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1.
Ann Hepatol ; 29(6): 101546, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39147130

RESUMO

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. For patients with advanced HCC, liver function decompensation often occurs, which leads to poor tolerance to chemotherapies and other aggressive treatments. Therefore, it remains critical to develop effective therapeutic strategies for HCC. Etiological factors for HCC are complex and multifaceted, including hepatitis virus infection, alcohol, drug abuse, chronic metabolic abnormalities, and others. Thus, HCC has been categorized as a "genomically unstable" cancer due to the typical manifestation of chromosome breakage and aneuploidy, and oxidative DNA damage. In recent years, immunotherapy has provided a new option for cancer treatments, and the degree of genomic instability positively correlates with immunotherapy efficacies. This article reviews the endogenous and exogenous causes that affect the genomic stability of liver cells; it also updates the current biomarkers and their detection methods for genomic instabilities and relevant applications in cancer immunotherapies. Including genomic instability biomarkers in consideration of cancer treatment options shall increase the patients' well-being.

2.
Clin Transl Oncol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958900

RESUMO

BACKGROUND: The correlation between breast cancer and hepatitis B virus (HBV) remains inconclusive. This study aims to explore the serological status of HBV infection and past infection in different age groups of female breast cancer patients, patients with benign breast diseases, and individuals undergoing routine physical examinations. METHODS: Serum data on HBV serological markers were collected and analyzed from 6072 female breast cancer patients first diagnosed from September 2012 to July 2020 at the First Affiliated Hospital of Chongqing Medical University, along with 4019 women with benign breast diseases and 54,740 healthy females undergoing routine physical examinations in the same period. The data were stratified by age for comparison between groups. RESULTS: The prevalence of HBV infection and past infection in the breast cancer group (7.9%, 55.1%) was higher than that in the benign breast disease group (6.5%, 39.1%) and the healthy females group(5.0%, 17.6%);the rate of only HBV surface antibody positivity (HBsAb ( +)) in the breast cancer group (10.3%) was lower than that in the benign breast disease group (26.9%) and the healthy females group (49.2%), with significant differences between the three groups (p < 0.05). Stratified by age, the prevalence of HBV infection in the breast cancer group (8%, 8.9%) and benign breast disease group (7.75%, 8.1%)was higher than that in the healthy females group (4.5%, 6.3%) in the 30-39 and 40-49 age group, respectively. The past infection rate of HBV in the breast cancer group (24.8%, 45.0%) was higher than that in the benign breast disease group (16.1%, 35.4%) in the ≤ 29 and 30-39 age group, respectively.. The past infection rate of HBV in the breast cancer group was higher than that in the healthy females group in all age groups, while the rate of only HBsAb ( +) in the breast cancer group was lower than that in the benign breast disease group and the routine physical examination group in all age groups. CONCLUSIONS: Breast cancer women and women with benign breast diseases have higher rates of hepatitis B virus infection and previous infections, with more significant differences among middle-aged women. Breast cancer women and women with benign breast diseases have lower rates of only HBsAb ( +) for HBV.

3.
World J Virol ; 13(1): 90384, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38616854

RESUMO

Hepatitis B virus (HBV) infection poses a global health concern without a definitive cure; however, antiviral medications can effectively suppress viral replication. This study delves into the intricate interplay between lipid metabolism and HBV replication, implicating molecular mechanisms such as the stearoyl coenzyme A desaturase 1 autophagy pathway, SAC1-like phosphatidylinositol phosphatase, and galectin-9 mediated selective autophagy of viral core proteins in regulating HBV replication. Within lipid droplets, perilipin 2 (PLIN2) emerges as a pivotal guardian, with its overexpression protecting against autophagy and downregulation stimulating triglyceride catabolism through the autophagy pathway. This editorial discusses the correlation between hepatic steatosis and HBV replication, emphasizing the role of PLIN2 in this process. The study underscores the multifaceted roles of lipid metabolism, autophagy, and perilipins in HBV replication, shedding light on potential therapeutic avenues.

