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1.
Expert Opin Drug Metab Toxicol ; 15(10): 779-785, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593639

RESUMO

Introduction: Interferon (IFN) had both antiviral and immunomodulatory effects, and was one of the approved treatments for hepatitis B virus (HBV). Herein, we reviewed the pharmacokinetics and pharmacodynamics of pegylated IFN-α (PegIFN-α) for the treatment of HBV. Areas covered: The steady-state serum levels of PegIFN-α were reached within 5 to 8 weeks, and the week 48 mean trough concentrations were approximately 2-fold higher than week 1. There was also no difference of the pharmacokinetics in male or female, healthy volunteers or patients with hepatitis B or C infection. PegIFN-α did not affect the metabolism of the cytochrome P450 (CYP) isozymes, except inhibition of CYP1A2. There was also no pharmacokinetic interaction between PegIFN-α and HBV nucleot(s)ide analogues (NUCs). Forty-eight weeks of PegIFN-α achieved 32% of HBeAg seroconversion, 32-43% of HBV DNA suppression, 41-59% of ALT normalization, and 3% of HBsAg seroconversion rate with a post-treatment durable response up to 80% in the initial responders. Expert opinion: On-treatment HBsAg titer guided the treatment of HBV with PegIFN-α. The recommendation of PegIFN-α and NUC combination or switch remained controversial. New immunotherapeutic agents are now in development. Although, PegIFN-α should continue to play a role in the treatment of HBV.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Antivirais/farmacologia , DNA Viral/efeitos dos fármacos , Interações de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Humanos , Interferon alfa-2/farmacocinética , Interferon alfa-2/farmacologia , Interferon-alfa/farmacocinética , Interferon-alfa/farmacologia , Masculino , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia
2.
Gastroenterol. hepatol. (Ed. impr.) ; 42(8): 502-511, oct. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-183892

RESUMO

La erradicación del virus de la hepatitis C (VHC) con esquemas libres de interferón (AAD) ha modificado la evolución de la enfermedad ya que más del 95% de los pacientes con cirrosis compensada logran la respuesta virológica sostenida. Sin embargo, el impacto de la erradicación del VHC sobre el desarrollo del carcinoma hepatocelular (CHC) es controvertido. Dicha controversia podría dividirse en diversos aspectos fundamentales: el impacto del AAD en la tasa de recurrencia del CHC, la asociación temporal entre el inicio de AAD y el desarrollo de la recurrencia del CHC y finalmente la agresividad de los CHC. Es por ello que esta revisión tiene por objetivo analizar los resultados disponibles en esta población de pacientes desde una perspectiva clínica donde se valoran los riesgos/beneficios de erradicar el VHC con AAD en el contexto de pacientes con CHC en respuesta completa


Eradication of the hepatitis C virus (HCV) with interferon-free therapies (DAAs) has modified the course of the disease, as the rate of patients with compensated cirrhosis who achieve a sustained virological response exceeds 95%. However, the impact on development of hepatocellular carcinoma (HCC) is currently in dispute. This argument could be divided into different key points: the impact of DAA on rate of HCC recurrence, the temporal link between starting DAAs and HCC recurrence, and finally, the aggressive pattern of HCC. Therefore, the aim of this review is to analyse the available results in this population of patients from a clinical perspective where the risks and benefits of HCV eradication with DAA therapies are evaluated in patients with complete response of HCC


Assuntos
Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Recidiva Local de Neoplasia/complicações , Antivirais/administração & dosagem
4.
Internist (Berl) ; 60(11): 1146-1150, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31486858

RESUMO

Respiratory syncytial virus (RSV) is worldwide a very important virus leading to infection of the respiratory system. In particular preterm babies, infants and elderly adults are prone to developing severe diseases such as bronchiolitis or pneumonia, which require intensive care and cause increased mortality. Although RSV is rapidly detected, preventive and therapeutic measures are limited. New antivirals are already in clinical trials.


