Viral Hepatitis in Brazil

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

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 20589

Special Issue Editors


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Guest Editor
Viral Hepatitis Ambulatory, Viral Hepatitis Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil
Interests: acute viral hepatitis; hepatitis A; hepatitis B; hepatitis C; hepatitis E; immune response; occult hepatitis; viral hepatitis during pregnancy; mother-to-infant transmission; vulnerable high-risk populations; rapid diagnostic tests; hemodialysis; indigenous populations
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Viral Hepatitis Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil
Interests: viral hepatitis; innovation in the diagnosis of hepatitis; molecular epidemiology; epidemiology; the biology of viral hepatitis; vulnerable high-risk populations; indigenous populations
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Viral hepatitis is a major global concern, as it contributes to the toll of deaths worldwide from infectious diseases and cancer. The five main types of hepatitis (A, B, C, D, and E) vary in transmission route, geographic distribution, and clinical outcome. Brazil is the sixth most populous country in the world, and has a diverse geographic distribution of these viruses and a diversity of country-specific strains. In order to achieve the WHO goal of eliminating viral hepatitis by 2030, diagnostic investigation in the general Brazilian population has been intensified—mainly key high risk populations—to help identify and treat chronic carriers and prevent new infections. This Special Issue of Viruses will address: 1) genetic variations in viral hepatitis, which may assist in understanding diverse types of responses (clinical outcome, treatment, immunological); 2) epidemiological studies in general and key populations; and 3) new diagnostic procedures that will assist in the elimination of these viruses.

Dr. Lia L. Lewis-Ximenez
Dr. Livia Melo Villar 
Guest Editors

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Keywords

  • viral hepatitis
  • Brazil
  • key populations
  • epidemiology
  • molecular epidemiology
  • therapy
  • diagnostics
  • immune response
  • clinical outcome
  • genotype

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Published Papers (9 papers)

