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1.
Medicine (Baltimore) ; 99(18): e20073, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358389

RESUMO

Individuals infected with hepatitis B virus (HBV) are often coinfected with human immunodeficiency virus (HIV). However, individuals with chronic HBV infection living with acute HIV infection have a significantly lower HBV viral load, along with higher HBeAg and HBsAg loss than HBV-infected individuals alone. Here, we investigated the possible role of natural killer cells (NK cell) function in this progressive course to explore the relationship between phenotypic/functional changes in NK cells during acute HIV infection and HBV clearance in patients with HIV/HBV coinfection.Peripheral blood NK cells from 38 patients with primary HIV infection, including 20 with untreated HIV infection and 18 treatment-naïve patients with HIV/HBV coinfection and 16 patients with chronic HBV infection, were enrolled in this study.We found that the HIV/HBV-coinfected individuals had higher levels of NK cells than the HBV-infected individuals, due to expansion of the CD56 NK cell population. The proportion of NK cells in CD56 and CD56 NK subsets was not found significant difference between HIV/HBV-coinfected and HBV-infected individuals. However, NKG2C levels on NK cells and subsets were significantly higher in HIV/HBV-coinfected individuals than in HBV-infected individuals, whereas NKG2A levels were unaffected or decreased. In addition, the levels of degranulation CD107a, cytotoxicity and IFN-γ production of NK cells were increased in HIV/HBV-coinfected individuals than in HBV-infected individuals. The level of IL-10 production of NK cells was decreased in HIV/HBV-coinfected individuals than in HBV-infected individuals. Furthermore, the level of HBV-DNA was inversely correlated with the proportion of NKG2C and NKG2CNKG2A NK cells, while positively correlated with the proportion of NKG2A and NKG2CNKG2A NK cells. IFN-γ production was inversely correlated with levels of HBV-DNA, but the CD107a expression and IL-10 production of NK cells were not correlated with HBV-DNA levels.These results demonstrate that the upregulation of NKG2C expression, but not of NKG2A expression on the surface of NK cells increases cytolytic capacity and the amounts of cytokines produced and may play a crucial role in HBV clearance during HIV/HBV-coinfection.


Assuntos
Infecções por HIV/epidemiologia , Hepatite B Crônica/epidemiologia , Células Matadoras Naturais/metabolismo , Adulto , Pequim , Estudos Transversais , Citometria de Fluxo , Antígenos de Superfície da Hepatite B/biossíntese , Antígenos E da Hepatite B/biossíntese , Humanos , Masculino , Carga Viral
2.
Medicine (Baltimore) ; 99(18): e19907, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358357

RESUMO

There has been no clear consensus on the optimal consolidation periods following HBeAg seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients. Our study aimed to prospectively compare relapse rates between 12 months' and 18 months' consolidation periods to see whether or not there is beneficial durability of tenofovir disoproxil fumarate (TDF) therapy with longer consolidation periods.We enrolled a total of 137 HBeAg-positive Asian CHB patients treated with TDF monotherapy. Forty-six patients achieved HBeAg SC. Then, they were randomly assigned to consolidation period of either 12 months (group A) or 18 months (group B). After stopping TDF therapy, all patients were followed up for 12 months.Thirteen patients (56.5%) relapsed in group A and 12 patients (52.2%) relapsed in group B after 12 months' follow-up (P = .958). Pretreatment HBsAg level is the only significant predictor for off-therapy recurrence by univariate analysis (P = .024). Baseline HBeAg >1000 S/CO in group B patients were significantly less likely to relapse than those of group A (P = .046). Baseline alanine aminotransferase (ALT) >133 U/L could significantly predict occurrence of HBeAg SC (P = .008; 95% CI: 0.545-0.763; AUC: 0.654).Overall, a prolonged consolidation period has no positive effect on TDF therapy on sustained viral suppression in HBeAg-positive Asian CHB patients. However, a prolonged consolidation period was beneficial to patients with high baseline semi-quantitative HBeAg levels in terms of off-treatment durability. Baseline ALT > 133 U/L could significantly predict the occurrence of HBeAg SC.


