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Control and Elimination of Viral Hepatitis

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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (15 July 2024) | Viewed by 18498

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Dr. María Cristina Navas

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Guest Editor

Departamento de Microbiología y Parasitología, Facultad de Medicina, University of Antioquia | UdeA, Medellin, Colombia
Interests: Hepatitis E virus Hepatitis B

Prof. Dr. Fernando de la Hoz-Restrepo

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Guest Editor

Departamento de Salud Pública, Universidad Nacional de Colombia, Bogota, Colombia
Interests: viral hepatitis epidemiology

Special Issue Information

Dear Colleagues,

The control and elimination of viral hepatitis is a priority of the World Health Organization (WHO). Since 2010, the World Health Assembly included hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV) infection as a priority, taking into account the burden and the cost to health systems of viral hepatitis. In 2016, the World Health Organization (WHO) presented the global strategy for the sector with the goal of a 65% reduction in mortality associated with viral hepatitis by the year 2030 and a 90% reduction in incidence.

The screening of blood units, the mandatory notification and registration of cases of cirrhosis and hepatocellular carcinoma, the strengthening of diagnosis and treatment systems, and the availability of antiviral treatment are the most important strategies. Nowadays, important advances have been made in public health and research in some countries that make the WHO global strategy viable in the medium term, although not with regard to the goal proposed for 2030.

This Special Issue of Microorganisms plans to collect recent research on the control and elimination of hepatitis virus. Original research articles and comprehensive reviews that cover hepatitis virus infection, epidemiology, molecular characterization, antiviral treatment, and antiviral agents are welcome.

Dr. María Cristina Navas
Prof. Dr. Fernando de la Hoz-Restrepo
Guest Editors

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Keywords

hepatitis virus infection
epidemiology
molecular characterization
vaccines
interventions
antiviral treatment
antiviral agents
validation of elimination

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Published Papers (11 papers)

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Research

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12 pages, 651 KiB

Open AccessArticle

Optimizing Hepatitis C Treatment Monitoring: Is Sustained Virologic Response at 4 Weeks Becoming the New Standard?

by Ivana Milošević, Ana Filipović, Branko Beronja, Nikola Mitrović, Maja Ružić, Jelena Simić, Nataša Knežević, Maria Pete, Nevena Todorović and Nataša Nikolić

Microorganisms 2024, 12(10), 2050; https://doi.org/10.3390/microorganisms12102050 - 10 Oct 2024

Viewed by 823

Abstract

This study, conducted at two university-based infectious disease clinics, included 216 patients with chronic hepatitis C. The primary objective was to assess the positive and negative predictive values, sensitivity, and specificity of achieving a sustained virological response (SVR) at 4 weeks compared to 12 weeks post-therapy. The results demonstrated a maximum sensitivity of 100% for achieving SVR at 12 weeks after reaching SVR at 4 weeks for all analyzed genotypes, except for genotype 1b treated with EBR/GZR therapy, where the specificity was 75%. Additionally, younger age and less advanced liver fibrosis were identified as independent predictors of achieving a sustained virological response at both 4 and 12 weeks. The significant normalization of various biochemical parameters was observed after treatment, indicating an overall improvement in liver function. This study suggests that shortening the monitoring period to 4 weeks might be effective for younger patients without significant fibrosis, potentially reducing loss to follow-up, which is a critical issue in HCV treatment. These findings align with the “test and treat” approach. Further research is needed to confirm these findings and incorporate them into official guidelines, which could simplify and enhance the effectiveness of HCV treatment protocols, aiding global efforts to eliminate HCV as a public health issue by 2030. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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22 pages, 3642 KiB

Open AccessArticle

FibroScan^® versus Biochemical Scores: A Study of Liver Fibrosis in HIV with HBV Co-Infection

by Giorgiana Nicoleta Lungu, Gheorghe Iulian Diaconescu, Florentina Dumitrescu, Anca Oana Docea, Radu Mitrut, Lucian Giubelan, Ovidiu Zlatian and Paul Mitrut

Microorganisms 2024, 12(6), 1213; https://doi.org/10.3390/microorganisms12061213 - 16 Jun 2024