Assuntos
Antivirais/administração & dosagem , Bronquiolite/diagnóstico , Bronquiolite/prevenção & controle , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/isolamento & purificação , Adulto , Idoso , Antivirais/uso terapêutico , Bronquiolite/tratamento farmacológico , Bronquiolite/virologia , Bronquiolite Viral/diagnóstico , Bronquiolite Viral/virologia , Humanos , Lactente , Recém-Nascido , Pneumonia/diagnóstico , Pneumonia/virologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/imunologia , Fatores de Risco
5.
Expert Opin Drug Saf ; 18(11): 1017-1030, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478398

RESUMO

Introduction: Human cytomegalovirus (HCMV) is a major contributor of morbidity and mortality, and its management is essential for the successful outcome of solid organ and hematopoietic stem cell transplantation. Areas covered: This review discusses the safety profiles of currently available and emerging antiviral drugs and the other strategies for HCMV prevention and treatment after transplantation. Expert opinion: Strategies for management of HCMV rely largely on the use of antiviral agents that inhibit viral DNA polymerase (ganciclovir/valganciclovir, foscarnet, and cidofovir/brincidofovir) and viral terminase complex (letermovir), with different types and degrees of adverse effects. An investigational agent, maribavir, exerts its anti-CMV effect through UL97 inhibition, and its safety profile is under clinical evaluation. In choosing the antiviral medication to use, it is important to consider these safety profiles in addition to overall efficacy. In addition to antiviral drugs, reduction of immunosuppression is often generally needed in the management of HCMV infection, but with a potential risk of allograft rejection or graft-versus-host disease. The use of HCMV-specific or non-specific intravenous immunoglobulins remains debated, while adoptive HCMV-specific T cell therapy remains investigational, and associated with unique set of adverse effects.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Infecções Oportunistas/prevenção & controle , Antivirais/efeitos adversos , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/administração & dosagem , Infecções Oportunistas/virologia , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos
6.
Expert Rev Clin Pharmacol ; 12(9): 867-874, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31456441

RESUMO

Introduction: Hepatitis B virus is an important cause of liver disease and has numerous extra-hepatic manifestations. HBV leads to important morbidity and mortality in the general population and recent evidence suggests a role of HBV in the incidence and progression of chronic kidney disease. Areas covered: The mechanisms underlying the link between HBV and CKD remain unclear. Nucleos(t)ide analogues for the antiviral treatment of HBV are currently available; these drugs are provided with high efficacy even in patients with CKD. Expert opinion: A recent meta-analysis of clinical studies showed that HBV results in a greater risk of CKD in the general population. According to an updated review (studies were identified from PubMed, EMBASE, and the Cochrane database), we retrieved six clinical studies (n = 1,034,773 unique patients), adjusted RR, 1.41 (95% CI, 1.09; 1.82, P < 0.001). The significant heterogeneity observed precluded more definitive conclusions. Various mechanisms have been cited to explain the greater risk of CKD among HBsAg positive carriers. Novel evidence shows that untreated HBV and therapy with nucleos(t)ide analogues are associated with increased and decreased risk of end-stage renal disease in CKD population, respectively. We recommend that patients with HBV are assessed for kidney function and urinary changes at baseline and over the follow-up.


Assuntos
Antivirais/administração & dosagem , Hepatite B/complicações , Insuficiência Renal Crônica/etiologia , Progressão da Doença , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/virologia , Testes de Função Renal , Nucleosídeos/administração & dosagem , Nucleotídeos/administração & dosagem , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/virologia , Fatores de Risco
7.
Medicine (Baltimore) ; 98(32): e16683, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393369