4.
Med Res Rev ; 44(5): 2015-2034, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38528684

RESUMO

The hepatitis B elimination is a goal proposed by the WHO to be achieved by 2030 through the adoption of synergistic measures for the prevention and chronic HBV infection treatment. Complete cure is characterized by the HBV elimination from the body and is the goal of the chronic hepatitis B treatment, which once achieved, will enable the hepatitis B elimination. This, today, has been a scientific challenge. The difficulty in achieving a complete cure is due to the indefinite maintenance of a covalently closed episomal circular DNA (cccDNA) reservoir and the maintenance and persistence of an insufficient and dysfunctional immune response in chronically infected patients. Among the measures adopted to eliminate hepatitis B, two have the potential to directly interfere with the virus cycle, but with limited effect on HBV control. These are conventional vaccines-blocking transmission and antiviral therapy-inhibiting replication. Vaccines, despite their effectiveness in protecting against horizontal transmission and preventing mother-to-child vertical transmission, have no effect on chronic infection or potential to eliminate the virus. Treatment with antivirals suppresses viral replication, but has no curative effect, as it has no action against cccDNA. Therapeutic vaccines comprise an additional approach in the chronic infection treatment, however, they have only a modest effect on the immune system, enhancing it temporarily. This manuscript aims to address (1) the cccDNA persistence in the hepatocyte nucleus and the immune response dysfunction in chronically infected individuals as two primary factors that have hampered the treatment and HBV elimination from the human body; (2) the limitations of antiviral therapy and therapeutic vaccines, as strategies to control hepatitis B; and (3) the possibly promising therapeutic approaches for the complete cure and elimination of hepatitis B.


Assuntos
Vacinas contra Hepatite B , Vírus da Hepatite B , Hepatite B , Humanos , Vírus da Hepatite B/efeitos dos fármacos , Vacinas contra Hepatite B/uso terapêutico , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Antivirais/uso terapêutico , Animais , DNA Circular , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia
5.
J Med Virol ; 96(2): e29463, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38345135

RESUMO

We present the case of a breakthrough infection by hepatitis B virus (HBV), intending to warn about the challenge that HBV represents for transfusion safety. Virological markers for HBV infection were assayed during a blood donor screening by detection of HBsAg, anti-HBc, and viral nucleic acid (HBV DNA) by a nucleic acid test (NAT). Additionally, samples were analyzed for detection of immunoglobulin M anti-HBc, HBeAg, anti-HBe, and anti-HBs. A first-time donor repeatedly tested positive for HBV DNA by NAT and nonreactive for HBV-serological markers of infection. He stated having completed the anti-HBV vaccination schedule; thus, study of anti-Hbs resulted in reactive at protective level (18 mIU/mL). The donor denied clinical symptoms of hepatitis and remained healthy during the follow-up period. 95 days postdonation, NAT was negative, seroconversion of anti-HBc ab was detected, and a significant increase in anti-HBs concentration was measured (>1000 mIU/mL). This is the first case of HBV-breakthrough infection reported in Argentina and to our knowledge, this potential threat to transfusion safety is novel in an HBV low-endemic region with high coverage of HBV vaccination. The occurrence of breakthrough infections challenges the current protocols for the identification of HBV-infected subjects, could be a source of silent HBV transmission.


Assuntos
Vírus da Hepatite B , Hepatite B , Masculino , Humanos , Vírus da Hepatite B/genética , Infecções Irruptivas , Doadores de Sangue , DNA Viral/genética , Antígenos de Superfície da Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B
6.
Bol. latinoam. Caribe plantas med. aromát ; 23(1): 152-159, ene. 2024. graf
Artigo em Inglês | LILACS | ID: biblio-1554187

RESUMO

Medicinal plants are used to cure diseases, and their replacement is frequent and affects public health. The genus Baccharis has representatives within the medicinal flora of Argentina, although the replacement of the species of this genus known under the vulgar name of "carqueja" by Baccharis spicata has been detected i n herbalists or markets of herbal products. The genotoxic safety of this species has been established in previous work of our group. The aim of this study was to evaluate the antiviral activity of an infusion made from B. spicata leaves against hepatitis B virus with the HepG2.2.15 cellular system and to determine cytotoxicity in HepG2.2,15, A549 and Vero cell lines. Infusion of B. spicata was active to inhibit HBV replication with an EC 50 of 22.54 µg/mL and a CC 50 of 190 µg/mL.


