Knowledge Update

Discovery of the Hepatitis C virus gets the Nobel Prize in Medicine this year

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Viral hepatitis is an infection that causes liver inflammation and damage. Inflammation is swelling that occurs when tissues of the body become injured or infected. Inflammation can damage organs. Researchers have discovered several different viruses link that cause hepatitis, including hepatitis A, B, C, D, and E. Out of these hepatitis C is the most dangerous type. Hepatitis C is a global health problem as the World Health Organization (WHO), reported 3-4 million people are newly infected with hepatitis C virus (HCV) every year and 71 million people have a chronic (prolonged) infection. Over four hundred thousand people die from hepatitis C - related liver diseases every year [1]. There is still no effective vaccine against hepatitis C.

Among various genotypes of HCV, genotype 1 is the most prevalent which accounts for 46% of all HCV infections, followed by genotype 3, which is 22% prevalent. Genotype 2 and 4 each has 13% prevalence [1]. A significant number of those who are chronically infected will subsequently develop cirrhosis or liver cancer. Antiviral medicines can cure more than 95% of persons with hepatitis C infection, thereby reducing the risk of death from cirrhosis and liver cancer, but access to diagnosis and treatment is low and quite expensive [2]. Harvoni is a combination drug containing both ledipasvir and sofosbuvir which is approved to treat patients with chronic hepatitis C virus infection is priced around $87,000 in USA [3].

Transmission

The hepatitis C virus is a blood borne virus. It is most commonly transmitted through:

  • Injecting drug use through the sharing of injection equipment;
  • The reuse or inadequate sterilization of medical equipment, especially syringes and needles in healthcare settings;
  • The transfusion of unscreened blood and blood products;
  • Sexual practices that lead to exposure to blood (for example, among men who have sex with men, particularly those with HIV infection or those taking pre-exposure prophylaxis against HIV infection).

HCV can also be transmitted sexually and can be passed from an infected mother to her baby; however, these modes of transmission are less common.

Discovery

In the 1940s, doctors knew there were two main types of infectious hepatitis. The first, transmitted by the hepatitis A virus, spread via contaminated food and water and tended to have little long-term impact on people. The second, spread by blood and body fluids, was more insidious. Patients could be silently infected for years before serious complications emerged – liver cancer and liver scarring is known as cirrhosis.

Researchers discovered hepatitis B in the 1960s, but it quickly became clear that it was not the only cause of the blood-borne infections. While studying hepatitis spread by blood transfusions, it was found that some patients were being infected by an unknown agent. By the mid-1970s, researchers had ruled out two known liver-damaging viruses, hepatitis A and hepatitis B, as the mystery contaminant. But without having determined what was infecting the blood-transfusion recipients, scientists referred to the blood-borne disease by what it wasn’t: ‘non-A, non-B hepatitis’.

Harvey J. Alter at the US National Institutes of Health was studying the occurrence of hepatitis in patients who had received blood transfusions. It was a great source of concern that a significant number of those receiving blood transfusions developed chronic hepatitis due to an unknown infectious agent. Alter and his colleagues showed that blood from these hepatitis patients could transmit the disease to chimpanzees, the only susceptible host besides humans. Subsequent studies also demonstrated that the unknown infectious agent had the characteristics of a virus [4].

The next breakthrough came from Michael Houghton and his colleagues at Chiron. Houghton and his co-workers created a collection of DNA fragments from nucleic acids found in the blood of an infected chimpanzee. The majority of these fragments came from the genome of the chimpanzee itself, but the researchers predicted that some would be derived from the unknown virus. On the assumption that antibodies against the virus would be present in blood taken from hepatitis patients, the investigators used patient sera to identify cloned viral DNA fragments encoding viral proteins. Following a comprehensive search, one positive clone was found. Further work showed that this clone was derived from a novel RNA virus belonging to the Flavivirus family and it was named Hepatitis C virus [4].

The discovery of Hepatitis C virus was decisive; but one essential piece of the puzzle was missing: could the virus alone cause hepatitis? To answer this question the scientists had to investigate if the cloned virus was able to replicate and cause disease. Charles M. Rice, a researcher at Washington University in St. Louis, along with other groups working with RNA viruses, noted a previously uncharacterized region in the end of the Hepatitis C virus genome that they suspected could be important for virus replication. Rice also observed genetic variations in isolated virus samples and hypothesized that some of them might hinder virus replication. Through genetic engineering, Rice generated an RNA variant of Hepatitis C virus that included the newly defined region of the viral genome and was devoid of the inactivating genetic variations. When this RNA was injected into the liver of chimpanzees, virus was detected in the blood and pathological changes resembling those seen in humans with the chronic disease were observed. This was the final proof that Hepatitis C virus alone could cause the unexplained cases of transfusion-mediated hepatitis [4].

For their seminal discoveries Harvey J. Alter, Michael Houghton, and Charles M. Rice were awarded the Nobel Prize in Physiology or Medicine 2020. 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 the Hepatitis C virus from the world population. To achieve this goal, international efforts facilitating blood testing and making antiviral drugs available across the globe is essential.

References:

  1. Jefferies M, Rauff B, Rashid H, Lam T, Rafiq S. Update on global epidemiology of viral hepatitis and preventive strategies. World J Clin Cases. 2018 Nov 6; 6(13): 589–599.
  2. Hepatitis C. World Health Organization. Assessed from: https://tinyurl.com/yx75t732
  3. Sarah Hand. The Top 4 Most Expensive Drugs in the US are Hepatitis C Treatments. July 31, 2017 in Blogs. https://tinyurl.com/y39l9avl
  4. The Nobel Prize in Physiology or Medicine 2020. Accessed from: https://tinyurl.com/y5sbqwv3

 

Dr. Sanjoy Kumar Pal is a Professor of Biology in Skyline University Nigeria. He has a PhD. in Animal Genetics from Indian Veterinary Research Institute, India.