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Pathogens
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Global Elimination of Viral Hepatitis
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Global Elimination of Viral Hepatitis

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

Deadline for manuscript submissions: closed (1 December 2021) | Viewed by 28939

Special Issue Editors

Dr. Mahmoud Reza Pourkarim

E-Mail Website
Guest Editor
Laboratory for Clinical and Epidemiological Virology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
Interests: hepatitis B virus; blood virome; emerging infectious diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Heidar Sharafi

E-Mail Website
Co-Guest Editor
Middle East Liver Diseases (MELD) Center, Tehran, Iran
Interests: hepatology; viral hepatitis; clinical laboratory science; fatty liver; hepatitis B; liver diseases; molecular diagnostics; chronic hepatitis C; chronic hepatitis B; hepatitis

Special Issue Information

Dear colleagues,

Five unrelated hepatotropic viruses are the cause of viral hepatitis, which is a major concern of global public health. Hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), and hepatitis E viruses (HEV) are different causes for acute and chronic types of hepatitis that can lead to life-threatening complications such as cirrhosis and hepatocellular carcinoma (HCC). Different strains of these viruses have distinct geographical distributions, with almost 600 million carriers worldwide. The annual mortality rate of viral hepatitis is around 1.5 million individuals, of which the majority are related to HBV and HCV infections. Relying on advanced diagnostic techniques and strategies for blood screening together with the availability of efficient vaccine and effective antiviral treatment for HBV and HCV, respectively, WHO has implemented a global elimination program in 2016 to end it in 2030. The success of this program depends on the improvement of our insight into the epidemiology, diagnosis, treatment, and prophylactic countermeasures of viral hepatitis. An update of these crucial topics could be achieved in a Special Issue of Pathogens.

In the form of a Special Issue, we aim to provide a collection of the most recent top research articles, comprehensive reviews, as well as short communications in line with viral hepatitis. Through this Special Issue, we are pinpointing the current situation and future perspectives of the viral hepatitis elimination program.

I am looking forward to your valuable involvement in this interesting Issue.

Dr. MahmoudReza Pourkarim
Dr. Heidar Sharafi
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
  • Elimination
  • Epidemiology
  • Therapy
  • Diagnostic
  • Virology
  • Clinical outcome

Published Papers (9 papers)

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Editorial

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3 pages, 197 KiB  
Editorial
World Hepatitis Day in 2022: Challenges of Viral Hepatitis Elimination in Elongated COVID-19 Pandemic
by Mahmoud Reza Pourkarim
Pathogens 2022, 11(9), 1002; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11091002 - 01 Sep 2022
Cited by 1 | Viewed by 1103
Abstract
Recently, the World Hepatitis Day (WHD) of 2022 was observed to raise awareness of the global burden of viral hepatitis [...] Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)

