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Pathogens
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Molecular Epidemiology, Host Genetic Factors, and Viral Hepatitis Related Liver...
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Molecular Epidemiology, Host Genetic Factors, and Viral Hepatitis Related Liver Diseases

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 16872

Special Issue Editors

Prof. Dr. Claus-Thomas Bock

E-Mail Website
Guest Editor
Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
Interests: molecular virology; viral hepatitis
Special Issues, Collections and Topics in MDPI journals
Dr. Daniel Todt

E-Mail Website1 Website2
Guest Editor
Molecular & Medical Virology, Ruhr University Bochum, Bochum, Germany
Interests: viral hepatitis; virus informatics; virus evolution; hepatitis E virus

Special Issue Information

Dear Colleagues,

Viral hepatitis is predominantly caused by five unrelated hepatotropic viruses, namely hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), and hepatitis E virus (HEV). Besides these hepatitis viruses, other viral infections can induce so-called concomitant viral hepatitis. Prominent agents include herpesviruses (cytomegalovirus (CMV), Epstein–Barr virus (EBV), herpes simplex virus (HSV)), adenoviruses, rubella viruses, the mumps virus, enteroviruses, and the yellow fever virus.

Hepatitis is an inflammation of the liver with multiple possible clinical courses and outcome. Acute hepatitis is the most common progression and resolves after 3 to 6 months depending on the virus. Acute hepatitis can be associated with fulminant hepatitis. Chronic hepatitis, in contrast, lasts longer than 3–6 months and can be associated with severe liver diseases such as cirrhosis and hepatocellular carcinoma. Although the WHO has implemented a global elimination program by 2030, there are still significant gaps in the knowledge of, for example, the molecular epidemiology and host factors in hepatitis virus infections and their impact on related liver diseases, which affect almost 600 million individuals worldwide and have an annual mortality rate of approximately 1.5 million. Sophisticated genetic analyses by Suh and colleagues provided the first direct evidence that Hepadnaviridae existed during the Early Mesozoic in land vertebrates more than 200 million years ago. Remarkably, the genome organization of HBV seems to have been conserved over this long period until today. In line with this, Krause-Kyora and colleagues identified HBV genomes in samples from individuals living in Europe in the Stone Age and Bronze Age (approximately 4500–7000 years ago). This implies that hepatitis virus infection was one of the first verified viral infections. To date, hepatitis viruses have adapted to vertebrates, mammals, and ultimately to humans over an intangible long lapse of time and have been bothering humans for thousands of years. Therefore, in accordance with the WHO’s goal of 2030, it is time now to control and eventually eradicate viral hepatitis.

In this Special Issue, we will summarize the current knowledge and aim to answer some of the many open questions on viral hepatitis infections in terms of epidemiology, prevention, treatment, virology, pathophysiology, diversity, and evolution. In addition, we will cover other clinical and basic research aspects in order to improve our knowledge on viral hepatitis pathogenesis, which influences virus replication, chronification, and risk assessment in humans.

We thus invite the submission of research and review manuscripts that cover any aspect of the pathogenesis, immunology, epidemiology, diagnosis, treatment, and prevention of viral hepatitis. We are looking forward to receiving your contributions, which will undoubtedly result in a valuable and high-ranking Special Issue that will promote further developments in the field of viral hepatitis and related liver diseases.

Prof. Dr. Claus-Thomas Bock
Dr. Daniel Todt
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • viral hepatitis
  • immunology
  • epidemiology
  • molecular epidemiology
  • genetic diversity
  • virology
  • host genetic factors
  • therapy
  • diagnostics
  • clinical outcome
  • liver diseases
  • virus evolution

Published Papers (6 papers)

