RESUMEN
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.
Asunto(s)
Hepatitis C Crónica/epidemiología , Hepatitis D Crónica/epidemiología , Virus de la Hepatitis Delta/aislamiento & purificación , Necrosis Hepática Masiva/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Hepacivirus/aislamiento & purificación , Anticuerpos Antihepatitis/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/virología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Hepatitis D Crónica/complicaciones , Hepatitis D Crónica/diagnóstico , Hepatitis D Crónica/virología , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/inmunología , Humanos , Pueblos Indígenas/estadística & datos numéricos , Masculino , Necrosis Hepática Masiva/diagnóstico , Necrosis Hepática Masiva/virología , Persona de Mediana Edad , ARN Viral/aislamiento & purificación , Venezuela/epidemiología , Adulto JovenRESUMEN
A basic question linked to differential patterns of gene expression is how cells reach different fates despite using the same DNA template. Since 5-hydroxymethylcytosine (5hmC) emerged as an intermediate metabolite in active DNA demethylation, there have been increasing efforts to elucidate its function as a stable modification of the genome, including a role in establishing such tissue-specific patterns of expression. Recently we described TET1-mediated enrichment of 5hmC on the promoter region of the master regulator of hepatocyte identity, HNF4A, which precedes differentiation of liver adult progenitor cells in vitro. Here, we studied the genome-wide distribution of 5hmC at early in vitro differentiation of human hepatocyte-like cells. We found a global increase in 5hmC as well as a drop in 5-methylcytosine after one week of in vitro differentiation from bipotent progenitors, at a time when the liver transcript program is already established. 5hmC was overall higher at the bodies of overexpressed genes. Furthermore, by modifying the metabolic environment, an adenosine derivative prevents 5hmC enrichment and impairs the acquisition of hepatic identity markers. These results suggest that 5hmC could be a marker of cell identity, as well as a useful biomarker in conditions associated with cell de-differentiation such as liver malignancies.
Asunto(s)
5-Metilcitosina/análogos & derivados , Diferenciación Celular/genética , Metilación de ADN/genética , Factor Nuclear 4 del Hepatocito/genética , Oxigenasas de Función Mixta/genética , Proteínas Proto-Oncogénicas/genética , 5-Metilcitosina/metabolismo , Desmetilación del ADN , Regulación del Desarrollo de la Expresión Génica/genética , Genoma/genética , Hepatocitos/metabolismo , Humanos , Regiones Promotoras Genéticas/genética , Células Madre/metabolismoRESUMEN
BACKGROUND: Occult hepatitis B infection (OBI) is characterized by the presence of hepatitis B virus (HBV) DNA in the absence of HBsAg in the serum of patients. The aim of this study was to characterize HBV infection among a Piaroa community, an Amerindian group which exhibits significant evidence of exposure to HBV but relatively low presence of HBsAg, and to explore the presence of OBI in this population. RESULTS: Of 150 sera, with 17% anti-HBc and 1.3% HBsAg prevalence, 70 were tested for the presence of HBV DNA. From these, 25 (36%) were found positive for HBV DNA by PCR in the core region. Two of these 25 sera were HBsAg positive, indicating an overt infection. Of the remaining 68 sera tested, 23 exhibited OBI. Of these, 13 were HBV DNA out of 25 anti-HBc positive (52%) and 10 HBV DNA positive, out of 43 anti-HBc negative (23%), with a statistical significance of p = 0.03. Viral DNA and HBsAg were present intermittently in follow up sera of 13 individuals. Sequence analysis in the core region of the amplified DNA products showed that all the strains belonged to HBV genotype F3. The OBI isolates displayed 96-100% nucleotide identity between them. One isolate exhibited the co-circulation of a wild type variant with a variant with a premature stop codon at the core protein, and a variant exhibiting a deletion of 28 amino acids. CONCLUSIONS: The frequency of OBI found in this Amerindian group warrants further studies in other communities exhibiting different degrees of HBV exposure.
