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1.
BMJ ; 370: m2200, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873599

RESUMO

Hepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/virologia , Replicação Viral/imunologia , Animais , DNA Viral/sangue , Saúde Global , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Humanos , Imunossupressão , Imunossupressores/uso terapêutico , Fatores de Risco
2.
Rev Med Suisse ; 16(704): 1538-1543, 2020 Sep 02.
Artigo em Francês | MEDLINE | ID: mdl-32880108

RESUMO

Hepatitis D virus causes chronic hepatitis D. The virus is defective, meaning it requires simultaneous presence of hepatitis B virus within the hepatocytes to complete its viral cycle. Globally, 15 to 20 millions people are estimated to be chronically co-infected by hepatitis B and D viruses. Current therapy remains limited to pegylated interferon alfa, which has an unsatisfactory success rate, several contraindications and many side effects. Drugs directly targeting the hepatitis D virus life cycle are being developed with promising results. These drugs target viral entry into hepatocytes, virion assembly or secretion from infected hepatocytes. This article provides an overview of the newly developed therapies and their efficacy.


Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite D Crônica/tratamento farmacológico , Vírus Delta da Hepatite/efeitos dos fármacos , Hepatite B Crônica/virologia , Hepatite D Crônica/virologia , Humanos , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico
3.
Medicine (Baltimore) ; 99(32): e21454, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769872

RESUMO

The impact of different antiviral regimen on prognosis of chronic hepatitis B (CHB) related hepatocellular carcinoma (HCC) remains to be explored.A total of 479 CHB-related HCC patients after curative liver resection were enrolled receiving tenofovir (TDF, TDF group) or lamivudine, telbivudine, and entecavir (non-TDF group). Both the overall survival and diseases-free survival were analyzed and compared.A total of 242 patients received TDF treatment and 237 patients received other antiviral regimen. Child-Pugh score, serum α-fetoprotein (AFP) level, total bilirubin level, status of hepatitis B e antigen (HBeAg), and cirrhosis were compared between groups. Kaplan-Meier analysis revealed that patients with TDF treatment had significantly longer overall survival than those of patients with other regimen (P = .015). Similarly, compared with patients with non-TDF treatment, disease-free survival time was longer (P = .042) in those with TDF treatment. Multivariate analysis showed that TDF treatment (P = .04), AFP level (P = .03) were significant independent factors associated with overall survival of CHB-related HCC patients. While TDF treatment (P = .04) and serum AFP level (P = .03) were independent factors associated with disease-free survival.Anti-virus treatment with TDF benefits for both overall survival and disease-free survival of CHB-related patients than other Nucleos(t)ide analogues.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/complicações , Hepatectomia , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/complicações , Tenofovir/uso terapêutico , Adulto , Carcinoma Hepatocelular/cirurgia , China , Estudos de Coortes , Feminino , Hepatite B Crônica/etiologia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento
4.
BMC Infect Dis ; 20(1): 590, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778058

RESUMO

BACKGROUND: Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy. METHODS: Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence. RESULTS: The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+ T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1- T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1- T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+ T cells had no significant difference. In addition, the levels of CD68+ mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05). CONCLUSIONS: The changes in the levels of CD8+PD-1+ T cells and CD68+ mononuclear cells may be related to the response to PEG-IFN-α therapy.


Assuntos
Antivirais/uso terapêutico , Linfócitos T CD8-Positivos/metabolismo , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Fígado/patologia , Polietilenoglicóis/uso terapêutico , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Fígado/metabolismo , Masculino , Receptor de Morte Celular Programada 1/metabolismo , Proteínas Recombinantes/uso terapêutico , Adulto Jovem
5.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32680878

