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Viruses
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Recent Progress in Hepatitis A Virus Research
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Recent Progress in Hepatitis A Virus Research

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 35961

Special Issue Editor

Dr. Sébastien Lhomme

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Guest Editor
1. Toulouse University Hospital, Purpan Hospital, Virology Department, Toulouse 31300, France
2. Inserm UMR 1291, CNRS UMR5051, Université Toulouse III, Toulouse, France.
Interests: quasi-enveloped viruses; epidemiology; pathogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Although the hepatitis A virus (HAV) is an ancient one, it is still a frequent cause of waterborne hepatitis, especially in tropical and subtropical countries. Outbreaks of hepatitis A also occur in specific populations, including in men who have sex with men. HAV continues to affect millions of individuals annually despite the availability of hepatitis A vaccines and as yet, there is no specific treatment for these infections. Acute infections are managed with general supportive care, individuals with hepatitis A and acute liver failure can be treated with N-acetylcysteine, while liver transplantation is considered for the sickest patients.

The description the two forms of HAV, cloaked in host-cell membranes in the blood and naked in the environment, has also opened up new fields of research on this old virus, especially on the HAV lifecycle and how the virus enters cells.

This Special Issue of Viruses focuses on our current knowledge of HAV and the direction of future research. We plan to assemble an up-to-date collection of research papers and reviews on HAV, its biology, molecular biology, epidemiology, virus–host interactions, and new treatments.

Dr. Sébastien LHOMME
Guest Editor

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. Viruses 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 2600 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

  • HAV
  • epidemiology
  • entry
  • life cycle
  • pathogenesis
  • immune response
  • vaccine
  • therapy

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Published Papers (8 papers)

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Editorial

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2 pages, 189 KiB  
Editorial
Special Issue “Recent Progress in Hepatitis A Virus Research”
by Sébastien Lhomme
Viruses 2022, 14(6), 1138; https://doi.org/10.3390/v14061138 - 25 May 2022
Viewed by 1469
Abstract
The hepatitis A virus (HAV) is still one of the leading causes of acute viral hepatitis worldwide, despite there being an anti-HAV vaccine [...] Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)

