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Laboratory for Hepatitis Virus Infections

Head:
Claus-Thomas Bock

Hepatitis E virus (HEV) infection is widespread worldwide and is a major health problem, particularly in developing countries. HEV infection is associated with large outbreaks in India, Asia and Africa and is one of the most common causes of acute hepatitis worldwide. Clinically, HEV infection is usually asymptomatic, but can also cause fulminant liver failure. Depending on the HEV genotype, HEV is transmitted fecal-orally (HEV 1 and HEV 2) and was previously considered a travel-associated disease. Since 2007, a steady increase in HEV cases reported under the IfSG (Infection Protection Act) has been observed in Germany, with 73 cases reported in 2007 and 3,773 in 2023. These were primarily autochthonous infections without a travel history, which are transmitted zoonotically through the consumption of undercooked animal products (usually pork meat) contaminated by HEV 3 or HEV 4. The mortality rate of HEV infection is around 2% and can be as high as >30% in pregnant women with HEV 1 or HEV 2 infection. Since 2008, chronic HEV infections have been observed, especially in immunosuppressed patients after organ transplantation and in HIV-infected persons. Chronic HEV infection can lead to severe liver inflammation, such as cirrhosis. Since the molecular and immunological mechanisms that can contribute to different clinical courses and the chronification of HEV infection are still largely unclear, the objectives are to optimize serological and molecular detection methods, determine pathogen variability and characterize chronification mechanisms using molecular virological methods.

The human hepatitis B virus (HBV), a small, strictly hepatotrophic DNA virus, is a member of the hepadnavirus family, which differs from all known DNA viruses due to its unusual replication mechanism, similar to that of retroviruses via reverse transcription. HBV is the causative agent of hepatitis B, one of the most important serious infectious diseases globally. According to WHO estimates, around two billion people (approx. 35% of the world's population) have had contact with HBV. Depending on the immune status of the HBV infected person and other factors (e.g. virus mutants), HBV infection can develop into a chronic form in around 10% of acute cases. Globally, around 269 million people are thought to have chronic hepatitis B (WHO 2023). HBV is mainly endemic in developing countries, such as Southeast Asia, Africa and South America with 5%-10% virus carrier rates. For Germany, recent surveys have shown a hepatitis B virus carrier rate of 0.3%. The prevalence rate of HBV depends not only on geographical distribution but also on risk behavior (e.g. intravenous drug use with non-sterile injection equipment). The clinical course of hepatitis B is highly variable and ranges from asymptomatic and inapparent to fulminant and severe liver inflammation, such as liver cirrhosis and hepatocellular carcinoma (HCC). Every year, around 820,000 people worldwide die as a result of a hepatitis, mostly due to HBV-induced liver cirrhosis and HCC. Acute and chronic hepatitis B is diagnosed using virological-serological and molecular biological methods in accordance with the guidelines for hepatitis B virus infection. Vaccination prophylaxis against HBV is recommended by the Standing Committee on Vaccination (STIKO) in Germany for children and adolescents.

The hepatitis C virus (HCV), a hepatotrophic single-stranded (+)-RNA virus, belongs to the flavivirus family and was first described in 1989. In contrast to hepatitis B, hepatitis C will become chronic in more than 80% of those infected. Around 170 million people worldwide (~3% of the world's population) are chronically infected with HCV. In addition to chronic hepatitis B, the chronic form of hepatitis C is responsible for the majority of all hepatocellular carcinomas and liver cirrhosis (27% and 25%, respectively) worldwide. HCV infection occurs geographically with varying prevalence. More than 20% of virus carriers are found in Asia and Africa. Across Europe, it is estimated that around 9 million people are chronically infected with HCV. In Germany, approx. 0.6% (approx. 500,000 people) (WHO, RKI 2009) are chronically infected with HCV.

Translational research activities of the hepatitis laboratory are aimed at scientific questions on the clinical relevance and sensitive detection of virus mutants (therapy response and chronification, especially in HEV) as well as investigations on inter- and intramolecular virus-host interactions, in particular the influence of hepatitis viruses on inflammatory signal transduction. The scientific activities are carried out in close collaboration with clinics and universities as well as in cooperation with national and international institutions (e.g. Nigerian CDC).

Service offering

  • Molecular detection of HEV RNA, HBV DNA, HCV RNA, HDV RNA using nucleic acid amplification techniques (PCR, RT-PCR, quantitative real time PCR)
  • Molecular genetic fine characterization of virus variants, in particular HEV (fine and genotyping; mutational analysis)

Current projects (as at 01/2024)

  • NiCaDe 2.0 (Nigeria Centre for Disease Control: Capacity Development for Preparedness and Response for Infectious Diseases II (NiCaDe II)); BMG funded: ZMII2-2523GHP033 (2023-2025)
  • ViRGiS 2.0 (Virus detection in the heart by next-generation sequencing); Pro FIT Verbundprojekt (RKI-Charité-IKDT); Co-funded by the European Regional Development Fund (EFRE); No. 10198831 (2023-2025)

