Decades of Research Results in Glory for Hepatitis C Investigators

While many in science and medical research do so under the radar for the profound desire to heal and care for others, it is nice to be recognized sometimes for crucial work.

That is what happened in 2020, when a trio of researchers and doctors were awarded with the Nobel Prize in Physiology and Medicine for their work discovering the hepatitis C virus (HCV).

For Harvey J. Alter, MD, Michael Houghton, PhD, and Charles M. Rice, PhD, the discovery of the virus was not to win any award, cash any prize, or have any building named after them, but to help people in what may be a crucial time for hepatitis research where it is realistic to drastically decrease or even eliminate the virus worldwide.

While the award was given to the 3 doctors in 2020, it is a culmination of their life’s work in identifying hepatitis C and fighting through challenges and roadblocks to find treatments that got us to a point where many experts believe the virus can be eradicated in the next few decades.

The Long History of Hepatitis C

The origin of the Nobel Prize for the 3 doctors dates back to the 1970s, when clinicians realized a rash of hepatitis cases could not be classified as either hepatitis A or B.

Alter, the Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the National Institutes of Health (NIH), began the push to classify the virus as a new form of hepatitis.

It wasn’t until the late 1980s, when a team that included Houghton, the Li Ka Shing Professor of Virology at the University of Alberta, was able to identify a diagnostic test for patients who were suffering from the unidentified hepatitis viral strain and identified fragments of viral DNA from these patients to reveal that the virus belonged to the same family as flaviviruses.

Really, this is where the challenge began in understanding the pathology of the virus.

In the 1990s, Rice, now a professor of virology at the Rockefeller University, identified a missing sequence at the end of flavivirus was needed for initiation of replication. Leading the charge to find the end of the HCV genome in 1996, Rice began to create a functional clone of the virus.

None of the advancements in treatment over the course of the last 25 years could have occurred without the work of the 3 now Prize winning doctors.

Blaine Hollinger, MD, Department of Molecular Virology and Epidemiology at Baylor College of Medicine, described his 3 colleagues as not only creative, but resilient to the setbacks that are commonplace in medical research.

“They are the kind of leaders that I think we need in science,” Hollinger told HCPLive®. “Not only are they do they have leadership where they can direct laboratories and so on, but they take a problem and they stick with it. So many people in science want to hit the home run, so they from one thing to another down the line rather than staying with a problem.”

The Current State of Hepatitis C

Overall, there are an estimated 70 million people globally with HCV infections, resulting in 400,000 annual deaths.

With new treatments becoming available and more knowledge about the actual virus, it is realistic that in the coming decades eradication could ultimately happen.

“The big push right now is to eliminate hepatitis C and they put a time limit of somewhere around 2030 to 2050,” Hollinger said. “We know how it’s spread in most patients. It’s primarily spread through most parts of the world by unsafe needles. It spreads through blood transfusions.”

Whether or not HCV is eradicated or even controlled much like polio currently is depends on a number of factors.

Diagnostic Testing and Preventative Care

For starters, there should be a global push to improve surveillance.

It is important to find out the true prevalence of the disease because much like the coronavirus, not everyone is symptomatic until they get the more serious liver disease.

Hollinger said testing is not really a problem, as there are relatively cheap tests available that can identify whether a patient is currently suffering from the virus or has antibodies from a past infection.

But there remains a need to do a better job of testing donated blood for traces of HCV in most of the underdeveloped parts of the world.

In the US, hospitals and medical facilities use nucleic acid tests or PCR tests, as well as other antibody markers. These tests allows those who collect blood to isolate infected donors before transfusing it to HCV negative recipients.

But these tests are expensive and largely only used in wealthy countries.

So how do poorer countries, where blood donors might be more likely to be HCV-positive, handle these challenges?

One way to ensure a clean transfusion is to not reuse needles.

But the cost for doing nucleic acid testing for blood donors can be expensive. There is a way to work around some of the cost challenges.

“A lot of these countries are getting better at doing this,” Hollinger said. “What they've tried to do is instead of individually looking at every inch of blood, they make a mini pool and so they pooled blood together from donors. The donors come in, you pull them in pools of 8, or 16, or 64, or something of that nature.”

Because HCV is fairly concentrated in the blood, if a mini pool turns up HCV positive the professionals can then test each individual within the pool and isolate the positive cases.

New Treatments Opens a New Frontier of Hepatitis Care

Unlike other versions or strains of hepatitis, approximately 70% of patients who contract HCV will become chronically infected. The numbers are significantly lower in hepatitis B cases were only 1-5% become chronically infected and hepatitis A cases, which result in virtually no chronic infections.

But the chronic nature of HCV will progress in 15-30% of patients over the course of a lifetime to cirrhosis, end-stage liver disease, or ultimately death.

Treatment has come a long way since cases first started sprouting up several decades ago. Current direct-acting antiviral (DAAs) medications have become so effective that they can cure the virus from 95-100% of patients within a short period of time, sometimes in as quickly as 2-3 months.

In previous simulations, investigators discovered extended life as a key advantage of this drug class. However, real-world evidence on the link between DAA treatment and reduced mortality is understudied.

But a study published earlier this year showed DAA treatment appeared to be associated with a decrease in mortality among Medicare beneficiaries with or without cirrhosis, suggesting that increasing access to these medications for all patients with HCV could improve population health regardless of disease progression.

Before the relatively recent advent of DAA treatment, HCV was treated with interferon, which could take a year to cure patients and only actually cured about half of the patients.

“We have made fantastic advances, and to know that we can actually ensure people eliminate the virus as long as they don't get reinfected,” Hollinger said.

Eradication Without a Vaccine

While confident in diagnosing and curing the virus, it has been difficult for researchers to develop an HCV vaccine.

Hollinger said this has been a challenge because of the different variants that exist within the virus.

“I think a vaccine will be necessary somewhere down the line,” he said. “Fortunately, as I said, we found a cure of a disease, and that was what a lot of us Nobel Prize was directed toward.”

Overall, if researchers are able to one day fully cure HCV it will be because of the steps taken several decades earlier.