Research

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10 pages, 399 KiB  
Article
Development and Evaluation of a Molecular Hepatitis A Virus Assay for Serum and Stool Specimens
by Robert A. Kozak, Candace Rutherford, Melissa Richard-Greenblatt, N. Y. Elizabeth Chau, Ana Cabrera, Mia Biondi, Jamie Borlang, Jaqueline Day, Carla Osiowy, Sumathi Ramachandran, Nancy Mayer, Laurel Glaser and Marek Smieja
Viruses 2022, 14(1), 159; https://doi.org/10.3390/v14010159 - 15 Jan 2022
Cited by 5 | Viewed by 3106
Abstract
Hepatitis A virus (HAV) is an emerging public health concern and there is an urgent need for ways to rapidly identify cases so that outbreaks can be managed effectively. Conventional testing for HAV relies on anti-HAV IgM seropositivity. However, studies estimate that 10–30% [...] Read more.
Hepatitis A virus (HAV) is an emerging public health concern and there is an urgent need for ways to rapidly identify cases so that outbreaks can be managed effectively. Conventional testing for HAV relies on anti-HAV IgM seropositivity. However, studies estimate that 10–30% of patients may not be diagnosed by serology. Molecular assays that can directly detect viral nucleic acids have the potential to improve diagnosis, which is key to prevent the spread of infections. In this study, we developed a real-time PCR (RT-PCR) assay to detect HAV RNA for the identification of acute HAV infection. Primers were designed to target the conserved 5′-untranslated region (5′-UTR) of HAV, and the assay was optimized on both the Qiagen Rotor-Gene and the BD MAX. We successfully detected HAV from patient serum and stool samples with moderate differences in sensitivity and specificity depending on the platform used. Our results highlight the clinical utility of using a molecular assay to detect HAV from various specimen types that can be implemented in hospitals to assist with diagnostics, treatment and prevention. Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)
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11 pages, 1380 KiB  
Communication
The Molecular Characterization of Hepatitis A Virus Strains Circulating during Hepatitis A Outbreaks in São Paulo, Brazil, from September 2017 to May 2019
by Samira Chuffi, Michele S. Gomes-Gouvêa, Luciana V. B. Casadio, Ana Catharina S. S. Nastri, Mario P. Gonzalez, André L. F. Cotia, Amanda G. D. Aranda, Simone B. Tenore, Suzane K. Ono, Fernanda M. Malta, Geraldine Madalosso, Paulo R. A. Ferreira, Flair J. Carrilho and João R. R. Pinho
Viruses 2022, 14(1), 73; https://doi.org/10.3390/v14010073 - 31 Dec 2021
Cited by 5 | Viewed by 1837
Abstract
Outbreaks of hepatitis A may occur in countries of medium and high socioeconomic levels in which the population generally exhibits an increased susceptibility in young adults to this infection if they are not vaccinated against the hepatitis A virus (HAV). In Europe, an [...] Read more.
Outbreaks of hepatitis A may occur in countries of medium and high socioeconomic levels in which the population generally exhibits an increased susceptibility in young adults to this infection if they are not vaccinated against the hepatitis A virus (HAV). In Europe, an outbreak involved approximately 22 European countries with 4475 cases reported from 2016 to 2018; most of them were men who have sex with men (MSM). This outbreak expanded to North and South America, including Brazil, particularly in São Paulo city with 1547 reported cases from 2016 to 2019. In the present study, we characterized the HAV strains involved in the acute hepatitis A cases identified in the reference centers of São Paulo city during this outbreak. A total of 51 cases with positive anti-HAV IgM were included, 80.4% male, 68.6% of them between 20 and 40 years old and 41.7% MSM. HAV RNA was detected in 92% (47/51) of the cases. Subgenotype IA of HAV was identified and most of the strains were closely related to that isolated in outbreaks that occurred in different European countries in 2016. These results showed the epidemiological relation between these outbreaks and reinforce the need to implement vaccination against hepatitis A for the adult population, particularly for a population with a high-risk behavior. Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)
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10 pages, 2243 KiB  
Article
Male-Dominant Hepatitis A Outbreak Observed among Non-HIV-Infected Persons in the Northern Part of Tokyo, Japan
by Masayuki Honda, Hiroyuki Asakura, Tatsuo Kanda, Yoshiko Somura, Tomotaka Ishii, Yoichiro Yamana, Tomohiro Kaneko, Taku Mizutani, Hiroshi Takahashi, Mariko Kumagawa, Reina Sasaki, Ryota Masuzaki, Shini Kanezawa, Kazushige Nirei, Hiroaki Yamagami, Naoki Matsumoto, Mami Nagashima, Takashi Chiba and Mitsuhiko Moriyama
Viruses 2021, 13(2), 207; https://doi.org/10.3390/v13020207 - 29 Jan 2021
Cited by 6 | Viewed by 2075
Abstract
Recently, we experienced an outbreak of acute hepatitis A virus (HAV) infection between 2018 and 2020. Herein, we describe this male-dominant HAV infection outbreak observed among non-human immunodeficiency virus (HIV)-infected persons in the northern part of Tokyo, Japan. Clinical information was collected from [...] Read more.
Recently, we experienced an outbreak of acute hepatitis A virus (HAV) infection between 2018 and 2020. Herein, we describe this male-dominant HAV infection outbreak observed among non-human immunodeficiency virus (HIV)-infected persons in the northern part of Tokyo, Japan. Clinical information was collected from patient interviews and from medical record descriptions. In the present study, 21 patients were retrospectively analyzed. A total of 90.4 and 33.3% of patients were males, and men who have sex with men (MSM), respectively. The total bilirubin levels and platelet counts tended to be lower in the MSM group than in the non-MSM group. C-reactive protein (CRP) levels tended to be higher in acute liver failure (ALF) patients than in non-ALF patients. Prolonged cholestasis was observed in one patient (4.8%). We also found that 18 HAV isolates belonged to HAV subgenotype IA/subgroup 13 (S13), which clustered with the HAV isolate (KX151459) that was derived from an outbreak of HAV infection among MSM in Taiwan in 2015. Our results suggest that the application of antivirals against HAV, as well as HAV vaccines, would be useful for the treatment and prevention of severe HAV infection. Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)
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12 pages, 1677 KiB  
Article
Hepatitis A Virus Strains Circulating in the Campania Region (2015–2018) Assessed through Bivalve Biomonitoring and Environmental Surveillance
by Giuseppina La Rosa, Pamela Mancini, Giusy Bonanno Ferraro, Marcello Iaconelli, Carolina Veneri, Rosa Paradiso, Dario De Medici, Teresa Vicenza, Yolande Therese Rose Proroga, Orlandina Di Maro, Anna Rita Ciccaglione, Roberto Bruni, Michele Equestre, Stefania Taffon, Angela Costantino, Maurizio Della Rotonda and Elisabetta Suffredini
Viruses 2021, 13(1), 16; https://doi.org/10.3390/v13010016 - 23 Dec 2020
Cited by 14 | Viewed by 3326
Abstract
The genetic diversity of Hepatitis A Virus (HAV) circulating in the Campania Region in years 2015–2018 was investigated through the monitoring of sentinel bivalve shellfish and water matrices. Overall, 463 water samples (71 sewage samples, 353 coastal discharge waters, and 39 seawaters samples), [...] Read more.
The genetic diversity of Hepatitis A Virus (HAV) circulating in the Campania Region in years 2015–2018 was investigated through the monitoring of sentinel bivalve shellfish and water matrices. Overall, 463 water samples (71 sewage samples, 353 coastal discharge waters, and 39 seawaters samples), and 746 bivalve shellfish samples were analyzed. Positivity for HAV was detected in 20/71 sewage samples, 14/353 coastal discharge waters, 5/39 seawaters, and 102/746 bivalve shellfish. Sixty-one of the positive samples were successfully sequenced and were characterized as genotype IA (n = 50) and IB (n = 11). The prevalent strain circulating in 2015 in both bivalves and waters was the IA strain responsible for the outbreak occurring around the same time in the Naples area. This variant was no longer identified in subsequent years (2017–2018) when, instead, appeared two of the IA variants of the multistate outbreak affecting men who have sex with men (MSM), VRD_521_2016, and RIVM-HAV16–090, with the former prevailing in both shellfish and water environments. HAV IB isolates were detected over the years in shellfish and in water matrices, but not in clinical samples, suggesting that this genotype had been circulating silently. An integrated surveillance system (environment/food/clinical cases) can be a useful tool to monitor changes in viral variants in the population, as well as an early warning system. Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)
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18 pages, 6506 KiB  
Article
Potentially Infectious Novel Hepatitis A Virus Strains Detected in Selected Treated Wastewater Discharge Sources, South Africa
by Saïd Rachida and Maureen Beatrice Taylor
Viruses 2020, 12(12), 1468; https://doi.org/10.3390/v12121468 - 19 Dec 2020
Cited by 12 | Viewed by 2726
Abstract
Hepatitis A virus (HAV) is a waterborne pathogen of public health importance. In South Africa (SA), unique HAV subgenotype IB strains have been detected in surface and wastewater samples, as well as on fresh produce at the point of retail. However, due to [...] Read more.
Hepatitis A virus (HAV) is a waterborne pathogen of public health importance. In South Africa (SA), unique HAV subgenotype IB strains have been detected in surface and wastewater samples, as well as on fresh produce at the point of retail. However, due to the use of molecular-based assays, the infectivity of the detected strains was unknown. Considering the potential shift of HAV endemicity from high to intermediate, which could increase the risk of severe symptomatic disease, this study investigated the identity of HAV strains detected before and after viability treatment of selected wastewater discharge samples. For one year, 118 samples consisting of sewage, treated wastewater discharge and downstream dam water were collected from five wastewater treatment plants (WWTP 1, 2, 3, 4 and 5). Unique HAV IB strains were detected in samples from all five WWTPs, with 11 of these strains carrying amino acid mutations at the immunodominant and neutralisation epitopes. A quasispecies dynamic of HAV has also been detected in sewage samples. The subsequent application of viability PCR revealed that potentially infectious HAV strains were discharged from WWTP 1, 2, 4 and 5 into the dam. Therefore, there is a potential risk of HAV exposure to communities using water sources downstream the WWTPs. Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)
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Review