Las plantas medicinales son empleadas para la cura de enfermedades, y su sustituc ión es frecuente y afecta a la salud pública. El género Baccharis posee representantes dentro de la flora medicinal de Argentina, aunque se ha detectado la sustitución de las especies de dicho género conocidas bajo el nombre vulgar de "carqueja" por Baccha ris spicata en herboristerías o mercados de productos herb arios . Se ha establecido la seguridad genotóxica de esta especie en trabajos previos de nuestro grupo. Este estudio buscó evaluar la actividad antiviral de una infusión elaborada a partir de hojas de B. spicata frente al virus de la hepatitis B con el sistema celular HepG2.2.15 y determinar la citotoxicidad en las líneas celulares HepG2.2.15, A549 y Vero. La infusión de B. spicata fue activa para inhibir la replicación del virus con un EC 50 de 22.54 µg/mL y un CC 50 de 190 µg/mL.


Assuntos
Antivirais/administração & dosagem , Extratos Vegetais/administração & dosagem , Baccharis/química , Hepatite B/tratamento farmacológico , Antivirais/farmacologia , Replicação Viral/efeitos dos fármacos , Extratos Vegetais/farmacologia , Linhagem Celular/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Folhas de Planta , Asteraceae , Medicina Tradicional
7.
Clin Transl Oncol ; 26(2): 326-337, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37402970

RESUMO

Hepatocellular carcinoma (HCC) caused by HBV, HCV infection, and other factors is one of the most common malignancies in the world. Although, percutaneous treatments such as surgery, ethanol injection, radiofrequency ablation, and transcatheter treatments such as arterial chemoembolization are useful for local tumor control, they are not sufficient to improve the prognosis of patients with HCC. External interferon agents that induce interferon-related genes or type I interferon in combination with other drugs can reduce the recurrence rate and improve survival in HCC patients after surgery. Therefore, in this review, we focus on recent advances in the mechanism of action of type I interferons, emerging therapies, and potential therapeutic strategies for the treatment of HCC using IFNs.


Assuntos
Carcinoma Hepatocelular , Interferon Tipo I , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Prognóstico , Resultado do Tratamento , Recidiva Local de Neoplasia
8.
Ann Hepatol ; 29(1): 101156, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37758118

RESUMO

INTRODUCTION AND OBJECTIVES: Occult hepatitis B virus (HBV) infection (OBI) is characterised by low levels of hepatitis B virus (HBV) DNA in the blood/liver of patients with negative hepatitis B surface antigen (HBsAg). This study aimed to determine the OBI prevalence and virological characteristics (viral genotypes and HBsAg mutants) in patients with an "anti-HBc only" serological profile. MATERIALS AND METHODS: A total of 24 900 serum samples were routinely screened for hepatitis B markers over a five-year period. All anti-HBc-positive/HBsAg-negative/anti-HBs-negative sera were selected and analysed for the presence of HBV DNA. Mutational analyses of the HBs gene and polymerase gene sequences were performed. RESULTS: 1749 (7.02%) sera were anti-HBc positive, and 113 (0.45%) sera had an "anti-HBc only" serological profile (HBsAg/anti-HBs negative). HBV DNA was detected in 12/113 (10.61%) "anti-HBc only" positive sera, representing 0.048% of all routinely tested samples. Due to extremely low viremia, HBV genome was successfully sequenced in only two sera where subgenotype D3 was confirmed. Mutational analyses of the S gene revealed multiple missense mutations. In addition to the M133I, Y134F, and G145R mutations, already associated with diagnostic escape, we also found nine novel OBI-related S-gene mutations - S136Y, F158L, K160N, E164G, S167L, A168V, L175S, S210I and F212C. CONCLUSIONS: We detected multiple known and novel S gene mutations in 2/12 (16.6%) OBI cases, nevertheless, further studies are required to determine their role in the pathogenesis of OBI. Understanding the frequencies of clinically relevant HBV mutations may contribute to improvement of diagnostic protocols.


