CATIE News

• A large study found an increased risk for liver cancer in some HIV-positive people
• HIV-positive people co-infected with hepatitis B or C had a 20-fold greater risk than people without these viruses
• There is a need for viral hepatitis screening, vaccination and treatment in vulnerable populations

Studies have found that HIV-positive people as a group have an increased risk for liver cancer compared to HIV-negative people. This risk is largely driven by co-infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV).

In general, cancer risk increases with age as several factors coincide. For instance, some processes that drive the development of cells to become abnormal and pre-cancerous are lengthy and, in such cases, it can take a long time before a tumour develops. Another factor is aging. The immune system is on the lookout for cancers, but as people grow older, the effectiveness of the immune system gradually weakens. This does not mean that everyone will get cancer. However, it does mean that the overall risk for cancer increases with age, particularly in people over the age of 50.

Although many HIV-positive people in North America are living AIDS-free thanks to HIV treatment (ART), their risk for cancer will increase with age, as it does for everyone else.

A North American study

Researchers in Canada and the U.S. pooled health-related information collected from more than 100,000 HIV-positive people in order to analyse trends in liver cancer. In this study, the researchers focused on the years 1996 to 2015. They found an increasing risk for liver cancer over time. This risk was most prominent among people who were chronically co-infected with HBV and/or HCV.

The researchers also found that people with an HIV viral load of 500 copies/mL or greater and a CD4+ count of less than 500 cells/mm³ were at heightened risk for the development of liver cancer, as were people who injected street drugs.

The researchers listed several interventions that could be taken to help reduce the risk for liver cancer among HIV-positive people. These interventions appear later in this bulletin.

Study details

Researchers analysed the medical records of 109,233 HIV-positive people. The average profile of participants upon entering the study was as follows:

• 85% men, 15% women
• age – 43 years
• major ethno-racial groups: white – 40.9%; black – 40.6%
• viral status: HIV alone – 70%; HIV + HBV – 6%; HIV + HCV – 20%; HIV + HBV + HCV – 2%; unassessed – 2%

Participants were monitored for five years.

Clinics in Canada (in Montreal and Southern Alberta) contributed about 7% of participants for the study.

Results

Over the course of the study, a total of 451 people developed liver cancer—an overall increase of 72%.

The risk for liver cancer was seen only in people aged 50 and older. The vast majority of people with liver cancer were men.

Trends

Below are trends involving a number of factors that had an impact on liver cancer risk.

Specific impact of viral hepatitis

Looking at trends over the course of the study, the researchers found that there was “no substantial change” in the rate of liver cancer for people with HIV infection alone. However, the researchers stated that among people co-infected with HBV or HCV there were 20-fold more cases of liver cancer compared to people with HIV alone. The researchers found that people co-infected with all three viruses —HIV, HBV and HCV—had 40-fold more cases of liver cancer than people with HIV alone.

Age

Although the overall age distributions of people with and without hepatitis co-infection were similar, researchers found that people with HIV alone were diagnosed with liver cancer at an older age, and people with HIV and HBV and/or HCV were diagnosed at a younger age. This suggests that the risk of liver cancer is accelerated in people with HBV and/or HCV and likely occurs at an earlier age as a result of this acceleration.

Immune system and HIV

The researchers found that in the most recent decade of the study, participants with a viral load of 500 copies/mL or greater had “an 80% increased risk [of developing liver cancer] compared to participants whose viral load was less than 500 copies/mL.” This elevated risk was independent of viral hepatitis co-infection.

Also, during the most recent decade of the study, participants with a CD4+ count of 500 cells/mm³ or lower had a 30% increased risk for developing liver cancer than people who had higher CD4+ cell counts. This risk was independent of viral hepatitis co-infection.

Vulnerable populations

Overall, researchers found that people who injected street drugs had an increased risk for liver cancer compared to gay and bisexual men. Researchers presumed that this risk was driven by viral hepatitis co-infection. However, the risk for liver cancer was still high even among people who injected street drugs who did not have hepatitis (although it was lower than the risk in people who injected street drugs who had hepatitis co-infection). The researchers theorize that this risk for liver cancer may be linked to the following issues:

• diabetes
• excess alcohol intake
• NAFLD (non-alcoholic fatty liver disease)
• smoking

Most of these nonviral issues have been increasing in the average person in the U.S. around the same time as the period studied.

Possible interventions

Given the strong connection between viral hepatitis and increased liver cancer risk, the researchers made the following suggestions for care providers and their HIV-positive patients, some of whom are co-infected with viral hepatitis:

• conduct randomized controlled trials “to evaluate the efficacy of more active cancer [screening]” among HIV-positive people
• prioritize “access to HCV treatment” for people with HCV infection
• effectively control HBV through antiviral drugs that are active against both HIV and HBV; the researchers noted that such drugs include 3TC, FTC and tenofovir
• screen patients for the presence of protective antibodies to HBV; if these antibodies are absent, offer vaccination
• encourage earlier initiation of ART; this should help reduce immunological dysfunction and inflammation, which could contribute to underlying issues that drive cancer formation

The researchers noted that on the whole “it is vital to address other [socio-economic] factors and health disparities to ameliorate the overall burden of [liver cancer] among aging [HIV-positive people]. Treatment strategies focused on HCV screening and early intervention for chronic HCV or HBV among people who inject drugs, as well as long-term management of risk behaviours, should be further explored.”

—Sean R. Hosein

Resources

Hepatitis C: An In-Depth Guide – CATIE

Understanding Cirrhosis of the Liver: First steps for the newly diagnosed – CATIE, Canadian Association of Hepatology Nurses (CAHN)

What Works: What you need to know if you have HIV and use drugs – CATIE

Best Practice Recommendations for Canadian Harm Reduction Programs – Working Group on Best Practice for Harm Reduction Programs in Canada

Estimated number of people who inject drugs and coverage of harm reduction programs in Canada – CATIE News

Harvoni (ledipasvir + sofosbuvir) – CATIE

Maviret (glecaprevir + pibrentasvir) – CATIE

REFERENCES:

1. Sun J, Althoff KN, Jing Y, et al. Trends in hepatocellular carcinoma incidence and risk among persons with HIV in the US and Canada, 1996-2015. JAMA Network Open. 2021; in press.
2. Laconi E, Marongiu F, DeGregori J. Cancer as a disease of old age: changing mutational and microenvironmental landscapes. British Journal of Cancer. 2020 Mar;122(7):943-952.
3. Frasca D, Blomberg BB. Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination. Immunity and Ageing. 2020 Nov 19;17(1):37.
4. Cheng F, Carroll L, Joglekar MV, et al. Diabetes, metabolic disease, and telomere length. Lancet Diabetes and Endocrinology. 2021 Feb;9(2):117-126.