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome classified into primary HLH and secondary HLH. Secondary HLH is always caused by autoimmune disease, infections, or cancer. The first-line therapy for secondary HLH is the HLH 2004 protocol, including dexamethasone, etoposide, and supportive therapy. However, up to 30% of patients, especially pediatric patients, remain unresponsive to first-line treatment, and the mortality rate reaches 50% in children with HLH. Furthermore, some children who have special conditions, such as an active virus infection, are not suitable for immunosuppressants treatment. Recently, several HLH-promoting cytokines have been identified, including interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 control the signaling of many cytokines, notably interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 inhibitors, such as ruxolitinib, have been successfully used to treat HLH in mice. Here, we report that a boy, diagnosed with HLH and high titer of hepatitis B virus-DNA copies, improved quickly, and the cytokine storm of HLH was alleviated after receiving ruxolitinib. Five days after ruxolitinib treatment, entecavir was introduced and serum titer results of hepatitis B virus-DNA returned negative. With 3 months of ruxolitinib treatment and following-up 1 year, the boy's situation maintained sustained remission. In this study, it is suggested that ruxolitinib might be a first-line drug, which could alleviate the cytokine storm of HLH. This treatment may be ushering in the age of glucocorticosteroid-free HLH treatment, which is particularly meaningful for children because it avoids the side effects of glucocorticosteroid.


Assuntos
Síndrome da Liberação de Citocina/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Pirazóis/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Criança , Síndrome da Liberação de Citocina/etiologia , Quimioterapia Combinada , Febre/etiologia , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/congênito , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Janus Quinases/antagonistas & inibidores , Masculino , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Pirazóis/farmacologia , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Carga Viral
6.
Medicine (Baltimore) ; 99(27): e21032, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629728

RESUMO

BACKGROUND: Chronic hepatitis B is often complicated with different degrees of hepatic fibrosis, which affects the quality of life. Nucleoside analogs are recommended by almost all guidelines in the world for the treatment of chronic hepatitis B. At present, there is no specific and effective chemical and biological agents for hepatic fibrosis. In China, Chinese compound prescription combined with nucleoside analogs have been used to treat hepatic fibrosis of chronic hepatitis B patients in more and more cases, and good results have been achieved. Several Chinese compound prescriptions that have been made into proprietary Chinese medicine for the convenience of use. This article aims to systematically evaluate the efficacy and safety of Chinese medicine compounds assisting nucleoside analogs in the treatment of hepatic fibrosis in chronic hepatitis B patients. METHOD: The following databases will be searched from their inception to September 2019: PubMed, EMBASE, EBSCOhost, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), VIP Database, Wanfang Database. Languages are limited to Chinese and English. The study includes randomized controlled trials using Chinese compound prescription combined with entecavir and Chinese compound prescription combined with tenofovir disoproxil fumarate to treat hepatic fibrosis of chronic hepatitis B patients. The primary outcomes including effective rate and biochemical parameters (levels of hyaluronic acid, laminin, pre-type-III collagen and type IV collagen will be tested. Additional outcomes include liver function indexes (levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin) and levels of hepatitis B virus DNA. Stata14.0 software will be used for meta-analysis. RESULT: The efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs for hepatic fibrosis of chronic hepatitis B patients will be assessed from the effective rate, biochemical parameters, liver function indexes, and levels of hepatitis B virus DNA. CONCLUSION: The conclusion of this study will be used to evaluate the efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs in the treatment of hepatic fibrosis of chronic hepatitis B patients, as well as the adjuvant effectiveness of Chinese compound prescriptions in combined therapy. PROSPERO REGISTRATION NUMBER: CRD42020156859.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Nucleosídeos/análogos & derivados , Antivirais/uso terapêutico , China/epidemiologia , Vírus de DNA/efeitos dos fármacos , Bases de Dados Factuais , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/psicologia , Testes de Função Hepática/métodos , Masculino , Nucleosídeos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tenofovir/uso terapêutico
7.
Dig Liver Dis ; 52(9): 937-941, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32703730