Date: 17.01.2024

Publications

  • Biedermann P, Klink P, Nocke MK, Papp CP, Harms D, Kebelmann M, Thürmer A, Choi M, Altmann B, Todt D, Hofmann J, Bock CT (2023): Insertions and deletions in the hypervariable region of the hepatitis E virus genome in individuals with acute and chronic infection
    Liv Int 43: 794-804. doi: 10.1111/liv.15517. more

  • Klink P, Harms D, Altmann B, Dörffel Y, Morgera U, Zander S, Bock CT*, Hofmann J* (*contribute equally) (2023): Molecular characterisation of a rabbit Hepatitis E Virus strain detected in a chronically HEV-infected individual from Germany
    One Health 16: 100528. doi: 10.1016/j.onehlt.2023.100528. more

  • Wu E, Koch N, Bachmann F, Schulz M, Seelow E, Weber U, Waiser J, Halleck F, Faber M, Bock CT, Eckardt KU, Budde K, Hofmann J, Nickel P, Choi M (2023): Risk Factors for Hepatitis E Virus Infection and Eating Habits in Kidney Transplant Recipients
    Pathogens 12 (6): 850. doi: 10.3390/pathogens12060850. more

  • Cao LC, Martin V, Linh LTK, Giang TT, Chau NTM, Anh TNP, Nghia VX, The NT, My TN, Sy BT, Toan NL, Song LH, Bock CT*, Velavan TP* (*contribute equally) (2023): High Hepatitis E Virus (HEV) Seroprevalence and No Evidence of HEV Viraemia in Vietnamese Blood Donors
    Viruses 15 (10): 2075. doi: 10.3390/v15102075. more

  • Dudareva S, Faber M, Zimmermann R, Bock CT, Offergeld R, Steffen G, Enkelmann J (2022): Epidemiologie der Virushepatitiden A bis E in Deutschland.
    Bundesgesundheitsbl 65 (2): 149-158. doi: 10.1007/s00103-021-03478-8. Epub Jan 14. more

  • Papp C, Biedermann P, Harms D, Wang B, Kebelmann M, Choi M, Thürmer A, Altmann B, Klink P, Hofmann J, Bock CT (2022): Advanced sequencing approaches detected insertions of viral and human origin in the viral genome of chronic hepatitis E virus patients.
    Sci Rep 12 (1): 1720. doi: 10.1038/s41598-022-05706-w. more

  • Tung TT, Schmid J, Nghia VX, Cao LC, Linh LTK, Rungsung I, Sy BT, My TN, The NT, Hoan NX, Meyer CG, Wedemeyer H, Kremsner PG, Toan NL, Song LH, Bock CT, Velavan TP (2022): Low Risk of Occult Hepatitis B Infection among Vietnamese Blood Donors.
    Pathogens. 11 (12): 10. doi: 10.3390/pathogens11121524. more

  • Opaleye OO, Akanbi OA, Osundare FA, Wang B, Adesina O, Oluremi AS, Sunday ST, Akindele AA, Klink P, Bock CT (2021): Prevalence and characteristics of hepatitis B and D virus infections among HIV-positive individuals in Southwestern Nigeria.
    Virol. J. 18 (1): 20. Epub Jan 15. doi: 10.1186/s12985-021-01493-4. more

  • Hoan NX, Hoechel M, Tomazatos A, Anh CX, Pallerla SR, Linh LTK, Binh MT, Sy BT, Toan NL, Wedemeyer H, Bock CT et al. (2021): Predominance of HBV genotype B and HDV genotype 1 in Vietnamese patients with chronic hepatitis.
    Viruses 13 (2): 346. Epub Feb 22. doi: 10.3390/v13020346. more

  • Osamudiamen FT, Akanbi OA, Oluwayelu DO, Bock CT, Klink P (2021): Serological evidence of avian HEV antibodies in apparently healthy chickens in southwest Nigeria.
    PLoS One 16 (2): e0247889. Epub Feb 26. doi: 10.1371/journal.pone.0247889. more

  • Velavan TP, Pallerla SR, Johne R, Todt D, Steinmann E, Schemmerer M, Wenzel JJ, Hofmann J, Shih JWK, Wedemeyer H, Bock CT (2021): Hepatitis E: an update on One Health and clinical medicine.
    Liver Int. 41 (7): 1462-1473. Epub May 7. doi: 10.1111/liv.14912. more

  • Osundare FA, Klink P, Majer C, Akanbi OA, Wang B, Faber M, Harms D, Bock CT, Opaleye OO (2020): Hepatitis E virus seroprevalence and associated risk factors in apparently healthy individuals from Osun State, Nigeria.
    Pathogens 9 (5): 392. Epub May 20. doi: 10.3390/pathogens9050392. more

  • Osamudiamen FT, Akanbi OA, Zander S, Oluwayelu DO, Bock CT, Klink P (2021): Identification of a putative novel genotype of avian hepatitis E virus from apparently healthy chickens in southwestern Nigeria.
    Viruses 13 (6): 954. Epub May 21. doi: 10.3390/v13060954. more