Assuntos
Antivirais/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Tenofovir/administração & dosagem , Adulto , Alanina Transaminase/sangue , Esquema de Medicação , Feminino , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Soroconversão/efeitos dos fármacos , Resposta Viral Sustentada , Fatores de Tempo
3.
Arch Virol ; 165(6): 1279-1288, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32240369

RESUMO

Mother-to-child transmission of hepatitis B virus (HBV) is the main route of transmission in Asia, and characterization of HBV quasispecies is needed to further understand virus evolution and adaptation. To understand changes in HBV during mother-to-child transmission, we enrolled nine pairs of mothers and children in the study, including a set of twins. Three groups were infected with HBV genotype C, and six groups were infected with HBV genotype B. The full-length HBV genome was amplified by PCR from serum samples before antiviral treatment, the whole viral genomes from each pair were sequenced, and the complexity and diversity of the quasispecies were analyzed. The entropy of transmitted HBV in children was found to be lower than their mothers, suggesting that there was a bottleneck effect during HBV transmission from the mother to the child. Selective evolution was shown by calculating πN and πS in the whole genomes, and the highest values were obtained for the X gene, which plays a role in viral replication and immune escape. All genotype C patients and only one genotype B pair had a πN/πS greater than 1 ratio, indicating that positive selection had occurred. In addition, quasispecies were found to be different between the twin children despite having the same mother, indicating that virus evolution is host-specific.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/transmissão , Hepatite B Crônica/virologia , Transmissão Vertical de Doença Infecciosa , Quase-Espécies , Transativadores/genética , Adulto , Criança , Pré-Escolar , China , DNA Viral/sangue , Evolução Molecular , Feminino , Genoma Viral , Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Especificidade de Hospedeiro/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Mutação , Filogenia , Reação em Cadeia da Polimerase , Gêmeos , Adulto Jovem
4.
Medicine (Baltimore) ; 99(14): e19647, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243396

RESUMO

Currently, the association of the initiation time of hepatitis B virus (HBV) screening and antiviral prophylaxis with adverse liver outcomes in cancer patients undergoing chemotherapy remains conflicting.This retrospective study was designed to determine the association of HBV screening and antiviral prophylaxis with adverse liver outcomes, and then proposed optimal management strategies on HBV screening and antiviral prophylaxis.We analyzed the medical data of Chinese cancer patients undergoing chemotherapy between 2000 and 2015. Descriptive statistics and Chi square tests were performed to analyze the basic characteristics of patients. Time-to-event analysis was used to determine incidence, and competing risk analysis was used to determine the hazard ratios (HRs) for outcomes.A total of 12,158 patients (81.1% with solid tumors) were analyzed. Among solid tumors patients, late screening and late antiviral therapy of chronic HBV were associated with higher incidence of hepatitis flare (HR 3.29, 95% confidence interval [CI] 2.26-4.79; HR 6.79, 95% CI 4.42-10.41), hepatic impairment (HR 2.96, 95% CI 2.03-4.32; HR 8.03, 95% CI 4.78-13.48), liver failure (HR 2.19, 95% CI 1.41-3.40; HR 14.81, 95% CI 6.57-33.42), and HBV-related death (HR 3.29, 95% CI 2.26-4.79; HR 8.30, 95% CI 4.95-13.91) in comparison with early screening and early therapy.Early HBV screening and antiviral therapy could reduce the risk of adverse liver outcomes among chronic HBV patients receiving chemotherapy. Hepatitis B surface antibody-positivity was associated with a decreased risk of liver failure and chronic HBV, late screening or late antiviral therapy were predictors of liver failure for patients with anti-tumor therapy. However, it should be applied cautiously into each types of solid tumors and hematologic malignancies because subgroup analysis according to type of cancer was not designed.


