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1.
Adv Exp Med Biol ; 1287: 69-80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034027

RESUMO

Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille syndrome, which is caused by mutations in the Jagged1 gene. Notch activation and hepatocarcinogenesis are closely associated since cancer signaling is affected by the development of liver cells and cancer stem cells. Gene expression and genomic analysis using a microarray revealed that abnormalities in Notch-related genes were associated with the aggressiveness of liver cancer. This pattern was also accompanied with α-fetoprotein- and EpCAM-expressing phenotypes in vitro, in vivo, and in clinical tissues. Hepatitis B or C virus chronic infection or alcohol- or steatosis-related liver fibrosis induces liver cancer. Previous reports demonstrated that HBx, a hepatitis B virus protein, was associated with Jagged1 expression. We found that the Jagged1 and Notch1 signaling pathways were closely associated with the transcription of covalently closed circular hepatitis B virus DNA, which regulated cAMP response element-binding protein, thereby affecting Notch1 regulation by the E3 ubiquitin ligase ITCH. This viral pathogenesis in hepatocytes induces liver cancer. In conclusion, Notch signaling exerts various actions and is a clinical signature associated with hepatocarcinogenesis and liver context-related developmental function.


Assuntos
Neoplasias Hepáticas , Receptores Notch/metabolismo , Transdução de Sinais , Hepatite/metabolismo , Hepatite/virologia , Vírus da Hepatite B/patogenicidade , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
2.
Arch Virol ; 165(10): 2361-2365, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32743697

RESUMO

In this study, we investigated the seroprevalence of anti-hepatitis D virus (HDV) antibodies in hepatitis B surface antigen (HBsAg)-positive children after 25 years of obligatory vaccination of infants against hepatitis B virus. This cross-sectional study included 120 treatment-naïve HBsAg-positive children, with a male-to-female ratio of 1.8:1 and a mean age of 7.8 ± 3.8 years (range, 1-17 years). Mothers were positive for HBsAg in 96.6% of the cases. HBeAg-positive chronic infection was observed in 60% of the cases, HBeAg-positive chronic hepatitis in 12.5%, and HBeAg-negative chronic infection in 26.7%. Anti-HDV antibodies were not detected in any of the cases. Thus, there is a lack of anti-HDV antibodies in HBsAg-positive children, despite the current burden in adults.


Assuntos
Anticorpos Anti-Hepatite/sangue , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Hepatite D Crônica/epidemiologia , Vírus Delta da Hepatite/imunologia , Adolescente , Criança , Pré-Escolar , Coinfecção , Estudos Transversais , Egito/epidemiologia , Feminino , Hepatite B/imunologia , Hepatite B/prevenção & controle , Hepatite B/virologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Hepatite D Crônica/sangue , Hepatite D Crônica/imunologia , Hepatite D Crônica/virologia , Vírus Delta da Hepatite/patogenicidade , Humanos , Lactente , Masculino , Estudos Soroepidemiológicos
3.
Medicine (Baltimore) ; 99(29): e21179, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702877

RESUMO

Nowadays most of the hepatitis B virus (HBV) infected population are adults, among which hepatitis B e antigen (HBeAg) negative infection occupied the largest proportion of HBV infection in China. HBeAg-negative patients are heterogeneous, and the corresponding interventions are different. Therefore, it is worth researching the infection characteristics of HBeAg-negative patients to help guide the interventions.A total of 11,738 treatment-naïve HBeAg-negative adult patients were randomly selected, and their demographic and medical history information were collected. The liver biochemistry, and HBV infection biomarkers including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg, hepatitis B e antibody (anti-HBe), hepatitis B core antibody (anti-HBc), and hepatitis B virus deoxyribonucleic acid (HBV-DNA) levels were tested. The infection characteristics and their influencing factors were explored.Sixty percent of the patients presented HBV-DNA-positive, of which 31.2% had HBV-DNA level higher than 2000 IU/mL, and 16.5% had HBV-DNA level higher than 20,000 IU/mL. HBV-DNA levels tended to increase along with the increasing of age, and the male patients had significant higher HBV-DNA levels than the female patients. Twenty-four percent of the patients had abnormal transaminase. The male patients were more vulnerable to abnormal transaminase (30.0%) than the female patients (18.4%). Fifty-five percent patients with HBV-DNA ≥20,000 IU/mL presented abnormal alanine aminotransferase (ALT) or aspartate transaminase (AST), which was significantly higher than that of patients with HBV-DNA levels below 20,000 IU/mL (19.0-21.7%). Multivariate logistic regression analyses revealed that the male patients and the patients with higher viral load had higher risk of having abnormal liver function.A considerable number of HBeAg-negative patients were virological active and had liver damage. It is necessary and urgent to carry out regular active interventions for the chronic HBV-infected patients.