Research

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16 pages, 551 KiB  
Article
Enduring Challenges despite Progress in Preventing Mother-to-Child Transmission of Hepatitis B Virus in Angola
by Luis Baião Peliganga, Marco Aurélio Pereira Horta and Lia Laura Lewis-Ximenez
Pathogens 2022, 11(2), 225; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11020225 - 08 Feb 2022
Cited by 1 | Viewed by 1776
Abstract
Sub-Saharan Africa has one of the highest rates of hepatitis B virus (HBV) infection globally, with an incidence of 1.5 million and 0.8 million yearly deaths, which drives synergistic efforts towards its elimination. To assess the risk of mother-to-child transmission of HBV infection, [...] Read more.
Sub-Saharan Africa has one of the highest rates of hepatitis B virus (HBV) infection globally, with an incidence of 1.5 million and 0.8 million yearly deaths, which drives synergistic efforts towards its elimination. To assess the risk of mother-to-child transmission of HBV infection, a cross-sectional study was conducted on 1012 pregnant women in Angola to investigate HBV serological and molecular profiles. The prevalence of HBV was 8.7% (n = 88), with hepatitis B core IgM antibody (anti-HBc IgM) positivity identified in 12.8%, hepatitis B “e” antigen (HBeAg) positivity in 30%, and HBV DNA ≥ 200,000 IU/mL in 28.2%. Family tracking studied 44 children, of which 11 (25%) received at least two doses of the hepatitis B vaccine. HBV was detected in 10/44 (22.7%) children, with vaccination reported in one infected child. Further testing identified anti-HBc IgM positivity in 3/10 (30%), HBeAg positivity in 55%, and both seromarkers in 20%. The results revealed the importance of antenatal HBV screening, antiviral prophylaxis for mothers with high viral loads or HBeAg positivity, and timely first-dose hepatitis B vaccines in newborns. Anti-HBc IgM positivity among pregnant women and children highlights prophylactic measures worth considering, including antenatal hepatitis B vaccination and catch-up vaccination to young children. Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
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12 pages, 267 KiB  
Article
Prevalence of Hepatitis B and Hepatitis C Infections among Incarcerated Individuals in Iran: A Cross-Sectional National Bio-behavioral Study in 2019
by Ghobad Moradi, Seyed Moayed Alavian, Fatemeh Gholami, Rashid Ramezani, Leila Ahangarzadeh, Yousef Moradi and Heidar Sharafi
Pathogens 2021, 10(11), 1522; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111522 - 21 Nov 2021
Cited by 3 | Viewed by 2446
Abstract
Introduction: To realize the global goals of eliminating hepatitis B virus (HBV) and hepatitis C virus (HCV) by 2030, it is necessary to monitor the status of disease among target populations and undertake the required interventions. This study is the third round of [...] Read more.
Introduction: To realize the global goals of eliminating hepatitis B virus (HBV) and hepatitis C virus (HCV) by 2030, it is necessary to monitor the status of disease among target populations and undertake the required interventions. This study is the third round of surveys to determine the prevalence of hepatitis B and C infections among incarcerated individuals in different provinces of Iran. Methods: This study was conducted in five provinces of Iran (including Kurdistan, Ardabil, West Azerbaijan, Markazi, and Semnan) in 2019. The subjects of the study were selected from incarcerated people in prisons of all provinces that had not been studied in the previous two rounds of the surveys (in 2015 and 2016) in Iran. In this study, 15 prisons were selected and 2475 incarcerated individuals were enrolled into the study based on the multistage sampling method; the selected subjects were surveyed and their dried blood spot (DBS) samples were collected to test HBsAg and HCV-Ab. In cases with a reactive result for HCV-Ab, an HCV-RNA test was also performed on their serum samples. The relationships between independent variables and outcomes were evaluated via logistic regression. Results: Of all participants (2475 subjects) enrolled in the study, 54.18% were selected from northern provinces and 45.82% from the central provinces. The prevalence of HCV-Ab and HBsAg among incarcerated individuals was 5.66% (95% CI: 4.81% to 6.64%) and 2.42% (95% CI: 1.89% to 3.11%), respectively. Among HCV-seropositive individuals, 73.68% (95% CI: 64.70% to 81.01%) had current HCV infection (detectable HCV-RNA). The results showed that histories of imprisonment, drug use, unprotected sexual contact, drug injection, tattooing, and younger age in the first-time drug use in incarcerated individuals significantly increased the risk of HCV transmission. Among these behaviors, drug injection was more likely than other behaviors to result in contracting HCV in incarcerated individuals (OR: 22.91; 95% CI: 14.92–35.18; p < 0.001). Conclusion: To achieve international and national strategies targeted to eliminate HCV and HBV by 2030, it is necessary to pay special attention to prisons in Iran. It is recommended to continue HBV vaccination of eligible people in prisons. Developing screening and treatment protocols for individuals with HCV infection in prisons can help the country to achieve HCV elimination goals. Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