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Research

10 pages, 1662 KiB  
Article
Low Risk of Occult Hepatitis B Infection among Vietnamese Blood Donors
by Tran Thanh Tung, Jürgen Schmid, Vu Xuan Nghia, Le Chi Cao, Le Thi Kieu Linh, Ikrormi Rungsung, Bui Tien Sy, Truong Nhat My, Nguyen Trong The, Nghiem Xuan Hoan, Christian G. Meyer, Heiner Wedemeyer, Peter G. Kremsner, Nguyen Linh Toan, Le Huu Song, C.-Thomas Bock and Thirumalaisamy P. Velavan
Pathogens 2022, 11(12), 1524; https://doi.org/10.3390/pathogens11121524 - 13 Dec 2022
Cited by 1 | Viewed by 2260
Abstract
Occult hepatitis B infection (OBI) is characterized by the presence of low levels of hepatitis B virus (HBV) DNA and undetectable HBsAg in the blood. The prevalence of OBI in blood donors in Asia ranges from 0.013% (China) to 10.9% (Laos), with no [...] Read more.
Occult hepatitis B infection (OBI) is characterized by the presence of low levels of hepatitis B virus (HBV) DNA and undetectable HBsAg in the blood. The prevalence of OBI in blood donors in Asia ranges from 0.013% (China) to 10.9% (Laos), with no data available from Vietnam so far. We aimed to investigate the prevalence of OBI among Vietnamese blood donors. A total of 623 (114 women and 509 men) HBsAg-negative blood donors were screened for anti-HBc and anti-HBs by ELISA assays. In addition, DNA from sera was isolated and nested PCR was performed for the HBV surface gene (S); a fragment of the S gene was then sequenced in positive samples. The results revealed that 39% (n = 242) of blood donors were positive for anti-HBc, and 70% (n = 434) were positive for anti-HBs, with 36% (n = 223) being positive for both anti-HBc and anti-HBs. In addition, 3% of blood donors (n = 19) were positive for anti-HBc only, and 34% (n = 211) had only anti-HBs as serological marker. A total of 27% (n = 170) were seronegative for any marker. Two of the blood donors (0.3%) were OBI-positive and sequencing revealed that HBV sequences belonged to HBV genotype B, which is the predominant genotype in Vietnam. Full article
(This article belongs to the Special Issue Molecular Epidemiology, Host Genetic Factors, and Viral Hepatitis Related Liver Diseases)
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9 pages, 864 KiB  
Article
Efficacy and Safety of Bulevirtide plus Tenofovir Disoproxil Fumarate in Real-World Patients with Chronic Hepatitis B and D Co-Infection
by Toni Herta, Magdalena Hahn, Melanie Maier, Janett Fischer, Johannes Niemeyer, Mario Hönemann, Albrecht Böhlig, Florian Gerhardt, Aaron Schindler, Jonas Schumacher, Thomas Berg, Johannes Wiegand and Florian van Bömmel
Pathogens 2022, 11(5), 517; https://doi.org/10.3390/pathogens11050517 - 27 Apr 2022
Cited by 20 | Viewed by 2552
Abstract
Background: The hepatitis B and D virus (HBV/HDV) hepatocyte entry inhibitor bulevirtide (BLV) has been available in Europe since July 2020, after the registrational trial MYR202. Real-life data on the efficacy and safety of BLV are sparse. Methods: We have analysed the course [...] Read more.
Background: The hepatitis B and D virus (HBV/HDV) hepatocyte entry inhibitor bulevirtide (BLV) has been available in Europe since July 2020, after the registrational trial MYR202. Real-life data on the efficacy and safety of BLV are sparse. Methods: We have analysed the course of treatment with BLV (2 mg/day) plus tenofovir disoproxil fumarate (TDF) (245 mg/day) in patients with chronic hepatitis delta (CHD). Virologic (≥2 log reduction in HDV RNA or suppression of HDV RNA below the lower limit of detection) and biochemical (normalisation of serum ALT) treatment responses after 24 weeks were defined according to the MYR202 trial. Results: Seven patients were recruited (four with liver cirrhosis Child–Pugh A). After 24 weeks, a virologic response was observed in five of seven and a biochemical response was seen in three of six patients with elevated serum ALT at baseline. Extended treatment data > 48 weeks were available in three cases: two presented with continuous virologic and biochemical responses and in one individual an HDV-RNA breakthrough was observed. Adverse effects were not recorded. Conclusions: The first real-life data of the approved dosage of 2 mg of BLV in combination with TDF confirm the safety, tolerability, and efficacy of the registrational trial MYR202 for a treatment period of 24 weeks and beyond. Full article
(This article belongs to the Special Issue Molecular Epidemiology, Host Genetic Factors, and Viral Hepatitis Related Liver Diseases)