Assuntos
Antígenos E da Hepatite B/análise , Vírus da Hepatite B/classificação , Hepatite B/virologia , Adulto , Idoso , Distribuição de Qui-Quadrado , China , Feminino , Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Humanos , Fígado/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Testes Sorológicos
4.
J Vis Exp ; (160)2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32568248

RESUMO

HBV mainly infects human hepatocytes, but it has also been found to infect extrahepatic tissues such as kidney and testis. Nonetheless, cell-based HBV models are limited to hepatoma cell lines (such as HepG2 and Huh7) overexpressing a functional HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP). Here, we used 293T-NE-3NRs (293T overexpressing human NTCP, HNF4α, RXRα and PPARα) and HepG2-NE (HepG2 overexpressing NTCP) as model cell lines. HBV infection in these cell lines was performed either by using concentrated HBV virus particles from HepG2.2.15 or co-culturing HepG2.2.15 with the target cell lines. HBcAg immunofluorescence for HBcAg was performed to confirm HBV infection. The two methods presented here will help us study HBV infection in non-hepatic cell lines.


Assuntos
Células HEK293/metabolismo , Células Hep G2/metabolismo , Vírus da Hepatite B/patogenicidade , Hepatite B/virologia , Hepatócitos/metabolismo , Humanos
5.
Acta Virol ; 64(2): 177-186, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32551786

RESUMO

Infection with hepatitis B virus (HBV) often leads to development of chronic liver disease. In fact, 10% of infected adults and almost 90% of infected infants develop chronic hepatitis B associated with severe liver diseases, including acute liver failure, liver cirrhosis or hepatocellular carcinoma. At present there is no effective cure for chronic hepatitis B. The current treatment of chronically infected patients is long-term, expensive and relies on treatment with nucleos(t)ide analogs in combination with immune therapies, that frequently lead to adverse side effects. Recently, the National Institute of Health proposed strategic plan for Trans-NIH research to cure hepatitis B. The key priority is better understanding of HBV life cycle and its interactions with host cell. Due to the fact that HBV is a small double stranded DNA virus encoding only a limited number of proteins, HBV replication widely relies on host cell pathways and proteins. As demonstrated by numerous reports, HBV core protein (HBc) which is the main component of viral nucleocapsid, plays multiple roles in HBV life cycle and is engaged in many protein interaction networks of the host cell. Several recent studies have shown that HBV proteins can be modified by different types of posttranslational modifications (PTMs) that affect their protein-protein interactions, subcellular localization and function. In this review, we discuss diverse PTMs of HBc and their role in regulation of HBc function in the context of HBV replication and pathogenesis. Keywords: hepatitis B virus; posttranslational modifications; HBV core protein; phosphorylation; ubiquitination; arginine methylation.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B/química , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica , Interações Hospedeiro-Patógeno , Processamento de Proteína Pós-Traducional , Vírus da Hepatite B/genética , Humanos
6.
Am J Trop Med Hyg ; 103(1): 169-174, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32431268

RESUMO

Hepatitis D virus (HDV) genotype III is endemic in the western Amazon basin and is considered to cause the most severe form of chronic viral hepatitis. Recently, noninvasive fibrosis scores to determine the stage of liver fibrosis have been evaluated in individuals positive for HDV genotype I, but their utility in HDV genotype III-positive patients is unknown. In this retrospective study conducted in an outpatient viral hepatitis referral clinic in the Brazilian Amazon region, the aspartate aminotransferase (AST) to Aspartate aminotransferase to Platelet Ratio Index (APRI) and Fibrosis Index for Liver Fibrosis (FIB-4) values were calculated and compared with histological fibrosis stages. Among the 50 patients analyzed, the median age at liver biopsy was 35.6 years, 66% were male, and all had compensated liver disease. Histological staging revealed fibrosis stages 0, 1, 2, 3, and 4 in four (8%), eight (16%), 11 (22), 11 (22%), and 16 (32%) patients, respectively. The area under the receiver operating curve (AUROC) of AST-to-alanine aminotransferase (ALT) ratio, APRI, and FIB-4 for detection of significant fibrosis (F ≥ 2) was 0.550 (P = 0.601), 0.853 (P < 0.001), and 0.853 (P < 0.0001), respectively. Lower AUROC values were obtained for cirrhosis: the AST-to-ALT ratio was 0.640 (P = 0.114), APRI was 0.671 (P = 0.053), and FIB-4 was 0.701 (P = 0.023). The optimal cutoff value for significant fibrosis for APRI was 0.708 (sensitivity 84% and specificity 92%) and for FIB-4 was 1.36 (sensitivity 76% and specificity 92%). Aspartate aminotransferase to Platelet Ratio Index and FIB-4 were less useful to predict cirrhosis. In contrast to recent reports from Europe and North America, both APRI and FIB-4 may identify significant fibrosis in HDV-III-infected patients from northwestern Brazil.