Viewed by 1440

Abstract

The study aimed to determine liver fibrosis in human immunodeficiency virus (HIV) positive individuals using transient elastography (FibroScan^®), Fibrosis-4 (FIB-4) score, and aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) in the HIV Department from Infectious Diseases Hospital “Victor Babeș” Craiova, Romania. Of the analyzed HIV-positive subjects (n = 161), 93 (57.76%) had HIV mono-infection, and 68 (42.24%) had Hepatitis B Virus (HBV) co-infection. The prevalence of advanced liver fibrosis was higher (F2: 11.76% and F3: 13.24%, F4: 4.41%) in the HIV-HBV co-infected group compared to the HIV mono-infected group. The univariate and multivariate analysis identified HBV co-infection (OR = 5.73) male sex (OR = 5.34), serum aspartate amino-transferase levels (Pearson’s rho = 0.273), low platelet count (Pearson’s rho = −0.149) and erythrocyte sedimentation rate (OR = 1.030) as risk factors for the presence of liver fibrosis. Body mass index (OR = 1.08), serum lipid levels (OR = 0.96), viral load at diagnosis (OR = 1.00005), and low CD4+ cell count (OR = 0.977) were also correlated with liver fibrosis. The FIB-4 and APRI scores were strongly correlated with each other. In conclusion, HBV co-infection seems to be a determinant factor for liver fibrosis development in people living with HIV, together with other risk factors. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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18 pages, 2340 KiB

Open AccessArticle

Hepatitis B Virus Prevalence among HIV-Uninfected People Living in Rural and Peri-Urban Areas in Botswana

by Motswedi Anderson, Thabo Mangogola, Bonolo B. Phinius, Gorata Mpebe, Christopher O. Aimakhu, Wonderful T. Choga, Basetsana Phakedi, Lynnette N. Bhebhe, Doreen Ditshwanelo, Kabo Baruti, Linda Mpofu-Dobo, Lebogang Othusitse, Tsholofelo Ratsoma, Tendani Gaolathe, Joseph Makhema, Roger Shapiro, Shahin Lockman, Sikhulile Moyo and Simani Gaseitsiwe

Microorganisms 2024, 12(6), 1207; https://doi.org/10.3390/microorganisms12061207 - 15 Jun 2024

Viewed by 1557

Abstract

(1) Background: we determined the prevalence of the hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened for the hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n = 2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013–2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24–46) and 64% (1360/2135) were female. HBV prevalence was 4.0% (86/2135) [95% CI: 3.3–4.9]) and ranged between 0–9.2%. Older participants (>35 years) had increased odds of HBV positivity (OR: 1.94; 95% CI: [1.32–2.86]; p = 0.001). Thirteen samples were sequenced and seven (53.8%) were genotype A, three (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3–4.9) among people without HIV in rural and peri-urban communities in Botswana with varying rates in different communities. A comprehensive national HBV program is required in Botswana to guide HBV prevention, testing and management. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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17 pages, 3902 KiB

Open AccessArticle

Epidemiology of Viral Hepatitis in the Indigenous Populations of the Arctic Zone of the Republic of Sakha (Yakutia)

by Vera S. Kichatova, Maria A. Lopatukhina, Ilya A. Potemkin, Fedor A. Asadi Mobarkhan, Olga V. Isaeva, Mikhail D. Chanyshev, Albina G. Glushenko, Kamil F. Khafizov, Tatyana D. Rumyantseva, Sergey I. Semenov, Karen K. Kyuregyan, Vasiliy G. Akimkin and Mikhail I. Mikhailov

Microorganisms 2024, 12(3), 464; https://doi.org/10.3390/microorganisms12030464 - 25 Feb 2024

Viewed by 1510

Abstract

The indigenous populations of the Arctic regions of Russia experience the lowest coverage of health-related services. We assessed the prevalence of hepatitis A, B, C, D and E viruses (HAV, HBV, HCV, HDV and HEV) among 367 healthy adult Native people of the Arctic zone of Yakutia. The HAV seroprevalence was above and increased with age. The anti-HEV IgM and IgG antibody detection rates were 4.1% and 2.5%, respectively. The average HBsAg detection rate was 4.6%, with no positive cases identified in participants aged under 30 years, confirming the effectiveness of the newborn vaccination program that began in 1998. Anti-HDV antibodies were detected in 29.4% of HBsAg-positive cases. The anti-HCV and HCV RNA detection rates peaked in the age cohort of 50–59 years (10.8% and 3.9%). No statistically significant gender differences in the prevalence of different viral hepatitis were observed. The time-scaled phylogenetic analysis demonstrated that all HBV genotype A and D strains isolated in this study were autochthonous and had an estimated most common recent ancestor (MCRA) age of around the 11th to 14th century. Unlike HBV, the HCV strains of subtypes 1b, 2a and 2k/1b were introduced from other regions of Russia in the 1980s and 1990s. The HCV 1b sequence analysis revealed a series of transmission events. In conclusion, these data emphasize the urgent need for expanded viral hepatitis screening and care programs in the indigenous populations of the Arctic zone of Yakutia. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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12 pages, 1293 KiB

