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Despite being one of the fastest viral diseases to be identified and cured by scientists, hepatitis C remains overlooked and underdiagnosed, risking millions of lives. Our latest In Conversation episode, dedicated to World Hepatitis Day, co to jest colofac mr looks at the timeline of how research around this viral disease has evolved while addressing the stigma associated with the unknown and discussing steps to take for a hepatitis C-free future.

Hepatitis C is a blood-borne viral disease that slowly progresses over time. Although curable, if left untreated, it can damage the liver, leading to cirrhosis and hepatocellular carcinoma (HCC), a type of liver cancer.

According to the World Health Organization, an estimated 58 million people have a chronic hepatitis C infection, and a further 1.5 million people get infected each year.

However, just a few decades back, this virus was nameless.

Until 1989, scientists had referred to it as non-A, non-B hepatitis. That year, researchers managed to identify and isolate the culprit behind this disease, naming it the hepatitis C virus (HCV).

Much was yet to be discovered about this virus, and initially, it was thought to only affect the liver alone. The biggest misconception also came from the belief that anything to do with the liver was associated with alcohol.

“Very few people understand that liver disease is a heterogeneous condition. Most people assume that anyone with anything wrong with their liver is a drinker. So liver disease in the public’s mind is focused on alcohol, and viral hepatitis and other causes of liver damage are very poorly understood,” said Prof. Graham Foster, professor of hepatology at the Queen Mary University of London.

The guests of the podcast listened to a vox pop conducted on the streets of London. The people interviewed were very uncertain about what hepatitis was:

“…I don’t know much about it to be fair. It’s in the liver right?”

For Rachel Halford, this is, unfortunately, not surprising “in the slightest” as even her own healthcare providers knew little about it when she was being treated.

She was diagnosed with hepatitis C in 1998.

“That was at a point having a history of substance misuse for more than 22 years, where really, my life had collided, I decided or I’d been forced to decide not to use drugs anymore. And once I stopped, I made a decision to have a [test].”

Rachel said that at the time her primary concern was HIV and that hepatitis C “really didn’t bother” her. However, when she tested positive for hepatitis C, she was assured by a nurse that it was not a death sentence.

“In fact, when the nurse told me she said, ‘You’re clear, you haven’t got HIV, but you’ve got hepatitis C, and don’t worry, you’ll die of something else first’.”
— Rachel Halford

Once a hepatitis C patient, Rachel is now the chief executive of the Hepatitis C Trust, a non-governmental organization that is staffed by 120 people who have all had hepatitis C and now work on a peer-to-peer basis with clients to reduce hepatitis C and its consequences.

For Rachel’s full story, efforts on erasing the stigma associated with hepatitis C and drug users, and more on what the future holds for hepatitis C treatment, you can listen to our podcast in full below, or on your preferred streaming platform.




A multi-faceted systemic disease

In the following months, Rachel would undergo several treatments with the medications that were available at the time. However, these caused many side effects for Rachel, including nausea, vomiting, and diarrhea.

However, once the treatment had cleared the virus, she realized that her itchy skin, irritable bowel symptoms, and brain fog were not from her drug use but from the hepatitis C itself.

“[I] noticed that I had a lot of really strange symptoms, which I wasn’t sure whether they were a consequence of hepatitis C, or whether they [were] what I’ve done to my own body through using drugs extensively. So, my legs would swell a lot, I’d get itchy skin, I’d bruise really easily. And I always had problems with my stomach,” she said.

With hepatitis C, after years of “silence”, it is not uncommon for patients to experience “a plethora of symptoms exactly as Rachel described,” said Prof. Foster.

“[If] you sit in a clinic, and you see people with hepatitis C and hepatitis B, what strikes you is how sick people with hepatitis C are. And that tells us that this is not related to the inflammation in the liver. There’s something else going on,” he said.

This is one area of research surrounding hepatitis C diagnosis and treatment has focused on in recent years. Scientists have uncovered the impact a viral disease like hepatitis C can have on other organs and systems in the body.

One particular organ is the brain.

“[W]hat is very clear is that people with hepatitis C have slightly abnormal magnetic resonance spectroscopy in the brain. So, if you look very carefully, at brain tissue from people with hepatitis C, it’s a little bit abnormal in a rather nonspecific fashion. We know that people have increased fatiguability, poor recovery times,” said Prof. Foster.