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Research

12 pages, 702 KiB  
Article
Before Direct-Acting Antivirals for Hepatitis C Virus: Evaluation of Core Protein R70Q and L/C91M Substitutions in Chronically Infected Brazilian Patients Unresponsive to IFN and/or RBV
by Letícia Bomfim Campos, Nathália Alves Araújo de Almeida, Catarina Góis de Santana, Evorah Nascimento Pereira Barbosa, Marco Aurelio Pereira Horta, Márcia Amendola Pires, Carlos Eduardo Brandão Mello, Vanessa Salete de Paula and José Júnior França de Barros
Viruses 2023, 15(1), 187; https://doi.org/10.3390/v15010187 - 09 Jan 2023
Cited by 2 | Viewed by 1504
Abstract
Although chronic hepatitis C has been effectively treated with direct-acting antivirals (DAAs), the use of conventional therapy with peg-interferon (Peg-IFN) or (predominantly) ribavirin (RBV), remains widespread. R70Q/H and L/C91M amino acid substitutions in the hepatitis C virus (HCV) core protein may modulate responses [...] Read more.
Although chronic hepatitis C has been effectively treated with direct-acting antivirals (DAAs), the use of conventional therapy with peg-interferon (Peg-IFN) or (predominantly) ribavirin (RBV), remains widespread. R70Q/H and L/C91M amino acid substitutions in the hepatitis C virus (HCV) core protein may modulate responses to IFN and/or RBV, and are associated with cirrhosis, hepatocellular carcinoma (HCC), insulin resistance, and liver steatosis. We evaluated the R70Q/H and L/C91M substitutions, clinical and epidemiological profiles, and risk factors of Brazilian patients chronically infected with HCV subgenotypes 1a and 1b (HCV-GT1a and HCV-GT1b) unresponsive to IFN and/or RBV therapy. Sequencing and pyrosequencing analyses and sociodemographic and clinical predictive variables were used to assess the relationship between R70Q/H and L/C91M substitutions. Leukocyte counts, ALT levels, and ALT/AST ratios were significantly reduced in treated individuals, but more of these patients had advanced fibrosis and cirrhosis. L91M was more prevalent (19.7%), occurring only in HCV-GT1b, followed by R70Q/P (11.5%) and R70P (1.4%). R70Q/P exhibited higher mean AST, ALT, and GGT values, whereas L91M showed higher mean GGT values. Pyrosequencing of the L91M position revealed mutant subpopulations in 43.75% of samples. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
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15 pages, 2603 KiB  
Article
Genomic Variability of Hepatitis B Virus Circulating in Brazilian Western Amazon
by Tárcio Peixoto Roca, Livia Melo Villar, Felipe Souza Nogueira Lima, Mariana Pinheiro Alves Vasconcelos, Lourdes Maria Pinheiro Borzacov, Eugênia de Castro e Silva, Bárbara Vieira do Lago, Mayara Torquato Lima da Silva, Luan Felipo Botelho Souza, Juan Miguel Villalobos Salcedo, Alcione de Oliveira dos Santos and Deusilene Souza Vieira
Viruses 2022, 14(10), 2100; https://doi.org/10.3390/v14102100 - 22 Sep 2022
Cited by 2 | Viewed by 1636
Abstract
The emergence of clinically relevant mutations in the hepatitis B virus (HBV) genome has been a matter of great debate because of the possibility of escape from the host’s immune system, the potential to cause more severe progression of liver diseases and the [...] Read more.
The emergence of clinically relevant mutations in the hepatitis B virus (HBV) genome has been a matter of great debate because of the possibility of escape from the host’s immune system, the potential to cause more severe progression of liver diseases and the emergence of treatment-resistant variants. Here we characterized the circulating variants of HBV in Rondônia State, in the north of Brazil. Serum samples of 62 chronic HBV carriers were subjected to PCR assays and clinical data were collected. Mutations and genotypes were characterized through direct sequencing. The findings show the presence of subgenotypes A1 (54.83%, 34/62), D3 (16.13%, 10/62), F2 (16.13%, 10/62), A2 (4.84%, 3/62), D2 (3.23%, 2/62), D1 (1.61%, 1/62), D4 (1.61%, 1/62) and F4 (1.61%, 1/62). Deletions in the pre-S2 region were found in 13.79% (8/58) of the samples, mutations in the S gene in 59.68% (37/62) and RT mutations in 48.39% (30/62). We found a variable genotypic distribution in different locations and important mutations related to immune escape and drug resistance in Western Amazonia, which contributed to genetic surveillance and provided important information to help control the disease. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
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10 pages, 1179 KiB  
Article
Hepatitis B Surface Antibody (Anti-HBs) Kinetics during Rituximab Chemotherapy and Performance of Hepatitis B Vaccine before Immunosuppression: Two Prospective Studies
