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Viruses
Special Issues
Hepatitis Viral Infections, Pathogenesis and Therapeutics
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Hepatitis Viral Infections, Pathogenesis and Therapeutics

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (1 February 2025) | Viewed by 7987

Special Issue Editor

Prof. Dr. Fan Zhu

E-Mail Website
Guest Editor
State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China
Interests: pathogenesis of retrovirus

Special Issue Information

Dear Colleagues,

The understanding and treatment of hepatitis virus infections are rapidly advancing, fostering great optimism. Our Special Issue will address various aspects of hepatitis virus infections, including the following:

  • Epidemiology and transmission: Studies on the spread, control, risk factors, and prevention of HBV, HCV, HDV, HAV, and HEV.
  • Molecular and cellular biology: Research on viral life cycles, host–virus interactions, and pathogenesis mechanisms.
  • Immunology: Insights into immune responses, including innate and adaptive immunity, immune evasion, and vaccine development.
  • Clinical studies: Investigations into clinical features, disease progression, diagnosis, and management of hepatitis virus infections.
  • Therapeutics and vaccines: Development and evaluation of antiviral therapies, novel treatments, and preventive vaccines.
  • Liver disease and complications: Studies on the progression to cirrhosis, liver fibrosis, and hepatocellular carcinoma.
  • Public health and policy: Analyses of public health strategies, policy implications, and global health perspectives. 

We invite researchers and clinicians to submit original research articles, comprehensive reviews, and short communications.

Prof. Dr. Fan Zhu
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

  • hepatitis A virus (HAV)
  • hepatitis B virus (HBV)
  • hepatitis C virus (HCV)
  • hepatitis D virus (HDV)
  • hepatitis E virus (HEV)
  • chronic liver disease
  • chronic hepatitis
  • liver cirrhosis
  • hepatocellular carcinoma (HCC)
  • liver cancer
  • antiviral therapy

