Stories & Reports
Professor Michael P. Manns is the clinical director of the HZI and the director of the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School (MHH) and of the Centre for Individualised Infection Medicine (CIIM).
Prof Manns, the World Hepatitis Day is being held each year on 28 July. Why is it so important to draw attention to this disease?
Nowadays, more people succumb to hepatitis and its secondary diseases than to HIV/AIDS. The majority of the hepatitis B and C patients has not even been diagnosed yet. Undetected cases are unfortunately not being treated with the effective forms of therapy that are now available – which is a dilemma.
The motto of this year's World Hepatitis Day is "Find the missing millions." Why do so many hepatitis virus infections remain undetected and what would it mean if more of them would be diagnosed?
There are basically no screening programmes in place, including in Germany. The German Liver Foundation has been fighting for years without success to have the GPT/ALT liver test included in the check-up 35, the health check for individuals from the age of 35. The World Health Organization WHO has set clear goals for the elimination of hepatitis C by the year 2030: diagnose 90 percent, treat 80 percent, and reduce the rate of fatality by 65 percent. Although this WHO goal may be attained in some countries, others are far from it. The curing rates of the new hepatitis C therapies are quite high by now, clearly in excess of 90 percent. But the WHO's goal of hepatitis C elimination by 2030 can be attained only if the patients receiving therapy clearly outnumber the new infections. This can be done only by introducing comprehensive screening programmes – and this applies to Germany as well.
How can one protect oneself from the harmful hepatitis B and C infections and how good are the treatment options?
There is no cure for hepatitis B, but the proliferation of the virus in the liver can be effectively suppressed by long-term medication, which prevents the disease from progressing. But there is a vaccination for hepatitis B. The vaccination is done at infant age. It is important to make this vaccination available to all people.
Sadly, there is no vaccination against hepatitis C available yet. But owing to the new therapies, hepatitis C has become the first chronic viral infection in humans that can be cured. The high curing rates of basically all clinical pictures of hepatitis C, now in excess of 90 percent, make the elimination of this disease by therapy alone seem conceivable, even without vaccination. One also needs to note here the large difference in the cost of hepatitis C therapies between so-called "high" and "low" income countries: The manufacturers permit the production of inexpensive generic medications through low license fees in countries with a low income level. Whereas a cycle of therapy in the Western world still costs more than $30,000, it is available for less than $100 in low income countries.
What are the major challenges from hepatitis infections in clinical settings and which research approaches do you use to meet them?
A viral hepatitis can be caused by any one of five different viruses: A, B, C, D, and E. Thus far, only hepatitis A cannot cause chronic hepatitis. Over the course of years, a chronic hepatitis can lead to so-called liver cirrhosis, which may become the basis of liver cancer. Hepatitis D is the most difficult form. It always presents as a double infection by hepatitis B and D viruses, since hepatitis D virus cannot proliferate without the aid of hepatitis B virus. So far, there is no specific and effective therapy against the hepatitis D virus. Interferons help only some of the patients. New therapies for hepatitis D are therefore urgently required and need to be developed with high priority. Moreover, hepatitis B cannot be cured yet, but the progress of disease can be impeded by long-term therapy. Major research efforts are therefore being expended in the search for new hepatitis B therapies aiming to cure the disease. The motto, nationally and internationally, of these programmes is "HBV-CURE". In the tropics, chronic hepatitis E is mainly an acute infectious disease. In temperate regions like Europe, genotype 3 of hepatitis E virus may lead to a chronic infection in patients whose immune system is weakened. The elucidation of the epidemiology and the development of new therapies for chronic hepatitis E are in the focus of current research. All these issues are also investigated by the TTU Hepatitis of the German Center for Infection Research (DZIF).
Dr Ott, many hepatitis infections still remain undetected and far more than one million people succumb to hepatitis B or C each year. In which regions of the world are these infections particularly common and why is this the case?