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13 pages, 2183 KiB  
Article
A Modular Hepatitis E Virus Replicon System for Studies on the Role of ORF1-Encoded Polyprotein Domains
by Filip Cierniak, Rainer G. Ulrich, Martin H. Groschup and Martin Eiden
Pathogens 2022, 11(3), 355; https://doi.org/10.3390/pathogens11030355 - 15 Mar 2022
Cited by 3 | Viewed by 2248
Abstract
Zoonotic hepatitis E virus (HEV) infection is an emerging cause of acute viral hepatitis in developed countries. Known reservoirs of zoonotic genotype 3 (HEV-3) are mainly pigs and wild boar, and to a lesser extent rabbits and deer. Rabbit hepatitis E virus (HEV-3ra) [...] Read more.
Zoonotic hepatitis E virus (HEV) infection is an emerging cause of acute viral hepatitis in developed countries. Known reservoirs of zoonotic genotype 3 (HEV-3) are mainly pigs and wild boar, and to a lesser extent rabbits and deer. Rabbit hepatitis E virus (HEV-3ra) is prevalent in rabbits worldwide and represents a particular risk for zoonotic infection. Current understanding of the molecular mechanisms of HEV pathogenesis is incomplete, particularly due to the limited availability of efficient and reliable cell culture systems. In order to identify genomic regions responsible for HEV propagation in cell culture, we developed a modular chimeric reporter replicon system based on cell culture-adapted (Kernow-C1/p6 and 47832mc) and rabbit-derived HEV strains. Replication in HepG2 cells was monitored on the basis of a Gaussia luciferase reporter gene that was inserted in place of the open reading frame (ORF) 2 of the HEV genome. Luciferase activity of rabbit HEV-derived replicons was significantly lower than that of Kernow-C1/p6 and 47832mc replicons. Serial exchanges of defined ORF1 segments within the Kernow-C1/p6 replicon backbone indicated that HEV replication in HepG2 cells is not determined by a single domain but rather by an interplay of longer segments of the ORF1-derived nonstructural polyprotein. This implies that a specific combination of viral factors is required for efficient HEV propagation in cell culture. Full article
(This article belongs to the Special Issue Molecular Epidemiology, Host Genetic Factors, and Viral Hepatitis Related Liver Diseases)
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14 pages, 1607 KiB  
Article
Comparison of Two Diagnostic Methods for the Detection of Hepatitis B Virus Genotypes in the Slovak Republic
by Mariia Logoida, Pavol Kristian, Andrea Schreiberova, Patrícia Denisa Lenártová, Veronika Bednárová, Elena Hatalová, Ivana Hockicková, Sylvia Dražilová, Peter Jarčuška, Martin Janičko, Štefan Porhinčák and Monika Halánová
Pathogens 2022, 11(1), 20; https://doi.org/10.3390/pathogens11010020 - 24 Dec 2021
Cited by 2 | Viewed by 2541
Abstract
The hepatitis B virus (HBV), belonging to the Hepadnaviridae family, is responsible for a global health concern still in the 21st century. The virus is divided into 10 genotypes, which differ in geographical distribution and in their effect on disease progression and transmission, [...] Read more.
The hepatitis B virus (HBV), belonging to the Hepadnaviridae family, is responsible for a global health concern still in the 21st century. The virus is divided into 10 genotypes, which differ in geographical distribution and in their effect on disease progression and transmission, susceptibility to mutations, and response to treatment. There are many methods for diagnostics of HBV and differentiating its genotypes. Various commercial kits based on real-time polymerase chain reaction (RT PCR) and hybridization available, as well as whole genome sequencing or the sequencing of only individual parts of the genomes. We compared a commercial kit AmpliSens HBV-genotype-FRT, based on RT PCR, with an adapted method of amplification of the surface genomic region combined with Sanger sequencing. In the examined samples we identified the A, B, C, D, and E genotypes. By PCR with Sanger sequencing, the genotypes were determined in all 103 samples, while by using the commercial kit we successfully genotyped only 95 samples, including combined genotypes, which we could not detect by sequencing. Full article
(This article belongs to the Special Issue Molecular Epidemiology, Host Genetic Factors, and Viral Hepatitis Related Liver Diseases)
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6 pages, 203 KiB  
Article
From Screening to Therapy: Anti-HCV Screening and Linkage to Care in a Network of General Practitioners and a Private Gastroenterology Practice