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

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Research

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11 pages, 1586 KiB  
Article
Plasma Interleukin-35 Levels Predict the Prognosis in Patients with HBV-Related Acute-on-Chronic Liver Failure
by Liujuan Ji, Xue Mei, Wei Yuan, Hongying Guo, Yuyi Zhang, Zhengguo Zhang, Ying Zou, Yu Liu, Hui Zhu, Zhiping Qian and Yinzhong Shen
Viruses 2024, 16(12), 1960; https://doi.org/10.3390/v16121960 - 20 Dec 2024
Cited by 1 | Viewed by 706
Abstract
This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional [...] Read more.
This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional infectious disease treatment center in China. Plasma levels of IL-35 at baseline were detected using ELISA. Plasma IL-35 levels in the HBV-ACLF group were the highest among all four groups. Furthermore, survivors exhibited significantly higher IL-35 levels than non-survivors (p < 0.001). IL-35 levels correlated with MELD (r = −0.678, p < 0.001), COSSH-ACLF IIs (r = −0.581, p < 0.001), alpha-fetoprotein (AFP) (r = 0.433, p < 0.001), creatinine (Cr) (r =−0.396, p = 0.001), and lactate (r =−0.38, p =0.001). The combination of plasma IL-35 and MELD score had the highest mortality prediction efficiency, with an area under the curve (AUC) of 0.895 (95% CI: 0.812–0.978, p < 0.001), a sensitivity of 80.6%, and a specificity of 93.9%. Additionally, the Kaplan–Meier analysis revealed that lower levels of IL-35 (≤191.5pg/mL) were associated with poorer survival rates in HBV-ACLF patients (p < 0.001). Our results demonstrated that IL-35 could be an effective predictive marker for the prognosis of HBV-ACLF and improve the predictive performance when combined with the MELD score. Full article
(This article belongs to the Special Issue Hepatitis Viral Infections, Pathogenesis and Therapeutics)
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14 pages, 3363 KiB  
Article
Activation-Induced Marker Assay to Identify and Isolate HCV-Specific T Cells for Single-Cell RNA-Seq Analysis
by Mohamed Eisa, Nicol Flores, Omar Khedr, Elsa Gomez-Escobar, Nathalie Bédard, Nourtan F. Abdeltawab, Julie Bruneau, Arash Grakoui and Naglaa H. Shoukry
Viruses 2024, 16(10), 1623; https://doi.org/10.3390/v16101623 - 17 Oct 2024
Viewed by 1761
Abstract
Identification and isolation of antigen-specific T cells for downstream transcriptomic analysis is key for various immunological studies. Traditional methods using major histocompatibility complex (MHC) multimers are limited by the number of predefined immunodominant epitopes and MHC matching of the study subjects. Activation-induced markers [...] Read more.
Identification and isolation of antigen-specific T cells for downstream transcriptomic analysis is key for various immunological studies. Traditional methods using major histocompatibility complex (MHC) multimers are limited by the number of predefined immunodominant epitopes and MHC matching of the study subjects. Activation-induced markers (AIM) enable highly sensitive detection of rare antigen-specific T cells irrespective of the availability of MHC multimers. Herein, we have developed an AIM assay for the detection, sorting and subsequent single-cell RNA sequencing (scRNA-seq) analysis of hepatitis C virus (HCV)-specific T cells. We examined different combinations of the activation markers CD69, CD40L, OX40, and 4-1BB at 6, 9, 18 and 24 h post stimulation with HCV peptide pools. AIM+ CD4 T cells exhibited upregulation of CD69 and CD40L as early as 6 h post-stimulation, while OX40 and 4-1BB expression was delayed until 18 h. AIM+ CD8 T cells were characterized by the coexpression of CD69 and 4-1BB at 18 h, while the expression of CD40L and OX40 remained low throughout the stimulation period. AIM+ CD4 and CD8 T cells were successfully sorted and processed for scRNA-seq analysis examining gene expression and T cell receptor (TCR) usage. scRNA-seq analysis from this one subject revealed that AIM+ CD4 T (CD69+ CD40L+) cells predominantly represented Tfh, Th1, and Th17 profiles, whereas AIM+ CD8 T (CD69+ 4-1BB+) cells primarily exhibited effector and effector memory profiles. TCR analysis identified 1023 and 160 unique clonotypes within AIM+ CD4 and CD8 T cells, respectively. In conclusion, this approach offers highly sensitive detection of HCV-specific T cells that can be applied for cohort studies, thus facilitating the identification of specific gene signatures associated with infection outcome and vaccination. Full article
(This article belongs to the Special Issue Hepatitis Viral Infections, Pathogenesis and Therapeutics)
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Review

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16 pages, 1524 KiB  
Review
Effect of Hepatitis E Virus on the Male Reproductive System: A Review of Current Evidence
by Ahmed A. Kotb, Mohamed A. El-Mokhtar and Ibrahim M. Sayed
Viruses 2025, 17(1), 66; https://doi.org/10.3390/v17010066 - 5 Jan 2025
Viewed by 901
Abstract
Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females. Several [...] Read more.
Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females. Several studies have investigated the impact of HEV on the male reproductive system; however, the available data are limited and conflicting. Assessment of the patients’ ejaculates/semen samples revealed that HEV particles are excreted in these fluids in cases of chronic infection but not acute infection. The excreted HEV particles are infectious to in vivo animal models and in vitro cell culture. However, the effect of HEV infection on male infertility is not confirmed. One study including human samples showed male infertility associated with HEV genotype 4 infection. Studies of HEV infection in animal models such as pigs, gerbils, and mice showed that HEV infection caused distortion on the testes, damage of the blood–testis barrier, and induction of inflammatory responses leading to abnormalities in the sperm. The excretion of HEV in the semen fluids raises concerns about HEV transmission via sexual transmission. However, all available data do not confirm the transmission of HEV through sexual intercourse. This review aims to summarize and critically assess the available studies investigating the influence of different HEV genotypes on the male reproductive system, providing insights into whether HEV contributes to reproductive impairment in men. Full article
(This article belongs to the Special Issue Hepatitis Viral Infections, Pathogenesis and Therapeutics)
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18 pages, 1481 KiB  
Review
Hepatitis B Viral Protein HBx: Roles in Viral Replication and Hepatocarcinogenesis
by Dong Li, Yassir Hamadalnil and Thomas Tu
Viruses 2024, 16(9), 1361; https://doi.org/10.3390/v16091361 - 26 Aug 2024
Cited by 4 | Viewed by 2693
Abstract
Hepatitis B virus (HBV) infection remains a major public health concern worldwide, with approximately 296 million individuals chronically infected. The HBV-encoded X protein (HBx) is a regulatory protein of 17 kDa, reportedly responsible for a broad range of functions, including viral replication and [...] Read more.
Hepatitis B virus (HBV) infection remains a major public health concern worldwide, with approximately 296 million individuals chronically infected. The HBV-encoded X protein (HBx) is a regulatory protein of 17 kDa, reportedly responsible for a broad range of functions, including viral replication and oncogenic processes. In this review, we summarize the state of knowledge on the mechanisms underlying HBx functions in viral replication, the antiviral effect of therapeutics directed against HBx, and the role of HBx in liver cancer development (including a hypothetical model of hepatocarcinogenesis). We conclude by highlighting major unanswered questions in the field and the implications of their answers. Full article
(This article belongs to the Special Issue Hepatitis Viral Infections, Pathogenesis and Therapeutics)
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Other