Assuntos
Vírus da Hepatite B/patogenicidade , Hepatite B/diagnóstico , Hepatite D/diagnóstico , Vírus Delta da Hepatite/patogenicidade , Cirrose Hepática/diagnóstico , Adulto , Alanina Transaminase/metabolismo , Área Sob a Curva , Aspartato Aminotransferases/metabolismo , Biomarcadores/análise , Plaquetas/patologia , Plaquetas/virologia , Brasil , Doença Crônica , Coinfecção , Feminino , Hepatite B/enzimologia , Hepatite B/patologia , Hepatite B/virologia , Hepatite D/enzimologia , Hepatite D/patologia , Hepatite D/virologia , Humanos , Cirrose Hepática/enzimologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Contagem de Plaquetas , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença
7.
BMC Med Genet ; 21(1): 88, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357928

RESUMO

BACKGROUND: Interleukin (IL) 28B polymorphisms encoding pro-inflammatory and anti-inflammatory cytokines trigger diverse clinical outcome of hepatitis virus infection. However, there is controversy concerning the association of IL28B polymorphisms with the outcome of hepatitis B virus (HBV) infection, with several studies obtaining inconsistent results. We performed a meta-analysis to evaluate the role of 3 single nucleotide polymorphisms (SNPs) rs12979860, rs12980275 and rs8099917 in the progression of HBV infection, overall and by ethnicity. METHODS: Searched PubMed, Embase and Wiley Online Library electronic databases using 'interleukin 28B', 'IL 28B', 'IL 28B polymorphism', 'hepatitis B virus', 'HBV', and performed meta- analysis for rs12979860, rs12980275 and rs8099917 in Asian and Caucasian populations under the dominant recessive and allele model. RESULTS: Eighteen studies were found in total and used for this meta-analysis, including 5587 cases and 4295 controls. The IL28B polymorphism rs12979860 had no association with HBV persistence (CC vs CT + TT: OR = 0.86, 95% CI = 0.76-1.00; TT vs CT + CC: OR = 1.14, 95% CI = 0.76-1.70; T vs C: OR = 1.03, 95% CI = 0.94-1.13). Similarly, neither rs12980275 nor rs8099917 had associations with HBV persistence (rs12980275 in AA vs AG + AA: OR = 1.15, 95% CI = 0.96-1.38; rs8099917 in TT vs GT + GG: OR = 1.15, 95% CI = 0.96-1.39). There was also no significant association of IL28B polymorphisms with persistent HBV infection in Asians or Chinese. There was no evidence of an association of rs12979860 with the HBV-related hepatocellular carcinoma susceptibility (T vs C: OR = 1.53, 95% CI = 0.96-2.43). CONCLUSION: IL28B polymorphisms had no association with the outcome of HBV infection overall, nor in the Asians and the Chinese. These 3 SNPs might not be relevant to the development of HBV infection.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Hepatite B/genética , Interferons/genética , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Genótipo , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/patogenicidade , Humanos , Interleucinas/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética
8.
Nat Struct Mol Biol ; 27(6): 581-588, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32451488

RESUMO

TENT4 enzymes generate 'mixed tails' of diverse nucleotides at 3' ends of RNAs via nontemplated nucleotide addition to protect messenger RNAs from deadenylation. Here we discover extensive mixed tailing in transcripts of hepatitis B virus (HBV) and human cytomegalovirus (HCMV), generated via a similar mechanism exploiting the TENT4-ZCCHC14 complex. TAIL-seq on HBV and HCMV RNAs revealed that TENT4A and TENT4B are responsible for mixed tailing and protection of viral poly(A) tails. We find that the HBV post-transcriptional regulatory element (PRE), specifically the CNGGN-type pentaloop, is critical for TENT4-dependent regulation. HCMV uses a similar pentaloop, an interesting example of convergent evolution. This pentaloop is recognized by the sterile alpha motif domain-containing ZCCHC14 protein, which in turn recruits TENT4. Overall, our study reveals the mechanism of action of PRE, which has been widely used to enhance gene expression, and identifies the TENT4-ZCCHC14 complex as a potential target for antiviral therapeutics.