RESUMO

Interferon-alpha (IFN-α) is currently the preferred antiviral treatment for children with chronic hepatitis B (CHB) aged >1-year-old. However, the evidence regarding the exact efficacy and safety in the real world is not sufficient. This study aimed to investigate the efficacy of IFN-α therapy in children with CHB and to provide a theoretical basis for practically identifying ideal antiviral therapies for CHB children.Clinical manifestations, baseline characteristics, related laboratory tests, and adverse events were retrospectively analyzed in children with CHB who visited the Children's Hospital of Fudan University, were treated with IFN-α and were followed up from January 2003 to October 2018.A total of 18 immune-active patients without advanced fibrosis were enrolled, and their average age at the start of treatment was 4.45 ±â€Š2.75 years old. IFN α-2b was administered subcutaneously by body surface area (BSA) category, based on 3 MU/m, for a median 48 weeks. Before treatment, the alanine aminotransferase (ALT) range was 81 to 409 U/L (median 158 U/L). The median hepatitis B virus (HBV)-DNA load was 9.89 × 10 IU/mL, and the HBV-DNA load varied from 3.10 × 10 to 4.56 × 10 IU/mL. The ALT levels of 17 children became normal at an average of 12 weeks during treatment, and those of 1 child became normal at 6 weeks after IFN-α withdrawal. Sixteen (88.9%, 16/18) children became HBV-DNA negative (<10 IU/mL) at an average of 24 weeks during treatment, while 1 became negative at 96 weeks after IFN-α withdrawal and 1 remained HBV-DNA positive. HBV e antigen (HBeAg) seroconversion occurred in 13 of 14 (92.9%, 13/14) HBeAg-positive patients at an average of 12 weeks during treatment. HBV s antigen (HBsAg) loss or seroconversion occurred in 4 (22.2%, 4/18) patients at an average of 21 weeks during treatment. Only mild flu-like symptoms and transient neutropenia appeared in some children at the early treatment stage. No severe abnormal results were observed in other laboratory parameters.The antiviral monotherapy of 48 weeks of IFN-α was well tolerated and good responded, which was associated with higher rates of HBeAg seroconversion and HBsAg clearance in the children in this study than in previously reported adults and pediatric patients.


Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Adolescente , Antivirais/farmacologia , Criança , Pré-Escolar , China , Estudos de Coortes , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Interferon-alfa/farmacologia , Masculino , Soroconversão/efeitos dos fármacos , Carga Viral/efeitos dos fármacos
8.
Pan Afr Med J ; 33: 26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384341

RESUMO

Introduction: approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In Seychelles, a total of 777 cases of hepatitis C were reported from 2002 to 2016, but up to mid of 2016, the cases were not being treated. Treatment with Harvoni, a combination of sofosbuvir and ledipasvir (SOF/LDV), is now being offered on the condition that the patient does not, or has stopped, injecting drugs. This paper is the first to establish the cost effectiveness of treating all cases of hepatitis C in Seychelles with Harvoni, as compared to no treatment. Methods: data extracted from literature was used to populate an economic model to calculate cost-effectiveness from Seychelles' government perspective. The model structure was also informed by the systematic review and an accompanying grading of economic models using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. A Markov model was developed, employing a lifetime horizon and costs and benefits were analysed from a payer's perspective and combined into incremental cost effectiveness ratios (ICERs). Results: the direct-acting antiviral (DAA), Harvoni, was found to be cost-saving in Seychelles hepatitis C virus (HCV) cohort, as compared to no treatment, with an ICER of € 753.65/QALY. The treatment was also cost-saving when stratified by gender, with the ICER of male and female being € 783.74/QALY and € 635.20/QALY, respectively. Moreover, the results obtained from acceptability curves showed that treating patients with Harvoni is the most cost-effective option, even for low thresholds. Conclusion: treating hepatitis C cases in Seychelles is cost-saving. It is worth developing a treatment programme to include all cases of hepatitis C, regardless of status of drug injection.


Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Antivirais/economia , Benzimidazóis/economia , Análise Custo-Benefício , Feminino , Fluorenos/economia , Hepatite C Crônica/economia , Humanos , Masculino , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Fatores Sexuais , Seicheles , Abuso de Substâncias por Via Intravenosa/epidemiologia , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/economia
9.
Braz J Med Biol Res ; 52(8): e8519, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389490

RESUMO

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.


Assuntos
Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Imidazóis/administração & dosagem , Transplante de Fígado/efeitos adversos , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral
10.
Medicine (Baltimore) ; 98(33): e16778, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415381