19 pages, 2953 KiB  
Article
Variable Proportions of Phylogenetic Clustering and Low Levels of Antiviral Drug Resistance among the Major HBV Sub-Genotypes in the Middle East and North Africa
by Rabaa Y. Athamneh, Ayşe Arıkan, Murat Sayan, Azmi Mahafzah and Malik Sallam
Pathogens 2021, 10(10), 1333; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101333 - 15 Oct 2021
Cited by 4 | Viewed by 3429
Abstract
Hepatitis B virus (HBV) infection remains a major public health threat in the Middle East and North Africa (MENA). Phylogenetic analysis of HBV can be helpful to study the putative transmission links and patterns of inter-country spread of the virus. The objectives of [...] Read more.
Hepatitis B virus (HBV) infection remains a major public health threat in the Middle East and North Africa (MENA). Phylogenetic analysis of HBV can be helpful to study the putative transmission links and patterns of inter-country spread of the virus. The objectives of the current study were to analyze the HBV genotype/sub-genotype (SGT) distribution, reverse transcriptase (RT), and surface (S) gene mutations and to investigate the domestic transmission of HBV in the MENA. All HBV molecular sequences collected in the MENA were retrieved from GenBank as of 30 April 2021. Determination of genotypes/SGT, RT, and S mutations were based on the Geno2pheno (hbv) 2.0 online tool. For the most prevalent HBV SGTs, maximum likelihood phylogenetic analysis was conducted to identify the putative phylogenetic clusters, with approximate Shimodaira–Hasegawa-like likelihood ratio test values ≥ 0.90, and genetic distance cut-off values ≤ 0.025 substitutions/site as implemented in Cluster Picker. The total number of HBV sequences used for genotype/SGT determination was 4352 that represented a total of 20 MENA countries, with a majority from Iran (n = 2103, 48.3%), Saudi Arabia (n = 503, 11.6%), Tunisia (n = 395, 9.1%), and Turkey (n = 267, 6.1%). Genotype D dominated infections in the MENA (86.6%), followed by genotype A (4.1%), with SGT D1 as the most common in 14 MENA countries and SGT D7 dominance in the Maghreb. The highest prevalence of antiviral drug resistance was observed against lamivudine (4.5%) and telbivudine (4.3%). The proportion of domestic phylogenetic clustering was the highest for SGT D7 (61.9%), followed by SGT D2 (28.2%) and genotype E (25.7%). The largest fraction of domestic clusters with evidence of inter-country spread within the MENA was seen in SGT D7 (81.3%). Small networks (containing 3-14 sequences) dominated among domestic phylogenetic clusters. Specific patterns of HBV genetic diversity were seen in the MENA with SGT D1 dominance in the Levant, Iran, and Turkey; SGT D7 dominance in the Maghreb; and extensive diversity in Saudi Arabia and Egypt. A low prevalence of lamivudine, telbivudine, and entecavir drug resistance was observed in the region, with almost an absence of resistance to tenofovir and adefovir. Variable proportions of phylogenetic clustering indicated prominent domestic transmission of SGT D7 (particularly in the Maghreb) and relatively high levels of virus mobility in SGT D1. Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
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13 pages, 1440 KiB  
Article
Tracking the Epidemiologic Shifts in Hepatitis A Sero-Prevalence Using Age Stratification: A Cross-Sectional Study at Jordan University Hospital
by Nariman Kareem, Khaled Al-Salahat, Faris G. Bakri, Yaser Rayyan, Azmi Mahafzah and Malik Sallam
Pathogens 2021, 10(9), 1081; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091081 - 26 Aug 2021
Cited by 1 | Viewed by 4107
Abstract
The study of hepatitis A virus (HAV) epidemiology and sero-prevalence has important public health implications. Changes in the epidemiology of hepatitis A can result in a larger pool of susceptible persons in countries with improved sanitation and hygienic conditions if vaccination is not [...] Read more.
