Suppression of chronic hepatitis B virus (HBV) infection to undetectable levels with use of antiretroviral therapy reduced the risk for developing hepatocellular carcinoma (HCC) by nearly 60% in patients coinfected with HIV, according to data from a longitudinal cohort study published in Hepatology.1

“This study highlights the importance of testing and regular care for HIV and chronic hepatitis B coinfected individuals as well as the value of programs and strategies that help coinfected individuals maximize antiretroviral adherence to achieve hepatitis B viral suppression,” said senior author Vincent Lo Re III, MD, MSCE, an associate professor of Medicine and Epidemiology at Penn Medicine.2

Chronic HBV infection is a leading risk factor for HCC because of inflammatory and viral-mediated pro-oncogenic mechanisms. However, limited data is available on the risk for HCC in patients coinfected with HBV and HIV.


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The researchers used data from 8354 HIV-infected patients with active HBV coinfection from the United States and Canada enrolled in the North American AIDS Cohort Collaboration on Research and Design between 1995 and 2016. Patients with acute HBV infection were excluded from the study and none of the patients had HCC at baseline.

A total of 115 patients (1.4%) developed HCC during 65,392 person-years of follow-up (incidence rate, 1.8  events/1,000 person-years [95% CI, 1.5-2.1]). The median duration of follow-up was 6.9 years. Of the nearly 2000 patients (23.8%) who were not on an HBV-active antiretroviral at study entry, 1,509 (76.0%) received therapy during follow-up.

Increased risk for HCC was associated with the following traditional risk factors for HCC: age 40 to 49 years (adjusted HR, 1.97), age ≥50 years (aHR, 2.55), heavy alcohol use (aHR, 1.52), and chronic HCV (aHR, 1.61). The risk of HCC was not linked to higher HIV RNA (>500 copies/mL) and greater consecutive months with detectable HIV or CD4+ percentage (<14%).

Detectable HBV Is Associated With Increased HCC Risk

Patients with detectable HIV and detectable hepatitis B had the highest risk of developing HCC compared with those with undetectable levels of both viruses (Table). The risk of HCC was also increased among patients with undetectable HIV and detectable HBV but was not significantly elevated in those with detectable HIV and undetectable HBV. Antiretroviral treatment for chronic HBV reduced the risk of developing HCC; the risk was reduced by 58% with sustained HBV suppression for at least 1 year.

Table. Risk for HCC Associated With Time-Updated HBV and HIV Viremia Status

StatusAdjusted Hazard Ratio (95% CI)
Undetectable HIV and HBVReference
Detectable HIV and HBV2.21 (1.17-4.18)
Undetectable HIV/detectable HBV1.77 (1.07-2.92)
Detectable HIV/undetectable HBV0.27 (0.06-1.14)
Table adapted from Lo Re et al.1

Monitoring HBV Viral Load Is Essential

“Most HIV providers do not regularly monitor hepatitis B viral load in practice, even while on antiretroviral treatment,” Dr Lo Re said. “Our data highlight the importance of regular assessment of hepatitis B viral load and achievement of hepatitis B suppression during antiretroviral therapy in people with HIV and chronic HBV coinfection.”

Heavy alcohol use (35%) and hepatitis C virus (HCV) coinfection (22%) were also associated with an increased risk of HCC in this cohort. Thus, interventions to reduce excessive drinking and use of direct-acting antiviral therapy targeted to chronic HCV infection could also help lower the risk of liver cancer in infected people, the study authors noted. Heavy alcohol use was defined as having 1) a diagnosis of alcohol dependence/abuse or 2) ≥3 drinks/day or ≥7 drinks/week for women and ≥4 drinks/day or ≥14 drinks/week for men.

The study is the first to show that HBV viremia is associated with HCC risk in a large, racially diverse cohort of HIV-infected adults outside of Asia, where HBV infections are typically acquired perinatally as opposed to via sexual or parenteral routes, the researchers noted.

The study was supported by the National Institute of Allergy and Infectious Diseases (R21-AI124868).

References

1. Nina Kim H, Newcomb CW, Carbonari DM, et al. Risk of hepatocellular carcinoma with hepatitis B viremia among HIV/hepatitis B virus-coinfected persons in North America. Hepatology. 2021 Mar 29. doi:10.1002/hep.31839

2. Penn medicine study suggests long-term suppression of hepatitis B in patients who are HIV-coinfected may lower cancer risk. May 21, 2021. Accessed June 11, 2021.   https://www.pennmedicine.org/news/news-releases/2021/may/penn-study-suggests-long-term-suppression-of-hepatitis-b-in-hiv-patients-may-lower-cancer-risk