RESUMO

BACKGROUND: The COVID-19 pandemic had a huge impact on national and regional health systems. The impact of SARS-CoV-2 on the quality of care for patients with liver disease is still unknown. AIMS: The Italian Association for the Study of the Liver (AISF) conducted a survey to assess the impact of SARS-CoV-2 on hepatology units activities in Italy. METHODS: A prospective web-based survey was proposed to all AISF active members. The survey was available online from April 8 2020, to May 3 2020, (lockdown phase in Italy). RESULTS: 194 AISF members answered the questionnaire, most of whom were specialists in Gastroenterology (41%) or Internal Medicine (28%), and worked in Northern Italy (51%). 26% of hepatology wards had been converted into COVID-19 wards, and 33% had bed reductions. All hepatological activities, including the management of patients with decompensated liver disease, liver transplant and HCC had been significantly reduced/stopped. The number of physicians answering that their practices had not been modified ranged between 0.6% (for chronic hepatitis) to 47% (for the execution of paracentesis). The recorded answers were consistent among different regions, and did not show any north-south gradient CONCLUSION: COVID-19 outbreak significantly impacted on hepatological clinical activity. This survey can serve as a basis to compare the impact of future measures aimed at delivering an acceptable level of liver care during a national pandemic or crisis.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Gastroenterologia/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hepatopatias/terapia , Pneumonia Viral/epidemiologia , Antivirais/uso terapêutico , Betacoronavirus , Carcinoma Hepatocelular/terapia , Doença Crônica , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/cirurgia , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Itália/epidemiologia , Cirrose Hepática/terapia , Neoplasias Hepáticas/terapia , Transplante de Fígado/estatística & dados numéricos , Programas de Rastreamento , Pandemias , Paracentese/estatística & dados numéricos , Qualidade da Assistência à Saúde , Inquéritos e Questionários
8.
Medicine (Baltimore) ; 99(24): e20583, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541488

RESUMO

To observe the efficacy of telbivudine in chronic hepatitis B (CHB) women with high viral load during pregnancy and the long-term effects on intelligence, growth, and development of the newborns.A total of 87 patients were included. Forty-two patients received telbivudine orally 600 mg per day and treatment initiated from 12 weeks after gestation until the 12th postpartum week. Forty-five patients were untreated according to principle of informed consent. All infants received injection of hepatitis B immune globulin (HBIG; 200 IU) and were vaccinated with recombinant HBV vaccine. Wechsler preschool intelligence scale was used to assess mental and neuropsychological developments of these children till they were 6 years old. Data including serum HBV DNA viral load, Apgar score, and scores of Wechsler preschool intelligence scale were analyzed and compared.Levels of both serum HBV DNA and ALT in patients who received telbivudine were significantly decreased at the 12th week after delivery, compared with baseline levels (P < .01). No significant changes were observed in patients not receiving telbivudine (P > .05). Serum HBV DNA and ALT levels at the 12th week after delivery in the telbivudine group were significantly lower than those of patients without telbivudine (P < .01). The serum HBsAg-positive rate in neonates 7 months of age was 0%, which was significantly lower than that in control group (11.11%) (P < .05). No statistical differences were observed between the 2 groups regarding maternal cesarean section rate, adverse pregnancy rate, postpartum bleeding rate, neonatal body mass, Apgar score, neonatal malformation incidence, or intelligence development of newborn.Telbivudine is effective to reduce the viral load in CHB mothers with high viral load and could lower the perinatal transmission rate. Both mental and physical development in neonates with exposure to telbivudine during perinatal period were similar to those without telbivudine exposure.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Telbivudina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Telbivudina/efeitos adversos , Resultado do Tratamento , Carga Viral , Adulto Jovem
9.
Int J Infect Dis ; 96: 562-566, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32474201

RESUMO

OBJECTIVES: The purpose of this study was to analyze the clinical characteristics of chronic hepatitis B (CHB) cured by antiviral therapy. METHODS: Forty-two patients with CHB were enrolled. All patients had been treated with peginterferon (Peg-IFN) in combination with nucleoside analogue (NA) therapy for variable amounts of time, and all had been successfully cured of the disease. RESULTS: The combined treatment time for all participants was 124.7 ± 58.8 weeks, and the average Peg-IFN treatment time was 102.6 ± 56.1 weeks. At 24 weeks, Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) had decreased more than 50% from baseline. Multivariate logistic regression analysis of the week 96 HBsAg-clearing group and the non-HBsAg-clearing group showed a statistically significant difference in baseline HBV DNA levels and week 48 HBsAg levels. Those which baseline HBV DNA was < 2.75 log10 IU/mL, and week 48 HBsAg levels were < 0.88 log10 IU/mL were more likely to achieve rapid HBsAg clearance at 96 weeks. This suggests that low levels of baseline HBV DNA and week 48 HBsAg are a predictor of rapid HBsAg clearance at 96 weeks. CONCLUSIONS: Individualized extension of combination therapy to more than 96 weeks depending on the patient's response and adverse reaction conditions can help achieve a clinical cure. Patients with low baseline HBV DNA and low HBsAg levels at 48 weeks achieve HBsAg clearance more quickly than other populations.


