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World Hep­ati­tis Day – Paul-Ehrlich-In­sti­tut is com­mit­ted to pro­tec­tive Vaccines and safe Blood Prod­ucts

28 July is World Hepatitis Day! It is not for nothing that this disease, caused by various hepatitis viruses, is highlighted on 28 July every year. Infections with hepatitis A and B viruses are among the most common infectious diseases worldwide, and both are preventable through vaccination. Paul-Ehrlich-Institut, responsible for the quality, safety and efficacy of vaccines and the safety of blood and blood components, plays an important role in protecting the population from hepatitis in Germany.

Hepatitis B Virus (Source: Kateryna Kon/Shutterstock.com)

There are various hepatitis viruses – from hepatitis A to hepatitis E (see background). Infections with hepatitis B viruses (HBV) are among the most common infectious diseases worldwide, and in chronic cases the hepatitis B and C infections are among the major causes of liver cirrhosis and liver cell cancer, which is the second leading cause of cancer-related deaths worldwide. According to estimates by the World Health Organization (WHO), every year 887,000 people worldwide die of hepatitis B.

World Hepatitis Day is organized globally by the World Hepatitis Alliance. In Germany, Deutsche Leberhilfe e.V. hosts World Hepatitis Day. The international motto is "Hep can’t wait", intended as a call to action to do more to curb these infections.

In terms of its general population, Germany is one of the low-prevalence regions, but certain risk groups are more frequently affected. In 2019 a total of 8,903 cases of hepatitis B were reported to the Robert Koch Institute in Germany, which equates to an incidence of 10.7 reported infections per 100,000 inhabitants.

The comparatively low frequency of hepatitis B infections in Germany compared to the global figures is due not only to hygiene measures and protection against infection during sexual intercourse but also, most significantly, the possibility of being vaccinated against hepatitis B (and hepatitis A). Vaccines for protection against hepatitis B have been available since 1982 and against hepatitis A since 1995, and they have proved to be highly effective with good tolerability. Another important pillar is the safety of blood and blood products.

Vaccines to protect against hepatitis A and B

In Germany, both monovalent (single vaccines) against hepatitis A or hepatitis B, bivalent combination vaccines against hepatitis A and B, and hexavalent combination vaccines with a hepatitis B component for children are available. Paul-Ehrlich-Institut is responsible for the quality, efficacy and safety of all vaccines, which involves the approval of clinical trials of new vaccine candidates as part of the licensing process, monitoring the safety of vaccines following authorisation, and batch testing (testing of production units) of vaccines in Germany. Only approved vaccines that have been batch-tested and approved by Paul-Ehrlich-Institut may be distributed and used in Germany.

Despite temporary and sometimes lengthy supply bottlenecks with the hepatitis A and hepatitis B vaccines, Paul-Ehrlich-Institut has always worked to ensure these vaccines were available in Germany and it has provided timely information about impending and existing supply bottlenecks.

Safety of blood and blood products

Another of the important tasks Paul-Ehrlich-Institut performs is to check the safety of blood and blood products and to order the necessary protective measures. All the minimum standards introduced can be viewed on Paul-Ehrlich-Institut’s website (see further information).

In the hemovigilance report, the Federal Institute regularly reports on notifications of severe transfusion reactions over a year and compares these with the reports from previous years. It thus becomes clear whether risk-minimization measures are effective and whether they are contributing to increasing the safety of blood components.

Following implementation of donor blood testing for anti-HBc in 2006, only four cases of HBV transmission through blood components have been confirmed between 2008 and 2019. Particularly, between 2016 and 2019 there were no confirmed cases of hepatitis B transmission. In 2019 two suspected cases of HCV transmission were confirmed for the first time in twelve years, caused by the same donor who was in the very early phase of infection at the time the donation was made. Ten suspected cases of HEV transmission through blood components were confirmed in 2019.
Since 1 January 2020, blood donors also have to be tested for the hepatitis E virus so an infection can be identified and transmission through blood components prevented.

"Infectious diseases are one of the most frequent causes of death worldwide. Paul-Ehrlich-Institut is committed to protecting people from infectious diseases, not only in Germany but also with its various activities in Europe and worldwide through its involvement with the WHO," explains Professor Klaus Cichutek, President of Paul-Ehrlich-Institut. This is the reason why Paul-Ehrlich-Institut hosts two WHO collaborating centres, the "WHO Collaborating Centre for Quality Assurance of Blood Products and In Vitro Diagnostic Devices", which has just been re-designated for the fifth time for another four years, and the "WHO Collaborating Centre for Standardization and Evaluation of Vaccines".