Open AccessArticle

How Possible Is the Elimination of Viral Hepatitis? An Analysis Based on the Global Burden of Disease from Hepatitis B and C, 1990–2019

by Nelson Alvis-Guzman, Nelson J. Alvis-Zakzuk and Fernando De la Hoz Restrepo

Microorganisms 2024, 12(2), 388; https://doi.org/10.3390/microorganisms12020388 - 15 Feb 2024

Viewed by 1391

Abstract

This study assesses the feasibility of hepatitis B (HBV) and C (HCV) elimination using an analysis of trends of epidemiology data (1990–2019) from the Global Burden of Disease Study. Joinpoint regression analysis was used to identify significantly changing points in the trends of Age-standardized Prevalence Rates (ASPR) and Age-standardized Mortality Rates (ASMR) and to estimate the annual percentage changes (APC) and the average annual percentage changes (AAPC) for the period. The Sociodemographic Index (SDI) was used to analyze trends between countries. The total percentage change of the ASPR (2019/1990) was −31.4% and −12.8% for HBV and HCV worldwide, respectively; the rate ratio (HBV/HCV) was 2.5. Mortality had decreased for HBV but not for HCV. The total percentage change for the ASMR (2019/1990) was −26.7% and 10.0% for HBV and HCV, respectively. While the ASMR of HBV decreased, HCV increased during this period. The percentage change in ASMR of HBV was highest in countries with high–middle SDI and lowest in countries with high SDI. For HCV, the percentage change in ASMR was highest in countries with high SDI (increase), and only in countries with low SDI did it decrease. The global HBV and HCV rates have fallen with different AAPCs associated with the SDI. Despite the advances, there is still a long way to go to achieve the 2030 elimination goals. An important challenge is related to finding a way to speed up the yearly rate at which the decline is happening. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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26 pages, 4274 KiB

Open AccessArticle

Non-Invasive Prediction Scores for Hepatitis B Virus- and Hepatitis D Virus-Infected Patients—A Cohort from the North-Eastern Part of Romania

by Laura Iulia Grecu, Camelia Sultana, Mariana Pavel-Tanasa, Simona Maria Ruta, Mihaela Chivu-Economescu, Lilia Matei, Ramona Gabriela Ursu, Elena Iftimi and Luminita Smaranda Iancu

Microorganisms 2023, 11(12), 2895; https://doi.org/10.3390/microorganisms11122895 - 30 Nov 2023

Cited by 2 | Viewed by 1741

Abstract

Approximately 62–72 million people are infected worldwide with HDV. Patients with chronic hepatitis D (CHD) have a higher risk of developing cirrhosis or hepatocellular carcinoma (HCC) and an increased mortality rate compared to those with chronic hepatitis B (CHB). The stage of liver fibrosis or the risk of developing HCC can also be estimated by non-invasive scores, which are cost effective, easier to apply, and reproducible. In this study, we aimed to evaluate the predictive value of four non-invasive scores (FIB-4, APRI, AST/ALT ratio, and aMAP) in assessing severe fibrosis/cirrhosis and the presence of HCC in patients with HBV/HDV superinfection, as compared with HBV mono-infection. Our 8-year retrospective analysis revealed that HDV-infected patients had a 2–3 times higher risk of developing cirrhosis and HCC than HBV-mono-infected subjects. High AST and ALT baseline levels qualified as independent predictors for cirrhosis development in both groups. The following fibrosis scores, FIB-4, APRI score, and AAR, were significantly increased when cirrhosis was present at baseline and showed a good prediction for developing cirrhosis in the CHD group. The aMAP score, a risk predictor for HCC, showed significantly higher values in patients with HCC in both groups. Nonetheless, non-invasive scores should always be considered for monitoring patients with CHB and CHD, but only when associated with other diagnosis methods. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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16 pages, 1724 KiB