The study of hepatitis A virus (HAV) epidemiology and sero-prevalence has important public health implications. Changes in the epidemiology of hepatitis A can result in a larger pool of susceptible persons in countries with improved sanitation and hygienic conditions if vaccination is not provided. The aim of this study was to investigate the prevalence of HAV immunoglobulin G (IgG) in Jordan. In addition, we aimed to identify the potential differences in HAV sero-prevalence based on age, among other variables. We recruited the study participants at Jordan University Hospital in Amman, Jordan, during October 2020–June 2021. Assessment of participants’ socio-demographic variables was done using a paper-based questionnaire. Testing for HAV IgG was based on a competitive enzyme linked immunosorbent assay (ELISA). The study population comprised 360 individuals with a median age of 18 years. The overall sero-prevalence of HAV in our study sample was 38.3%. Divided by age, the sero-prevalence of HAV was 8.2%, 12.3%, and 20.8% among individuals aged 10 years or less, 15 years or less, and 30 years or less, respectively. The estimated age at mid-population immunity was between 21 and 30 years. Besides age, individuals residing outside the Central region of Jordan had a significantly higher HAV sero-prevalence. Additionally, the use of filtered municipal water was associated with a lower sero-prevalence of HAV compared with the use of unfiltered municipal water among individuals aged 15 years or less. The results of this study suggest an intermediate to low endemicity of HAV in Jordan. An epidemiologic shift of HAV sero-prevalence with a declining rate of positivity for HAV IgG was noticed in this study. This highlights the importance of the recently introduced HAV vaccination in Jordan. Future research to evaluate the public health benefits of HAV vaccination in Jordan is recommended. Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
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13 pages, 2699 KiB  
Article
Pharmacotherapy Profiles in People with Opioid Use Disorders: Considerations for Relevant Drug–Drug Interactions with Antiviral Treatments for Hepatitis C
by Andreas Hintz, Tim Umland, Gero Niess, Mehtap Guendogdu, Anika Moerner and Frank Tacke
Pathogens 2021, 10(6), 648; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10060648 - 24 May 2021
Cited by 1 | Viewed by 2746
Abstract
People who inject drugs (PWID) are often affected by physical and psychological diseases and prone to co-medication. In Germany, about 50% of PWID are on opioid substitution therapy (OST). Comprehensive data on pharmacotherapy in these patients may help to select antiviral therapy against [...] Read more.
People who inject drugs (PWID) are often affected by physical and psychological diseases and prone to co-medication. In Germany, about 50% of PWID are on opioid substitution therapy (OST). Comprehensive data on pharmacotherapy in these patients may help to select antiviral therapy against hepatitis C virus (HCV) infections and avoid drug–drug interactions (DDIs). We compared co-medication profiles based on statutory health insurance prescriptions (IQVIA database) of PWID (n = 16,693), OST (n = 95,023) and treated HCV patients (n = 7886). Potential DDIs with the most widely used HCV direct-acting agents (Sofosbuvir/Velpatasvir, Glecaprevir/Pibrentasvir and Elbasvir/Grazoprevir) were evaluated based on the Liverpool DDI database. Co-medication was present in 57% of PWID, 57% of OST, 44% of patients on HCV therapy and 46% in a subgroup receiving OST+HCV therapy (n = 747 of 1613). For all groups, co-medication belonging to ATC-class N (nervous system) was most commonly prescribed (in 75%, 68%, 41% and 62% of patients, respectively). Contraindications (i.e., DDIs precluding HCV therapy) were infrequent (0.4–2.5% of co-medications); potential DDIs with HCV therapies were shown for 13–19% of co-medications, namely for specific substances including some analgesics, antipsychotics, anticoagulants, lipid lowering drugs and steroids. In conclusion, concomitant pharmacotherapy is common and clinically relevant when treating HCV infection in PWID. Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
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13 pages, 1620 KiB  
Article
Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells
by Mohamed A. El-Mokhtar, Essam R. Othman, Maha Y. Khashbah, Ali Ismael, Mohamed AA Ghaliony, Mohamed Ismail Seddik and Ibrahim M. Sayed
Pathogens 2020, 9(4), 295; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040295 - 17 Apr 2020
Cited by 26 | Viewed by 2846
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found [...] Read more.
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission. Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
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Review