Research

Research in all the areas in which it is active for regulatory purposes is a unique Paul-Ehrlich-Institut selling point. This also includes research into hepatitis viruses. In particular, the Virology Department at Paul-Ehrlich-Institut conducts intensive research work on the hepatitis viruses B, C and E. The key focus of this work is to gain insights into the virus-associated pathogenesis and to thus lay the foundations for a novel vaccine platform. This novel vaccine platform addresses HBV and aims to provide therapeutic vaccination for chronically HBV-infected patients in addition to preventive vaccination.

Another essential aspect of HBV research concerns the characterization of various HBV genotypes, which clearly differ in their pathogenicity. In cooperation with the Frankfurt University Teaching Hospital, here the lifecycle of the various genotypes is being examined on a comparative basis in order to clarify the differing progressions of the disease and to find new therapeutic approaches. Of particular interest here are the processes that enable the virus to be ejected from the cell.

A key area of Paul-Ehrlich-Institut HCV research is studying the influence of HCV on the intracellular radical levels. Radicals are highly reactive molecules which, for example, play an essential role in tumour development and in control of regenerative processes. Through a complex mechanism, HCV leads to a significant increase in the radical levels in order to activate processes for its release, which conversely plays an essential role, however, in HCV-associated pathogenesis.

HEV, as a so-called zoonotic pathogen (transmission from animals to humans) is increasingly posing a serious problem with around 44,000 fatal infections every year. There is no specific therapy for an HEV infection. Paul-Ehrlich-Institut has been able to establish cell culture models for the propagation of the virus that permit detailed study of the lifecycle of these viruses. The focus here is on ways of identifying and characterizing cellular antiviral mechanisms in order to thus define starting points for the development of therapeutics. Initial findings include the observation that a change in the intracellular cholesterol levels has a very significant influence on the release of HEV.

Background

They actually belong to different virus families and are not related to each other, but hepatitis viruses all have one thing in common: Infection can lead to inflammation of the liver (hepatitis). Hence the name, since hepatocytes are liver cells. They differ in both disease progression and in the route of infection:

Hepatitis A is excreted from the intestine. Transmission is faecal-oral through contact or smear infection as a result of personal contact as well as through contaminated food, water, or utensils. Infections occur sporadically, endemically, or in the form of epidemics.

Like hepatitis A, hepatitis B is also a widespread hepatitis virus. According to information from the WHO, around two billion people worldwide have contracted an HBV infection and around three percent of the global population are chronically infected with HBV. Transmission occurs via the blood and bodily secretions.

Hepatitis C is widespread worldwide. According to estimates by the World Health Organization (WHO), around 71 million people worldwide and thus around one percent of the global population are infected with hepatitis C. Transmission occurs through contact with contaminated blood and bodily secretions.

Hepatitis D requires the hepatitis B virus for its own replication (reproduction). Infection with hepatitis D therefore only occurs in combination (as a simultaneous infection or downstream as a superinfection). As with hepatitis B, transmission occurs through infected blood or infected bodily fluids.

Hepatitis E: In industrialized nations such as Germany, the hepatitis E infection occurs primarily as a so-called zoonotic transmission via the consumption of insufficiently cooked pork or game meat or products made from these. To prevent transmission via blood products, in 2019, Paul-Ehrlich-Institut ordered donor testing for HEV virus particles for blood components destined for transfusions and stem cell preparations.

Publications

Peiffer KH, Spengler C, Basic M, Jiang B, Kuhnhenn L, Obermann W, Zahn T, Glitscher M, Loglio A, Facchetti F, Carra G, Kubesch A, Vermehren J, Knop V, Graf C, Dietz J, Finkelmeier F, Hermann E, Trebicka J, Grünweller A, Zeuzem S, Sarrazin C, Lampertico P, Hildt E (2020): Quadruple mutation GCAC1809-1812TTCT acts as a biomarker in healthy European HBV carriers.
JCI Insight 5: e135833.
Online-Abstract


Bender D, Hildt E (2019): Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis.
Int J Mol Sci 20: 4659.
Text


Glitscher M, Martín DH, Woytinek K, Schmidt B, Tabari D, Scholl C, Stingl JC, Seelow E, Choi M, Hildt E (2021): Targeting cholesterol metabolism as efficient antiviral strategy against the Hepatitis E virus.
Cell Mol Gastroenterol Hepatol 12: 159-180.
Online-Abstract

Updated: 28.07.2021