Abstract
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. To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. 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. 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. HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. 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. 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.
Highlights
Hepatocellular carcinoma (HCC) incidence increased by 75% between 1990 and 2015, making hepatocellular carcinoma (HCC) one of the most common cancers and leading causes of cancer death worldwide.[1]
HCC incidence rate (IR) remained constant among HIV-monoinfected persons or those coinfected with hepatitis B virus (HBV), but from 1996 to 2015, IRs increased among People with HIV (PWH) coinfected with hepatitis C virus (HCV) or those with triple infection
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 combination antiretroviral therapy (cART) era
Summary
Hepatocellular carcinoma (HCC) incidence increased by 75% between 1990 and 2015, making HCC one of the most common cancers and leading causes of cancer death worldwide.[1]. People with HIV (PWH) have a higher burden of HCC4,5 and end-stage liver disease[6,7,8] compared with people without HIV because of the high prevalence of coinfection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV),[9,10,11] risk behaviors,[12] and immune dysfunction.[13,14] Since the advent of combination antiretroviral therapy (cART), PWHs have prolonged survival, resulting in a notable increase in the number of PWHs older than 50 years,[15] concurrent with the age when many cancers are diagnosed in the general population.[16] Previous studies[4,17,18,19,20] found increasing incidence of several non–AIDS-defining cancers, including HCC, in the modern cART era, in part attributable to aging of the PWH population. Trends and risk factors associated with HCC in North America, which had progressive cART uptake before the widespread use of hepatitis C treatments, may inform expectations for other regions with a substantial burden of HIV and HBV-HCV coinfection but with delayed cART scale-up and limited access to viral hepatitis treatment. We assessed temporal trends for HCC among PWH in the cART era, comparing HCC rates by viral hepatitis infection, risk populations, and HIV disease severity using data from a large cohort consortium, the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)
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