In some African countries, chronic infection by the hepatitis B virus (HBV) is relatively common in the general population, which means that the HBV prevalence is high. Likewise, there are specific regions and countries that are strongly afflicted by hepatitis C virus (HCV), e.g. this is known to be the case in Egypt. This is due to a variety of causes: These may be pathogen-specific, for example in terms of the predominant genotype of HCV or HBV in a region. In the case of HBV, the way, in which the infection took place, and the age, at which the infection occurred, also has to be considered. The earlier in life a person becomes infected, the more likely the infection turns chronic if it remains untreated. This is particularly serious from a medical and a health policy point of view as diagnostic capacities and treatment options are limited in some countries. In addition, there is a risk for co-infections due to the high prevalence of other infections, like with HIV.
You and your colleagues are currently conducting a study on hepatitis B in Burkina Faso. Which kind of data do you gather and what is the goal of your study?
The aim of the study is to determine the sero-status of chronic HBV infection in a representative population. This implies the collection and analyses of blood samples in order to determine how common chronic HBV infection is in the population and which fraction of the population has been vaccinated against HBV. In addition, interviews are conducted with study participants in order to assess specific risk factors for the infection. So far, only scarce data on hepatitis were available from Burkina Faso with most of them focussing on special groups of individuals, e.g. those living in urban areas. This is an issue in many West African countries that lack the corresponding resources, since their populations in rural regions differ in terms of health status, health information status, and access to diagnostics and health care. Due to the high endemicity of chronic HBV in that country, comprehensive research also on risk factors and causes is warranted. We are carrying out the study in Burkina Faso in close cooperation with the University Hospital Heidelberg and the Centre de Recherche en Santé de Nouna (CRSN) in Burkina Faso. Both of our cooperation partners can look back on several years of joint research work, which is a great advantage for the implementation of an epidemiological project of this scale.
How serious are the other classical hepatitis viruses? Do you conduct research in this area?
The seriousness of a pathogen for human health also depends on socio-demographic factors of the afflicted person, for example on the person's age, as well as the access to medical care. In case of hepatitis A, i.e. an infection that does not take a chronic course, we do see an epidemiologic transition, which means an increasing susceptibility in certain age groups. In Europe, this concerns older individuals, who are not protected by a vaccination and did not experience a natural infection with the hepatitis A virus (HAV) at younger age. Accordingly, they tend to experience more serious and even life-threatening courses of the disease. In order to research epidemiologically relevant questions on HAV transition and susceptibility, colleagues from our department have developed a serological test that can differentiate between immunity elicited by HAV infection or by HAV vaccination. This test will be used in serological studies in South America and produce information concerning the prevention needs and age groups at risk.
With regard to an infection by the hepatitis E virus (HEV), the afflicted group of persons is a main criterion for how "harmful" the virus is. Pregnant women and immuno-compromised people are particularly vulnerable for HEV infection outcomes and the infection can even become chronic.
The WHO set an ambitious goal, i.e. the elimination of viral hepatitis as a global threat by 2030. In your view as a researcher, what has to happen for this goal to be attained? What are the most urgent issues that need to be resolved?
HBV has some special characteristics that speak for the possibility of elimination: for example the fact that the virus only affects humans, the known transmission ways and the existence of an effective vaccine against this virus. WHO-established national and regional goals for hepatitis control are useful landmarks to assess control efforts. One measure is the broader implementation of the Hepatitis B vaccination for new-borns, namely the hepatitis B birth dose. This is relevant especially in countries where virus transmission occurs from mother to child during birth.
Reliable epidemiologic data assist in assessing hepatitis control goals, for example on the disease burden and the change over time. We as epidemiologists are working on this, e.g. by conducting sero-epidemiological surveys with sampling and recording of relevant data, such as vaccination and infection status. Studies of this type are needed especially in regions with a high estimated HBV prevalence, in which only few people are aware of their health status or their infection. Since surveys of this type require extensive staffing and financial resources and the infrastructure needed for the studies is not yet established in some countries, more global attention, especially to chronic hepatitis diseases, is crucial.
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