In 10 seconds? In this installment of our Cancer Gone Viral series, we talk about the Hepatitis C virus (HCV), the poster child of the opioid epidemic. It’s responsible for causing liver cancer but luckily, there’s a cure… if you catch it in time.
Finally some good news! But what’s the link between opioids and cancer? Ever since unethical opioid marketing practices started in the 1990s, North America has been caught in an opioid epidemic that has tragically claimed over 600,000 lives in the US and Canada. And if the opioid epidemic is the villain, Hepatitis C Virus (HCV) is its sidekick, riding on its coattails and putting those chronically infected at a 10-20 times higher risk for liver cancer.
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Back up. How is the Hepatitis C virus connected to the opioid crisis? OK, let me give you a bit of historical context. The company Purdue pharma (since prosecuted) employed harmful marketing practices that led doctors to over-prescribe the very addictive opioid OxyContin, which led to a bunch of its users getting hooked. Many factors, including the high cost and restricted supply, lead a proportion of those struggling with opioid misuse to switch to heroin, an illicit injectable opioid with similar pain-relieving effects. This is where HCV comes in.
Right, and how does a drug user get a cancer-inducing virus? OK. Hepatitis C virus is spread by blood-to-blood contact. And needles shared between people using heroin are the perfect vector for it to hop from one person to another. And while heroin carries the immediate risk of overdose (particularly if it is laced with fentanyl—an even more potent and therefore dangerous opioid), HCV is not to be underestimated either. It is one of the deadliest human infectious diseases due to its role in causing liver failure and liver cancer—leading to more than 14,000 deaths in the US in 2019. The worst part is: that most people infected with HCV don’t know they have it (estimates range from 50 to 85%)!
Why don’t they know? Like all cancer-causing viruses, HCV can cause a slow-burning chronic infection, which frequently doesn’t cause noticeable symptoms until much damage is done. And while the opioid epidemic is driving worrisome increases in HCV infection, increasing rates of HCV-associated liver cancer (which takes decades to form) are being seen nowadays among the baby boomer generation (birth dates between 1945-1965). In this generation, most HCV cases are thought to have been contracted through receiving blood from contaminated blood banks (another public health disaster which has since been addressed and resolved through rigorous testing processes).
Yikes. So, how does HCV cause cancer? HCV turns our livers into virus factories and maintains high levels of virus production over the course of infection so that it can infect anyone whose blood encounters even the tiniest drop of infected blood. Outside of injection drug use, HCV has to enter the recipient’s bloodstream through a wound to establish an infection. Our immune systems work to clear this blatant infection and even manage to cure approximately 1/3 of all infections at an early stage before the disease goes ‘chronic’ or long-lasting. However, for the remaining 2/3 of those infected, what happens is a constant yet fruitless warzone in our liver (AKA chronic infection).
And that’s bad in terms of cancer because… Well, our immune systems are made to handle infections quickly by spewing out anti-viral proteins (ex. Type I interferons). But if the first assault is unsuccessful, our immune response may start to 'turn off' the attack which unwittingly helps HCV achieve a long-lasting infection (AKA chronic infection)! But without resolution of the infection, the immune assault will continue to some degree—spitting out substances meant to kill cells with HCV—but with little benefit. Over years, cell and tissue damage caused by HCV infection, combined with the harmful immune environment it helps culture, can take a big toll on the livers of those infected and lead to liver cirrhosis.
What’s cirrhosis… I know that’s still not cancer! Cirrhosis is scarring and permanent damage to the liver tissue. Liver cancer associated with HCV develops from liver cirrhosis in 90% of the cases. Once cirrhosis kicks in, our liver cells are no longer healthy and our immune system is exhausted from its decades-long battle (AKA the perfect breeding ground for mutations to arise and cancer to develop). And once cirrhosis is diagnosed in patients, each year 0.5-10% of patients will develop liver cancer.
So, what’s being done? You said there was a cure… Yes! The treatment for HCV became available in 2013 and it can cure over 95% of cases! So, the key to combating future cases of liver cancer amongst those who’ve gotten HCV during the opioid epidemic is widespread testing (amongst vulnerable populations) and connecting those infected with the cure before it can develop into cancer. Although this is more easily said than done, as injection drug users are a historically marginalized and under-resourced population.
Yes, that is tough. How do we overcome that? Public health efforts are underway to connect current or past injection drug users with HCV testing as well as resources to prevent future spread, like clean needles. Of course, for baby boomers, testing is equally important, particularly if they received blood before 1992. The CDC now recommends screening for all US adults at least one time and during every pregnancy (since HCV can be passed to a child).
How HCV avoids our immune system
One of the ways that anti-viral proteins (called Type I Interferons) produced by our immune system, ‘interfere’ with viral replication is by turning off our cells’ capacity to make new proteins (referred to as cellular transcription and translation)—a vital cellular function that viruses need to tap into to survive.
But HCV circumvents this issue through its IRES (internal ribosome entry site) feature, which can highjack our cells’ protein-making machinery (AKA ribosomes).
This is an ingenious trick because it results in ONLY HCV proteins being made (since our own protein production is shut off) and greatly facilitates its replication.
So, no wonder HCV infection is so hard to hack!
Dr. Talia Henkle has distilled 6 research papers, saving your 21 hours of reading time
The Science Integrity Check of this 3-min Science Digest was performed by Dr. Jacquelyn Bedsaul.