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Viruses
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Hepatitis B Virus Research in Italy: From Epidemiology to Treatment
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Hepatitis B Virus Research in Italy: From Epidemiology to Treatment

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 44398

Special Issue Editor

Dr. Tommaso Stroffolini

E-Mail Website
Guest Editor
Azienda Policlinico Umberto, Rome, Italy
Interests: epidemiology; natural history; treatment of acute and chronic hepatitis virus infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

More than fifty years since the discovery of the Australian antigen, hepatitis B virus (HBV) infection still represents a continuous challenge. Vaccination against HBV has represented a milestone for the control of this devastating disease, and there is optimism for new effective drugs for the treatment of hepatitis B.

This Special Issue titled “Hepatitis B virus research in Italy: from epidemiology to treatment” will include a range of invited articles from Italian researchers. Italy was the first country to adopt a peculiar model of HB vaccination policy (the combined immunization for 3-month-old infants and for 12-year-old children, limited to the first 12 years of the campaign for the latter category), which has nearly eliminated the acute infection. Moreover, important insights have been provided from Italian researchers on the epidemiology, prevention, natural history, diagnostics, and treatment of HBV infection.

Articles in this Issue will deal with these topics with the collaboration of Italian researchers who have greatly improved the worldwide knowledge regarding HBV infection. Finally, an article will deal with major negative side effect of the existence of HBsAg (i.e., the defective RNA hepatitis delta virus (HDV)), first discovered in Italy in the second half of the 1970s by Rizzetto et al. (Gut.1977;18:997-1003).

Dr. Tommaso Stroffolini
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 B virus
  • hepatitis B
  • hepatitis B chronic hepatitis
  • hepatocellular carcinoma

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Published Papers (8 papers)

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Research

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11 pages, 674 KiB  
Article
Effectiveness of Hepatitis B Vaccination Campaign in Italy: Towards the Control of HBV Infection for the First Time in a European Country
by Tommaso Stroffolini, Filomena Morisco, Luigina Ferrigno, Giuseppina Pontillo, Giuseppina Iantosca, Valentina Cossiga, Simonetta Crateri, Maria Elena Tosti and the SEIEVA Collaborating Group
Viruses 2022, 14(2), 245; https://doi.org/10.3390/v14020245 - 26 Jan 2022
Cited by 11 | Viewed by 2985
Abstract
Background: In 1991, a mass immunization campaign against the hepatitis B virus (HBV) for children and teenagers was introduced in Italy. This study evaluated the impact of the immunization campaign on the incidence and modes of HBV transmission. Method: Acute HBV cases of [...] Read more.
Background: In 1991, a mass immunization campaign against the hepatitis B virus (HBV) for children and teenagers was introduced in Italy. This study evaluated the impact of the immunization campaign on the incidence and modes of HBV transmission. Method: Acute HBV cases of viral hepatitis were reported to the National Surveillance System (SEIEVA). Hepatitis A cases reported to the same system were used as controls to calculate the adjusted odds ratios and the population attributable risk for potential risk factors. Results: The incidence of acute HBV declined from 5.0 in 1990 to 0.4 in 2019 per 100,000 population. The fall was almost total in people targeted by the campaign: in 2019, zero cases (100% reduction) in the age-group 0–14 years and 0.1 cases per 100,000 population (99.4% reduction) in the age-group 15–24 years were reported. In the decade 2010–2019, nearly one-fifth (19.3%) of cases occurred in foreigners. Intravenous drug use is no longer a risk factor (OR = 0.7; 95% CI = 0.5–1.02). Beauty treatments, risky sexual exposure, and household contact with an HBsAg carrier were found to be independent predictors of acute hepatitis B. Conclusions: The HB vaccination campaign proved effective in minimising acute HBV in Italy. Control of the infection is close to being reached for the first time in Europe. Full article
(This article belongs to the Special Issue Hepatitis B Virus Research in Italy: From Epidemiology to Treatment)
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Review

