Hepatitis E virus defies alcohol-based hand sanitizers

Evidence-based medicine is based on the results of controlled studies and provides the scientific basis for our medical decision-making. However, in order to conduct studies under the most "controlled" conditions possible, there are inclusion and exclusion criteria that must be met by the participating patients. For the inclusion of patients with liver cancer, these criteria often represent a hurdle for treatment within therapy studies: for example, liver function must not fall below certain threshold values, the type and number of possible previous therapies is not arbitrary, and the general condition of the participants should still be good at the time of the start of therapy.

"Conducting studies under the most controlled conditions possible is important to ensure an objective assessment of the investigational medicinal products. In our everyday clinical work, however, we often see patients who would not fully meet the classic inclusion criteria of clinical trials - and as treating physicians, we are faced with the question of whether and which therapy is appropriate and effective for our patients," explains Anna Saborowski, research group leader and assistant physician in the Clinical Department of Gastroenterology, Hepatology and Endocrinology.

Based on the results of the IMbrave150 study (Finn et al, NEJM 2020, DOI: 10.1056/NEJMoa1915745), the combination of the immune checkpoint inhibitor atezolizumab and the angiogenesis inhibitor bevacizumab has been considered the new standard in the first-line treatment of hepatocellular carcinoma (HCC) since the end of 2020. In the article "Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience" , recently published in the scientific journal "Therapeutic Advances in Medical Oncology ", the group led by Arndt Vogel and Anna Saborowski addresses the question of how the efficacy and safety of the combination therapy of atezolizumab and bevacizumab is presented in a "real" patient collective outside of a clinical trial. Tiago de Castro, assistant physician at the Clinical Department of Gastroenterology, Hepatology and Endocrinology, and first author of the study, together with colleagues from Essen, Mainz, Lübeck, Munich and Vienna, evaluated data from over 140 patients with HCC who received appropriate therapy at the local centers. "The patients who would have met the inclusion criteria of the pivotal study also showed a good treatment response and survival in our retrospective analysis. However, around every second patient had at least one exclusion criterion. Overall survival in this patient group was significantly worse and clinically relevant decompensation of liver function occurred more frequently during treatment," reports Mr. de Castro.

"Overall, our data confirm the effectiveness of the combination approach in everyday clinical practice, but also underline the overriding importance of preserved liver function at the start of treatment," emphasizes Prof. Arndt Vogel, Head of the Gastro-Oncology Day Clinic. For clinicians, the study outlines a "horizon of expectation" for patients with HCC and reinforces the use of combination therapy even in previously treated patients.

Hepatitis E virus defies alcohol-based hand disinfectants

The hepatitis E virus (HEV) can cause serious liver inflammation and is the most common cause of acute virus-mediated hepatitis worldwide. Infections can be prevented through appropriate hygiene measures. Scientists from TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover Medical School (MHH) and Ruhr University Bochum (RUB), together with partners from the industry, have investigated the effectiveness of various common hand disinfectants against HEV. They were able to show that most formulations do not completely inactivate the virus. They have now published these results in the high-ranking Journal of Hepatology (impact factor 25).

In Germany and Europe, HEV has its natural reservoir in pigs. The infection can spread from animals to humans, which is called a zoonosis. This often happens through incompletely heated or raw meat products such as minced meat. In tropical regions of the world, infections occur via contaminated water, sometimes causing large outbreaks. "Some of these infections could possibly be prevented with the right hygiene measures", says Patrick Behrendt, physician in the Department of Gastroenterology, Hepatology and Endocrinology at MHH and head of the junior research group "Translational Virology" at TWINCORE. This includes, above all, correct hygienic hand disinfection in everyday clinical practice when dealing with hepatitis E patients and infected animals.

Together with the team of Eike Steinmann, formerly head of the research group "Virus Transmission" at TWINCORE and since 2018 head of the Department of Molecular and Medical Virology at Ruhr University Bochum, Behrendt has investigated whether common hand disinfectants can render the virus harmless. "We tested the effect of the alcohols ethanol and propanol, both individually and in the mixing ratios recommended by the WHO, and also commercial hand disinfectants," says Steinmann. "However, only one product that contained another component was effective."

Normally, HEV occurs non-enveloped and, like all non-enveloped viruses, is very resistant to chemical influences. However, virus particles circulating in the blood of patients are surrounded by a lipid envelope. "Not all disinfectants are effective against enveloped and non-enveloped viruses at the same time," says Steinmann. "We used both forms of HEV for our tests."

Although some of the disinfectants tested are certified to inactivate both enveloped and non-enveloped viruses, they were not sufficiently effective against HEV. "The alcoholic components dissolve the lipid envelope, but the resulting "naked" viruses are still infectious," says Dr. Behrendt. So HEV is literally hard to break down. The decisive advantage was a product that contains phosphoric acid as well as alcohol. This neutralized all the virus particles sufficiently.

"We were able to show that HEV can resist most common hand disinfectants," says Behrendt. "We hope that these findings will be taken into consideration in the future when hygiene measures are recommended for handling contaminated meat products and in HEV outbreak situations."