Assuntos
Hepatite B Crônica , Hepatite B , Adulto , Humanos , Vírus da Hepatite B/genética , Antígenos de Superfície da Hepatite B , DNA Viral/genética , Prevalência , Croácia/epidemiologia , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B
9.
Rev. Assoc. Med. Bras. (1992, Impr.) ; Rev. Assoc. Med. Bras. (1992, Impr.);70(7): e20240091, 2024. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1565039

RESUMO

SUMMARY OBJECTIVE: We aimed to evaluate the risk of hepatitis B virus reactivation in rheumatic patients using anti-tumor necrosis factor-alpha drugs and the awareness of physicians about hepatitis B virus reactivation. METHODS: Demographic characteristics, pre- and post-treatment hepatitis markers, and laboratory parameters of patients receiving anti-tumor necrosis factor-alpha therapy in our rheumatology clinic were retrospectively examined. RESULTS: A total of 448 patients, 240 (53.6%) female and 208 (46.4%) male, were evaluated. Their mean age was 48.02±14.64 years. While HBsAg was examined in 443 (98.9%) patients before treatment, 7 (1.6%) patients were found to be HBsAg positive. While anti-HBc IgG was examined in 405 (90.4%) patients, it was positive in 69 (17%) patients. HBs Ag (total 446-99.6%) test was performed in three patients who were not tested for HBsAg before the treatment, and anti-HBc total (431-96.2% total) test was performed in 26 patients who were not tested for anti-HBc total. All HBsAg positive patients and 17 (24.6%) of those with previous hepatitis B received antiviral treatment. While the median follow-up period of the patients was 24 (6-60) months, no patient developed hepatitis B virus reactivation. CONCLUSION: The screening rates and awareness of physicians providing anti-tumor necrosis factor-alpha therapy for hepatitis B virus infection were found to be higher compared to similar studies. Hepatitis B virus reactivation did not develop in any patient. Since the risk of hepatitis B virus reactivation is low, especially in patients with previous hepatitis B, it would be more appropriate to follow up the patients without giving antiviral prophylaxis.

10.
Hematol., Transfus. Cell Ther. (Impr.) ; 45(4): 428-434, Oct.-Dec. 2023. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1528638

RESUMO

ABSTRACT Introduction: In Brazil, the blood donor screening for hepatitis B virus (HBV) includes laboratory testing for serological (HBsAg and Anti-HBc) and molecular (HBV DNA) markers. This study aims to correlate serology reactive results with HBV DNA detection among blood donors with at least one HBV infection marker detected in a blood bank in northern Brazil. Method: A retrospective search for HBV reactive blood donor data from January 2017 to December 2019 was performed. Serological screening was performed by chemiluminescent microparticle immunoassays Architect HBsAg and Architect Anti-HBc, whereas molecular screening was performed by the HBV nucleic acid test (HBV NAT). Main results: A total of 556 HBsAg reactive results were detected, between positive (47.66%) and inconclusive (52.34%). A total of 3,658 Anti-HBc reactive results were detected, between positive (83.71%) and inconclusive (16.29%). None of the inconclusive results were associated with HBV DNA detection. The HBV DNA detection rates were 47.55% among HBsAg positive samples and 4.08% among Anti-HBc positive samples. The signal-to-cutoff (S/CO) ratio median of HBV NAT positive samples was superior in comparison to HBV NAT negative samples (p < 0.0001). The thresholds found to optimize sensitivity and specificity were 404.15 for Architect HBsAg and 7.77 for Architect Anti-HBc. Three blood donors were in the window period and 1 occult HBV infection case was detected. Conclusion: High S/CO ratios were more predictive of HBV DNA detection. However, a number of HBV NAT positive samples gave low values, while some HBV NAT negative samples showed high values, reaffirming the significance of molecular testing to enhance transfusion safety.

