What started for the successful team of the „Wonder of Bern“ with a small sting, ended in a big medical defeat: Nearly all players were infected through a harmless vitamin injection with the Hepatitis virus C (HVC). Some of them got severely ill. According to today’s knowledge, the team doctor failed to disinfect the syringes sufficiently.
Unfortunately this is not an isolated incident: We know several comparable occasions in medical history like for example the break out of HVC 1978/1979 in the former GDR as a result of an anti-D rhesus prophylaxis for women. 2867 women were infected while being treated with contaminated sera against a blood group incompatibility between rhesus-negative mothers and rhesus-positive children. The disaster in Egypt was even worse: In the 1950s to the 1980s, the governmental health authorities tried to extinguish the worm disease bilharzias. During the large-scale campaign, the physicians presumably used insufficiently disinfected cannulae – the result: About 6 million people were infected with HVC.
No symptoms – no attention?
Worldwide more than 170 million people have the same destiny. Many are not aware of this virus in their body since liver diseases hardly cause any pain in the beginning. And the symptoms of a HVC infection often are more like flu than a serious disease. In course of time though, more than 70 percent of the cases develop a chronic liver infection. “Today we have the opportunity to help many of the affected people”, emphasizes Prof. Dr. Michael P. Manns, Deutsche Leberstiftung (German liver foundation). This is why an early detection, e. g. by determination of the GPT-value (glutamic pyruvic transaminase) is so important. If it is increased you have to go to the root of things by doing specific tests to identify proteins and genetic components of the HVC.
If you say “A”…
In principle, science distinguishes between hepatitis viruses A, B, C, D, and E. Proven transfer paths are contaminated food, unclean drinking water (hepatitis A/E) respectively sexual contacts and blood-to-blood contacts (hepatitis B/D). While hepatitis A and E cannot become chronic, variations B and D might take in same cases a chronic course and in the end lead to liver cell carcinoma. Vaccination is the best protection against hepatitis A and B. Then variation D does not stand a chance anyways since it is not able to develop into an infection by itself. And for hepatitis E, a vaccination is under way.
…you have to go all the way to “C”
The hepatitis C virus however, frequently causes a chronic infection, in its course possibly causing liver cirrhosis and later liver cell carcinoma. Also possible are diseases of the immune complex. Patients get infected especially through blood-to-blood contact, for example through needle-stick injuries or when using unclean medical instruments or lousy hygiene in piercing- and tattoo studios. Experts even consider transfer by sexual contact a possibility.
Today, contaminated conserved blood respectively blood products are a serious problem in poorer countries. Many of the hospitals simply cannot afford the costly examinations of donated blood – a standard HIV test in Brazil for example costs more than 100 Dollars for a single sample. Here, a newly developed procedure is supposed to help, created at the Bernhard-Nocht-Institute for Tropical medicine in Hamburg. According to Dr. Jan Felix Drexler it will cost 19 Dollars. The procedure recognizes regions in the genetic material matching in all pathogenic types. This method is also suitable to evaluate success of a therapy. The hepatitis C virus has six different variations – i. e. genetic versions – and 30 subtypes. Those genetic versions are particularly relevant to forecast therapy success. Chances for success are significantly higher with genotype 2 and 3 compared to version 1.
A cocktail against the virus
Specialists mainly try to eliminate virus-own factors thus stopping reduction of the intruder. Golden standard here is a treatment with pegylated Interferon and Ribavirin for 24 to 48 weeks, depending on the genotype of the virus. Ribavirin works against numerous DNA- and RNA-viruses by inhibiting the vital enzyme polymerase. As a result, viruses cannot reproduce their genetic material. The trick in applying pegylated interferons: The slow release of the actual active agent from the bond with the polymer polyethylene glycol. The active agent has to be injected only once a week. Already in 2008, the European Commission has approved of an abridged 16-week therapy with Peginterferon alfa-2 and Ribavirin for genotypes 2 and 3. Requirements are a low virus load at the beginning of the treatment and the patient has to be freed of the virus within four weeks.
Telaprevir might be the new drug of choice in the near future for patients with the viral genotype 1, particularly those not responding to a standard therapy. This active agent targets for a viral enzyme as well. Especially with a combination of Telaprevir, Ribavirin and Peginterferon, round about half of the patients were treated successfully on a permanent basis. Head of the study Prof. Dr. Stefan Zeuzem: “We assume that this drug is able to halve the approximately one-year therapy period and to increase the healing rate of hepatitis C genotype 1 infected patients from nearly 50 to up to 70 percent”. But in more than half of the cases, the test persons developed a skin rash when treated with the triple combination. So this therapeutic option is mainly eligible for cases where the standard therapy has failed.
Albinterferon might be an alternative to Peginterferon. The according preparation would have to be applied only every other week. In studies, it proved to be just as effective against HVC of all three genotypes as pegylated Interferon. Novartis however announced in April that the application for market approval in Europe has been withdrawn. The authorities had required further data requiring new clinical trials.
Turn off all taps
Researchers at the University Hospital Freiburg got to the nub of the mechanisms how a tumor develops by HVC. Lymphotoxin alpha und beta are the two messengers they discovered causing chronic liver inflammation respectively liver cell cancer in animal tests. A stop to the signal transmission weakens the inflammation and stopped the development of cancer. “Blocking the signal path could be the basis for new therapeutic approaches for treatment of chronic liver inflammation”, says Dr. Nicholas Zeller. And if worst comes to worst targeted inhibition of a genetic factor might help. “When hepatitis C viruses do not react to a combination therapy, it is connected to an overproduction of the Interferon stimulating gene 15 in the liver”, explains Prof. Dr. Jörg Friedrich Schlaak of the University Hospital Essen. ISG15 – as it is abbreviated – benefits the reproduction of virus particles in the body by inhibiting other genes which could keep the intruder in check. A genetic test helps with the decision which treatment to make. Then it would be also considerable to down-regulate genetic activities by small interfering RNAs, little nucleic acid building blocks. In addition a team at the University Hospital Heidelberg was able to identify the protein cyclophilin A in liver cells – essential for the reproduction of HVC. The active agent Ciclosporin, already applied in organ transplantations, inhibits this protein and thus also the reproduction of the viral intruders. On the look-out for further substances without effect on the immune system, Prof. Dr. Rolf Bamberger and his team succeeded in synthesizing an offspring. The bond abbreviated “DEBIO-025” has proven effective according to Novartis in phase-II tests and monotherapy as well as in combination with the standard treatment. Currently the substance is undergoing clinical phase IIb in order to find a suitable dosage.
Hygiene – still the most important
At the Hanover Medical University, scientists focused on the question: How robust is the HVC really? The good news: it’s enough to use the standard disinfections to inactivate it. “On the other hand, the virus is pretty stable in room temperature. And it keeps alive in a fluid for three weeks”, emphasizes the researcher Sandra Ciesek. “Practically, this means that the strict hygiene measures are really justified.” The best protection against an infection with HVC is a vaccination – provided it would exist. Commercially available vaccines have a common principle: They activate the production of antibodies against viral intruders in the human body. Pathogens like HCV “hiding” in body-own cells cannot be reached with it. Scientists at the Robert Koch-Institute (RKI) are hoping for help by the immune system. “The identification of dendtritic cells mobilizing the cellular immune response, is a decisive step towards the development of new vaccines”, as Richard Krozcek at the RKI points out.