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB. METHODS: In this multicenter, randomized, double-blind, double-dummy, noninferiority phase 3 clinical trial (ClinicalTrials.gov identifier: NCT02287857), 330 Chinese patients with CHB [hepatitis B envelope antigen-positive (HBeAg) (+): 232] were randomly assigned to receive Qingzhong (group A: 161 patients) or Viread (group B: 169 patients) 300 mg once daily for 48 weeks. Subsequently, all patients were administered Qingzhong 300 mg once daily from week 49 to week 240. The primary end point was the degree of decline of plasma hepatitis B virus (HBV) DNA levels at week 48 and the secondary endpoints were viral suppression, normalization of alanine aminotransferase (ALT) levels, hepatitis B surface antigen (HBsAg)/HBeAg loss or seroconversion, and virological breakthrough. RESULTS: Among patients with CHB who were HBeAg (+), the mean HBV DNA titer decreased similarly between the groups at week 48. The percentages of patients who achieved undetectable HBV DNA were similar between the groups (85.11% and 82.35% in groups A and B, respectively) and similar losses of HBeAg and HBeAg seroconversion rates were achieved. Moreover, for patients with CHB who were HBeAg (-), reductions in HBV DNA were similar. Among all patients with CHB, the rates of normalization of ALT and the loss of HBsAg were similar. The overall incidence of adverse events was comparable between the groups. CONCLUSION: In conclusion, the 48-week administration of Qingzhong showed noninferior efficacy and safety profiles compared to Viread in Chinese patients with CHB.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , China , Método Duplo-Cego , Esquema de Medicação , Composição de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem , Resultado do Tratamento , Adulto Jovem
11.
Int J Infect Dis ; 86: 201-207, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31394205

RESUMO

OBJECTIVES: The aim of this study was to identify the predictors of relapse after the withdrawal of nucleos(t)ide analog (NA) therapy in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). METHODS: The PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched through January 2019. A random-effects model meta-analysis was performed, with hazard ratios (HR) and 95% confidence intervals (CI) used as summary statistics. RESULTS: Seventeen studies were included in the meta-analysis. Age (HR=1.022 per year), baseline hepatitis B surface antigen (HBsAg) (HR=1.509 per log IU/l), end of treatment (EOT) HBsAg level (HR=1.896 per log IU/l), EOT HBsAg level ≥1000 IU/ml (HR=1.749), and HBsAg decline from baseline to EOT (HR=0.748 per log IU/l) were associated with virological relapse. The predictors of clinical relapse were baseline HBsAg level (HR=1.312 per log IU/l), EOT HBsAg level (HR=1.458 per log IU/l), EOT HBsAg level ≥100IU/ml (HR=3.199) or ≥1000 IU/ml (HR=1.810), and duration of consolidation therapy (HR=0.991 per month). CONCLUSIONS: This meta-analysis indicates that age, the duration of consolidation therapy, and levels of baseline and EOT HBsAg were factors predictive of relapse in HBeAg-negative CHB patients who discontinued NA treatment.


Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/administração & dosagem , Suspensão de Tratamento , Adulto , Antivirais/uso terapêutico , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Masculino , Nucleosídeos/uso terapêutico , Modelos de Riscos Proporcionais , Recidiva
12.
Acta Gastroenterol Belg ; 82(2): 273-277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314188

RESUMO

BACKGROUND AND STUDY AIMS: The aim of this study was to enlighten the controversy about the renal safety of entecavir, tenofovir, and telbivudine treatments in chronic hepatitis B (CHB) patients by comparing these treatments in real-world conditions. PATIENTS AND METHODS: We retrospectively enrolled 104 treatment-naive patients with CHB monoinfection into our study. Patients were treated with entecavir monotherapy (n=38), tenofovir monotherapy (n=35), or telbivudine monotherapy (n=31). We then compared and statistically analyzed the effects of these drugs on the estimated glomerular filtration rate (eGFR) over a 24-month follow-up period. RESULTS: In the entecavir group, time-dependent change in eGFR was not statistically significant (p = 0.357). There was a statistically significant increase in eGFR in the telbivudine group at 12 months (p<0.001) and at 24 months (p<0.001) and, in contrast, a statistically significant decrease in the tenofovir group at 12 months (p<0.001) and at 24 months (p<0.001). There was no significant relationship between entecavir and eGFR change (p = 0.763). We found that tenofovir and telbivudine were independent predictors of eGFR change (decrease in eGFR, p<0.001 and increase in eGFR, p = 0.001, respectively). CONCLUSIONS: We recommend close follow-up of renal functions, especially for patients treated with tenofovir. Telbivudine was superior to the other drugs in terms of renal function. We conclude that an individualized therapy program considering treatment efficacy and side effects is the best option for patients.


