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The National Reference Center (NRC) for hepatitis B viruses (HBV) and hepatitis D viruses (HDV) has been located at the Institute of Medical Virology of the Justus Liebig University (JLU) in Giessen, Germany, since its establishment in 2011. This paper describes the NRC's areas of activity and related experience.The NRC offers comprehensive consulting services on all diagnostic and clinical aspects of acute and chronic HBV and HDV infections for the Public Health Service (ÖGD), diagnostic laboratories, clinics, research institutes, and physicians in private practice. Uncertain diagnostic findings can be analyzed and interpreted and epidemiological correlations clarified with the HBV/HDV special diagnostics established at the NRC using state-of-the-art molecular, biochemical, and genetic laboratory tools. The NRC has access to a strain collection of many well-characterized and cloned HBV/HDV isolates, allowing comparative analysis and evaluation of antiviral resistance mutations and immune escape variants. Together with its national and international partner institutions, the NRC initiates and supervises, among other things, interlaboratory studies for the diagnosis of HBV resistance and immune escape for the establishment and validation of international World Health Organization (WHO) standards and for the improvement of quantitative HDV genome determination. The NRC actively participates in current recommendations and guidelines on HBV and HDV and the recommendations of medical societies. It also highlights current HBV/HDV-relevant aspects with contributions in the form of national and international lectures as well as original articles and comments in national and international journals., (© 2022. The Author(s).)

Hepatitis B virus (HBV) causes acute or chronic hepatitis B. Local outbreaks of HBV infections in skilled nursing facilities is a matter of growing concern in developed countries. Here, we investigated two outbreaks of hepatitis B that recently occurred in nursing homes in Germany. The outbreak at location A was associated with acute fulminant hepatitis with fatal outcome in several cases, while individuals infected at location B developed asymptomatic or mild hepatitis B. Sequence analysis of viruses involved in these outbreaks revealed different, but unique HBV strains for each location. Each of the strains produced high viremia of more than 10(9) virions/mL serum. We found that the mild course of hepatitis B at location B was caused by a circulating wild-type HBV genotype A2 strain, which is commonly found in Central Europe. Complete genome sequences of isolates obtained from infected patients revealed nearly 100% sequence identity at the nucleotide level as well as expression of HBV e protein (HBeAg), a known T cell tolerogen in the incubation or chronic phases of HBV infection. By contrast, the outbreak at location A was associated with an HBV genotype D2 variant that lacked HBeAg expression, suggesting that immunopathology and selection of specific HBV variants played a major role in the severe (or even fulminant) acute hepatitis observed at location A. Importantly, all patients were diagnosed with type 2 diabetes mellitus, a known risk factor for healthcare-associated transmission of HBV. The study leads us to suggest that, besides strict adherence to hygiene standards, additional efforts are required to reduce the risk of HBV transmission and fulminant disease progression in healthcare settings and nursing homes. In this context, a general screening for HBsAg and active hepatitis B vaccination should be considered for people living in nursing homes, especially for those with diagnosed diabetes or other predisposing factors for HBV transmission., (Copyright © 2015. Published by Elsevier GmbH.)