Assuntos
Antivirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/virologia , Hepatite B Crônica/tratamento farmacológico , Programas de Rastreamento/estatística & dados numéricos , Neoplasias/virologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Antineoplásicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , China/epidemiologia , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Humanos , Incidência , Fígado/efeitos dos fármacos , Fígado/virologia , Falência Hepática/induzido quimicamente , Falência Hepática/epidemiologia , Falência Hepática/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Ativação Viral , Adulto Jovem
5.
Zhonghua Gan Zang Bing Za Zhi ; 28(2): 179-182, 2020 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-32164074

RESUMO

Small interfering RNA (siRNA) is mainly involved in RNA interference for stopping gene translation by targeting and degrading HBV-transcribed mRNA. Targeting and stability in siRNA can be enhanced via chemical modification, combination use and improved delivery system. Clinical studies have identified JNJ-3989 (ARO-HBV) and ARB-1740 as well-tolerated siRNA drugs, which significantly reduce HBsAg levels. This article expounds the main mechanisms of siRNA in inhibiting HBsAg expression, improving target and stability as well as relevant preclinical and clinical studies.


Assuntos
Vírus da Hepatite B/efeitos dos fármacos , RNA Interferente Pequeno/farmacologia , Replicação Viral/efeitos dos fármacos , DNA Viral/análise , Antígenos de Superfície da Hepatite B/análise , Vírus da Hepatite B/genética , Hepatite B Crônica , Humanos , Interferência de RNA
6.
N Engl J Med ; 382(11): 1018-1028, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32160663

RESUMO

BACKGROUND: More information is needed about the long-term effects of low-dose aspirin (≤160 mg) on incident hepatocellular carcinoma, liver-related mortality, and gastrointestinal bleeding in persons with chronic hepatitis B or hepatitis C virus infection. METHODS: Using nationwide Swedish registries, we identified all adults who received a diagnosis of chronic hepatitis B or hepatitis C from 2005 through 2015 and who did not have a history of aspirin use (50,275 patients). Patients who were starting to take low-dose aspirin (14,205 patients) were identified by their first filled prescriptions for 90 or more consecutive doses of aspirin. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional-hazards regression modeling, we estimated the risk of hepatocellular carcinoma and liver-related mortality, accounting for competing events. RESULTS: With a median of 7.9 years of follow-up, the estimated cumulative incidence of hepatocellular carcinoma was 4.0% among aspirin users and 8.3% among nonusers of aspirin (difference, -4.3 percentage points; 95% confidence interval [CI], -5.0 to -3.6; adjusted hazard ratio, 0.69; 95% CI, 0.62 to 0.76). This inverse association appeared to be duration-dependent; as compared with short-term use (3 months to <1 year), the adjusted hazard ratios were 0.90 (95% CI, 0.76 to 1.06) for 1 to less than 3 years of use, 0.66 (95% CI, 0.56 to 0.78) for 3 to less than 5 years of use, and 0.57 (95% CI, 0.42 to 0.70) for 5 or more years of use. Ten-year liver-related mortality was 11.0% among aspirin users and 17.9% among nonusers (difference, -6.9 percentage points [95% CI, -8.1 to -5.7]; adjusted hazard ratio, 0.73 [95% CI, 0.67 to 0.81]). However, the 10-year risk of gastrointestinal bleeding did not differ significantly between users and nonusers of aspirin (7.8% and 6.9%, respectively; difference, 0.9 percentage points; 95% CI, -0.6 to 2.4). CONCLUSIONS: In a nationwide study of patients with chronic viral hepatitis in Sweden, use of low-dose aspirin was associated with a significantly lower risk of hepatocellular carcinoma and lower liver-related mortality than no use of aspirin, without a significantly higher risk of gastrointestinal bleeding. (Funded by the National Institutes of Health and others.).


