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. 2021 Feb 1;4(2):e2037512.
doi: 10.1001/jamanetworkopen.2020.37512.

Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015

Jing Sun  1 , Keri N Althoff  1 , Yuezhou Jing  1 , Michael A Horberg  2 , Kate Buchacz  3 , M John Gill  4 , Amy C Justice  5 , Charles S Rabkin  6 , James J Goedert  6 , Keith Sigel  7   8 , Edward Cachay  9 , Lesley Park  10 , Joseph K Lim  11 , H Nina Kim  12 , Vincent Lo Re 3rd  13   14   15 , Richard Moore  16 , Timothy Sterling  17 , Marion G Peters  18 , Chad J Achenbach  19 , Michael Silverberg  20 , Jennifer E Thorne  16 , Angel M Mayor  21 , Heidi M Crane  22 , Mari M Kitahata  22 , Marina Klein  23   24 , Gregory D Kirk  1   16 ; North American AIDS Cohort Collaboration on Research and Design of IeDEA
Affiliations

Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015

Jing Sun et al. JAMA Netw Open. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Althoff reported serving on the Scientific Advisory Board for TioHealth Inc and being a consultant for the All of Us study. Dr Gill reported receiving honoraria over last 3 years from being an ad hoc member of the Canadian National HIV Advisory Boards to Merck Gilead and ViiV. Dr Cachay reported receiving grants and other support from Gilead Sciences and grants from Merck Sciences outside the submitted work. Dr Lim reported receiving research contracts (to Yale University) from Allergan, Conatus, Genfit, Gilead, and Intercept. Dr Peters reported being a consultant to Abbott, Aligos, Antea, and Antios in the last 12 months. Dr Silverberg reported receiving ongoing research grants from Gilead, Inc. Dr Thorne reported being a consultant for Gilead. Dr Klein reported receiving grants for investigator-initiated studies from ViiV Healthcare, Merck, and Gilead; research grants from Janssen; and personal fees from ViiV Healthcare, Bristol-Myers Squibb, AbbVie, and Gilead outside the submitted work and reported being supported by a Canada Research Chair Tier 1 (CRC-232178). No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Incidence of Hepatocellular Carcinoma by Age and Viral Hepatitis Coinfection Groups Stratified by Calendar Era
Hepatitis B virus (HBV) infection was defined by detection of either hepatitis B surface antigen, hepatitis B e antigen, or HBV DNA in serum or plasma at any time during observation. Hepatitis C virus (HCV) infection was defined by the detection of HCV antibody seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation.
Figure 2.
Figure 2.. Age Distribution and Age of Hepatocellular Carcinoma (HCC) Onset by Viral Hepatitis Coinfection Groups
Hepatitis B virus (HBV) infection was defined by detection of either hepatitis B surface antigen, hepatitis B e antigen, or HBV DNA in serum or plasma at any time during observation. Hepatitis C virus (HCV) infection was defined by the detection of HCV antibody seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. Dashed vertical lines denote median age at HCC diagnosis in each group, and solid vertical lines denote mean age at HCC diagnosis.
See this image and copyright information in PMC

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