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22 pages, 816 KiB  
Review
Digital Marketing: A Unique Multidisciplinary Approach towards the Elimination of Viral Hepatitis
by Mohammadreza Pourkarim, Shahnaz Nayebzadeh, Seyed Moayed Alavian and Seyyed Hassan Hataminasab
Pathogens 2022, 11(6), 626; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11060626 - 29 May 2022
Cited by 8 | Viewed by 4020
Abstract
New technologies are supported by the global implementation of the internet. These improvements have deeply affected various disciplines of sciences and consequently changed services such as daily business, particularly health sectors. Innovative digital marketing strategies utilize the channels of social media and retrieved [...] Read more.
New technologies are supported by the global implementation of the internet. These improvements have deeply affected various disciplines of sciences and consequently changed services such as daily business, particularly health sectors. Innovative digital marketing strategies utilize the channels of social media and retrieved user data to analyze and improve relevant services. These multidisciplinary innovations can assist specialists, physicians and researchers in diagnostic, prophylaxis and treatment issues in the health sector. Accordingly, compared to recent decades, health decision makers are more accurate and trustful in defining new strategies. Interestingly, using social media and mobile health apps in current pandemics of SARS-CoV-2 could be an important instance of the key role of these platforms at the local and global level of health policies. These digital technologies provide platforms to connect public health sectors and health politicians for communicating and spreading relevant information. Adding influencers and campaigns to this toolbox strengthens the implementation of public health programs. In 2016, the WHO adopted a global program to eliminate viral hepatitis by 2030. Recent constructive measures that have been used in the battle against COVID-19 could be adopted for the elimination of viral hepatitis program. The presented evidence in our narrative review demonstrates that the application of digital marketing tools to create campaigns on social media, armed with professional influencers, can efficiently consolidate this program. The application of different strategies in using these popular tools will raise the public awareness about viral hepatitis. Subsequently, the availability of an effective vaccine for HBV and antiviral medication for HCV can motivate the audience to take steps towards prophylaxis and screening methods against these infectious illnesses. The encouragement of health policy makers to apply digital communication technologies and comprehensive roadmaps to implement this global program will certainly decrease the burden of viral hepatitis worldwide. Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
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26 pages, 817 KiB  
Review
Systematic Review and Meta-Analysis of Global Prevalence of HBsAg and HIV and HCV Antibodies among People Who Inject Drugs and Female Sex Workers
by Roya Rashti, Heidar Sharafi, Seyed Moayed Alavian, Yousef Moradi, Amjad Mohamadi Bolbanabad and Ghobad Moradi
Pathogens 2020, 9(6), 432; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060432 - 31 May 2020
Cited by 23 | Viewed by 5167
Abstract
The main objective of this study was to evaluate the prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C virus (HCV) and hepatitis B virus (HBV) and their co-infections among people who inject drugs (PWID) and female sex workers (FSWs). Data sources [...] Read more.
The main objective of this study was to evaluate the prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C virus (HCV) and hepatitis B virus (HBV) and their co-infections among people who inject drugs (PWID) and female sex workers (FSWs). Data sources were searched from January 2008 to October 2018 in different databases. Data were analyzed in Stata 16 software using the Metaprop command. The results showed that the prevalence of HIV, HCV and HBV among PWID was 15%, 60% and 6%, respectively. The prevalence of HIV, HCV and HBV among FSWs was 5%, 1% and 3%, respectively. The prevalence of HIV/HCV, HIV/HBV, HCV/HBV and HIV/HCV/HBV co-infections among PWID was 13%, 2%, 3% and 2%, respectively. The prevalence of HIV/HCV and HIV/HBV co-infections among FSWs was 3% and 1%, respectively. The results show that the prevalence of HCV and HIV infections in PWID and the prevalence of HIV in FSWs is higher than their prevalence in the general population. Interventions for the prevention of HIV and HCV in PWID appear to be poor, and may not be sufficient to effectively prevent HIV and HCV transmission. Full article
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
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