Rising Morbidity: Viral Hepatitis Co-Infection with HIV and Age All Associated with Increased Rates of Liver Cancer

In February, researchers associated with numerous universities across Canada and the United States published one of the most comprehensive data reviews thus far conducted on the incidence rates of the most common type of liver cancer among people living with HIV/AIDS (PLWHA) and PLWHA co-infected with viral hepatitis. The study reviewed data collected as part of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), conducted between 1996 and 2015, with clinical data from 109,283 participants. Conclusions from the study were fairly straight-forward: the combination of HIV status (mono-infection), co-infection with viral hepatitis (HBV and/or HCV) and age all correlated with an increased chance of developing liver cancer (hepatocellular carcinoma [HCC]). The hope of researchers, as evidenced in the study’s introduction was to “inform expectations for other regions with a substantial burden of HIV and HBV-HCV coinfection but with delayed cART [combination antiretroviral therapy] scale-up and limited access to viral hepatitis treatment”.

While most research papers wait to include study limitations at the end, I prefer to open with them as prefacing allows for contextualizing data. The first and primary limitation on the review is clinical information reviewed was necessarily from those people linked to care and correlations provided by the data in the study cannot be applied to the diagnosed-but-not-in-care or undiagnosed population. Second, researchers note, information on relevant, individual health factors were missing from significant portions of participants data (example: smoking and drinking habits, natural clearance of HCV, fibrosis score, and HIV exposure risk). Additionally, data collection was not uniform across all participating entities at the time of linkage to care, though a quality analysis was used to help even things out and ensure the integrity of data comparisons. This lack of uniform protocol also included certain sites not administering or participants not receiving HCV or HBV screening. The last, though likely most significant limitation of the study is the data were collected prior to the advent of curative direct acting agents (DAAs) for HCV, and conclusions cannot be made on the potential positive impacts of readily available DAAs.

A limitation not mentioned and data unassessed is any reference between older ART regimens and newer ones, in which toxicity and tolerability is commonly known to be considerably improved with newer regimens. Liver health monitoring is fairly standard, among other relevant patient labs, for PLWHA because of a relationship between ART and liver health. While it’s understandable researchers who generally enjoy significant funding from manufacturers may wish to avoid broaching this topic, not mentioning the issue, even to say “we can’t make any conclusions on cART tolerability and toxicity as an indicator for adherence or risk of developing HCC” misses an incredibly important elephant in the room for researchers, providers, and patients alike.

Instead, researchers chose to focus on cART “eras” (1996-2000 [A], 2001-2005[B], and 2006-2015[C]), in which there’s a positive correlation between age and era; or those aging with HIV were more likely to be diagnosed with HCC. Highest rates of HCC diagnosis by cART area are as follows: A – between 50 and 60 years-old (HBV co-infection with HIV), B – lower end 70-80 (HCV co-infection with HIV), and C – upper end 70-80 (HCV and HBV co-infection with HIV). This data is particularly valuable on its own, however, as the associated risk cohort shift appears to be very closely related to age (ie. those in the upper end of the C “era” are also those to first receive effective cART and the 20-year age gap between the C and A cART eras).

Ultimately, PLWHA were more than 3 times as likely as the general population to develop HCC and more than 20 times more likely to develop HCC if co-infected with viral hepatitis. HCC incidence among study participants fell along rather predictable lines in terms of HIV related clinical monitoring metrics; those with higher viral loads and lower CD4 counts were more likely to develop HCC.

The study’s finding highlight the need for ensuring access to DAAs and HBV vaccines, ready ART uptake upon linkage to care, and strengthening the integrity of AIDS Drug Assistance Programs, Medicaid Programs, and care provided to incarcerated persons – specifically, ensuring the inclusion of coverage of DAAs in these.

Advocates, providers, and patients can review DAA coverage inclusion in ADAPs and Medicaid and harm reduction policies impacting HIV and HCV with Community Access National Network’s quarterly HIV-HCV Co-Infection Watch report.