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12 pages, 1196 KiB  
Review
Towards a Functional Cure for Hepatitis B Virus: A 2022 Update on New Antiviral Strategies
by Elisabetta Degasperi, Maria Paola Anolli and Pietro Lampertico
Viruses 2022, 14(11), 2404; https://doi.org/10.3390/v14112404 - 29 Oct 2022
Cited by 13 | Viewed by 4560
Abstract
Chronic infection with hepatitis B virus (HBV) represents one of the main causes of the development of cirrhosis and its complications. Treatment with potent third-generation nucleos(t)ide analogues (NUCs) results in >99% HBV DNA undetectability, and prevents fibrosis progression and liver-related complications. However, NUCs [...] Read more.
Chronic infection with hepatitis B virus (HBV) represents one of the main causes of the development of cirrhosis and its complications. Treatment with potent third-generation nucleos(t)ide analogues (NUCs) results in >99% HBV DNA undetectability, and prevents fibrosis progression and liver-related complications. However, NUCs are not able to induce the so-called functional cure, which is hepatitis B surface antigen (HBsAg) loss and anti-HBs seroconversion. Consequently, NUC treatment is currently intended as being long-term or lifelong, resulting in the need for clinical monitoring and potentially suffering from compliance issues. Consequently, drug development in HBV has the goal of developing new agents in order to achieve a functional cure for HBV. Currently, the three main strategies include the following: inhibition of viral replication, inhibition of viral antigens, and immune modulation. This review summarizes the most recent updates concerning HBV compounds among these three main classes. Full article
(This article belongs to the Special Issue Hepatitis B Virus Research in Italy: From Epidemiology to Treatment)
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8 pages, 437 KiB  
Review
Management of Chronic Hepatitis B in HIV-Coinfected Patients
by Massimo Fasano, Maria Cristina Poliseno, Josè Ramon Fiore, Sergio Lo Caputo, Antonella D’Arminio Monforte and Teresa Antonia Santantonio
Viruses 2022, 14(9), 2022; https://doi.org/10.3390/v14092022 - 13 Sep 2022
Cited by 6 | Viewed by 4143
Abstract
Hepatitis B virus infection occurs in approximately 7% of people living with HIV (PLWH), with substantial regional variation and higher prevalence among intravenous drug users. Early studies on the natural history of HIV/HBV coinfection demonstrated that in coinfected patients, chronic hepatitis B (CHB) [...] Read more.
Hepatitis B virus infection occurs in approximately 7% of people living with HIV (PLWH), with substantial regional variation and higher prevalence among intravenous drug users. Early studies on the natural history of HIV/HBV coinfection demonstrated that in coinfected patients, chronic hepatitis B (CHB) has a more rapid progression than in HBV-monoinfected patients, leading to end-stage liver disease complications, including hepatocellular carcinoma. Therefore, the adequate management of CHB is considered a priority in HIV-coinfected patients. Several guidelines have highlighted this issue and have provided recommendations for preventing and treating HBV infection. This article discusses the management of liver disease in patients with HIV/HBV coinfection and summarizes the current and future therapeutic options for treating chronic hepatitis B in this setting. Full article
(This article belongs to the Special Issue Hepatitis B Virus Research in Italy: From Epidemiology to Treatment)
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13 pages, 2120 KiB  
Review
A Review of HDV Infection
by Gian Paolo Caviglia, Alessia Ciancio and Mario Rizzetto
Viruses 2022, 14(8), 1749; https://doi.org/10.3390/v14081749 - 10 Aug 2022
Cited by 26 | Viewed by 4271
Abstract
Hepatitis D is the most severe viral hepatitis. Hepatitis D virus (HDV) has a very small RNA genome with unique biological properties. It requires for infection the presence of hepatitis B virus (HBV) and is transmitted parenterally, mainly by superinfection of HBsAg carriers [...] Read more.
Hepatitis D is the most severe viral hepatitis. Hepatitis D virus (HDV) has a very small RNA genome with unique biological properties. It requires for infection the presence of hepatitis B virus (HBV) and is transmitted parenterally, mainly by superinfection of HBsAg carriers who then develop chronic hepatitis D. HDV has been brought under control in high-income countries by the implementation of HBV vaccination, and the clinical pattern has changed to a chronic hepatitis D seen in ageing patients with advanced fibrotic disease; the disease remains a major health concern in developing countries of Africa and Asia. Every HBsAg-positive subject should be tested for HDV serum markers by reflex testing, independently of clinical status. Vaccination against HBV provides the best prophylaxis against hepatitis D. The only therapy available so far has been the poorly performing Interferon alfa; however, several new and promising therapeutic approaches are under study. Full article