Open AccessArticle

Immunoinformatics and Evaluation of Peptide Vaccines Derived from Global Hepatitis B Viral HBx and HBc Proteins Critical for Covalently Closed Circular DNA Integrity

by Umar Saeed, Zahra Zahid Piracha, Salman Alrokayan, Tajamul Hussain, Fahad N. Almajhdi and Yasir Waheed

Microorganisms 2023, 11(12), 2826; https://doi.org/10.3390/microorganisms11122826 - 21 Nov 2023

Cited by 3 | Viewed by 1732

Abstract

The Hepatitis B virus (HBV) HBx and HBc proteins play a crucial role in associating with covalently closed circular DNA (cccDNA), the primary factor contributing to intrahepatic viral persistence and a major obstacle in achieving a cure for HBV. The cccDNA serves as a reservoir for viral persistence. Targeting the viral HBc and HBx proteins’ interaction with cccDNA could potentially limit HBV replication. In this study, we present epitopes identified from global consensus sequences of HBx and HBc proteins that have the potential to serve as targets for the development of effective vaccine candidates. Furthermore, conserved residues identified through this analysis can be utilized in designing novel, site-specific anti-HBV agents capable of targeting all major genotypes of HBV. Our approach involved designing global consensus sequences for HBx and HBc proteins, enabling the analysis of variable regions and highly conserved motifs. These identified motifs and regions offer potent sites for the development of peptide vaccines, the design of site-specific RNA interference, and the creation of anti-HBV inhibitors. The epitopes derived from global consensus sequences of HBx and HBc proteins emerge as promising targets for the development of effective vaccine candidates. Additionally, the conserved residues identified provide valuable insights for the development of innovative, site-specific anti-HBV agents capable of targeting all major genotypes of HBV from A to J. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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14 pages, 2090 KiB

Open AccessArticle

Genetic Diversity of Hepatitis B and C Viruses Revealed by Continuous Surveillance from 2015 to 2021 in Gabon, Central Africa

by Haruka Abe, Yuri Ushijima, Rodrigue Bikangui, Georgelin Nguema Ondo, Christelle M. Pemba, Vahid R. Zadeh, Patrick I. Mpingabo, Hayato Ueda, Selidji T. Agnandji, Bertrand Lell and Jiro Yasuda

Microorganisms 2023, 11(8), 2046; https://doi.org/10.3390/microorganisms11082046 - 9 Aug 2023

Cited by 5 | Viewed by 1921

Abstract

Viral hepatitis remains one of the largest public health concerns worldwide. Especially in Central Africa, information on hepatitis virus infections has been limited, although the prevalence in this region has been reported to be higher than the global average. To reveal the current status of hepatitis B and C virus (HBV and HCV) infections and the genetic diversity of the viruses, we conducted longitudinal surveillance in Gabon. We detected 22 HBV and 9 HCV infections in 2047 patients with febrile illness. Genetic analyses of HBV identified subgenotype A1 for the first time in Gabon and an insertion generating a frameshift to create an X-preC/C fusion protein. We also revealed that most of the detected HCVs belonged to the “Gabon-specific” HCV subtype 4e (HCV-4e), and the entire nucleotide sequence of the HCV-4e polyprotein was determined to establish the first reference sequence. The HCV-4e strains possessed resistance-associated substitutions similar to those of other HCV-4 strains, indicating that the use of direct-acting antiviral therapy may be complex. These results provide a better understanding of the current situation of hepatitis B and C virus infections in Central Africa and will help public health organizations develop effective countermeasures to eliminate chronic viral hepatitis in this region. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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15 pages, 1668 KiB

Open AccessArticle

Epidemiology and Genetic Diversity of Hepatitis B Virus and Hepatitis Delta Virus Infection in Indigenous Communities in Colombia

by Melissa Montoya-Guzman, Jaime Martinez, Diana Castro-Arroyave, Carlos Rojas and Maria-Cristina Navas

Microorganisms 2023, 11(7), 1739; https://doi.org/10.3390/microorganisms11071739 - 3 Jul 2023