Assuntos
Antivirais/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Telbivudina/administração & dosagem , Tenofovir/administração & dosagem , Antivirais/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Guanina/administração & dosagem , Guanina/efeitos adversos , Humanos , Rim/fisiopatologia , Nefropatias/patologia , Testes de Função Renal , Masculino , Estudos Retrospectivos , Telbivudina/efeitos adversos , Tenofovir/efeitos adversos , Timidina/administração & dosagem , Timidina/efeitos adversos , Resultado do Tratamento
13.
PLoS Genet ; 15(6): e1008181, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31216276

RESUMO

The increasing worldwide prevalence of Hepatocellular carcinoma (HCC), characterized by resistance to conventional chemotherapy, poor prognosis and eventually mortality, place it as a prime target for new modes of prevention and treatment. Hepatitis C Virus (HCV) is the predominant risk factor for HCC in the US and Europe. Multiple epidemiological studies showed that sustained virological responses (SVR) following treatment with the powerful direct acting antivirals (DAAs), which have replaced interferon-based regimes, do not eliminate tumor development. We aimed to identify an HCV-specific pathogenic mechanism that persists post SVR following DAAs treatment. We demonstrate that HCV infection induces genome-wide epigenetic changes by performing chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) for histone post-translational modifications that are epigenetic markers for active and repressed chromatin. The changes in histone modifications correlate with reprogramed host gene expression and alter signaling pathways known to be associated with HCV life cycle and HCC. These epigenetic alterations require the presence of HCV RNA or/and expression of the viral proteins in the cells. Importantly, the epigenetic changes induced following infection persist as an "epigenetic signature" after virus eradication by DAAs treatment, as detected using in vitro HCV infection models. These observations led to the identification of an 8 gene signature that is associated with HCC development and demonstrate persistent epigenetic alterations in HCV infected and post SVR liver biopsy samples. The epigenetic signature was reverted in vitro by drugs that inhibit epigenetic modifying enzyme and by the EGFR inhibitor, Erlotinib. This epigenetic "scarring" of the genome, persisting following HCV eradication, suggest a novel mechanism for the persistent pathogenesis of HCV after its eradication by DAAs. Our study offers new avenues for prevention of the persistent oncogenic effects of chronic hepatitis infections using specific drugs to revert the epigenetic changes to the genome.


Assuntos
Carcinoma Hepatocelular/genética , Epigênese Genética/genética , Hepacivirus/genética , Hepatite C/genética , Neoplasias Hepáticas/genética , Idoso , Antivirais/administração & dosagem , Biópsia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Cromatina/genética , Epigênese Genética/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Hepatite C/virologia , Código das Histonas/genética , Histonas/genética , Interações Hospedeiro-Patógeno/genética , Humanos , Interferons/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Resposta Viral Sustentada
14.
Vet Microbiol ; 233: 147-153, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176401

RESUMO

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a typical neurotropic virus that can cause obvious nerve damage. Integrin α5ß1 is a transmembrane macromolecular that closely related to neurological function. We recently demonstrated that integrin α5ß1 plays a critical role in PHEV invasion in vitro. To determine the function and mechanism of integrin α5ß1 in virus proliferation in vivo, we established a mouse model of PHEV infection. Integrin α5ß1-FAK signaling pathway was activated in PHEV-infected mice by qPCR, Western blotting, and GST pull-down assays. Viral proliferation and integrin α5ß1-FAK signaling pathway were significantly inhibited after intravenous injection of ATN-161, an integrin α5ß1 inhibitor. Through a histological analysis, we found that ATN-161-treated mice only showed pathological changes in neuronal cytoplasmic swelling at 5 day post-infection. In summary, our results provide the first evidence that ATN-161 inhibits the proliferation of PHEV in mice and explores its underlying mechanisms of action.