Assuntos
Citomegalovirus/genética , Vírus da Hepatite B/genética , Interações Hospedeiro-Patógeno/fisiologia , RNA Viral/metabolismo , Linhagem Celular , Citomegalovirus/patogenicidade , Vírus da Hepatite B/patogenicidade , Humanos , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Filogenia , RNA Nucleotidiltransferases/genética , RNA Nucleotidiltransferases/metabolismo , RNA Viral/química
9.
Artigo em Inglês | MEDLINE | ID: mdl-32397342

RESUMO

Background: The aim of our work is to objectify the manner of transmission of HBV infection in young adult and middle-aged Roma people who live in the settlements. Methods: We used data from the cross-sectional study HepaMeta. We analyzed Roma people living in the settlements in East Slovakia, who have had HBsAg and anti HBc IgG antibodies examined. Results: We analyzed a cohort of 452 Roma participants with a mean of age 34.67 ± 9.14 years-159 (35.2%) were males. HBsAg positivity was diagnosed in 12.4% and the presence of anti HBc IgG antibodies was confirmed in 52% of participants. Prevalence of HBsAg positivity increases significantly with higher age, (p = 0.026), as well as the presence of anti HBc IgG antibodies (p < 0.0001). The prevalence of HBsAg positivity has doubled and anti HBc IgG positivity has tripled within two decades (<25 years vs. 35-45 years) in Roma settlements in East Slovakia. Conclusions: These findings allow us to express an opinion that horizontal transmission in adulthood may play an important role in the spreading of HBV infection.


Assuntos
Vírus da Hepatite B , Hepatite B , Roma , Abuso de Substâncias por Via Intravenosa , Adulto , Idoso , Estudos Transversais , Hepatite B/epidemiologia , Hepatite B/transmissão , Anticorpos Anti-Hepatite B , Vírus da Hepatite B/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , Eslováquia/epidemiologia , Adulto Jovem
10.
PLoS One ; 15(4): e0232211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32330203

RESUMO

BACKGROUND: Circulating microRNAs (miRNAs) have been shown to dysregulate in many cancer types including hepatocellular carcinoma (HCC). The purpose of this study was to examine the potential diagnostic or prognostic roles of circulating miRNAs in patients with hepatitis B virus (HBV)-related HCC. METHODS: Paired cancerous and adjacent non-cancerous liver tissue specimens of patients with HBV-related HCC were used as a discovery set for screening 800 miRNAs by a Nanostring quantitative assay. Differentially expressed miRNAs were then examined by SYBR green quantitative RT-PCR in a validation cohort of serum samples obtained from 70 patients with HBV-related HCC, 70 HBV patients without HCC and 50 healthy controls. RESULTS: The discovery set identified miR-223-3p, miR-199a-5p and miR-451a significantly lower expressed in cancerous tissues compared with non-cancerous tissues. In the validated cohort, circulating miR-223-3p levels were significantly lower in the HCC group compared with the other groups. The combined use of serum alpha-fetoprotein and miR-223-3p displayed high sensitivity for detecting early HCC (85%) and intermediate/advanced stage HCC (100%). Additionally, serum miR-223-3p had a negative correlation with tumor size and BCLC stage. On multivariate analysis, serum miR-223-3p was identified as an independent prognostic factor of overall survival in patients with HCC. In contrast, circulating miRNA-199a-5p and miR-451a did not show any clinical benefit for the diagnosis and prognostic prediction of HCC. CONCLUSIONS: Our results demonstrated that miR-223-3p was differentially expressed in cancerous compared with paired adjacent non-cancerous tissues. In addition, circulating miRNA-223-3p could represent a novel diagnostic and prognostic marker for patients with HBV-related HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , MicroRNA Circulante/genética , Hepatite B Crônica/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico
11.
PLoS One ; 15(4): e0232208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32320459