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Hemorragia Gastrointestinal/induzido quimicamente , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Neoplasias Hepáticas/mortalidade , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Risco , Suécia/epidemiologia
7.
Mol Immunol ; 120: 179-186, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32169738

RESUMO

BACKGROUND: The NLRP3 inflammasome has been suggested to play a crucial role in host antiviral defense, including against hepatitis B virus (HBV) infection. In the present study, we measured expression of NLRP3 and its related cytokines in patients with different stages of HBV-related acute-on-chronic liver failure (HBV-ACLF), a pattern of end-stage liver disease that occurs frequently in patients with chronic HBV (CHB) infection or HBV-related cirrhosis. METHODS: A total of 75 subjects including 30 HBV-ACLF patients, 30 CHB patients, and 15 healthy controls (HCs) were enrolled. The NLRP3 inflammasome and its components (caspase-1, interleukin (IL)-1ß, and IL-18) were measured in peripheral blood mononuclear cells (PBMCs), macrophages, and liver using flow cytometry, quantitative real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. The LPS was used to evaluate changes in NLRP3 and its related cytokines in CD14+ monocytes which may reflect immune status. Cytokine expression was measured using RT-PCR. RESULTS: Patients with HBV-ACLF had lower NLRP3 inflammasome expression in peripheral CD14+ monocytes, particularly in the middle-to-late stage, but higher expression in liver macrophages compared to CHB and HCs. Compared with H-LPS or L-LPS alone, L-LPS sequential H-LPS can significantly inhibit the expression of NLRP3 and its related cytokines. CONCLUSION: Differential expression patterns of the NLRP3 inflammasome in the periphery and liver might be related to immune dysfunction and recruitment of monocytes to the injured liver during disease progression. Persistent systemic inflammation is likely a cause of compromised immune status in patients with HBV-ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada/imunologia , Hepatite B Crônica/imunologia , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/metabolismo , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/metabolismo , Humanos , Inflamassomos/sangue , Inflamassomos/metabolismo , Fígado/imunologia , Fígado/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
10.
Medicine (Baltimore) ; 99(5): e18898, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000393

RESUMO

BACKGROUND: A recent study has reported that there are >240 million patients infected with chronic hepatitis B (CHB) worldwide. Once patients with CHB start antiviral treatment, they need to take antiviral drugs for a long period, which may lead to a series of side effects, and the resistance to the antiviral drugs may also emerge. We aim to evaluate the efficacy and safety of kushenin (KS) combined with entecavir (ETV) for chronic hepatitis B. METHODS: Randomized controlled trials (RCTs) of KS combined with ETV for CHB will be identified from PubMed, EMBASE, Web of Science, The Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, Chongqing VIP, Wangfang Data. Literature screening and data extraction will be independently performed by 2 researchers. The cochrane collaboration tool for assessing risk of bias will be applied to evaluate the risk of bias of the RCTs included. The extracted data will be analyzed by Rev-man 5.3.0 software. RESULTS: A high-quality synthesis of current evidence on the efficacy and safety of KS combined with ETV for CHB will be provided in this study. CONCLUSION: This systematic review will aim to evaluate the efficacy and safety of KS combined with ETV for CHB. PROSPERO REGISTRATION NUMBER: CRD42019124790.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Pterocarpanos/uso terapêutico , Quimioterapia Combinada , Guanina/uso terapêutico , Humanos , Metanálise como Assunto , Fitoterapia , Sophora , Revisões Sistemáticas como Assunto
11.
Medicine (Baltimore) ; 99(8): e19201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080106

RESUMO

Hepatitis B virus (HBV) is one of the commonest chronic infections, especially in Asia and Africa, which put a heavy burden worldwide. With the advanced knowledge of HBV, early detection, primary care, and hepatology have made huge progression than before. However, the relationship between gender, age, and different key parameters in HBV patients remains to be determined.In this study, we measured various physiological and biochemical indexes in a large cohort of HBV patients as well as healthy control. We investigated the strength of correlations among those indexes and reported instantaneous imaging results. Moreover, we examined the effects of various grouping modes such as by gender or age on liver stiffness measurement (LSM) and controlled attenuation parameters (CAPs). We compared their diagnostic values for hepatic fibrosis in HBV patients.The results showed that specimens from a healthy control were obviously clustering tightly together, while the specimens from the HBV patients were clustering into several subgroups. Direct bilirubin (DB), total bilirubin (TB), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) occurred together with the diagnosis of HBV. Furthermore, groups categorized by Gender had significant effects on fibrotouch measurement not only in HBV patients but also in healthy control.Our research was to evaluate the actual effects of various parameters on Fibrotouch and make improvement of the critical value of those medical indexes.