11.
Viruses ; 15(11)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38005864

RESUMO

The hepatitis B virus (HBV), comprising of ten genotypes (A-J), has been a silent threat against humanity, constituting a public health problem worldwide. In 2016, the World Health Organization set forth an impressive initiative for the global elimination of viral hepatitis by 2030. As the target date approaches, many nations, particularly in the Latin American region, face challenges in designing and implementing their respective elimination plan. This review aimed to portray the state of knowledge about the epidemiological, molecular, and clinical characteristics of HBV genotype H (HBV/H), endemic to Mexico. PubMed, Scopus, Web of Science, and Google Scholar were searched to compile scientific literature over 50 years (1970-2022). A total of 91 articles were organized into thematic categories, addressing essential aspects such as epidemiological data, risk factors, HBV genotype distribution, HBV mixed infections, clinical characteristics, and vaccination. The prevalence and its associated 95% confidence interval (95% CI) were estimated using the Metafor package in R programming language (version 4.1.2). We provide insights into the strengths and weaknesses in diagnostics and prevention measures that explain the current epidemiological profile of HBV/H. Training, research, and awareness actions are required to control HBV infections in Mexico. These actions should contribute to creating more specific clinical practice guides according to the region's characteristics. Mexico's elimination plan for HBV will require teamwork among the government health administration, researchers, physicians, specialists, and civil society advocates to overcome this task jointly.


Assuntos
Vírus da Hepatite B , Hepatite B , Humanos , Vírus da Hepatite B/genética , México/epidemiologia , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/genética , Genótipo , Prevalência , DNA Viral/genética
12.
J Med Virol ; 95(10): e29195, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37881005

RESUMO

Hepatitis B e antigen (HBeAg) loss represents a late stage of chronic hepatitis B virus (HBV) infection associated with a drastic decrease in HBV-DNA, a lower risk of disease progression, and the occurrence of several mutations in the preCore/core region. However, the underlying mechanisms supporting the downregulation of viral replication have yet to be elucidated. In the present study, the analysis of the frequency of subgenotype D1 core protein (HBc) mutations associated with HBeAg status revealed a higher mutation rate in HBeAg-negative sequences compared to HBeAg-positive ones. Particularly, 22 amino acids exhibited a higher frequency of mutation in HBeAg-negative sequences, while the remaining residues showed a high degree of conservation. Subsequently, the assessment of HBc mutants derived from HBeAg-negative patients in viral structure and replicative capacity revealed that HBc mutations have the ability to modulate the subcellular localization of the protein (either when the protein was expressed alone or in the context of viral replication), capsid assembly, and, depending on specific mutation patterns, alter covalently closed circular DNA (cccDNA) recycling and up- or downregulate viral replication. In conclusion, HBc mutations associated with HBeAg-negative status impact on various stages of the HBV life cycle modulating viral replication during the HBeAg-negative stage of infection.


Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Humanos , Antígenos E da Hepatite B/genética , Antígenos E da Hepatite B/análise , Mutação , Replicação Viral , DNA Viral/genética , DNA Viral/análise
13.
Pathogens ; 12(9)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37764954

RESUMO

Hepatitis B virus (HBV) is a challenge for global health services, affecting millions and leading thousands to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. HBV genotyping has revealed unique geographical patterns and relationships with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the human host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

14.
Braz J Microbiol ; 54(4): 3299-3305, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37673839

RESUMO

Duck hepatitis B virus (DHBV) infection model was frequently used as the experimental model for human hepatitis B virus (HBV) research. In order to decipher the genetic characteristics of DHBVs from Anhui province of China, 120 duck liver tissue samples were collected and subjected to PCR screening, and 28 samples were detected as DHBV positive. Subsequently, five DHBV-positive samples were selected for genome-wide amplification and a comprehensive analysis. Comparative analysis of complete genome sequences using the MegAlign program showed that five strains of DHBVs shared 94.5-96.3% with each other and 93.2-98.7% with other reference strains in GenBank. The phylogenetic analysis showed that all five DHBV strains belonged to the evolutionary branch of "Chinese DHBV" isolates or DHBV-2. Importantly, three potential intra-genotypic recombination events, between strains AAU-6 and Guilin, strains AAU-1 and GD3, and strains AAU-6 and AAU-1, were respectively found using the RDP and SimPlot softwares and considered the first report in avihepadnaviruses. These results not only improve our understanding for molecular prevalence status of DHBV among ducks, but also provide a reference for recombination mechanism of HBV.


