How Decades of Research Are Finally Helping Us Understand (and Hopefully, Combat) Hepatitis

In the last half-century, the exploration of hepatitis viruses has proven to be very challenging and at times,  controversial. Trailblazing researchers have devoted decades to unraveling the origins, transmission methods, and potential means of halting these diseases. But it has absolutely been worth the effort.

Unraveling the hepatitis viruses has not only transformed our understanding of these pathogens but also laid the foundation for creating efficient diagnostic instruments, therapies, and preventative strategies to tackle hepatitis worldwide. Nevertheless, this journey was anything but simple or effortless.

A Virus Behind Hepatitis

In the early 1950s, Baruch S. Blumberg worked several months in Suriname, a tropical country covered in lush rainforests. He spent his time there in the isolated town of Moengo, which back then, could only be accessed by river. While in Moengo, he helped to deliver babies, performed clinical services, and undertook the first malaria survey done in that region.

He was also struck by how the people in the area, which came from different ethnical backgrounds, reacted differently to infectious diseases. Over the next decade, he’d gather a diverse set of human blood samples, looking at why some people contract diseases in an environment and others don’t, and why their reaction to infection is so different sometimes.

His attention was drawn to some blood samples from an Aboriginal Australian patient. The patient’s blood contained a unique protein that Blumberg called the ‘Australian antigen.’ In a landmark study, Blumberg would go on to describe how the antigen only appeared in connection with a form of jaundice caused by a disease that was then called “serum hepatitis“.

We now call this disease hepatitis B, and Blumberg had discovered the “smoking gun” of the disease’s infectious agent.

People had been looking for the virus responsible for hepatitis B for years. Mind you, microscopes weren’t nearly as good then as they are now and you couldn’t actually “see” the virus. Previous research suggested that a virus was to blame, but attempts to uncover it failed, despite a lot of effort (and even some extremely unethical studies by other researchers).

Blumberg found an elegant way to uncover the virus behind this disease and published groundbreaking work. But he didn’t stop there.

Along with his colleagues, Blumberg developed a screening test for the hepatitis B virus, found ways to prevent it from spreading via blood transfusions, and developed a vaccine. The vaccine was distributed freely and within a decade, reduced the infection rate in children in China from 15% to 1%.

Nowadays, blood donations are routinely scanned to determine a hepatitis B virus infection, which has helped reduce transmission. In many countries around the world, babies are vaccinated for hepatitis B within 24 hours of birth with either two or three more doses later on.

Still, in some countries, especially when vaccination is not prevalent, hepatitis B is still a major challenge – and it’s not the only problematic type of viral hepatitis.

Hepatitis B, Hepatitis C

By the mid-1970s, Harvey J. Alter, Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the National Institutes of Health, figured out something was wrong. As a young doctor, Alter had collaborated with Blumberg on the “Australian antigen.” But Alter was seeing that some blood transfusions, that were clear of the viruses for both hepatitis A and B, were giving people hepatitis symptoms.

Alter and his colleagues found an alarming number of hepatitis cases spread thusly, but they couldn’t find the virus. They named it “non-A, non-B hepatitis” (NANBH), a designation that was meant to be short-lived.

Harvey J. Alter held a lecture online about Hepatitis C during the 70th Lindau Nobel Laureate Meeting.

But it wasn’t that short-lived. Over a decade passed until a team led by Michael Houghton used an innovative approach called molecular cloning to identify the unknown pathogen. Alter confirmed a link between NANBH cases and the pathogen discovered by Houghton’s team, and the pathogen became known as hepatitis C.

Still, there was a shadow of a doubt.

Two groups, working in parallel, identified a region of the virus’ genome that seemed to play a role in its replication. Kunitada Shimotohno, working at the National Cancer Center Research Institute in Tokyo, and Charles Rice, working at Washington University in St Louis, came to the same conclusion in quick succession. But Rice took it one step further, getting the virus to replicate in chimpanzees. This was conclusive evidence that this pathogen was causing hepatitis C.

Alter, Houghton, and Rice were awarded the Nobel Prize in Physiology or Medicine in 2020 for discovering and characterising the hepatitis C virus.

Interview with Professor Thomas Perlmann, Secretary of the Nobel Assembly at Karolinska Institutet and of the Nobel Committee for Physiology or Medicine, after the announcement of the Nobel Prize 2020

As with hepatitis B, the understanding of this virus paved the way for the development of screening methods. But it was harder to find treatments for hepatitis C.

Until recently, treatments required weekly injections and oral medications that had serious side effects. But that’s starting to change. Nowadays, hepatitis C is often curable with only oral medications that are taken for two to six months. In fact, over 95% of all cases are curable thusly.

But many people who have the disease are unaware of it. The World Health Organization (WHO) estimates that some 58 million people globally are living with chronic hepatitis C, and every year, the disease claims 290,000 lives.

However, there are positive signs. Blood screening is performed routinely, and the number of new infections has decreased by 90%. In fact, some experts are even looking at ending the threat posed by hepatitis.

Can we Eradicate Viral Hepatitis?

Hepatitis is a weird disease. There is evidence that 5,000 years ago, the ancient Sumerians described cases of hepatitis, though they attributed them to a devil named Ahhazu. In 400 BC, the Greek physician Hippocrates also documented some cases of hepatitis.

It took thousands of years to get to the “Australian antigen” and uncover the real culprits behind these diseases. In the relatively short time that has passed since then, we’ve made a lot of progress. Could we actually end viral hepatitis, or at least end its global spread and limit it to isolated pockets?

The WHO seems to believe so. WHO’s global hepatitis strategy aims to reduce new hepatitis infections by 90% by 2030. The organisation wants a multifaceted approach that is focused especially on low- and middle-income countries and includes a mixture of vaccination, diagnostic tests, medicines, and education campaigns.

This goal may be a bit optimistic, but just the fact that we can have an aim like this shows how far we’ve progressed in our fight against hepatitis. Without pioneering research, this would have never been possible.

We still have a lot of work to do to stop viral hepatitis, but thanks to pivotal work by Nobel Laureates, we’re one step closer to success.