by João Marcello de Araujo-Neto, Gabriela Sousa Guimarães, Flavia Ferreira Fernandes and Marcelo A. Soares
Viruses 2022, 14(8), 1780; https://doi.org/10.3390/v14081780 - 15 Aug 2022
Cited by 3 | Viewed by 1808
Abstract
Rituximab promotes strong immunosuppression leading to a high risk of hepatitis B reactivation (HBV-R) and chronic infection. Current recommendations on HBV-R prevention are expensive and poorly individualized. In resolved hepatitis B patients, previous studies suggest that anti-HBs titers before immunosuppression can predict HBV-R [...] Read more.
Rituximab promotes strong immunosuppression leading to a high risk of hepatitis B reactivation (HBV-R) and chronic infection. Current recommendations on HBV-R prevention are expensive and poorly individualized. In resolved hepatitis B patients, previous studies suggest that anti-HBs titers before immunosuppression can predict HBV-R risk. However, guidelines claim that additional data are necessary before recommending spare drug prophylaxis in patients with high anti-HBs titers. On the other hand, in patients with no previous contact with HBV, guidelines recommend vaccine before immunosuppression despite minimal evidence available. To shed light on these knowledge gaps, two prospective studies were conducted to evaluate anti-HBs in hematological cancer patients treated with rituximab. In the first study, anti-HBs-positive patients were referred for following up antibody titers before and during immunosuppression. Patients with anti-HBs ≥ 100 mIU/mL before immunosuppression had no negative seroconversion (anti-HBs loss), in contrast to 18% of those with anti-HBs < 100 mIU/mL. In the second study, patients with no previous contact with HBV were invited to receive HBV vaccine before rituximab chemotherapy. None seroconverted with anti-HBs. In conclusion, both studies reinforce the need to review concepts about HBV prevention during immunosuppression on current guidelines. Narrowing the use of drug prophylaxis and improving vaccine indications are recommended. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
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15 pages, 322 KiB  
Article
Hepatitis B and C in Immigrants and Refugees in Central Brazil: Prevalence, Associated Factors, and Immunization
by Thaynara Lorrane Silva Martins, Grazielle Rosa da Costa e Silva, Carla de Almeida Silva, Davi Oliveira Gomes, Bruno Vinícius Diniz e Silva, Megmar Aparecida dos Santos Carneiro, Leonora Rezende Pacheco, Natalia Motta de Araujo, Margareth Santos Zanchetta, Sheila Araujo Teles and Karlla Antonieta Amorim Caetano
Viruses 2022, 14(7), 1534; https://doi.org/10.3390/v14071534 - 14 Jul 2022
Cited by 1 | Viewed by 1459
Abstract
Introduction: Eliminating hepatitis B and C in immigrant and refugee populations is a significant challenge worldwide. Given the lack of information in Brazil, this study aimed to estimate the prevalence of infections caused by hepatitis B and C viruses and factors associated with [...] Read more.
Introduction: Eliminating hepatitis B and C in immigrant and refugee populations is a significant challenge worldwide. Given the lack of information in Brazil, this study aimed to estimate the prevalence of infections caused by hepatitis B and C viruses and factors associated with hepatitis B in immigrants and refugees residing in central Brazil. Methods: An observational, cross-sectional, and analytical study was conducted from July 2019 to January 2020 with 365 immigrants and refugees. Hepatitis B was detected by a rapid immunochromatographic test, enzyme immunoassay, and chemiluminescence, and hepatitis C by rapid immunochromatographic test. Multiple analysis was used to assess factors associated with hepatitis B infection. Results: Of the participants, 57.8% were from Haiti and 35.6% were from Venezuela. Most had been in Brazil for less than 2 years (71.2%). The prevalence of HBV infection and exposure was 6.6% (95% CI: 4.5–9.6%) and 27.9% (95% CI: 23.6–2.8%), respectively, and 34% had isolated anti-HBs positivity. Reporting a sexually transmitted infection was statistically associated with HBV infection (OR: 7.8; 95% CI: 2.3–26.4). No participant with positive anti-HCV serology was found. Conclusions: The study showed that participants were outside the reach of prevention and control actions for hepatitis B. Therefore, public health strategies must be designed to reach, inform, and vaccinate this group. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
11 pages, 296 KiB  
Article
Association of Pre-S/S and Polymerase Mutations with Acute and Chronic Hepatitis B Virus Infections in Patients from Rio de Janeiro, Brazil