Assuntos
Vírus da Hepatite B do Pato , Animais , Humanos , Vírus da Hepatite B do Pato/genética , Filogenia , Reação em Cadeia da Polimerase/métodos , Vírus da Hepatite B/genética , Patos/genética , Patos/microbiologia , DNA Viral/genética , Fígado
15.
Am J Transl Res ; 15(8): 4971-4983, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37692960

RESUMO

OBJECTIVE: Despite the availability of a highly effective and safe vaccine against hepatitis B virus (HBV) infection for 40 years, still almost 300 million persons are estimated to be chronically infected by this virus worldwide. The World Health Organization (WHO) has proposed a plan for hepatitis elimination by 2030. However, several factors, such as the reduction and limitation in vaccination campaigns or vaccine hesitancy (VH) in some regions of the World, might have played a role in limiting the worldwide coverage of hepatitis B prophylaxis. This review aims to describe which factors, such as VH, may be hampering the WHO 2030 goal for hepatitis B eradication. METHODS: The review describes the development and characteristics of the HBV vaccine, from the first plasma-derived to the recombinant one. Eventual limitations in its effectiveness and particularly VH were reviewed. RESULTS: The apparent pitfalls of the HBV vaccine, such as long-term effectiveness, vaccine-escape mutants, and adverse effects, were proven not to be a concern for this vaccine. However, VH persists and was even intensified by the COVID-19 pandemic. CONCLUSIONS: Many barriers still exist, such as vaccine availability, lack of awareness of the benefits of HBV vaccination, and VH. HBV VH seems to be eventually overcome in many settings with active education campaigns and information, stressing the importance of developing these strategies to achieve the 2030 goal of the WHO.

16.
J Clin Transl Hepatol ; 11(5): 1023-1034, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37577226

RESUMO

Background and Aims: Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations. Methods: This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger's sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool. Results: Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L (n=2) and rt180M+rt204V+rt202G (n=1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18). Conclusions: The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico.

17.
Front Public Health ; 11: 1162705, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325314

RESUMO

Background: Hard-to-reach, vulnerable and cross-border populations are often disproportionately affected by communicable diseases. Epidemiological data on viral hepatitis in French Guiana and Suriname are available for urban areas, but not for remote communities. The Maroni River, which separates FG and Suriname, is home to Tribal and Indigenous communities. Reaching these populations is challenging due to logistical constraints, cultural and language barriers, and mistrust of outsiders. Objectives: We aimed to conduct an epidemiological study of viral hepatitis [Maroni Hepatites Virales (MaHeVi)] in this remote and complex area. Here, we describe the operational hurdles and solutions required to achieve this. Methods: We undertook a preliminary assessment of the area with local community leaders and health workers to gain approval of MaHeVi, acceptance of blood sampling, and suggestions for adapting the study to cultural and logistical constraints. Anthropological assessments were conducted through focus groups and interviews with key individuals to assess knowledge, beliefs and risk factors for VH. Results: MaHeVi was well received by the local communities. The approval of the community leaders was crucial for the implementation and acceptance of the study. The main adaptations were hiring community health mediators to overcome cultural and language differences, using blotting paper instead of venipuncture for logistical and acceptability reasons, and adapting communication materials. Conclusion: Careful preparation and tailoring of the communication materials and research protocol have enabled the successful implementation of the study. This process could be replicated in this area and transferred to other complex contexts combining borders, logistical hurdles and populations requiring cultural adaptations.


