Finding the right treatment for patients with hepatitis C
Two years ago, Dr John McLauchlan, Associate Director of the MRC-University of Glasgow Centre for Virus Research, wrote about two new research consortia, HCV Research UK and STOP-HCV, aiming to make sure that patients infected with hepatitis C receive the right treatment. To mark World Hepatitis Day, he’s back to give us an update ― and some good news about the treatment of chronic hepatitis in the UK.
Since I wrote that first blog post in 2013, both consortia have made considerable progress, and the context in which they are operating has changed dramatically.
One of the most exciting things is that new antivirals are becoming available that can cure patients of their infection. It’s not an understatement to say this new family of drugs (called direct-acting antivirals) are transformative ― clinical trials have shown that it is now possible to clear the virus in a high percentage of those who are infected.
The drugs can be taken as pills, so injections of interferon ― the previous drug of choice which can have nasty side-effects ― are no longer necessary for many patients. The length of treatment is also shorter, so fewer people are likely to stop taking treatment due to side effects.
So what contributions will HCV Research UK and STOP-HCV make as we enter this new era?
Firstly, HCV Research UK, established through funding from the Medical Research Foundation, set out to recruit a cohort of 10,000 patients. Theconsortium’s aim was to enable research into fundamental clinical and scientific questions about the virus by making clinical data and samples available from the cohort.
We have exceeded that figure and the clinical network has grown to about 60 clinical centres across the UK. This is now providing data and samples for more than 30 academic studies, including those in the STOP-HCV consortium.
At the point when the 10,000 cohort target was in sight and we were planning to wind down recruitment, NHS England announced plans to make the new antivirals available, before NICE approval, to seriously ill patients in desperate need of treatment.
Given the scale of the network that HCV Research UK had established, we agreed to collect data on the outcome of treatment for the NHS. This has led to the creation of a unique cohort of more than 700 patients with serious liver disease as a result of HCV infection who are receiving the new therapies.
There’s been much excitement about the results from the cohort. Our findings show that, even though these patients have the most severe liver disease, almost 80 per cent have successfully responded to treatment and are now cured of infection.
Half of the patients who have responded also show improved liver function, showing that clearing the virus can also reverse liver disease.
Crucially, we now need to work out why a significant proportion of the patients did not respond to therapy. This is where their data and samples are vital. There are a number of UK groups working with HCV Research UK to answer this question, principally STOP-HCV which is funded by the MRC as part of its Stratified Medicine Initiative to work out the most effective treatment options for those infected with HCV.
In most of the patients who have not responded, the virus emerges again after treatment. This could be because the virus develops resistance to the drugs, or because of slight variations in the genetic makeup of individual patients.
STOP-HCV is ideally placed to solve this conundrum. It has developed innovative approaches to determining the diversity of HCV genomes in infected patients, meaning that any virus mutations that result in resistance to the new antivirals will be found.
The consortium is also investigating the host genetics of patients by looking for small changes in their DNA that may be linked to poor response. Together, these powerful methods will guide the development of predictors for response to the new antivirals.
Still a way to go
There is also a tragic side to the introduction of the new therapies. Many patients sadly died while on therapy because their livers were already seriously damaged.
This underlines the human cost of chronic HCV infection and the need to treat patients before the onset of serious disease. In a forward-thinking initiative, STOP-HCV has partnered with HCV Research UK to put together a cohort of patients with cirrhosis, an early sign that may signal irreparable damage to the liver.
These patients will be studied over the next five years to discover any biomarkers that predict serious disease, including liver cancer. Those who successfully clear the virus will also be monitored to investigate the long-term effects of successful cure.
As more patients receive therapy, there will also be screening of treatment failure to observe any signs of drug resistant virus emerging in the infected population.
We still have some way to go to defeat HCV but we now have more firepower in our arsenal. As the campaign to mark World Hepatitis Day states, ‘4,000 deaths a day around the world, is 4,000 too many’.
HCV Research UK was funded from two endowments to the Medical Research Foundation by Effie Miller Munro and Alfred Tartellin. All members of HCV Research UK and STOP-HCV express their sincere gratitude to the patients who have graciously provided their data and samples for research activities.