Assuntos
Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
12.
Medicine (Baltimore) ; 99(8): e19248, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080129

RESUMO

Although serum bile acids and total cholesterol (TC) are closely related to liver cirrhosis, the potential diagnostic value of total bile acid-to-cholesterol ratio (TBA/TC) for liver fibrosis is unclear. The present study aimed to evaluate the value of TBA/TC in the diagnosis of cirrhosis and the relationship between TBA/TC and significant liver fibrosis in chronic hepatitis B virus (HBV) infected patients without cholestasis.667 patients with alkaline phosphatase (ALP) ≤ 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) ≤ 3 ULN were rigorously included in this cross-sectional study. Liver biopsy was performed in 32 patients and METAVIR scoring system was used to evaluate liver fibrosis stage. Liver ultrasound elastography was performed in 138 patients, significant fibrosis was defined as fibrosis ≥ F2. Multiple logistic regression as well as receiver operating characteristic (ROC) curves analyses were performed.Compared to patients with non-cirrhosis, TBA and TBA/TC were significantly higher in cirrhosis while TC was significantly lower (all P < .001). In multivariate analysis, TBA/TC was also independently associated with cirrhosis [odds ratio (OR) = 1.102, 95% confidence interval (CI): 1.085-1.166]. The area under the curve (AUC) of TBA/TC (0.87) was almost equivalent to the aspartate aminotransferase to platelet ratio index (APRI, AUC = 0.84) and fibrosis 4 score (FIB-4, AUC = 0.80), and the optimal cut-off value for TBA/TC to diagnose cirrhosis was 2.70. Among the patients performed liver biopsy, TBA/TC were significantly higher both in significant fibrosis and cirrhosis as well as significantly correlated with fibrosis stage (all P < .001). Furthermore, In patients performed liver ultrasound elastography, TBA/TC was also independently associated with significant fibrosis (OR = 1.040, 95% CI: 1.001-1.078).Assessment of TBA/TC could serve as an additional marker of significant liver fibrosis and cirrhosis in non-cholestatic chronic HBV infection.


Assuntos
Ácidos e Sais Biliares/sangue , Colesterol/sangue , Hepatite B Crônica/complicações , Cirrose Hepática/etiologia , Adulto , Biomarcadores , Biópsia , Estudos Transversais , Técnicas de Imagem por Elasticidade , Feminino , Hepatite B Crônica/sangue , Humanos , Cirrose Hepática/sangue , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença
13.
Mikrobiyol Bul ; 54(1): 66-78, 2020 Jan.
Artigo em Turco | MEDLINE | ID: mdl-32050879

RESUMO

It has been estimated that currently 350-400 million people have been chronically infected with the hepatitis B virus (HBV) worldwide and approximately one million people die each year due to HBV related diseases. It has been suggested that the viral and host factors, especially the host immune system, may play a role in the chronicity of the HBV infection. Stimulator of interferon genes (STING) is one of the members of the pattern recognition receptor (PRR) that detects the presence of DNA in a human cell, activate synthesis of various cytokines and this protein is thought to be an important member of the immune system against HBV infection. Based on the assumption that there may be a relationship between the differences of STING expression in individuals and HBV chronicity, the aim of this study was to investigate STING gene expression levels in individuals naturally immunized against HBV, in chronic hepatitis B infected patients and in normal individuals who have not been exposed to HBV. A total of 90 volunteers have been included in the study from the age range of 18 to 65, in which the first group consists of 30 individuals naturally immunized against HBV, the second group consists of 30 chronically hepatitis B infected patients while the third group consists of 30 healthy population members who have not been exposed to HBV. Whole blood samples were taken from each participant and peripheral blood mononuclear cells (PBMC) were isolated afterwards. Total RNA was isolated from PBMC. After the synthesis of cDNA from the total RNA, STING gene expression levels were determined by real time polymerase chain reaction (Rt-PCR) method. Normalization was performed by applying the 2-ΔΔCT formula after Rt-PCR procedure. STING expression level of the naturally immunized group was calculated as 0.084 ± 0.026 on average, average STING expression level of healthy population group was 0.082 ± 0.032 and STING expression level of chronically infected patients group was 0.075 ± 0.022 on average. There was no statistically significant difference between the groups (p> 0.05). To our knowledge, this is the first study investigating the role of STING expression in the chronicity of HBV. Although there was no statistically significant difference between the groups, the data that showed STING expression levels in naturally immunized individuals were approximately 10% higher than those in chronic hepatitis B patients and was considered as an important finding.


