News & Events
News & Events
[2021 World Hepatitis Day] Our Efforts towards Hepatitis Elimination
2021-07-28
2021 World Hepatitis Day – Can't Wait
Every year on July 28th is World Hepatitis Day to enhance awareness and encourage prevention, diagnosis, and treatment!
People living with viral hepatitis can't wait to be tested and get lifesaving therapies or vaccines.
.png)
WHO Website Screen Capture (Source: https://www.who.int/campaigns/world-hepatitis-day/2021)What is viral hepatitis?
Viral hepatitis is either an acute or chronic inflammation of the liver (hepatitis) caused by viruses. (https://www.cdc.gov/hepatitis/index.htm)
.jpg)
Hepatitis B Virus (Source: Institut Pasteur)
Current status
Global Burden
Approximately 325 million people worldwide are currently infected with hepatitis viruses. Viral hepatitis is the major cause of acute and chronic liver diseases, responsible for about 1.4 million deaths each year globally.
Five hepatitis viruses have been described (hepatitis A, B, C, D, and E virus (HAV, HBV, HCV, HDV, and HEV)). However, despite the name similarities of the viruses, all causing liver diseases, they are entirely different. HBV and HCV, transmitted by blood, causing frequently chronic hepatitis, are responsible for about 90% of case fatalities. In contrast, HAV and HEV, transmitted primarily fecal-oral, mainly cause acute hepatitis and are responsible for 10% of deaths. An HDV superinfection in HBV patients leads to chronic hepatitis D, which accelerates the deterioration of the liver and increases the likelihood of organ failure and death. Interestingly, HDV is stealing the envelope of HBV; thereby, HDV is becoming a parasitic virus of HBV.
In South Korea
About 4~5% and 1% of the Korean population is chronically infected with HBV and HCV.
Furthermore, HAV infection decreased after the outbreak with 60,000 infected patients in 2009, but as the epidemiology of HAV has changed, infection among adults has increased since 2014, and 14,000 patients were reported in 2019.
Concerning HEV, in >30% of people with frequent contact with raw pork meat, HEV-specific antibodies are being detected, indicating a cleared virus infection. These data suggest that HEV is quietly circulating in the Korean society.
What are the medical needs?
There are unmet medical needs for all the hepatitis viruses as indicated above; however, the total number of patients point to HBV as the most urgent need. Currently, chronic hepatitis B is incurable. Consequently, the main goal is to identify and develop curative therapies.
______________________________________________________________________________________________________
.png)
______________________________________________________________________________________________________
The Discovery of Hepatitis C Virus & 2020 Nobel Prize in Physiology or Medicine
The 2020 Nobel Prize in Physiology or Medicine is awarded jointly to Harvey J. Alter, Michael Houghton, and Charles M. Rice for the discovery of hepatitis C virus, which raised awareness about hepatitis worldwide and bolstered global efforts to develop therapeutics.
______________________________________________________________________________________________________
The 2020 Nobel Prize in Physiology or Medicine is awarded jointly to Harvey J. Alter, Michael Houghton, and Charles M. Rice for the discovery of hepatitis C virus, which raised awareness about hepatitis worldwide and bolstered global efforts to develop therapeutics.
______________________________________________________________________________________________________
Institut Pasteur Korea's Research on Viral Hepatitis
Developing first-in-class drug candidates and state-of-the-art platforms to study all aspects of viral hepatitis
Since 2007, Applied Molecular Virology (AMV) Lab., led by Prof. Marc Windisch, has been tackling hepatitis. His team first worked on HCV using the then-new infectious HCV cell culture system to screen for novel inhibitors, mainly focusing on viral entry. With the development of curative HCV drugs by international companies, since 2012, the AMV Lab. has focused on HBV. Due to a lack of suitable cell culture systems to investigate HBV in laboratories, the AMV Lab. developed a cell culture platform supporting the entire HBV life cycle, and that also supports the multiplication of patient-derived HBV. (Fig. 1) (Journal of Hepatology, 2019; PMID: 31077792).
.jpg)
Fig. 1: HBV infection using patient-derived virus. HBV isolated from patients' blood is directly used to infect liver-derived cells in a laboratory (Journal of Hepatology, 2019; Koenig and Yang et al.).
In addition, the team was the first worldwide demonstrating how the virus spreads from one infected liver cell to their neighboring cells in cell culture (Fig. 2).
.png)
Fig. 2: HBV spreads to adjacent liver cells. Full-well images of HBV-infected (green) and uninfected (red) cells at 4?weeks post-infection (wpi). Cell-to-cell distance analysis grouped HBV-infected cells into clusters highlighted using pseudo-colors. Infected cells either untreated (DMSO) or treated with HBV (anti-HBs, LMV (lamivudine)) and HDV (MyrB) drugs (Journal of Hepatology, 2019; Koenig and Yang et al.).In addition, the AMV Lab. evaluated the stability of infectious HBV particles under different environmental conditions (e.g., temperature, pH, etc.) and in the presence of various hand disinfectants. As a result, they demonstrated that HBV particles are stable at 98°C for 2 minutes (Journal of Hepatology, 2019; PMID: 31493444), and that the virus remains stable at up to 50% of ethanol (Journal of Infectious Diseases, 2019; PMID: 30358855). Furthermore, Prof. Windisch's team utilized the novel HBV platform, developed a phenotypic assay, and screened for novel inhibitors (Fig. 3) (Journal of Hepatology Reports, 2021; PMID: 34222850).
.jpg)
Fig. 3: High content screening strategy. HBV life cycle and drug screening campaign (left to right). The strategy supports the investigation of early (passage 1) and late (passage 2) steps of the viral life cycle (Journal of Hepatology Reports, 2021; Yang and Koenig et al.; PMID: 34222850).
Currently, a first-in-class HBV-HDV inhibitor is being characterized, and drug properties are being evaluated and improved.
To address the medical needs of acute hepatitis E, the AMV Lab. teamed up with Prof. Steinmann's laboratory at the Ruhr University in Bochum, Germany, to develop an image-based screening assay with HEV subgenomic replicons. And together with the screening team at IPK, the AMV Lab. screened FDA-approved drugs intending to repurpose them quickly to acute hepatitis E therapy. At present, identified drugs are being characterized in Korea and Germany to understand how they inhibit the virus.
To address the medical needs of acute hepatitis E, the AMV Lab. teamed up with Prof. Steinmann's laboratory at the Ruhr University in Bochum, Germany, to develop an image-based screening assay with HEV subgenomic replicons. And together with the screening team at IPK, the AMV Lab. screened FDA-approved drugs intending to repurpose them quickly to acute hepatitis E therapy. At present, identified drugs are being characterized in Korea and Germany to understand how they inhibit the virus.
.jpg)
Prof. Windisch commented: "We are working on solutions that benefit patients either directly or indirectly by developing first-in-class drug candidates and state-of-the-art platforms to study all aspects of viral diseases. We generate knowledge and therapeutic opportunities which may benefit patients in the future who are suffering from viral hepatitis."
Meet the AMV Lab.!
.png)
In front of Café Pasteur. Mr. Jaewon Yang, Prof. Marc P. Windisch, Mrs. Eunji Jo, Dr. Alexander Koenig, Ms. Diana Ko (from left to right).