The 2020 Nobel Prize for Physiology or Medicine was jointly awarded to Harvey J. Alter, Michael Houghton, and Charles M. Rice “for the discovery of Hepatitis C Virus” . Hepatitis C is a type of liver inflammation caused by a bloodborne virus: Hepatitis C Virus, or HCV. It had eluded researchers for many years before its eventual discovery in 1989.
Along with the ability to treat a novel disease, the discovery of HCV also provided us with new diagnostic technologies, making it a very significant contribution to the field of physiology and medicine. The nuances of the story behind this Nobel Prize will be discussed throughout the course of this article.
Hepatitis refers to the inflammation of the liver. It is caused by five different strains of Hepatitis Virus: A, B, C, D, and E, all of which cause very distinct forms of the disease. While all five types differ in severity and onset of symptoms, common signs of hepatitis include jaundice, mild fever, and abdominal pain, among others.
Hepatitis A is transferred via contaminated food or water and, in most cases, leads to acute inflammation.
Hepatitis B and C are both bloodborne forms of the disease. Although they both can lead to chronic hepatitis, that outcome is more common in the case of Hepatitis C. The contraction of either form of the disease is, together, the most common cause of liver cancer .
Hepatitis D is an infection that only occurs in people with Hepatitis B. The contraction of HDV can lead to a poorer prognosis due to the dual infection with HBV and HDV.
Hepatitis E is transmitted via undercooked pork or wild game, or contaminated water. Like Hepatitis A, it generally leads to acute inflammation.
Hepatitis C is a form of Viral Hepatitis that occurs due to bloodborne infection of the Hepatitis C Virus or HCV. HCV is a positive sense, single-stranded RNA virus part of the Flavivirus family. It is transmitted via exposure to contaminated blood via injections, intravenous drug usage, or transfusions. It may also spread due to unprotected sexual contact. An estimated 70% of people infected by HCV will develop chronic hepatitis .
It was first identified in the mid-1970s. At the time, it was named non-A, non-B hepatitis. It is unique as it has a relatively long incubation period (2 weeks – 6 months). In most cases, it results in chronic liver inflammation.
Hepatitis C is often not detected soon after infection since most acute cases are asymptomatic. Those who do display symptoms of acute hepatitis will often experience jaundice, fever, fatigue, nausea and vomiting, abdominal pain, and/or dark coloured urine. About 80% of cases are only detected once the disease progresses to chronic inflammation, causing mild to severe liver damage.
Currently, treatment of Hepatitis C involves the usage of direct-acting antivirals (DAAs). These drugs target enzymes essential for the replication of HCV, thus preventing the growth of the virus within the human body. The most effective DAA therapy thus far has been a combination of the drugs sofosbuvir and ledipasvir . Although highly effective, many DAA therapies are quite expensive, which means that treatment is not accessible to everyone that needs it.
There is currently no vaccine available against HCV infection. Disease prevention efforts involve limiting chances of exposure to HCV through proper screening of blood used for transfusions, proper sterilization, and disposal of injection, harm-reduction tactics directed towards drug users, etc.
DISCOVERY OF HCV
In the 1970s, Harvey J. Alter studied the occurrence of chronic hepatitis in several people after they had received blood transfusions. Although many of these cases could be attributed to Hepatitis B, it became very clear that some of these were being caused by a completely different virus. Hepatitis A was also ruled out as a cause. Alter and his colleagues determined that the infection was transmitted via the blood of infected patients. The disease had characteristics of a viral infection and was subsequently named non-A, non-B hepatitis.
The next goal was to identify the virus. The genetic sequence of the novel virus was isolated by Michael Houghton and his colleagues. The team extracted DNA fragments from the blood of a chimpanzee infected with the virus. Although the majority of these fragments belonged to the chimpanzee, a few were foreign genetic material from the virus. It was assumed that the blood of infected patients would contain antibodies against the virus. This assumption was used to identify cloned viral DNA that would code for the virus’s required proteins. The cloned DNA was later discovered to have originated from an RNA virus belonging to the family Flavivirus, which was named the Hepatitis C Virus.
Michael Houghton’s method of isolation of viral genetic material had been untested at the time. As a result, not only did he contribute significantly to early research on the Hepatitis C Virus (HCV), he also revolutionized the field of microbiology as a whole.
Although the virus had been identified, it was then necessary to determine whether HCV was alone responsible for causing hepatitis or if there were other factors involved. Charles M. Rice identified a region of the viral genome that was previously uncategorized. It was determined that this region could be significant to the replication of the virus. Rice also observed some sequences that may prevent replication. He used genetic engineering to synthesize RNA containing only the portion that would promote replication. This RNA was injected into a chimpanzee, who began to exhibit symptoms that lined up with the presentation of Hepatitis C in humans. Thus, Rice proved that the Hepatitis C Virus alone could cause the illness.
The discovery of the Hepatitis C Virus was instrumental in understanding how Hepatitis C could be prevented. Studying how the virus is transmitted and where it is most prevalent allows us to systematically reduce infection rates. Additionally, isolating the cause of Hepatitis C meant that we were one step closer to eliminating the disease.
The global effort to eradicate HCV has led to the development of numerous highly effective antiviral therapies. An effort is being made to ensure the availability of these drugs worldwide.
The discovery of HCV also contributed to the development of highly sensitive blood tests for the virus. The ability to detect the presence of the virus in a given blood sample has allowed us to drastically reduce the number of cases from transfusions.
The discovery of HCV has had a massive effect on the field of medicine. Its impact on the ongoing battle against viral disease adequately explains the Nobel Committee’s decision to award the 2020 prize for Physiology or Medicine to Alter, Houghton, and Rice.
Viral diseases continue to be one of modern medicine’s greatest adversaries. The efforts to develop more affordable treatments and/or a vaccine for Hepatitis C will likely continue for the foreseeable future.
The work done by Harvey J. Alter, Michael Houghton, and Charles M. Rice is commendable. There is no doubt that the efforts made by them and their teams have shaped the world of medicine in hugely significant ways.
Although there is still a long way to go to completely eradicate the Hepatitis C Virus, it is important to acknowledge the advancements being made every day and the people responsible. With the help of science, we may see several potentially deadly diseases, like Hepatitis C, eradicated within our lifetimes.
 “The Nobel Prize in Physiology or Medicine 2020.” NobelPrize.org, October 5, 2020. https://www.nobelprize.org/prizes/medicine/2020/press-release/
 “Hepatitis.” World Health Organization. World Health Organization. Accessed November 29, 2020. https://www.who.int/health-topics/hepatitis
 “Hepatitis C.” World Health Organization. World Health Organization, July 27, 2020. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
 “Story of Discovery: Hepatitis C: from Non-A, Non-B Hepatitis to a Cure.” National Institute of Diabetes and Digestive and Kidney Diseases. U.S. Department of Health and Human Services, June 9, 2016. https://www.niddk.nih.gov/news/archive/2016/story-discovery-hepatitis-c-from-non-a-non-b-hepatitis-cure