Cited by 1 | Viewed by 2159

Abstract

Despite the universal vaccination program, there are still regions and territories with a high prevalence of Hepatitis B Virus infection (HBV), such as the Amazon basin, where several indigenous communities live. Additionally, Hepatitis Delta Virus (HDV) is a defective that requires the hepatitis B surface antigen (HBsAg) for the assembly and release of de novo viral particles. Therefore, hepatitis D could be the result of HBV/HDV coinfection or HDV superinfection in individuals with chronic hepatitis B. Among the high prevalence HDV populations are indigenous communities of America. This study aims to describe and characterize the frequency of HBV and HDV infection, viral genotypes and HBV immune escape mutants in indigenous populations from different regions of Colombia. The diagnosis of hepatitis B and hepatitis D was confirmed by serological markers. Moreover, the HBV and HDV genome were amplified by PCR and RT-PCR, respectively, and, subsequently, the phylogenetic analysis was performed. We characterized 47 cases of chronic hepatitis B, 1 case of reactivation and 2 cases of occult hepatitis B infection (OBI). Furthermore, a high prevalence of HDV infection was identified in the study population (29.33%, 22/75) and the circulation of several HBV genotypes and subgenotypes (F1b, F3, F4, and D). Interestingly, this is the first report of the HDV genotype I circulation in this country. These findings demonstrated that HBV and HDV infections are still public health problems in indigenous communities in Colombia. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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Review

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12 pages, 936 KiB

Open AccessReview

Hepatitis C Diagnosis and Treatment Among Indigenous People in a Canadian Context: Challenges and Community-Led Solutions

by Kate P. R. Dunn, Mia J. Biondi and Samuel S. Lee

Microorganisms 2024, 12(11), 2364; https://doi.org/10.3390/microorganisms12112364 - 19 Nov 2024

Viewed by 574

Abstract

The historical and ongoing impacts of the influence of colonization are experienced by Indigenous people in systemic racism, inequity in healthcare access, and intergenerational trauma; originating in the disruption of a way of life and seen in a grief response, with links to disparate hepatitis C virus (HCV) prevalence. Despite this, the focus often remains on the increased incidence without a strengths-based lens. Although HCV is a global concern that can result in cirrhosis, liver failure, or cancer, diagnosing and linking people to care and treatment early can prevent advanced liver disease. Efforts to engage certain priority populations are occurring; however, historical context and current practices are often forgotten or overlooked. This is especially true with respect to Indigenous people in Canada. This review considers the published literature to elucidate the context of historical and ongoing colonizing impacts seen in the current HCV treatment gaps experienced by Indigenous people in Canada. In addition, we highlight strengths-based and Indigenous-led initiatives and programming that inspire hopefulness and steps toward community-engaged solutions to meet the World Health Organization Goals of eliminating HCV as a public health threat. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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18 pages, 1469 KiB

Open AccessReview

An Update on Viral Hepatitis B and C in Mexico: Advances and Pitfalls in Eradication Strategies

by Marina Campos-Valdez, Manuel Alejandro Castro-García, Martha Eloísa Ramos-Márquez, Carmen Magdalena Gurrola-Díaz, Adriana María Salazar-Montes and Laura Verónica Sánchez-Orozco

Microorganisms 2024, 12(7), 1368; https://doi.org/10.3390/microorganisms12071368 - 3 Jul 2024

Viewed by 2063

Abstract

In Mexico, hepatitis B and C infections are a significant burden on the health system. The aim of this narrative review was to analyze the state of the art on hepatitis B and C in Mexico by searching and studying available data in academic articles and government reports and statements on epidemiology, prevention, treatment, and elimination strategies undertaken by the Mexican government. Even where the government has implemented a hepatitis B vaccination strategy to reduce its incidence, a very low proportion of people complete the vaccination schedule. Regarding hepatitis C, there is a National Elimination Program that emphasizes the importance of screening, diagnosis, and treatment focused on the population at risk. With the implementation of this program, more than a million fast tests have been carried out and the positive cases have been verified by viral load. Infected patients are tested to determine liver function, fibrosis stage, and coinfection with HBV and/or HIV. Patients without cirrhosis and/or coinfections are treated in first-level care centers, while those with cirrhosis and/or comorbidities are referred to specialists. The possibility of hepatitis C eradication in Mexico seems more likely than eradication of hepatitis B; however, major challenges remain to be overcome to reach both infections’ elimination. Full article

(This article belongs to the Special Issue Control and Elimination of Viral Hepatitis)

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