Assuntos
Antivirais/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Nucleosídeos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adulto , Quimioterapia Combinada , Feminino , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/genética , Antígenos E da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(6): 924-928, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32564561

RESUMO

Objective: To analyze the association of two single-nucleotide polymorphisms (SNP) [Calcitonin gene related peptide (CGRP) rs155209 and receptor activity modifying protein 1 (RAMP1) rs3754701] and the prognosis of chronic hepatitis B patients who were under interferon therapy. Methods: A total of 317 patients and their anticoagulant blood samples were collected in this study. The SNPs in the CGRP and region RAMP1 were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Logistic regression method was used to assess the results from different phenotypic outcomes between cases and controls, after adjusted for sex and age in co-dominant, dominant and recessive genetic models. Results: Data from this study clearly demonstrated the relevance of CGRP rs155209 and RAMP1 rs3754701 with DNA response and ALT response. RAMP1 rs3754701T was strongly associated with both DNA response and ALT response (OR=2.277, 95%CI: 1.386-3.741, P=0.001; OR=1.694, 95%CI: 1.073-2.675, P=0.024). However, CGRP rs155209C was less prone to DNA response and ALT response (OR=0.150, 95%CI: 0.083-0.271, P<0.001; OR=0.583, 95%CI: 0.367-0.925, P=0.022). Conclusions: Results from our study suggested that both RAMP1 rs3754701 and CGRP rs155209 were associated with the prognosis of patients under interferon therapy in Han population, from the northern parts of China while RAMP1 rs3754701T was a protective factor for both ALT response and DNA response, but CGRP rs155209C carriers were less prone to DNA and ALT responses.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Interferons/uso terapêutico , Proteína 1 Modificadora da Atividade de Receptores/genética , China , Humanos , Polimorfismo Genético , Prognóstico
11.
Am J Gastroenterol ; 115(8): 1217-1225, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32355123

RESUMO

INTRODUCTION: Chronic hepatitis B (CHB) remains a major worldwide public health concern. Besifovir dipivoxil maleate (BSV) is a new promising treatment for CHB. However, long-term efficacy and safety have not yet been evaluated. Therefore, the goal of the study is to determine the antiviral efficacy and safety of BSV treatment over a 144-week duration (BSV-BSV) in comparison with those of a sequential treatment with tenofovir disoproxil fumarate (TDF) followed by a 96-week duration BSV administration (TDF-BSV). METHODS: After 48 weeks of a double-blind comparison between BSV and TDF treatments, patients continued the open-label BSV study. We evaluated antiviral efficacy and drug safety up to 144 weeks for BSV-BSV and TDF-BSV groups. The primary endpoint was a virological response (hepatitis B virus DNA < 69 IU/mL). RESULTS: Among the 197 patients enrolled, 170 and 158 patients entered the second-year and third-year open-label phase extensional study, respectively, whereas 153 patients completed the 144-week follow-up. The virological response rate over the 144-week period was 87.7% and 92.1% in BSV-BSV and TDF-BSV groups, respectively (P = 0.36). The rates of ALT normalization and HBeAg seroconversion were similar between the groups. No drug-resistant mutations to BSV were noted. Bone mineral density and renal function were well preserved in the BSV-BSV group and were significantly improved after switching therapy in TDF-BSV patients. DISCUSSION: This extensional study of a phase 3 trial (NCT01937806) suggests that BSV treatment is efficacious and safe for long-term use in treatment-naïve and TDF-experienced patients with CHB.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adulto , Antivirais/administração & dosagem , Densidade Óssea , Método Duplo-Cego , Esquema de Medicação , Feminino , Guanina/administração & dosagem , Guanina/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/administração & dosagem , República da Coreia , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico , Resultado do Tratamento , Carga Viral
12.
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
13.
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
14.
PLoS One ; 15(4): e0230893, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275726