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7 pages, 631 KiB  
Brief Report
Hazardous Alcohol Use and Its Effect on Direct-Acting Antiviral Therapy Initiation among People with Active Injection Drug Use and Current Hepatitis C Infection
by Hamidreza Karimi-Sari, Gregory M. Lucas, Katie Zook, Brian Weir, Miles Landry, Susan G. Sherman, Kathleen R. Page and Oluwaseun Falade-Nwulia
Viruses 2024, 16(9), 1416; https://doi.org/10.3390/v16091416 - 5 Sep 2024
Viewed by 928
Abstract
Background: Hepatitis C virus (HCV) infection and hazardous alcohol use are both preventable causes of morbidity and mortality among people who inject drugs (PWID). In the general population, hazardous alcohol is associated with a reduced likelihood of HCV treatment initiation. Less is known [...] Read more.
Background: Hepatitis C virus (HCV) infection and hazardous alcohol use are both preventable causes of morbidity and mortality among people who inject drugs (PWID). In the general population, hazardous alcohol is associated with a reduced likelihood of HCV treatment initiation. Less is known about the prevalence and impact of hazardous alcohol use on direct-acting antiviral (DAA) therapy initiation among PWID with active injection drug use. Methods: PWID were recruited via street outreach in Baltimore, Maryland, between 2018 and 2019 and were enrolled in a study cohort. Participants completed a study survey and underwent HCV testing. Self-reported DAA therapy initiation was evaluated at follow-up visits every six months. Hazardous alcohol use was determined based on an AUDIT-C score of ≥4 for men or ≥3 for women. Data were analyzed using multivariable logistic regression with generalized estimating equations. Results: Of the 720 PWID recruited, 291 had detectable HCV RNA, and only 134 were aware of their HCV infection. The mean (±standard deviation) age of those that were aware of their infection was 48.7 (±10.3) years, with a slight majority (53.0%) being male and predominantly African American (64.9%). The majority (80/134, 59.7%) met criteria for hazardous alcohol use. Only 16 (11.9%) PWID reported DAA therapy initiation within six months, and 20 (14.9%) reported it within 12 months of follow-up. Hazardous alcohol use (aOR = 1.23, 95% CI = 0.43–3.53) was not associated with DAA treatment initiation. Conclusions: There was a high prevalence of hazardous alcohol use, low rates of oral DAA therapy initiation, and no association between self-reported hazardous alcohol use and initiation of oral DAA therapy in our sample of PWID that were aware of their chronic HCV infection. Strategies to increase HCV treatment uptake in PWID with active drug use are urgently needed and should integrate alcohol and drug use evaluation and care. Full article
(This article belongs to the Special Issue Hepatitis Viral Infections, Pathogenesis and Therapeutics)
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