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Risk of HCC With Hepatitis B Viremia Among HIV/HBV-Coinfected Persons in North America
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In this large sample of HIV/HBV‐coinfected persons from North America, we found that all detectable measures of HBV viremia, including time‐updated detectable HBV >200 IU/mL, higher current HBV DNA, and greater consecutive months of detectable HBV, were associated with increased risk of HCC. There was a biological gradient of risk of HCC with higher HBV DNA, especially at levels >200,000 IU/mL. Notably, neither CD4+ percentage nor any definition of HIV viremia was associated with increased HCC risk. In analyses evaluating both detectable HIV and HBV, the risk of HCC was highest when HBV viremia was detectable. Finally, sustained HBV suppression with HBV‐active ART for ≥1 year was associated with a 58% reduction in HCC risk.
Older age, heavy alcohol use, and chronic HCV coinfection-all known risk factors for HCC in cohorts with monoinfected HBV(29)-also significantly increased the risk of HCC in our cohort of persons coinfected with HIV/HBV. Heavy alcohol use and HCV coinfection were prevalent in our cohort and may continue to influence the natural history of HCC despite HBV suppression. Our findings suggest that avoiding excessive alcohol consumption and initiating antiviral therapy for chronic HCV infection might help to reduce the risk of HCC among persons coinfected with HIV/HBV.
29 March 2021
Background and Aims

Chronic HBV is the predominant cause of HCC worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multicohort study of individuals coinfected with HIV/HBV.
Approach and Results
We included persons coinfected with HIV/HBV within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995-2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted HRs (aHRs [95% CIs]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, HCV), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA).
Among 8,354 individuals coinfected with HIV/HBV (median age, 43 years; 93% male; 52.4% non-White), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5-2.1] events/1,000 person-years).
Risk factors for HCC included age 40-49 years (aHR, 1.97 [1.22-3.17]), age ≥50 years (aHR, 2.55 [1.49-4.35]), HCV coinfection (aHR, 1.61 [1.07-2.40]), and heavy alcohol use (aHR, 1.52 [1.04-2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56-1.43]) and time-updated CD4+ percentage <14% (aHR, 1.03 [0.56-1.90]) were not.
The risk of HCC was increased with time-updated HBV DNA >200 IU/mL (aHR, 2.22 [1.42-3.47]) and was higher with each 1.0 log10 IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05-1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1 year significantly reduced HCC risk (aHR, 0.42 [0.24-0.73]).

Individuals coinfected with HIV/HBV on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.


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