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Indio Americano o Nativo de Alaska , Biomarcadores/sangre , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Niño , Preescolar , Femenino , Genotipo , Anticuerpos contra la Hepatitis B/inmunología , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/etnología , Hepatitis B Crónica/inmunología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Prevalencia , Venezuela/epidemiologíaRESUMEN
Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related death worldwide. Globally, the most important HCC risk factors are Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV), chronic alcoholism, and dietary exposure to aflatoxins. We have described the epidemiological pattern of 202 HCC samples obtained from Colombian patients. Additionally we investigated HBV/HCV infections and TP53 mutations in 49 of these HCC cases. HBV biomarkers were detected in 58.1% of the cases; HBV genotypes F and D were characterized in three of the samples. The HCV biomarker was detected in 37% of the samples while HBV/HCV coinfection was found in 19.2%. Among TP53 mutations, 10.5% occur at the common aflatoxin mutation hotspot, codon 249. No data regarding chronic alcoholism was available from the cases. In conclusion, in this first study of HCC and biomarkers in a Colombian population, the main HCC risk factor was HBV infection.
RESUMEN
Hepatitis B viruses (HBV) are responsible for over 50% of the worldwide attributable risk of hepatocellular carcinoma (HCC) and this figure increases even further in regions of high endemicity. Systematic sequencing of HBV genomes has identified that this common virus existed as eight distinct genotypes (denoted A-H), each regrouping variants with less than 8% divergence in their DNA sequence. These genotypes differ by their geographic distribution in populations around the globe. There is evidence that HBV genotypes also differ by their pathogenic properties, including their risk of persistence as chronic infection and their capacity to induce precursor disease or cancer. On the other hand, HBV genes may undergo mutations that become selected during the course of chronic infection and progressive liver disease. The most significant of these mutations in the context of HCC are those occurring in the pre-core (Pre-C) and basal core promoter (BCP) regions. These mutations may upregulate HBV expression and increase its virulence. These mutations may occur in all HBV genotypes but are more common in genotypes associated with more severe disease and cancer, in particular genotype C. Understanding the molecular basis of pathological variations between HBV variants is critical for prediction of disease severity. It will also be important to determine whether differences among genotypes may have an impact on the long-term protective efficacy of universal HBV vaccination.
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Carcinoma Hepatocelular/virología , Variación Genética , Virus de la Hepatitis B/genética , Neoplasias Hepáticas/virología , Genoma Viral , Genotipo , Humanos , Mutación , Regiones Promotoras Genéticas , Factores de RiesgoRESUMEN
A sentinel study on viral hepatitis is currently being carried out in the village of Cavunge in a semiarid rural region of the state of Bahia, northeastern Brazil. This study has identified individuals in whom anti-HBc IgG was the only serological marker for hepatitis B virus (HBV). This serological pattern may constitute evidence of occult HBV infection. This study Investigated the possibility of occult hepatitis B virus infection in individuals in a rural community who tested positive for anti-HBc IgG alone. A cross-sectional population-based study. ELISA III was performed on serum samples to test for serological viral markers, and ultrasensitive PCR (US-PCR) was used to assess viremia. Among the 1,536 serum samples, 3.6% (n=55) were positive for anti-HBc alone. Four years after this first serological survey, 31 of those 55 individuals (56.3%) were retested, and 11 (35.5%) remained anti-HBc positive alone. Two of these 31 (6.5%) were HBV-DNA positive based on US-PCR, with normal aminotransferase levels in both cases. Cases of occult hepatitis B infection were identified in this semiarid rural community of northeastern Brazil, where endemicity of HBV is moderate.
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Enfermedades Endémicas , Anticuerpos Antihepatitis/sangre , Hepatitis B/diagnóstico , Inmunoglobulina G/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Brasil/epidemiología , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis B/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Población Rural , Sensibilidad y Especificidad , Vigilancia de GuardiaRESUMEN
A sentinel study on viral hepatitis is currently being carried out in the village of Cavunge in a semiarid rural region of the state of Bahia, northeastern Brazil. This study has identified individuals in whom anti-HBc IgG was the only serological marker for hepatitis B virus (HBV). This serological pattern may constitute evidence of occult HBV infection. This study Investigated the possibility of occult hepatitis B virus infection in individuals in a rural community who tested positive for anti-HBc IgG alone. A cross-sectional population-based study. ELISA III was performed on serum samples to test for serological viral markers, and ultrasensitive PCR (US-PCR) was used to assess viremia. Among the 1,536 serum samples, 3.6 percent (n=55) were positive for anti-HBc alone. Four years after this first serological survey, 31 of those 55 individuals (56.3 percent) were retested, and 11 (35.5 percent) remained anti-HBc positive alone. Two of these 31 (6.5 percent) were HBV-DNA positive based on US-PCR, with normal aminotransferase levels in both cases. Cases of occult hepatitis B infection were identified in this semiarid rural community of northeastern Brazil, where endemicity of HBV is moderate.