by Camilla Rodrigues de Almeida Ribeiro, Katrini Guidolini Martinelli, Vinícius da Motta de Mello, Natália Spitz, Oscar Rafael Carmo Araújo, Lia Laura Lewis-Ximenez, Natalia Motta Araujo and Vanessa Salete de Paula
Viruses 2022, 14(7), 1375; https://doi.org/10.3390/v14071375 - 24 Jun 2022
Cited by 1 | Viewed by 1521
Abstract
Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. [...] Read more.
Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
8 pages, 279 KiB  
Article
Comparison of Patients Monoinfected with Hepatitis C Virus and Coinfected with Hepatitis B/C in the Amazon Region of Brazil
by Regiane M. A. Sampaio, Paola Eduarda F. Dantas, Maria Inês C. da Silva, Joseane R. da Silva, Patrícia F. Nunes, Amanda C. Gomes and Luisa C. Martins
Viruses 2022, 14(5), 856; https://doi.org/10.3390/v14050856 - 21 Apr 2022
Viewed by 1572
Abstract
Hepatitis B and C are the most common causes of liver disease worldwide. The two infections share many similarities such as a global distribution, the same routes of transmission, hepatotropism, and the ability to cause chronic infection. The consequences of HBV/HCV coinfection are [...] Read more.
Hepatitis B and C are the most common causes of liver disease worldwide. The two infections share many similarities such as a global distribution, the same routes of transmission, hepatotropism, and the ability to cause chronic infection. The consequences of HBV/HCV coinfection are still being studied. The aim of this study is to describe and compare the epidemiological and laboratory profile and the degree of hepatic fibrosis between HCV-monoinfected and HBV/HCV-coinfected patients in the Brazilian Amazon region. ELISA tests were used for the investigation of HBV and HCV serological markers, and molecular tests were used for the detection and genotyping of these viruses. Additionally, transaminases were measured, and a FibroScan was performed for the analysis of liver function. A total of 328 patients with HCV participated in the study. The serological prevalence of HCV/HBV coinfection was 10.77%. A comparison of risk factors between the monoinfected and coinfected groups showed that illicit drug use, sharing sharp instruments, and tattooing/piercing are significantly associated with coinfection. The monoinfected patients had a higher HCV load than the coinfected patients. A viral interaction was observed in this study in which the presence of a coinfection with HBV appears to influence HCV replication. Further studies are necessary to better understand this interaction. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
14 pages, 1178 KiB  
Article
PAGE-B and REACH-B Predicts the Risk of Developing Hepatocellular Carcinoma in Chronic Hepatitis B Patients from Northeast, Brazil
by Alessandra Porto de Macedo Costa, Marcos Antonio Custódio Neto da Silva, Rogério Soares Castro, Ana Leatrice de Oliveira Sampaio, Antônio Machado Alencar Júnior, Márcia Costa da Silva and Adalgisa de Souza Paiva Ferreira
Viruses 2022, 14(4), 732; https://doi.org/10.3390/v14040732 - 31 Mar 2022
Cited by 4 | Viewed by 5520
Abstract
This study aims to evaluate the accuracy of the PAGE-B and REACH-B scores in predicting the risk of developing HCC in patients with chronic hepatitis B regularly followed up at a reference service in the State of Maranhão. A historical, longitudinal, retrospective cohort [...] Read more.
This study aims to evaluate the accuracy of the PAGE-B and REACH-B scores in predicting the risk of developing HCC in patients with chronic hepatitis B regularly followed up at a reference service in the State of Maranhão. A historical, longitudinal, retrospective cohort study, carried out from the review of medical records of patients with chronic Hepatitis B. PAGE-B and REACH-B scores were calculated and the accuracy of the scores in predicting the risk of HCC in the studied population was evaluated. A total of 978 patients were included, with a median age of around 47 years, most of them female and not cirrhotic. HCC was identified in 34 patients. Thrombocytopenia, high viral load, male gender and age were associated with the occurrence of HCC. The ROC curve for the PAGE-B score showed a value of 0.78 and for the REACH-B score of 0.79. The cutoff point for PAGE-B was 11 points for greater sensitivity and for REACH-B 7.5 points considering greater sensitivity and 9.5 points considering greater specificity. PAGE-B and REACH-B scores were able to predict the risk of developing HCC in the studied population. The use of risk stratification scores is useful to reduce costs associated with HCC screening. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
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13 pages, 1828 KiB  