Assuntos
Hepatite B Crônica , Hepatite B , Imunidade Inata , Proteínas de Membrana , DNA Viral , Hepatite B/genética , Vírus da Hepatite B , Hepatite B Crônica/genética , Humanos , Imunidade Inata/genética , Interferons , Leucócitos Mononucleares , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , RNA Mensageiro/genética
14.
Mikrobiyol Bul ; 54(1): 95-109, 2020 Jan.
Artigo em Turco | MEDLINE | ID: mdl-32050881

RESUMO

Chronic hepatitis B (CHB) is an important public health problem in the world and Turkey. The aim of this study was to evaluate the histological, virological, serological and biochemical response rates in CHB patients receiving tenofovir or entecavir therapy. Control liver biopsies were performed on patients who received tenofovir or entecavir therapy for one year or longer. Histopathological grading was scored according to the modified Knodell system. Eighty-seven CHB patients were included in this study, 56 patients were receiving tenofovir and 31 patients were receiving entecavir therapy. Patients in two treatment groups were similar in terms of baseline parameters (p> 0.05). At the end of the treatment, there was a significant decrease in mean values of HBV DNA, alanine aminotransferase and necroinflammatory scores for both groups (p<0.001); however, no statistically significant change was observed in fibrosis scores (p> 0.05). Histological responses were obtained 66.1% from the tenofovir group and 54.8% from the entecavir group. Treatment with tenofovir and entecavir resulted with improvement in Ishak fibrosis scores in 12.5% and 12.9% of the patients, respectively. For 14.3% of the tenofovir-treated patients and for 22.6% of the entecavir-treated patients, the Ishak fibrosis scores worsened. Baseline intermediate/ advanced fibrosis stage (Ishak fibrosis score: 3-6) was found as independent determinant factor on histological response and improvement of fibrosis score (OR= 3.99, p= 0.01; OR= 31.67, p= 0.002; respectively) and treatment duration longer than five years is an independent determinant for improvement of necroinflammatory score (OR= 5.79, p= 0.02). There was no significant difference in the virological, serological, biochemical and, histological responses and improvement of necroinflammatory and fibrosis scores between tenofovir and entecavir groups (p> 0.05). Similar histological, virological, serological and biochemical responses were obtained in patients with CHB receving tenofovir and entecavir treatments. Further studies involving a large number of patients receiving long-term therapy should be done to understand the effects of antiviral treatments on healing of liver histology.


Assuntos
Antivirais , Guanina/análogos & derivados , Hepatite B Crônica , Tenofovir , Antivirais/uso terapêutico , Guanina/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Humanos , Fígado/patologia , Estudos Retrospectivos , Tenofovir/uso terapêutico , Resultado do Tratamento , Turquia
16.
Am J Gastroenterol ; 115(3): 406-414, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31895708