(This article belongs to the Special Issue Hepatitis B Virus Research in Italy: From Epidemiology to Treatment)
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12 pages, 1970 KiB  
Review
HBeAg-Negative/Anti-HBe-Positive Chronic Hepatitis B: A 40-Year-Old History
by Ferruccio Bonino, Piero Colombatto and Maurizia R. Brunetto
Viruses 2022, 14(8), 1691; https://doi.org/10.3390/v14081691 - 30 Jul 2022
Cited by 9 | Viewed by 4711
Abstract
Hepatitis B “e” antigen (HBeAg) negative chronic hepatitis B (CHB), 40 years since discovery in the Mediterranean area, has become the most prevalent form of HBV-induced liver disease worldwide and a major health care burden caused by HBV infection. A great deal of [...] Read more.
Hepatitis B “e” antigen (HBeAg) negative chronic hepatitis B (CHB), 40 years since discovery in the Mediterranean area, has become the most prevalent form of HBV-induced liver disease worldwide and a major health care burden caused by HBV infection. A great deal of knowledge accumulated over the last decades provides consistent evidence on the bimodal dynamics of the expression of structural and non-structural forms of the viral core proteins which associate with different virologic and clinic–pathologic outcomes of HBV infection. In absence of serum HBeAg, the presence and persistence of HBV replication causes and maintains virus-related liver injury. Thus, in clinical practice it is mandatory to screen HBV carriers with HBeAg-negative infection for the early diagnosis of HBeAg-negative CHB since antiviral therapy can cure HBV-induced liver disease when started at early stages. Full article
(This article belongs to the Special Issue Hepatitis B Virus Research in Italy: From Epidemiology to Treatment)
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13 pages, 982 KiB  
Review
Hepatitis B Vaccination: A Historical Overview with a Focus on the Italian Achievements
by Luisa Romano’ and Alessandro R. Zanetti
Viruses 2022, 14(7), 1515; https://doi.org/10.3390/v14071515 - 11 Jul 2022
Cited by 23 | Viewed by 4469
Abstract
Vaccination is the most effective way to control and prevent acute and chronic hepatitis B, including cirrhosis and HCC, on a global scale. According to WHO recommendations, 190 countries in the world have introduced hepatitis B vaccination into their national childhood immunization programs [...] Read more.
Vaccination is the most effective way to control and prevent acute and chronic hepatitis B, including cirrhosis and HCC, on a global scale. According to WHO recommendations, 190 countries in the world have introduced hepatitis B vaccination into their national childhood immunization programs with an excellent profile of safety, immunogenicity, and effectiveness. Following vaccination, seroprotection rates are close to 100% in healthy children and over 95% in healthy adults. Persistence of anti-HBs is related to the antibody peak achieved after vaccination. The peak is higher the longer the antibody duration is. Loss of anti-HBs does not necessarily mean loss of immunity since most vaccinated individuals retain immune memory for HBsAg and rapidly develop strong anamnestic responses when boosted. Evidence indicates that the duration of protection can persist for at least 35 years after priming. Hence, booster doses of vaccines are currently not recommended to sustain long-term immunity in healthy vaccinated individuals. In Italy, vaccination against hepatitis B is met with success. In 2020, Italy became one of the first countries in Europe to be validated for achieving the WHO regional hepatitis B control targets. Full article
(This article belongs to the Special Issue Hepatitis B Virus Research in Italy: From Epidemiology to Treatment)
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16 pages, 579 KiB  
Review
Occult Hepatitis B Virus Infection: An Update
by Carlo Saitta, Teresa Pollicino and Giovanni Raimondo
Viruses 2022, 14(7), 1504; https://doi.org/10.3390/v14071504 - 8 Jul 2022
Cited by 53 | Viewed by 8228
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar [...] Read more.
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host’s immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the “overt” infection, favoring the development of hepatocellular carcinoma. Full article
(This article belongs to the Special Issue Hepatitis B Virus Research in Italy: From Epidemiology to Treatment)
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25 pages, 711 KiB  
Review
Hepatitis B Virus-Associated Hepatocellular Carcinoma
by Giacomo Emanuele Maria Rizzo, Giuseppe Cabibbo and Antonio Craxì
Viruses 2022, 14(5), 986; https://doi.org/10.3390/v14050986 - 7 May 2022
Cited by 63 | Viewed by 9509
Abstract
Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead [...] Read more.
Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice. Full article
(This article belongs to the Special Issue Hepatitis B Virus Research in Italy: From Epidemiology to Treatment)
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