RESUMO

INTRODUCTION: Hepatitis B virus infection is a global public health problem. Though, the disease is endemic in sub-Saharan Africa, little is known about its epidemiology among pregnant women in Ghana. This study sought to determine the seroprevalence of Hepatitis B virus infection and associated factors among pregnant women attending antenatal care at Korle-Bu Teaching Hospital; Ghana's largest hospital. METHODS: We conducted a facility-based cross-sectional survey among 232 antenatal attendants. Participants were recruited using systematic random sampling technique and screened with HBsAg Rapid Test. Data was analyzed with the aid of Statistical Package for Social Sciences (SPSS), version 23.0. Results were presented using descriptive statistics, Fisher's Exact test and Logistic Regression analysis. RESULTS: Two hundred and twenty-one (221) of the total sample (n = 232) agreed to participate in this study; representing a response rate of 95%. The mean age of the participants was 31 years and standard deviation of 5.3. The mean gestational period at recruitment was 28 weeks and standard deviation of 6.8. Majority of the participants were married (83.3%), parous (69.6%), educated (91.4%) and employed (90.5%). The prevalence of HBsAg was 7.7%. We found no significant association between socio-demographic characteristics of the participants and HBV infection. CONCLUSION: Seroprevalence of 7.7% indicates moderate endemicity. Socio-demographic characteristics did not influence HBV infection among pregnant women attending antenatal care at Korle-Bu Teaching Hospital. The findings provide empirical evidence that will contribute to knowledge of HBV epidemiology in Ghana.


Assuntos
Vírus da Hepatite B/patogenicidade , Hepatite B/epidemiologia , Adolescente , Adulto , Estudos Transversais , Feminino , Gana/epidemiologia , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/metabolismo , Hospitais de Ensino/métodos , Humanos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Cuidado Pré-Natal/métodos , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Adulto Jovem
12.
BMC Infect Dis ; 20(1): 230, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188424

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem worldwide. More than 2 billion people have been exposed to HBV, and about 257 million individuals are chronic carriers of HBV. HBV reactivation has been increasingly reported in HBV carriers who have undergone immunosuppression or chemotherapy, resulting in mortality. Treatment of hypothalamic/pituitary tumors in HBV carriers requires extensive care to avoid HBV reactivation as steroid therapy is required after surgery for hypothalamic/pituitary tumors. CASE PRESENTATION: This retrospective review identified 5 patients, who were HBV carriers positive for hepatitis B surface antigen among 1352 patients with surgically treated hypothalamic/pituitary tumor in Kohnan Hospital between February 2007 and April 2017. Transsphenoidal surgery was performed with particular attention to prevent damage to the pituitary gland, with delicate manipulation to minimize postoperative steroid coverage. All patients received nucleot(s)ide analogue to control HBV-DNA levels before the surgery. As a result, all patients had a good clinical course. Blood examinations found a transient increase of liver enzymes and HBV-DNA levels in all patients, which started to decrease within 2 weeks after surgery. No specific treatment other than nucleot(s)ide analogues was needed to maintain liver function, and all patients returned to their previous activities including reinstatement. CONCLUSION: Initiation of nucleot(s)ide analogues administration prior to the surgery for hypothalamic/pituitary tumors can be an effective strategy for preventing reactivation in HBV carriers. Appropriate screening of the patient's HBV phase, optimal timing of nucleot(s)ide analogues -administration, and administration period of nucleot(s)ide analogues need to be established.


Assuntos
Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Neoplasias Hipotalâmicas/cirurgia , Neoplasias Hipofisárias/cirurgia , Idoso , DNA Viral/sangue , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Vírus da Hepatite B/fisiologia , Humanos , Neoplasias Hipotalâmicas/virologia , Imunossupressão , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/virologia , Estudos Retrospectivos , Esteroides/uso terapêutico , Ativação Viral/efeitos dos fármacos
13.
An Bras Dermatol ; 95(2): 200-202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32173140

RESUMO

Erythema elevatum diutinum is a small vessel vasculitis which is benign, rare, and chronic. It is clinically characterized by violaceous, brown, or yellowish plaques, nodules, and papules. It has been associated with autoimmune, infectious, and neoplastic processes. The following case describes a patient with hepatitis B virus and human immunodeficiency virus with CD4 count<200mm3, HIV-seropositive for 16 years, and diagnosed with hepatitis B virus at the hospital. The patient was treated with oral dapsone 100mg/day, showing regression after seven months of treatment. The authors found three cases in the literature of association of erythema elevatum diutinum, human immunodeficiency virus, and hepatitis B virus.