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12 pages, 467 KiB  
Review
Hepatitis A: Epidemiology, High-Risk Groups, Prevention and Research on Antiviral Treatment
by Marion Migueres, Sébastien Lhomme and Jacques Izopet
Viruses 2021, 13(10), 1900; https://doi.org/10.3390/v13101900 - 22 Sep 2021
Cited by 56 | Viewed by 11893
Abstract
The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by ingesting contaminated water or food. The virus is endemic in low-income countries where sanitary [...] Read more.
The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by ingesting contaminated water or food. The virus is endemic in low-income countries where sanitary and sociodemographic conditions are poor. Paradoxically, improving sanitary conditions in these countries, which reduces the incidence of HAV infections, can lead to more severe disease in susceptible adults. The populations of developed countries are highly susceptible to HAV, and large outbreaks can occur when the virus is spread by globalization and by increased travel and movement of foodstuffs. Most of these outbreaks occur among high-risk groups: travellers, men who have sex with men, people who use substances, and people facing homelessness. Hepatitis A infections can be prevented by vaccination; safe and effective vaccines have been available for decades. Several countries have successfully introduced universal mass vaccination for children, but high-risk groups in high-income countries remain insufficiently protected. The development of HAV antivirals may be important to control HAV outbreaks in developed countries where a universal vaccination programme is not recommended. Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)
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9 pages, 611 KiB  
Review
Mechanisms of Hepatocellular Injury in Hepatitis A
by Minghang Wang and Zongdi Feng
Viruses 2021, 13(5), 861; https://doi.org/10.3390/v13050861 - 8 May 2021
Cited by 14 | Viewed by 7495
Abstract
Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that [...] Read more.
Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8+ T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection. Full article
(This article belongs to the Special Issue Recent Progress in Hepatitis A Virus Research)
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