Assuntos
Antivirais/administração & dosagem , Betacoronavirus 1/fisiologia , Integrina alfa5beta1/antagonistas & inibidores , Peptídeos/administração & dosagem , Replicação Viral , Animais , Betacoronavirus 1/genética , Modelos Animais de Doenças , Integrina alfa5beta1/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
15.
Medicine (Baltimore) ; 98(22): e15732, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145288

RESUMO

BACKGROUND: There are currently no FDA-approved biological or chemical drugs for the treatment of HBV-related liver fibrosis or cirrhosis. Some Chinese patent medicines have proven to be effective in this area. OBJECTIVE: The network meta-analysis (NMA) is to evaluate whether entecavir combined with Chinese patent medicine, such as "fuzhenghuayu capsules," "anluohuaxian pills," "fufangbiejiaruangan tablets," shows superior efficiency compared with entecavir alone for the treatment of chronic HBV-related liver fibrosis or cirrhosis. To evaluate which Chinese patent medicine is the most effective at improving liver fibrosis or cirrhosis in chronic hepatitis B-infected patients? METHODS: Registration of protocol: the protocol was published in the PROSPERO database (identification number: CRD42018112547). We will search PubMed, EMbase, Medline, Cochrane, China Network Knowledge Infrastructure (CNKI), and Wanfang for randomized controlled trials (RCTs) or "prospective cohort studies" of "fuzhenghuayu capsules," "anluohuaxian pills," "fufangbiejiaruangan tablets" respectively combined with entecavir in the treatment of chronic HBV-related liver fibrosis or cirrhosis from their inception to September 30, 2018. R 3.3.3 and GeMTC 0.14.3 software will be used for data analysis.


Assuntos
Antivirais/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Guanina/análogos & derivados , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Medicamentos sem Prescrição/administração & dosagem , Quimioterapia Combinada , Feminino , Guanina/administração & dosagem , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/virologia , Masculino , Metanálise como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisão Sistemática como Assunto , Resultado do Tratamento
16.
Molecules ; 24(9)2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058822

RESUMO

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4-7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.


Assuntos
Antivirais/administração & dosagem , Vírus da Febre Aftosa/fisiologia , Febre Aftosa/tratamento farmacológico , Ribonucleosídeos/administração & dosagem , Animais , Antivirais/química , Antivirais/farmacologia , Linhagem Celular , Surtos de Doenças , Febre Aftosa/epidemiologia , Febre Aftosa/virologia , Vírus da Febre Aftosa/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Camundongos , Ribonucleosídeos/química , Ribonucleosídeos/farmacologia , Suínos , Proteínas Virais/metabolismo , Replicação Viral/efeitos dos fármacos
17.
Z Gastroenterol ; 57(5): 584-592, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083746

RESUMO

BACKGROUND: The urgent need in HCV-infected patients with liver disease mandated the rapid implementation of IFN-free DAA combination therapies following their regulatory approval in 2014 and 2015 without full knowledge of the optimal combinations and regimens. Investigating the evolution of the DAA utilization patterns and treatment outcomes could provide learnings for future situations. METHODS: This was an analysis of a prospective observational database from the German Hepatitis C Registry (DHC-R) covering a period from May 2014 to September 2015. Adult patients had evidence of chronic HCV GT1 or GT4 infection and were treated with an IFN-free combination regimen of simeprevir (SMV) + sofosbuvir (SOF) or other IFN-free regimens: daclatasvir + sofosbuvir (DCV + SOF), ledipasvir/sofosbuvir (SOF/LDV), paritaprevir/r + ombitasvir ± dasabuvir (PrOD), with or without ribavirine (R). RESULTS: A total of 5496 subjects were followed during the period. During this period, clinical recommendations and treatment patterns evolved rapidly in response to new evidence from clinical trials and clinical routine and regulatory approval of additional regimens. High SVR12 rates were seen in this cohort, even in hard-to-treat patient subgroups. In the multivariate analysis, gender, age, advanced cirrhosis, and intensified treatment for cirrhotics were associated with treatment outcome. CONCLUSION: Despite limited knowledge of the optimal utilization of the newly approved DAA combinations and treatment durations as well as their comparative efficacy and safety profiles, high SVR rates were achieved regardless of the DAA combination. These outcomes were facilitated by the rapid adaptation of clinical recommendations. Future situations with high unmet medical need may follow a similar approach.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , Benzimidazóis/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada , Fluorenos/administração & dosagem , Hepacivirus/genética , Hepatite C/virologia , Hepatite C Crônica/virologia , Humanos , Estudos Prospectivos , Sistema de Registros , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
18.
Mymensingh Med J ; 28(2): 465-469, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31086168

RESUMO

We report three cases of acute lymphoblastic leukemia (ALL) those were suffered from cytomegalovirus retinitis (CMVR) during maintenance phase therapy. Ophthalmologic examination for loss of vision prompted diagnosis of cytomegalovirus retinitis. Administration of anticytomegalovirus drugs led to complete regression of active retinitis. CMVR should be in mind for children with ALL on maintenance of medical aid, even in those without hematopoietic stem cell transplantation state.