RESUMO

OBJECTIVES: It was suggested that normalization of serum alanine aminotransferase (ALT) levels at 1 year of antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B (CHB). However, it remains unclear whether earlier ALT normalization is associated with lower hepatocellular carcinoma (HCC) risk, independent of fatty liver or cirrhosis and on-treatment virological response (VR), in patients with CHB. METHODS: We analyzed 4,639 patients with CHB who initiated treatment with entecavir or tenofovir using landmark analysis and time-dependent Cox analysis. We defined normal ALT as ≤35 U/L (men) and ≤25 U/L (women) and VR as serum hepatitis B virus DNA <15 IU/mL. RESULTS: During a median 5.6 years of treatment, 509 (11.0%) patients developed HCC. ALT normalization occurred in 65.6% at 1 year and 81.9% at 2 years and was associated with a significantly lower HCC risk in landmark (P < 0.001) and time-dependent Cox analyses (adjusted hazard ratio [AHR] 0.57; P < 0.001). Compared with ALT normalization within 6 months, delayed ALT normalization at 6-12, 12-24, and >24 months was associated with incrementally increasing HCC risk (AHR 1.40, 1.74, and 2.45, respectively; P < 0.001), regardless of fatty liver or cirrhosis at baseline and VR during treatment. By contrast, neither earlier VR (AHR 0.93; P = 0.53) nor earlier hepatitis B e antigen seroclearance (AHR 0.91; P = 0.31) was associated with a significantly lower HCC risk. DISCUSSION: In patients with CHB treated with entecavir or tenofovir, earlier ALT normalization was independently associated with proportionally lower HCC risk, regardless of fatty liver or cirrhosis at baseline and on-treatment VR.


Assuntos
Alanina Transaminase/sangue , Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/virologia , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Adulto , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Feminino , Seguimentos , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Risco , Tenofovir/uso terapêutico , Resultado do Tratamento
17.
Anticancer Res ; 40(1): 245-252, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892573

RESUMO

AIM: It has been shown that the integration of hepatitis B virus (HBV) gene into the host genome is a high-risk factor for development of hepatocellular carcinoma (HCC). However, the relationship between HBV S-integrated human extra spindle pole bodies-like 1 (ESPL1) gene and HCC is unknown. This study was designed to detect HBV S-integrated human ESPL1 fusion gene in patients with HCC for potentially using this fusion gene as a biomarker for HCC diagnosis. PATIENTS AND METHODS: Nineteen and 70 patients with chronic hepatitis B (CHB) were recruited to the experimental and control groups, respectively, and both groups underwent an effective nucleoside/nucleotide analog therapy and follow-up for HCC occurrence for up to 11 years. HCC tissues were obtained by surgical resection from the experimental group, while liver tissues were collected by liver biopsy in the control group prior to treatment with nucleoside/nucleotide analogs. Alu polymerase chain reaction was used to assess HBV S gene integration in the liver tissues from both groups. HBV S-integrated human ESPL1 fusion gene was then detected in patients with HBV S gene integration using a gene database. RESULTS: All patients in the experimental group developed HCC, whereas no HCC was diagnosed in the control group. HBV S gene integration was identified in 12 out of 19 HCC tissues in the experimental group, giving a detection rate of 63.2%, which was significantly greater than that of 15.7% (11/70) in the control group (p<0.001). We further showed that HBV S-integrated human ESPL1 fusion gene was detected in eight patients (rate of 66.7%) among the 12 patients with HCC with HBV S gene integration in the experimental group, whereas the fusion gene was not detectable in any of the patients in the control group (p=0.001). CONCLUSION: This research demonstrates a high detection rate of HBV S-integrated human ESPL1 fusion gene in patients with HBV-related HCC and shows that this fusion gene appears to be associated with HCC development in patients with CHB. These findings suggest that HBV S-integrated human ESPL1 fusion gene may potentially serve as a biomarker for early detection of HCC in HBV-infected populations.