He also said that other symptoms patients experience, such as irritable bowel, muscle, and joint pains, are also due to the virus and its effect on the immune system.

“[Hepatitis C] is a very potent infection that stirs up all sorts of immunological responses and leads to this plethora of symptoms,” he said, adding that patients often report they “can feel the virus within their system.”

“Patients will come into my clinic and say, ‘I know the virus is gone, I feel better. [I] just feel the difference.’ And in those very, very few patients who relapse and the virus returns, people will come into the clinic and say, I know it’s back. [T]hey’re very well aware of how devastating it can be,” he said.

Rachel said she knew exactly how that felt:

“[In] 2007, I was contacted by my hospital to access treatment, and I did. I did the old treatment which no longer exists— interferon and ribavirin.”

She said she had never associated the brain fog and cognitive symptoms she experienced with hepatitis C until she received treatment for a year.

“[A]fter a year of doing the interferon treatment, when I did clear the virus eventually, the difference in my cognitive function was enormous. My memory was incredible. I had no idea that hepatitis C had had such an impact on my brain. Foggy brain is what people call it because everything’s just not quite right.”
— Rachel Halford

This aspect of hepatitis C—symptoms such as brain fog, bowel issues, and immune evasion—also bears resemblances with long COVID. Prof. Foster said research on long COVID has helped challenge many assumptions about hepatitis C.

“A lot of people were very disparaging about the symptoms. I remember when we first published a paper years ago on hepatitis C-associated symptoms, quite a lot of people spoke to me and said, ‘You’re talking nonsense. They come to you because they’re tired.’ think that attitude has now changed and COVID-19 has helped that enormously,” he said.

Treatment: then vs. now

With little known about this disease until a few years before her diagnosis, Rachel was lucky enough to get information about the genotype of hepatitis C she had thanks to rapid advances in research on the disease.

“[T]he hepatitis C virus was probably the first or one of the earlier viruses to be attacked genetically. And it was the right virus at the right time because we had genome sequencing, but we couldn’t do very long bits of DNA. [H]epatitis C is only about 10,000 bases long, and that was well within the range of the sequencing technologies,” Prof. Foster said.

He said Peter Simmonds in Scotland was one of the drivers for the genetic analysis of hepatitis C, recognizing that there were different strains and that they were from different geographies.

This aided in developing life-saving therapies for hepatitis C.

There are very few people who can clear the hepatitis C virus from their system without the help of medication. Hence, research around treatments for hepatitis C has been crucial.

“There’s a particular mutation in a gene called IL 28. That seems to predispose [people] to clearing hepatitis C. So, although the virus can get around 80% of people’s immunity, there are a handful of people out there who managed to evade the virus defenses, and they can get in there and kill it,” said Prof. Foster.

The first—and for a while, the only—treatment to get approval for the treatment of hepatitis C was interferon. It came in the form of injections called recombinant interferon-alfa (IFNa) based on a protein produced by the immune system that fights infections and other diseases.

Not only was the treatment incredibly lengthy—taking as long as 48 weeks—but it was also largely ineffective, helping only a third of patients. In addition, it caused many side effects that drove patients to quit halfway.

Reducing side effects

Soon after in the mid-90s, scientists tried adding different medications to the mix such as the antiviral drug ribavirin (RBV).

“When I started treating patients with hepatitis C, we used interferon—an injectable cytokine. [T]hat really had a whole plethora of side effects and cured about 10 to 20% of patients. We quickly worked out that if we added a second drug, ribavirin to it, that would double the response rates to nearly 40%,” Prof. Foster recalled.

However, this coupling also meant more side effects. Different genotypes of hepatitis C also seemed to respond differently to this combination.

In the following years, scientists explored various other medications which included protease inhibitors (PIs).

“So, there was a huge focus to find a better treatment for genotype one [which was not as sensitive to interferon and ribovirin]. And that led to another generation of tablet-based treatments, the protease inhibitors,” said Prof. Foster.

However, these were also abandoned due to side effects and interaction with other medications.