Assuntos
Hepatite Viral Humana , Humanos , Guiana Francesa/epidemiologia , Suriname/epidemiologia , Fatores de Risco , Estudos Epidemiológicos
18.
Viruses ; 15(6)2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37376630

RESUMO

Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV) can be transmitted by blood transfusion. Most transmission occurs during the acute viremic phase (AVP), before antibody development. To reduce transmission risk, individual donor nucleic acid testing (ID-NAT) is used. In Puebla, Mexico, serological tests and ID-NAT have been applied to screen blood donors and detect individuals in AVP. In the present study, 106,125 blood donors' data in two periods (2012-2015 and 2017-2019) were analyzed. The residual risk (RR) values were calculated considering ID-NAT results. The RR for HIV was 14 in 1 million donations or 1 in 71,428, the RR for HVC was 6.8 in 1 million donations or 1 in 147,058 and, for HBV, it was 156 in 1 million donations, or 1 in 6410. Previously, it was predicted that the transmission RR of these viruses would be reduced in Mexico through better screening with NAT. The use of ID-NAT has, indeed, increased the safety of blood reserves for HIV and HCV. However, more research is needed to determine why the residual risk of HBV did not decrease as much over the study period. ID-NAT is an important complementary tool for blood donor screening that should be implemented.


Assuntos
Infecções por HIV , HIV-1 , Hepatite B , Hepatite C , Humanos , Vírus da Hepatite B/genética , Hepacivirus/genética , Bancos de Sangue , México/epidemiologia , Centros de Atenção Terciária , HIV-1/genética , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Doadores de Sangue , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Viremia/diagnóstico , Doença Iatrogênica , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Técnicas de Amplificação de Ácido Nucleico/métodos
19.
Biomedicines ; 11(6)2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37371770

RESUMO

Hepatitis B virus (HBV) is an enveloped DNA human virus belonging to the Hepadnaviridae family. Perhaps its main distinguishable characteristic is the replication of its genome through a reverse transcription process. The HBV circular genome encodes only four overlapping reading frames, encoding for the main canonical proteins named core, P, surface, and X (or HBx protein). However, pre- and post-transcriptional gene regulation diversifies the full HBV proteome into diverse isoform proteins. In line with this, hepatitis B virus X protein (HBx) is a viral multifunctional and regulatory protein of 16.5 kDa, whose canonical reading frame presents two phylogenetically conserved internal in-frame translational initiation codons, and which results as well in the expression of two divergent N-terminal smaller isoforms of 8.6 and 5.8 kDa, during translation. The canonical HBx, as well as the smaller isoform proteins, displays different roles during viral replication and subcellular localizations. In this article, we reviewed the different mechanisms of pre- and post-transcriptional regulation of protein expression that take place during viral replication. We also investigated all the past and recent evidence about HBV HBx gene regulation and its divergent N-terminal isoform proteins. Evidence has been collected for over 30 years. The accumulated evidence simply strengthens the concept of a new paradigm of the canonical HBx, and its smaller divergent N-terminal isoform proteins, not only during viral replication, but also throughout cell pathogenesis.

20.
Mol Biol Rep ; 50(8): 6435-6443, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37326752

RESUMO

BACKGROUND: Acute or chronic HBV infection in an individual can be laboratory characterized according to the serological profile of the viral markers in the bloodstream, and the dynamics monitoring of these markers is necessary to assess the disorder course and the infection outcome. However, under certain circumstances unusual or atypical serological profiles may be observed in both acute and chronic HBV infection. They are considered as such because they do not properly characterize the form or infection clinical phase or because they seem inconsistent, considering the viral markers dynamics in both clinical contexts. This manuscript comprises the analysis of an unusual serological profile in HBV infection. METHODS AND RESULTS: This clinical-laboratory study, had as reference a patient who presented clinical profile suggestive of acute HBV infection after recent exposure, whose laboratory data were initially compatible with this clinical presentation. However, the serological profile analysis and its monitoring demonstrated unusual pattern of viral markers expression, which has been observed in several clinical contexts, and is often associated a number of agent- or host-related factors. CONCLUSION: The serological profile analyzed here, associated with the biochemical markers serum levels found, is indicative of active chronic infection, consequence of viral reactivation. This finding suggests that in the event of unusual serological profiles in HBV infection, if the influence of agent- or host-related factors is not properly considered and neither the viral markers dynamics properly analyzed, there may be mistake in the infection clinical diagnosis, especially when the patient's clinical and epidemiological history is unknown.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Antígenos de Superfície da Hepatite B , Biomarcadores , DNA Viral
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