Assuntos
Grupo com Ancestrais do Continente Asiático , Vírus da Hepatite B/genética , Neoplasias Hepáticas/genética , Proteínas de Fusão Oncogênica/genética , Separase/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B Crônica/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/metabolismo , Separase/metabolismo , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
18.
Medicine (Baltimore) ; 99(1): e18462, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895778

RESUMO

Proinflammatory interleukin-26 (IL-26) is involved in chronic inflammation; however, the role of IL-26 in chronic hepatitis B (CHB) remains unknown.In this study, serum IL-26 was quantified in a cohort of CHB patients at baseline and during telbivudine (LdT) treatment.Our results showed that the serum IL-26 level was significantly elevated in CHB patients compared with that in healthy controls and was time-dependently decreased during LdT treatment, accompanying hepatitis B e antigen (HBeAg) seroconversion and reduced serum levels of hepatitis B virus (HBV) DNA, aspartate transaminase, and alanine transaminase across baseline and treatment. In addition, the serum level of IL-26 exhibited a similar declining trend to that of T helper 17 (Th17) cell-secreted IL-17 during LdT treatment in CHB patients. The percentage of IL-26-expressing CD4 cells was significantly higher than that of IL-26-expressing CD4 cells isolated from the peripheral blood mononuclear cells of CHB patients, suggesting that serum IL-26 might be mainly released from CD4 T cells. Furthermore, the baseline mRNA levels of IL-26 and orphan nuclear receptor RORγt-an important transcription factor expressed by Th17 cells-were positively correlated and displayed the same declining trend across the baseline and LdT treatment in CHB patients, suggesting that Th17 cells could be a possible cellular source of the increased serum IL-26 in CHB patients.Taken together, our results suggest that serum IL-26, possibly produced by Th17 CD4 cells, is a novel and potential biomarker for CHB prognosis and treatment.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Interleucinas/sangue , Adulto , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Telbivudina/uso terapêutico , Células Th17/imunologia , Adulto Jovem
19.
Expert Rev Gastroenterol Hepatol ; 14(2): 113-125, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31951758

RESUMO

Introduction: Multiple studies have revealed a strong relationship between the development of nephropathy and hepatitis B virus (HBV) infection. The underlying pathogenesis of hepatitis B-related glomerulonephritis (HBV-GN) involves immune complexes, which can be isolated from kidney tissues. Clearance of HBV antigenemia improves renal impairment and proteinuria in HBV-GN patients.Areas covered: In this review, we present our current understanding of the epidemiology, pathogenesis, pathology, diagnosis, and treatment of HBV-GN. We discuss the advantages and disadvantages of oral nucleoside/nucleotide analogs (NAs), and the main pharmaceutical treatment for hepatis B.Expert opinion: Currently, antiviral agents are the main HBV-GN therapeutic agents. Although no randomized controlled clinical trials have compared the efficacy of interferon (IFN) and NA, we suggest IFN treatment for pediatric patients (IFN-α in patients ≥1 year; pegIFN-α in patients ≥3 years) considering treatment duration and absence of resistance. Novel NAs have brought about promising treatment options involving high efficacy viral suppression and low resistance rates. NAs with a high barrier to resistance (e.g. entecavir) are recommended as first-line therapy of HBV-GN. Immunosuppression monotherapy, such as corticosteroids, is of little benefit and potentially harmful to HBV-GN patients due to the possibility of viral reactivation.


Assuntos
Glomerulonefrite/diagnóstico , Glomerulonefrite/tratamento farmacológico , Hepatite B Crônica/imunologia , Complexo Antígeno-Anticorpo/imunologia , Antivirais/uso terapêutico , Glomerulonefrite/epidemiologia , Glomerulonefrite/etiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Doenças do Complexo Imune/imunologia , Doenças do Complexo Imune/patologia , Doenças do Complexo Imune/virologia , Imunossupressores/uso terapêutico , Interferon-alfa/uso terapêutico , Rim/imunologia , Rim/patologia , Nucleosídeos/efeitos adversos , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico
20.
Int J Infect Dis ; 92: 184-188, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978574

RESUMO

BACKGROUND: There are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. METHODS: All HCV infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. Logistic regression model was used to determine factors associated with SVR. RESULTS: Among 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pre-treatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). CONCLUSION: HBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. Though not statistically significant, the virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Feminino , Hepacivirus/genética , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade
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