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Hepatocellular Carcinoma on the Rise Among HIV-Positive Individuals


Rates of hepatocellular carcinoma were highest among persons living with HIV who have higher RNA levels, lower CD4 cell counts, or used injection drugs.

Hepatocellular carcinoma (HCC) incidence rate and risk trended upward in a recent study that researched development of the cancer among 109,238 persons living with HIV (PWH) and who were coinfected with hepatitis B (HBV) and/or C virus (HCV). The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study investigated the ultimate diagnosis of the cancer among PWH between 1996 and 2015, and results were published recently in JAMA Network Open.

The large patient group from the United States and Canada accounted for 723,441 person-years of follow-up, 85.1% were male, 40.9% were White, 40.6% were Black, 19.5% had HIV and HCV, 5.8% had HIV and HBV, and 1.9% had HIV, HBC, and HCV (triple infection). Their median (interquartile range [IQR]) age was 43 (IQR, 36-51) years.

“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,” the authors noted, despite the frequent occurrence of coinfection with HBV or HCV, which increase risk for the cancer. “Understanding incidence trends and risk factors associated with HCC in aging PWH is critical to developing evidence-based interventions aimed at reducing HCC burden.”

The overall incidence of HCC by 2015 was 0.41% (96.9% of whom were male), while the crude HCC incidence rate (IR) jumped from 0.28 case per 1000 person-years in 1996-2000 to 0.75 case per 1000 person-years in 2006-2015. To see changes, the investigators compared 3 periods: 1996 to 2000 (early cART era), 2001 to 2005 (middle cART era), and 2006 to 2015 (modern cART era).

IRs (all per 1000 person-years) of HCC rose the most among PWH who also had HCV or those with triple infection between the study start and end years:

  • PWH plus HCV: 0.34 to 2.39 cases
  • Triple infection: 0.65 to 4.49 cases

Consistent IRs, meanwhile, were seen among PWH or who also had HBV.

In addition, having a recent HIV RNA level at or above 500 copies/mL (IR ratio [IRR], 1.8; 95% CI, 1.4-2.4) and a CD4 cell count at or below 500 cell/mcL (IRR, 1.3; 95% CI, 1.0-1.6) indicated an individual had a higher risk of developing HCC between 2006 and 2015. Following adjustment for HBV or HCV coinfection, however, the highest IRR of 2.0 (95% CI, 1.3-2.9) was seen among PWH who used injection drugs.

Adjusting for covariates of age, sex, race, and HIV transmission risk category (men who have sex with men [MSM], injection drug users, heterosexual contact, other/unknown) equated to a 72% increase in HCC IR (adjusted IRR, 1.72; 95% CI, 1.03-2.87). However, when just accounting for age, persons who had just HIV had an older median age when their HCC was diagnosed vs coinfection with HIV and HBV: 61 (IQR, 53-68) vs 54 (IQR, 47-58) years. For transmission risk category, most cases of HCV were seen in injection drug users, and most cases of HBV were seen in MSM.

The overall median follow-up was 5 (IQR, 2-10) years, which was just about equal to that for the 99.59% who did not develop HCC (5 [IQR, 2-11] years) and the 0.41% who did (7 [IQR, 3-10] years).

The authors’ findings are important, they say, because the confirm that HCC is on the rise in North America and that increased survival rates among PWH could lead to even greater HCC rates thanks to ART, which in turn increases patient exposure to HIV and chronic liver diseases.

“Appreciating the substantial risk associated with HIV-HCV coinfection and the public health burden, access to hepatitis C treatment among PWH should be prioritized,” they conclude. “Conversely, although lacking a cure, antiviral therapy has been shown to provide long-term benefits for patients with chronic HBV without HIV.”

Additional areas in which to make progress include prioritizing HBV vaccination and antibody testing among PWH, as well as more widespread and earlier HBV-active ART.

Generalization of these findings is limited due to lack of information on PWH not receiving care, unavailable date on other potential risk factors for HCC (eg, natural clearance, smoking status, obesity), and potential misclassification or underestimation of HBV and HCC coinfection.


Sun J, Althoff KN, Jing Y, et al; North American AIDS Cohort Collaboration on Research and Design of IeDEA Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015. JAMA Netw Open. Published online February 1, 2021. doi:10.1001/jamanetworkopen.2020.37512

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