by David Petroff, Olaf Bätz, Katrin Jedrysiak, Anja Lüllau, Jan Kramer, Hjördis Möller, Renate Heyne, Burkhard Jäger, Thomas Berg and Johannes Wiegand
Pathogens 2021, 10(12), 1570; https://doi.org/10.3390/pathogens10121570 - 02 Dec 2021
Cited by 3 | Viewed by 1973
Abstract
(1) Background: Low rates of hepatitis C virus (HCV) diagnosis and sub-optimal linkage to care constitute barriers toward eliminating the infection. In 2012/2013, we showed that HCV screening in primary care detects unknown cases. However, hepatitis C patients may not receive further diagnostics [...] Read more.
(1) Background: Low rates of hepatitis C virus (HCV) diagnosis and sub-optimal linkage to care constitute barriers toward eliminating the infection. In 2012/2013, we showed that HCV screening in primary care detects unknown cases. However, hepatitis C patients may not receive further diagnostics and therapy because they drop out during the referral pathway to secondary care. Thus, we used an existing network of primary care physicians and a practice of gastroenterology to investigate the pathway from screening to therapy. (2) Methods: HCV screening was prospectively included in a routine check-up of primary care physicians who cooperated regularly with a private gastroenterology practice. Anti-HCV-positive patients were referred for further specialized diagnostics and treatment if indicated. (3) Results: Seventeen primary care practices screened 1875 patients. Twelve individuals were anti-HCV-positive (0.6%), six of them reported previous antiviral HCV therapy, and one untreated patient was HCV-RNA-positive (0.05% of the population). None of the 12 anti-HCV-positive cases showed up at the private gastroenterology practice. Further clinical details of the pathway from screening to therapy could not be analyzed. (4) Conclusions: The linkage between primary and secondary care appears to be problematic in the HCV setting even among cooperating partners, but robust conclusions require larger datasets. Full article
(This article belongs to the Special Issue Molecular Epidemiology, Host Genetic Factors, and Viral Hepatitis Related Liver Diseases)
11 pages, 1701 KiB  
Article
Evaluation of a Novel CLIA Monotest Assay for the Detection of Anti-Hepatitis E Virus-IgG and IgM: A Retrospective Comparison with a Line Blot and an ELISA
by Karl Dichtl, Julia Zimmermann, Martin B. Koeppel, Stephan Böhm and Andreas Osterman
Pathogens 2021, 10(6), 689; https://doi.org/10.3390/pathogens10060689 - 01 Jun 2021
Cited by 5 | Viewed by 3729
Abstract
Despite the increasing relevance of Hepatitis E, an emerging disease endemic in developing and with increasing numbers of sporadic cases in industrialized countries, commercial tests are mainly based on batch oriented serological assays. In this retrospective study, we compared a line immunoassay (LIA; [...] Read more.
Despite the increasing relevance of Hepatitis E, an emerging disease endemic in developing and with increasing numbers of sporadic cases in industrialized countries, commercial tests are mainly based on batch oriented serological assays. In this retrospective study, we compared a line immunoassay (LIA; recomLine HEV, Mikrogen) and an ELISA (EIA; Anti-Hepatitis E Virus ELISA, Euroimmun) with a novel chemoluminescence immunoassay in a monotest format (CLIA; Hepatitis E VirClia, Vircell). Twenty sera of PCR proven cases of hepatitis E and 68 blood samples serologically pre-characterized were included. Applying the WHO reference standard, the CLIA demonstrated the highest analytical sensitivity for IgG and IgM. The combinations of CLIA/EIA (IgG and IgM) and CLIA/LIA (IgG) measurements showed substantial correlation. Compared to overall antibody detection (seropositivity in ≥2 assays), CLIA correlation was excellent, outperforming LIA (IgM) and EIA (IgG and IgM). Minor IgM cross reactivity in samples of patients with acute EBV infection was observed in all three assays. The CLIA showed good performance in diagnostic samples compared to established LIA and EIA assays. Due to its ready-to-use monotest format, the CLIA allows simple, time- and cost-effective handling of single samples. These qualities make the assay suitable for diagnostics, especially in the emergency setting and for low-throughput laboratories. Full article
(This article belongs to the Special Issue Molecular Epidemiology, Host Genetic Factors, and Viral Hepatitis Related Liver Diseases)
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