Assuntos
Infecções por HIV/complicações , Hepatite B/complicações , Vasculite Leucocitoclástica Cutânea/patologia , Vasculite Leucocitoclástica Cutânea/virologia , Adulto , Biópsia , HIV/patogenicidade , Vírus da Hepatite B/patogenicidade , Humanos , Masculino
14.
Virus Genes ; 56(2): 109-119, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32026198

RESUMO

The nomenclature of the hepatitis B virus (HBV) genes and their products has developed stepwise, occasionally in an erratic way, creating many misunderstandings, especially among those who do not know the structure of HBV and its genome in detail. One of the most frequent misunderstandings, even presented in leading journals, is the designation of HBV "e"-antigen as envelope or early antigen. Another problem area are the so-called "pre" regions in the HBV genome present upstream of both the core and the surface genes of HBV, inadvertently suggesting that they may be a part of corresponding precursor proteins. Misnomers and misclassifications are frequent in defining the subgenotypes and serological subtypes of HBV. Even the well-established terminology for HBV surface (HBs) or HBV core (HBc) antigen deviates from the conventional virological nomenclature for viral envelopes or capsid proteins/antigens, respectively. Another matter of undesirable variability between publications is the numbering of the nucleotides and the graphical representation of genomic maps. This editorial briefly explains how the nomenclature evolved, what it really means, and suggests how it could be adapted to today's knowledge.


Assuntos
Anticorpos Anti-Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Epitopos/genética , Epitopos/imunologia , Variação Genética/genética , Variação Genética/imunologia , Hepatite B/genética , Hepatite B/virologia , Anticorpos Anti-Hepatite B/classificação , Antígenos do Núcleo do Vírus da Hepatite B/classificação , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/classificação , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/classificação , Vírus da Hepatite B/patogenicidade , Humanos , Terminologia como Assunto
15.
Int J Med Sci ; 17(2): 170-175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32038100

RESUMO

Background: The aim of this study was to describe biochemical, virological features and Mother-to child-transmission (MTCT) rate in chronic hepatitis B (CHB) women who stopped antiviral therapy before or in the early pregnancy. Methods: This was a single-center, retrospective study. Forty-three CHB women who stopped treatment before or in the early pregnancy and 103 CHB women with tenofovir disoproxil fumarate (TDF) treatment throughout pregnancy were enrolled. The virological and biochemical flares during pregnancy and postpartum period were studied. MTCT rates were also compared. Results: During pregnancy, ALT flares (43.9% vs 1.0%) and viral rebound (31.7% vs 0) were more common in women who stopped treatment (P<0.001). Postpartum ALT flares were less frequent in women with treatment than those stopped treatment (0 vs 6/35, P = 0.001). The birth defect rate in the mothers who stopped treatment did not statistically differ from that of mothers treated throughout pregnancy (4.9 % vs 3.9 %, P = 1.000). There were no significant differences of gestational complications between the two groups, except intrahepatic cholestasis of pregnancy (12.2% vs 0, P = 0.002). The rate of MTCT in mothers who discontinued treatment was higher (2.4% vs 0, P = 0.285), although there was no statistically significant. Conclusion: ALT flares were common in mothers who discontinued antiviral therapy. Thus, these pregnant women should be monitored closely. Cessation of treatment was not recommended although no hepatic failure was observed. Larger studies are needed to evaluate the safety of discontinuation before pregnancy.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Tenofovir/efeitos adversos , Adulto , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Antígenos E da Hepatite B , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Hepatite B Crônica/transmissão , Hepatite B Crônica/virologia , Humanos , Transmissão Vertical de Doença Infecciosa , Período Pós-Parto/fisiologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Tenofovir/uso terapêutico , Carga Viral/genética
16.
Sci Rep ; 10(1): 2753, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066795

