PY - 2021/4/13/medline SP - e2037512 EP - e2037512 JF - JAMA network open JO - JAMA Netw Open VL - 4 IS - 2 N2 - Importance: People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era. Objective: To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. Design, Setting, and Participants: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020. Exposures: HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. Main Outcomes and Measures: HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. Results: Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection. Conclusions and Relevance: HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk. SN - 2574-3805 UR - https://www.unboundmedicine.com/medline/citation/33595662/Trends_in_Hepatocellular_Carcinoma_Incidence_and_Risk_Among_Persons_With_HIV_in_the_US_and_Canada_1996_2015_ L2 - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2020.37512 DB - PRIME DP - Unbound Medicine ER -