RESUMO

BACKGROUND AND AIMS: Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. METHODS: A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up. RESULTS: The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. CONCLUSIONS: Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Internacionalidade , Polietilenoglicóis/uso terapêutico , Adulto , Feminino , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Hepatite B Crônica/metabolismo , Humanos , Interferon-alfa/efeitos adversos , Masculino , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Segurança , Resultado do Tratamento
15.
JAMA Netw Open ; 3(4): e201844, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32271388

RESUMO

Importance: To achieve the World Health Organization goal of viral hepatitis elimination by 2030, it is important to estimate current rates of chronic hepatitis B (CHB) diagnosis and treatment. Objective: To provide an accurate accounting of the number of patients with CHB aged 6 years or older who have not yet been diagnosed in the United States. Design, Setting, and Participants: This cross-sectional study used the commercial US Truven Health MarketScan Database (138 634 154 privately insured individuals in January 2007 to December 2014) to identify patients with CHB diagnosis and the National Health and Nutrition Examination Survey to estimate the actual number of privately insured persons with CHB. Based on sex and age distribution derived from the US Census Bureau, we calculated the total population with CHB and the proportion of those who remained undiagnosed among the 198 073 302 privately insured individuals. Next, we identified diagnosed CHB patients who received 1 or more prescription for CHB medications to calculate the treatment rate for those with severe disease states, such as cirrhosis and hepatocellular carcinoma, that would warrant treatment. Analyses were performed from October 2017 to January 2020. Main Outcomes and Measures: The rate and number of patients with CHB who remained undiagnosed and treatment rates for patients with CHB who have cirrhosis or hepatocellular carcinoma. Results: Among the 198 073 302 privately insured individuals (48.55% male; 15.52% aged 6-17 years; 84.48% aged ≥18 years), there were 511 029 (95% CI, 317 733-704 325) individuals with CHB, but only 95 075 of these had been diagnosed, yielding a diagnosis rate of only 18.60% (95% CI, 13.50%-29.92%), meaning that 81.40% (95% CI, 70.08%-86.50%) were undiagnosed. The treatment rates were 34.79% (95% CI, 33.31%-36.27%) for those with cirrhosis and 48.64% (95% CI, 45.59%-51.69%) for those with hepatocellular carcinoma. Conclusions and Relevance: In this study, only approximately 1 in 5 privately insured patients with CHB had been diagnosed. Only one-third of patients with CHB who had cirrhosis and one-half who had hepatocellular carcinoma received antiviral therapy. Further efforts are needed to improve the current situation of poor connection to care for patients with CHB, especially for those with advanced liver disease.


Assuntos
Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Seguro Saúde/estatística & dados numéricos , Inquéritos Nutricionais/métodos , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Criança , Estudos Transversais , Gerenciamento de Dados , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Seguro Saúde/tendências , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologia , Adulto Jovem
16.
Cancer Treat Rev ; 86: 102011, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32213376

RESUMO

The treatment paradigm of several cancers has dramatically changed in recent years with the introduction of immunotherapy. Most oncology trials involving immune checkpoint inhibitors (ICIPs) have routinely excluded patients with HIV infection and chronic viral hepatitis B (HBV) and C (HCV) due to concerns about viral reactivation, fears of increased toxicity, and the potential lack of efficacy in these patient subgroups. However, with current antiviral therapies, HIV and HBV infections have become chronic diseases and HCV infections can even be cured. Broadening cancer trial eligibility criteria in order to include cancer patients with chronic viral infections can maximize the ecological validity of study results and the ability to understand the ICPIs' benefit-risk profile in patients with these comorbidities. In this review, we examined the evidence on the efficacy and safety of using ICPIs in cancer patients with concurrent chronic viral infections.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Infecções por HIV/fisiopatologia , Hepatite B Crônica/fisiopatologia , Hepatite C Crônica/fisiopatologia , Neoplasias/tratamento farmacológico , Neoplasias/virologia , Ensaios Clínicos como Assunto , Infecções por HIV/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias/imunologia
18.
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
19.
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
20.
Lancet Gastroenterol Hepatol ; 5(5): 441-453, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32087795