RESUMO

Hepatitis E virus (HEV) infection contributes to a considerable proportion of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B virus (HBV) infection. This study aimed to predict the prognosis of chronic HBV infection patients precipitating acute HEV infection. A total of 193 patients were enrolled in this study. The performances of three chronic liver disease prognostic models (CTP score, MELD score, and CLIF-C ADs) were analyzed for predicting the development of ACLF following HEV superimposing chronic HBV infection. Subsequently, the performances of five ACLF prognostic assessment models (CTP score, MELD score, CLIF-C ACLFs, CLIF-C OFs, and COSSH-ACLFs) were analyzed for predicting the outcome of those ACLF patients. Of 193 chronic HBV infection patients precipitating acute HEV infection, 13 patients were diagnosed ACLF on admission, 54 patients developed to ACLF after admission, and 126 patients had non-ACLF during the stay in hospital. For predicting the development of ACLF, CTP score yielded a significantly higher AUROC compared with MELD score and CLIF-C ADs (0.92, 0.88, and 0.86, respectively; all p < 0.05). For predicting the poor prognosis of ACLF patients, the COSSH-ACLFs yielded a significantly higher AUROC compared with CLIF-C ACLFs, CLIF-C OFs, MELD score, and CTP score (0.89, 0.83, 0.81, 0.67, and 0.58, respectively; all p < 0.05). In conclusion, the stepwise application of CTP score and COSSH-ACLFs can predict the prognosis of chronic HBV infection patients precipitating acute HEV infection.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/diagnóstico , Vírus da Hepatite E/patogenicidade , Hepatite E/diagnóstico , Doença Aguda , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/patologia , Insuficiência Hepática Crônica Agudizada/virologia , Adulto , Idoso , Bilirrubina/sangue , Biomarcadores/sangue , Coinfecção , Creatinina/sangue , Feminino , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/mortalidade , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Hepatite E/mortalidade , Hepatite E/patologia , Hepatite E/virologia , Vírus da Hepatite E/crescimento & desenvolvimento , Humanos , Testes de Função Hepática , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida
17.
Sci Rep ; 10(1): 1528, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001731

RESUMO

Hepatitis B virus (HBV) is the main causative viral agent for liver diseases in China. In liver injury, exosomes may impede the interaction with chromatin in the target cell and transmit inflammatory, apoptosis, or regeneration signals through RNAs. Therefore, we attempted to determine the potential functions of exosomal RNAs using bioinformatics technology. We performed RNA sequencing analysis in exosomes derived from clinical specimens of healthy control (HC) individuals and patients with chronic hepatitis B (CHB) and acute-on-chronic liver failure caused by HBV (HBV-ACLF). This analysis resulted in the identification of different types and proportions of RNAs in exosomes from the HC individuals and patients. Exosomes from the CHB and HBV-ACLF patients showed distinct upregulation and downregulation patterns of differentially expressed genes compared with those from the HC subjects. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway analysis further confirmed different patterns of biological functions and signalling pathways in CHB and HBV-ACLF. Then we chose two upregulated RNAs both in CHB and HBV-ACLF for further qPCR validation. It confirmed the significantly different expression levels in CHB and HBV-ACLF compared with HC. Our findings indicate selective packaging of the RNA cargo into exosomes under different HBV attacks; these may represent potential targets for the diagnosis and treatment of HBV-caused liver injury.


Assuntos
Insuficiência Hepática Crônica Agudizada/genética , Exossomos/genética , Hepatite Crônica/genética , Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/diagnóstico , Adulto , Estudos de Casos e Controles , China , Bases de Dados Genéticas , Testes Diagnósticos de Rotina/métodos , Feminino , Hepatite B/sangue , Hepatite B/genética , Hepatite B/metabolismo , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/virologia , Hepatite Crônica/sangue , Hepatite Crônica/diagnóstico , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Transcriptoma/genética
18.
Transfusion ; 60(2): 334-342, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31909495

RESUMO

BACKGROUND: Chinese blood donors with unconfirmed serological and/or molecular screening results are deferred permanently. This study investigated the implementation and performance of a follow-up program aiming to improve the notification and management of deferred donors in Dalian, China. STUDY DESIGN AND METHODS: From January 2013 to February 2018, 411,216 donations were tested for HBsAg, anti-HCV, anti-HIV/HIV antigen, and antibodies to Treponema pallidum. HBV, HCV, and HIV nucleic acid testing (NAT) was performed in mini-pools of six or in individual donations (IDs). Reactive donations were evaluated further with alternative serological assays and ID-NAT re-testing. A follow-up procedure was developed to evaluate a subset of deferred donors that were either potential NAT yield cases, serology non-reactive and NAT non-repeated reactive (NRR), or serology NRR irrespective of NAT result. RESULTS: Serological and molecular routine, plus supplemental testing, identified HBV, HCV, HIV, and TP in 503 (0.12%), 392 (0.09%), 156 (0.04%), and 2041 (0.49%) donations, respectively. Overall, 683 of 4156 (16.4%) eligible donors and 205 donors deferred prior 2013 participated in the program. They included 664 serology NRR and 224 NAT yield cases, and 58.8% repeat donors. All markers combined, follow-up documented false reactivity, primary acute infections, and OBI in 61.9% (550/888), 3.3% (29/888), and 12.8% (114/888) of these donors, respectively. Isolated anti-HBc or anti-HBs reactivity was observed in 22% of cases. CONCLUSION: Follow-up testing refined infection status in 78.0% (693/888) of deferred donors with unconfirmed screening results. This high false-positive rate encouraged to reevaluate the current screening strategies and to consider donor reentry.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Hepatite B/epidemiologia , Programas de Rastreamento/métodos , China/epidemiologia , Feminino , HIV/imunologia , HIV/patogenicidade , Antígenos de Superfície da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Hepatite C/epidemiologia , Humanos , Masculino , RNA Viral/genética , Treponema pallidum/imunologia , Treponema pallidum/patogenicidade
19.
Am J Physiol Gastrointest Liver Physiol ; 318(3): G401-G409, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905024