Assuntos
Retinite por Citomegalovirus/diagnóstico , Olho/virologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Doença Aguda , Antineoplásicos/efeitos adversos , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Criança , Citomegalovirus , Retinite por Citomegalovirus/tratamento farmacológico , Retinite por Citomegalovirus/virologia , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Acuidade Visual
19.
BMC Gastroenterol ; 19(1): 65, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046700

RESUMO

BACKGROUND: Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. METHODS: Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 µg/kg/wk. 24 weeks or 1.5 µg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA < 2000 IU/mL. RESULTS: The proportions of patients achieving sustained SR among patients who had SR at EOS were high in three treatment groups (61.9, 65.5, 76.5%, respectively, p = 0.46); treatment with PEG-IFN alfa-2b 1.5 µg/kg/wk. 48 weeks had the highest proportion of a sustained CR among patients who had CR at EOS (75.0%, p = 0.05). A considerable number of patients achieved sustained SR (18.2-29.9%) and sustained CR (14.8-18.3%) after EOS despite no further NA treatment. At the LTFU, rates of SR and CR were less than 70.0 and 50.0%, respectively, among all enrolled patients regardless of additional nucleos(t)ide analogs before the LTFU. CONCLUSIONS: PEG IFN alfa-2b therapy had considerable off-treatment sustainability in Chinese HBeAg positive chronic hepatitis B patients with serological and complete responses.


Assuntos
Antivirais/uso terapêutico , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Resposta Viral Sustentada , Adulto , Antivirais/administração & dosagem , China , Feminino , Seguimentos , Hepatite B Crônica/sangue , Humanos , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Masculino , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Adulto Jovem
20.
Biomed Res Int ; 2019: 2639248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061822

RESUMO

Pentraxin 3 (PTX3) plays a pathogenic role in experimental models of chronic liver injury and contributes to the progression of fibrosis. The detection of advanced fibrosis (METAVIR F≥3) is important to identify patients who are in urgent need of antiviral treatments versus those whose treatment could be deferred (F≥2). The aim was to assess the diagnostic value of PTX3 as a potential biomarker for clinically significant and advanced fibrosis. PTX3 associations with biochemical and histological parameters of inflammatory activity and fibrosis were investigated in 138 patients with chronic viral hepatitis C (HCV) before antiviral treatment. METAVIR histological scores of activity and fibrosis were obtained. PTX3 was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of serum PTX3 levels was compared to that of other fibrosis markers, including transforming growth factor-ß 1 (TGF-ß 1), hyaluronic acid (HA), aspartate transaminase to platelet ratio index (APRI), fibrosis score based on four factors (FIB4), gamma-glutamyltranspeptidase to platelet ratio (GPR), and the liver stiffness measurement (LSM) by transient elastography (FibroScan®). In HCV patients the PTX3 level increased in parallel with the METAVIR histological score of activity, being independently associated with the METAVIR fibrosis score (P < 0.001). Using the receiver operating characteristics analysis, the best marker for detecting F≥2 and F≥3 was PTX3 with AUC = 0.802 and AUC = 0.867, respectively. The area under the curve of PTX3 for predicting significant fibrosis (F≥2) was significantly greater than those for the GPR ratio (AUC = 0.648) and FIB-4 score (AUC = 0.770) and similar to that for APRI index (AUC = 0.831). PTX3 provided clinically relevant diagnostic accuracy as a single marker of significant fibrosis.


Assuntos
Proteína C-Reativa/metabolismo , Hepatite C Crônica/sangue , Cirrose Hepática/sangue , Fígado/metabolismo , Componente Amiloide P Sérico/metabolismo , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Técnicas de Imagem por Elasticidade , Feminino , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/tratamento farmacológico , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/dietoterapia , Cirrose Hepática/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta1/sangue , gama-Glutamiltransferase/sangue
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