Article
The IL6-174G/C Polymorphism Associated with High Levels of IL-6 Contributes to HCV Infection, but Is Not Related to HBV Infection, in the Amazon Region of Brazil
by Maria Alice Freitas Queiroz, Angélica Menezes Santiago, Tuane Carolina Ferreira Moura, Ednelza da Silva Graça Amoras, Simone Regina Souza da Silva Conde, Izaura Maria Vieira Cayres-Vallinoto, Ricardo Ishak and Antonio Carlos Rosário Vallinoto
Viruses 2022, 14(3), 507; https://doi.org/10.3390/v14030507 - 28 Feb 2022
Cited by 2 | Viewed by 2202
Abstract
The dysregulation of cytokine production can lead to an inefficient immune response, promoting viral persistence that induces the progression of chronic viral hepatitis. The study investigated the association of the IL6-174G/C polymorphism with changes in cytokine levels and its influence on the persistence [...] Read more.
The dysregulation of cytokine production can lead to an inefficient immune response, promoting viral persistence that induces the progression of chronic viral hepatitis. The study investigated the association of the IL6-174G/C polymorphism with changes in cytokine levels and its influence on the persistence and progression of chronic hepatitis caused by HBV and HCV in 72 patients with chronic hepatitis B (HBV), 100 patients with hepatitis C (HCV), and a control group of 300 individuals. The genotyping of the IL6-174G/C polymorphism was performed by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). HCV patients with the wild-type genotype (GG) had a higher viral load (p = 0.0230). The plasma levels of IL-6 were higher among patients infected with HBV and HCV than among the control group (p < 0.0001). Patients with HCV were associated with increased inflammatory activity (A2–A3; p < 0.0001). In hepatitis C, carriers of the GG genotype had higher levels of IL-6 (p = 0.0286), which were associated with A2–A3 inflammatory activity (p = 0.0097). Patients with A2–A3 inflammatory activity and GG genotype had higher levels of IL-6 than those with the GC/CC genotype (p = 0.0127). In conclusion, the wild-type genotype for the IL6-174G/C polymorphism was associated with high levels of IL-6 and HCV viral load and inflammatory activity, suggesting that this genotype may be a contributing factor to virus-induced chronic infection. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
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17 pages, 1667 KiB  
Article
Increase in Hepatitis A Cases Linked to Imported Strains to Rio de Janeiro, Brazil: A Cross-Sectional Study
by Vinicius M. Mello, Lucas M. Bianchi, Paulo Sergio F. Sousa, Pedro S. Tavares, Daniel R. G. Di Salvo, Cleber F. Ginuino, Nathalia A. A. Almeida, Carlos A. S. Fernandes, Francisco C. A. Mello, Livia M. Villar, Lia L. Lewis-Ximenez and Barbara V. Lago
Viruses 2022, 14(2), 303; https://doi.org/10.3390/v14020303 - 01 Feb 2022
Cited by 2 | Viewed by 2288
Abstract
This study aims to evaluate the epidemiological and molecular features associated with HAV transmission in adults in Rio de Janeiro during a period of increased registered cases of HAV (2017–2018). Socio-epidemiological data and serum samples from anti-HAV IgM+ individuals were obtained. HAV RNA [...] Read more.
This study aims to evaluate the epidemiological and molecular features associated with HAV transmission in adults in Rio de Janeiro during a period of increased registered cases of HAV (2017–2018). Socio-epidemiological data and serum samples from anti-HAV IgM+ individuals were obtained. HAV RNA was RT-PCR amplified and sequenced for further phylogenetic and phylogeographic analyses. From fifty-two HAV IgM+ individuals, most were men (78.85%; p = 0.024), aged 20–30 years old (84.61%; p < 0.001), resided in the Rio de Janeiro north zone (31/52; 59.62%; p = 0.001), and are men who have sex with men (MSM) (57.69%; p = 0.002). Sexual practices were more frequent (96%) than others risk factors (food-borne (44%), water-borne (42.31%), and parenteral (34.62%)). Individuals who traveled to endemic regions had a 7.19-fold (1.93–36.04; p < 0.01) increased risk of HAV. Phylogenetic analysis revealed four distinct clades of subgenotype IA, three of them comprised sequences from European/Asian MSM outbreaks and one from Brazilian endemic strains. Bayesian Inference showed that the imported strains were introduced to Brazil during large mass sportive events. Sexual orientation and sexual practices may play a role in acquiring HAV infection. Public policies targeting key populations must be implemented to prevent further dissemination of HAV and other STIs. Full article
(This article belongs to the Special Issue Viral Hepatitis in Brazil)
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