  • Adesina OA, Akanbi OA, Opaleye OO, Japhet MO, Wang B, Oluyege AO, Klink P, Bock CT (2021): Detection of Q129H immune escape mutation in apparently healthy hepatitis B virus carriers in southwestern Nigeria.
    Viruses 13 (7): 1273. Epub Jun 29. doi: 10.3390/v13071273. more

  • Huy PX, Chung DT, Linh DT, Hang NT, Rachakonda S, Pallerla SR, Linh LTK, Tong HV, Dung LM, Mao CV, Wedemeyer H, Bock CT et al. (2021): Low prevalence of HEV infection and no associated risk of HEV transmission from mother to child among pregnant women in Vietnam.
    Pathogens 10 (10): 1340. Epub Oct 17. doi: 10.3390/pathogens10101340. more

  • Eshetu A, Hauser A, An der Heiden M, Schmidt D, Meixenberger K, Ross S, Obermeier M, Ehret R, Bock CT, Gunsenheimer-Bartmeyer B, Bremer V, Bannert N (2020): Establishment of an anti-hepatitis C virus IgG avidity test for dried serum/plasma spots.
    J. Immunol. Methods 479: 112744. Epub Jan 17. doi: 10.1016/j.jim.2020.112744. more

  • Schulz M, Biedermann P, Bock CT et al. (2020): Rituximab-containing treatment regimens may imply a long-term risk for difficult-to-treat chronic hepatitis E.
    Int. J. Environ. Res. Public Health 17 (1): pii: E341. Epub Jan 3. doi: 10.3390/ijerph17010341. more

  • Enkelmann J, Gassowski M, Nielsen S, Wenz B, Ross S, Marcus U, Bremer V, Zimmermann R; DRUCK-Study group (also for RKI Bock CT, Bannert N, Santos-Hövener C) (2020): High prevalence of hepatitis C virus infection and low level of awareness among people who recently started injecting drugs in a cross-sectional study in Germany, 2011–2014: missed opportunities for hepatitis C testing.
    Harm Reduct. J. 17 (1): 7. Epub Jan 10. doi: 10.1186/s12954-019-0338-y. more

  • Eshetu A, Hauser A, Schmidt D, Gunsenheimer-Bartmeyer B, Bremer V, Obermeier M, Ehret R, Volkwein A, Bock CT, Bannert N (2020): Comparison of two immunoassays for concurrent detection of HCV antigen and antibodies among HIV/HCV co-infected patients in dried serum/plasma spots.
    J. Virol. Methods 279: 113839. Epub Feb 19. doi: 10.1016/j.jviromet.2020.113839. more

  • Binh MT, Hoan NX, Giang DP, Tong HV, Bock CT et al. (2020): Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma.
    Sci. Rep. 10 (1): 2797. Epub Feb 18. doi: 10.1038/s41598-020-59667-z. more

  • Wang B, Harms D, Yang XL, Bock CT (2020): Orthohepevirus C: An expanding species of emerging hepatitis E virus variants.
    Pathogens 9 (3): pii: E154. Epub Feb 25. doi: 10.3390/pathogens9030154. more

  • Harms D, Choi M, Allers K, Wang B, Pietsch H, Papp CP, Hanisch L, Kurreck J, Hofmann J, Bock CT (2020): Specific circulating microRNAs during hepatitis E infection can serve as indicator for chronic hepatitis E.
    Sci. Rep. 10 (1): 5337. Epub Mar 24. doi: 10.1038/s41598-020-62159-9. more

  • Osundare FA, Klink P, Majer C, Akanbi OA, Wang B, Faber M, Harms D, Bock CT, Opaleye OO (2020): Hepatitis E virus seroprevalence and associated risk factors in apparently healthy individuals from Osun State, Nigeria.
    Pathogens 9 (5): 392. Epub May 20. doi: 10.3390/pathogens9050392. more

  • Scholz J, Falkenhagen A, Bock CT, Johne R (2020): Reverse genetics approaches for hepatitis E virus and related viruses.
    Curr. Opin. Virol. 44 (Oct): 121–128. Epub Aug 17. doi: 10.1016/j.coviro.2020.07.004. more

  • Pallerla SR, Harms D, Johne R, Todt D, Steinmann E, Schemmerer M, Wenzel JJ, Hofmann J, Shih JWK, Wedemeyer H, Bock CT, Velavan TP (2020): Hepatitis E virus infection: circulation, molecular epidemiology, and impact on global health.
    Pathogens 9 (10): E856. Epub Oct 20. doi: 10.3390/pathogens9100856. more

  • Pallerla SR, Schembecker S, Meyer CG, Linh LTK, Johne R, Wedemeyer H, Bock CT et al. (2020): Hepatitis E virus genome detection in commercial pork livers and pork meat products in Germany.
    J. Viral Hepat.: Epub Sep 1. doi: 10.1111/jvh.13396. more