The breakthrough, according to Prof. Foster, came when German physician of Ralf BartenSchlager became “the first person to crack the replication of hepatitis C, and put it in the public domain” by growing hepatitis C in the laboratory. In his footsteps, various scientists such as Nobel-winning Charlie Rice took up the research and made improvements.

“Once the drug companies were given a replication model. They tested their drug libraries, they came up with molecules, and they got onto the market and we got rid of interferon,” he said.

In the late 2010s, scientists developed several drug therapies with low side effects profiles and high cure rates. One, for example, was sofosbuvir/velpatasvir/voxilaprevir‎ (Vosevi), which gained Food and Drug Administration (FDA) approval in 2017, and made HCV undetectable in 96-97% of patients’ blood.

Future threat: Silent progression

Although awareness around hepatitis C is increasing, there is still much to be done to educate the public. Efforts so far have focused on accurate information and encouraging widespread testing.

“It saddens me greatly, that there is such a lack of awareness,” said Rachel. Nowadays even though there is more awareness which does reduce the stigma around it slightly, “ultimately, it is a really stigmatized disease.”

“[W]hen I was diagnosed, if I went to the dentist, I had to be the last person on the list because no one [knew] about hepatitis, and they thought that I [was] dirty, basically.”
— Rachel Halford

Prof. Foster said that despite dramatic reductions in hepatitis C cases in the U.K., in the U.S. the number of people with hepatitis C is still increasing, particularly among young people. In that sense, current practices and attitudes toward drug users will have to change.

“[T]hose young people I’m afraid are spreading the virus. And many young women are infecting their children. So the American approach to needle exchange, which is to criminalize drug use, really hasn’t worked. [I]t’s very important that we reiterate the message that hepatitis C is a preventable disease, provided you make drug users part of the society that we live in, provide them with the equipment they need, and simply hepatitis C will melt away,” he said.

“[W]hen you stop seeing someone as a drug user, and see them as a person who at this stage of their life is using drugs, the world changes. And that really, for me, is a tragedy that we’re still discriminating against people who use drugs [when it comes to hepatitis C treatment].”
— Prof. Graham Foster

Testing and early detection, as with many other diseases, hence, are particularly crucial in the fight against hepatitis C.

“We know that hepatitis C is a slowly progressive virus in terms of liver damage. But what’s becoming increasingly clear is that once you’ve incubated the virus for 20 or so years, the virus really does start to accelerate,” explained Prof. Foster.

Decades after unknowingly being infected, many patients are having to face the reality of irreversible damage from cirrhosis or liver cancer.

“[W]hat we’re starting to see are patients infected 30-40 years ago, who are really getting into trouble with cirrhosis, with liver cancer. The tragedy is that if we find hepatitis C early and we eliminate the virus, the liver disease stops progressing, and the cancer risk disappears. But once the liver already has cirrhosis, I’m afraid the risk of liver cancer continues even when we clear the virus,” said Prof. Foster.

Efforts for elimination

Prof. Foster also stressed that elimination is not stopping all efforts to fight it.

“[W]e’ve seen with COVID-19, for example, that if you take your foot completely off the brake, then the virus will take over again. So, I think we need to challenge our assumption that elimination means we walk away and say we’re moving from large numbers of infected people that need constant attention to a small number that needs a little bit of help here and there,” he said.

Current campaigns in the U.K. and the U.S. are urging those with a past history of injection drug use—especially those 30-40 years ago—to get tested and treated before they develop cirrhosis.

“I think in England, I’m very confident that over the next few years, probably fewer rather than more years, we will move from a program where hepatitis C is a major problem to an area where it’s a minor problem. And I think elimination is defined as reducing the rate of infection to below the level where it’s a public health hazard,” Prof. Foster said.

He added, however, “And I think it’s really important that we understand that eliminating hepatitis C doesn’t mean we stop, it means we get it to a low level, and then we keep it down at that level.”

Rachel also touched on how most of the people with undiagnosed hepatitis C come from marginalized communities who may not have access to healthcare or treatment.

“[O]ne of the things about us reaching elimination is [that] it’s not going to happen alone. We also need to do some work around harm reduction; we need to make sure that there is enough needle and syringe provision, because [while] we can find people who are in drug services, there are a lot of people that don’t access drug services,” she said.

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