RESUMO

Hepatitis B virus (HBV)-related hepatocarcinogenesis is not necessarily associated with the liver fibrotic stage and is occasionally seen at early fibrotic stages. MicroRNAs (miRNAs) are essentially 18- to 22-nucleotide-long endogenous noncoding RNAs. Aberrant miRNA expression is a common feature of various human cancers. The aberrant expression of specific miRNAs has been shown in hepatocellular carcinoma (HCC) tissue compared with nontumor tissue. Thus, we examined targetable miRNAs as a potential new biomarker related to the high risk of HBV-related hepatocarcinogenesis, toward the prevention of cancer-related deaths. HCC tissue samples from 29 patients who underwent hepatectomy at our hospital in 2002-2013 were obtained. We extracted the total RNA and analyzed it by microRNA array, real-time RT-PCR, and three comparisons: 1) HBV-related HCC and adjacent nontumor tissue, 2) HCV-related HCC and adjacent nontumor tissue, and 3) non-HBV-, non-HCV-related HCC and adjacent nontumor tissue. We also performed a functional analysis of miRNAs specific for HBV-related HCC by using HBV-positive HCC cell lines. MiR-210-3p expression was significantly increased only in the HBV-related HCC tissue samples. MiR-210-3p expression was upregulated, and the levels of its target genes were reduced in the HBV-positive HCC cells. The inhibition of miR-210-3p enhanced its target gene expression in the HBV-positive HCC cells. In addition, miR-210-3p regulated the HBx expression in HBV-infected Huh7/NTCP cells. The enhanced expression of miR-210-3p was detected specifically in HBV-related HCC and regulated various target genes, including HBx in the HBV-positive HCC cells. MiR-210-3p might, thus, be a new biomarker for the risk of HBV-related HCC.NEW & NOTEWORTHY Our present study demonstrated that miR-210-3p is the only microRNA with enhanced expression in HBV-related HCC, and the enhanced expression of miR-210-3p upregulates HBx expression. Therefore, miR-210-3p might be a pivotal biomarker of HBV-related hepatocarcinogenesis, and the inhibition of miR-210-3p could prevent inducing hepatocarcinogenesis related to HBV infection.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transformação Celular Viral , Vírus da Hepatite B/metabolismo , Hepatite B/virologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Transativadores/metabolismo , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Regulação Viral da Expressão Gênica , Hepatite B/complicações , Vírus da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , MicroRNAs/genética , Transdução de Sinais , Transativadores/genética , Replicação Viral
20.
Virus Genes ; 56(2): 168-173, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31897927

RESUMO

Integration of HBV DNA into host chromosomes was found in most of the patients with chronic hepatitis B (CHB). In this study, using inverse nested PCR (invPCR), we found the integration site chrX: 111,009,033, which inserted into the p21-activated kinase 3 (PAK3) gene in HepG2.2.15 cells. The viral-human chimeric transcripts were also observed and, significant differences of the copy numbers of integration site chrX: 111,009,033 (P = 0.012) and intra-cell HBV DNA levels (P = 0.027) were found between the cells with and without H2O2 treatment, respectively. This study may provide a novel insight into the elucidation of etiology of HBV integration.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Integração Viral/genética , Quinases Ativadas por p21/genética , DNA Viral/genética , DNA Viral/isolamento & purificação , Células Hep G2 , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/transmissão , Hepatite B Crônica/virologia , Hepatócitos/virologia , Humanos , Replicação Viral/genética
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