RESUMO

BACKGROUND: Treatment with tenofovir disoproxil fumarate has been associated with renal toxicity or reductions in bone mineral density, or both, in some patients with chronic hepatitis B virus (HBV) infection. Tenofovir alafenamide is a tenofovir prodrug with high intrahepatic concentrations of active drug and reduced systemic tenofovir exposures compared with tenofovir disoproxil fumarate. In patients with chronic HBV, tenofovir alafenamide has shown efficacy non-inferior to that of tenofovir disoproxil fumarate with improved renal and bone safety. With this non-inferiority study, we aimed to evaluate the efficacy and safety of tenofovir alafenamide in patients with HBV infection switching from tenofovir disoproxil fumarate who are virally suppressed. METHODS: Patients with chronic HBV infection who had been receiving tenofovir disoproxil fumarate for 48 weeks or more and who had HBV DNA less than the lower limit of quantification (LLOQ) for at least 12 weeks were recruited to this randomised, multicentre, double-blind, phase 3 non-inferiority study. Patients were randomly assigned in a 1:1 ratio to receive tenofovir alafenamide 25 mg once a day or to continue tenofovir disoproxil fumarate 300 mg once a day. The primary efficacy endpoint was loss of virological control, defined as the proportion of patients who received at least one dose of study drug who had HBV DNA of at least 20 IU/mL at week 48 by the modified US Food and Drug Administration (FDA) snapshot algorithm. Key safety endpoints were changes in hip and spine bone mineral density, estimated creatinine clearance by Cockcroft-Gault, and markers of bone turnover and renal tubular function. The study was powered for non-inferiority in efficacy of tenofovir alafenamide versus tenofovir disoproxil fumarate with a 4% margin. Investigators and patients were unaware of treatment allocation and on-treatment results. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT02979613. FINDINGS: Participants in this study were enrolled between Dec 29, 2016, and Oct 20, 2017. 541 patients were screened and 490 patients were randomly assigned to switch to tenofovir alafenamide or to stay on tenofovir disoproxil fumarate. Two patients assigned to receive tenofovir alafenamide did not receive treatment; thus the full analysis set for efficacy and safety analyses consisted of 243 patients in the tenofovir alafenamide group and 245 in the tenofovir disoproxil fumarate group. At week 48, one patient from each treatment group (both <1%) had HBV DNA of at least 20 IU/mL (difference in proportion 0·0%, 95% CI -1·9 to 2·0), thereby showing non-inferior efficacy of tenofovir alafenamide to tenofovir disoproxil fumarate. Patients who received tenofovir alafenamide had significantly increased bone mineral density at hip (mean change 0·66% [SD 2·08] vs -0·51% [SD 1·91]; difference in least square means 1·17% [95% CI 0·80 to 1·54; p<0·0001]) and at spine (mean change 1·74% [3·46] vs -0·11% [3·13]; difference in least square means 1·85% [1·24 to 2·46; p<0·0001]), creatinine clearance by Cockcroft-Gault relative to tenofovir disoproxil fumarate (median change 0·94 mL/min [IQR -4·47 to 6·24] vs -2·74 mL/min [-7·89 to 1·88]; p <0·0001), and improved markers of bone turnover and tubular function at week 48. The most common treatment-emergent adverse events were upper respiratory tract infection (18 [7%] of 243 patients in the tenofovir alafenamide group and 16 [7%] of 245 patients in the tenofovir disoproxil fumarate group) and nasopharyngitis (13 [5%] of 243 patients in the tenofovir alafenamide group and 12 [5%] of 245 patients in the tenofovir disoproxil fumarate group). The incidence of grade 3 and above adverse events and serious adverse events was low and similar between groups. No viral resistance was observed in patients who qualified for viral sequencing. INTERPRETATION: These findings suggest that tenofovir alafenamide can be substituted for tenofovir disoproxil fumarate in patients with HBV infection for improved safety without a loss of efficacy. FUNDING: Gilead Sciences.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , DNA Viral/sangue , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Antivirais/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Creatinina/sangue , Método Duplo-Cego , Substituição de Medicamentos , Feminino , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringite/induzido quimicamente , Insuficiência Renal/induzido quimicamente , Infecções Respiratórias/induzido quimicamente , Resposta Viral Sustentada
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