Discovery of Hepatitis C Virus Brings Nobel Prize

October 5, 2020

Two Americans and a British scientist share the 2020 Prize for Physiology or Medicine for work in the 1970s through the 1990s. The rise of agents to treat hepatitis C virus has created vexing questions in managed care.

Two Americans and a British scientist today were awarded the 2020 Nobel Prize in Physiology or Medicine for discoveries that led to the identification of the hepatitis C virus (HCV). Although hepatitis A and B viruses had been identified, most blood-borne hepatitis cases could not be explained prior to work by Harvey J. Alter, MD, of the National Institutes of Health (NIH); Michael Houghton, PhD, a British citizen now of the University of Alberta; and Charles M. Rice, PhD, now of Rockefeller University.

Discovery of this new virus, “revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives,” according to the statement early today from the Nobel Assembly at the Karolinska Institutet in Stockholm, Sweden.

Worldwide, 71 million people have HCV, although many are unaware they have it, according to the World Health Organization. Blood tests have since between developed to detect HCV, and the development of a group of agents called direct acting antivirals (DAAs) can now cure it, raising the possibility that the disease can be eliminated, according to the Nobel Assembly statement.

However, the rise DAAs has raised vexing issues in managed care. The drugs first reached the market at $84,000 a course, causing some payers to balk at giving them to patients who were not seriously ill. US guidelines call for screening all adults born between 1946 and 1964, who may have contracted HCV before good tests for the disease were available.

The arrivals of DAAs has led to the development of new pricing models so that public payers, such as state Medicaid programs, could absorb large, unforeseen costs. The so-called subscription model pioneered in Louisiana may be replicated for future episodes when a public payer faces the need to pay for thousands, even millions, of doses of a new antiviral agent.

Discovery of Hepatitis C

Hepatitis is an inflammation of the liver typically caused by viral infections, although it can also be caused by alcohol abuse, autoimmune disease, and the effects of the environment. By the 1940s, researchers had isolated hepatitis A, which is transmitted through food or water, which has transient effects. A second type, which is spread through blood and bodily fluids can lead to more serious long-term health effects, such as cirrhosis of the liver or cancer.

One such of blood-borne agent was found in the 1960s, and the 1976 Nobel Prize in Physiology or Medicine was awarded to Baruch Blumberg for what we now call hepatitis B.

Alter, working at NIH, discovered in 1972 that that hepatitis still occurred in patients who had received blood transfusions, and whatever blood-borne agent was causing the disease was not being screened out by the new tests that had been developed for hepatitis A or B. Alter and his colleagues showed blood from patients infected by this unknown agent could transmit disease to chimpanzees, and the hunt was on for this new hepatitis virus.

While working for a pharmaceutical company, Houghton and his colleagues spent the late 1980s isolating the genetic sequence of the virus. They collected DNA fragments from an infected chimpanzee, and matched fragments of the unknown virus with those in serum from patients with hepatitis, until they were able to find a match or “clone.” More work showed this clone was a novel RNA virus in the Flavivirus family, which the researchers named the hepatitis C virus in a 1989 paper. Rice, while working as a researcher at Washington University in St. Louis, was then able to show that this new virus could, in fact, cause hepatitis. He found a new area of the HCV genome responsible for replication, and in additional experiments with chimpanzees showed that when the new RNA variant of HCV reached the liver unimpeded, it would cause hepatitis.

The Nobel committee said the honorees contributed to a sea change in public health.

“Thanks to their discovery, highly sensitive blood tests for the virus are now available and these have essentially eliminated post-transfusion hepatitis in many parts of the world, greatly improving global health,” the Nobel statement said. “Their discovery also allowed the rapid development of antiviral drugs directed at hepatitis C. For the first time in history, the disease can now be cured, raising hopes of eradicating hepatitis C virus from the world population."