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1.
Am J Obstet Gynecol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960017

RESUMO

There is an increasing burden of hepatitis C virus (HCV) among persons of reproductive age, including pregnant and breastfeeding women, in many regions worldwide. Routine health services during pregnancy present a critical window of opportunity to diagnose and link women with HCV infection for care and treatment to decrease HCV-related morbidity and early mortality. Effective treatment of HCV infection in women diagnosed during pregnancy also prevents HCV-related adverse events in pregnancy and HCV vertical transmission in future pregnancies. However, linkage to care and treatment for women diagnosed in pregnancy remains insufficient. Currently, there are no best practice recommendations from professional societies to ensure appropriate peripartum linkage to HCV care and treatment. We convened a virtual Community of Practice (CoP) to understand key challenges to the HCV care cascade for women diagnosed with HCV in pregnancy, highlight published models of integrated HCV services for pregnant and postpartum women, and preview upcoming research and programmatic initiatives to improve linkage to HCV care for this population. Four-hundred seventy-three participants from 43 countries participated in the CoP, including a diverse range of practitioners from public health, primary care, and clinical specialties. The CoP included panel sessions with representatives from major professional societies in obstetrics/gynecology, maternal fetal medicine, addiction medicine, hepatology, and infectious diseases. From this CoP, we provide a series of best practices to improve linkage to HCV treatment for pregnant and postpartum women, including specific interventions to enhance co-location of services, treatment by non-specialist providers, active engagement and patient navigation, and decreasing time to HCV treatment initiation. The CoP aims to further support antenatal providers in improving linkage to care by producing and disseminating detailed operational guidance and recommendations and supporting operational research on models for linkage and treatment. Additionally, the CoP may be leveraged to build training materials and toolkits for antenatal providers, convene experts to formalize operational recommendations, and conduct surveys to understand needs of antenatal providers. Such actions are required to ensure equitable access to HCV treatment for women diagnosed with HCV in pregnancy and urgently needed to achieve the ambitious targets for HCV elimination by 2030.

2.
Liver Int ; 41(7): 1494-1497, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33905164

RESUMO

We aimed to assess the pregnancy outcome in women with chronic HCV who had negative pregnancy test prior to the anti-HCV course and had unintended pregnancy while on HCV treatment. Hundred patients with a mean age of 30 ± 6.7 y were included and advised to withhold antivirals and continue follow-up in viral hepatitis and obstetrics centres till delivery. All patients received a 12-weeks regimen of anti-HCV [sofosbuvir plus daclatasvir (SOF/DCV): n = 95, SOF/DCV plus ribavirin: n = 3, and paritaprevir/ritonavir/ombitasvir plus ribavirin: n = 2]. Only nine patients completed the full antiviral course against medical advice, and 91 stopped between on-treatment weeks 4 and 8. Eighty-eight patients delivered full-term babies, eight had preterm babies and two had abortions. Of the nine patients who completed the full course of DAAs, seven (77.8%) delivered normal babies, attended their post-treatment week 12 visit, and all (100%) achieved sustained virological response. No major antiviral-related adverse events were reported.


Assuntos
Antivirais , Hepatite C Crônica , Antivirais/efeitos adversos , Quimioterapia Combinada , Egito , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Ribavirina/uso terapêutico , Sofosbuvir , Resposta Viral Sustentada , Resultado do Tratamento
3.
Arch Virol ; 166(3): 949-954, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33492523

RESUMO

No specific antiviral drugs have been approved for the treatment of COVID-19. This study aimed to evaluate the efficacy of favipiravir in treatment of COVID-19. This was a multicenter randomized controlled study including 96 patients with COVID- 19 who were randomly assigned into a chloroquine (CQ) group and a favipiravir group. None of the patients in the favipiravir group needed mechanical ventilation (p = 0.129). One patient (2.3%) in the favipiravir group and two patients (4.2%) in the CQ group died (p = 1.00). Favipiravir is a promising drug for COVID-19 that decreases the hospital stay and the need for mechanical ventilation.ClinicalTrials.gov Identifier NCT04351295.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Pirazinas/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Adulto , Cloroquina/uso terapêutico , Feminino , Humanos , Tempo de Internação , Masculino , Respiração Artificial/estatística & dados numéricos , Resultado do Tratamento
4.
J Pediatr Hematol Oncol ; 43(1): e45-e50, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32769568

RESUMO

AIM OF THE STUDY: The national Egyptian hepatitis B virus (HBV) vaccination program coverage of all infants started in 1992. The study aimed to assess immunity against HBV and occurrence of HBV breakthrough infections in vaccinated polytransfused children with malignancies. PATIENTS AND METHODS: Eighty-nine polytransfused children with malignancies were recruited; 37 were on chemotherapy (male:female 20:17; mean age 7.7±4.0 y), and there were 52 naive patients (male:female 31:21; mean age 7.6±3.2 y). In addition, 162 age-matched and sex-matched healthy controls were recruited. Patients' sera were tested for quantitative anti-hepatitis B surface (HBs) (enzyme-linked immunoassays technique), hepatitis B surface antigen (HBsAg), total anti-hepatitis B core, and HBV-DNA (nested polymerase chain reaction for surface, core, and x-regions). RESULTS: There was a significant lower percentage of having protective anti-HBs (10 to 100 IU/L) level among those receiving chemotherapy (13.5%) than those without (44.2%) and controls (32.1%). Twenty-one (67.7%) of those on chemotherapy were HBsAg positive compared with 10 (32.2%) of those without. Overall, 46 patients were HBV-DNA positive; 38 were c-region positive, 5 were s-region positive, 2 positive for the c-region and the s-region, and 1 tested positive for the c-region and the x-region. Of 46 patients, 20 were also positive for HBsAg (overt infection), while 26 had occult HBV infection (HBsAg-negative). Anti-HBs ≥10 IU/L co-existed among 45% of patients with overt infection and in 50% of those with occult infection. There was nonsignificant impact of receiving chemotherapy on the level of HBV-DNA. CONCLUSIONS: Vaccinated children with malignancies, especially those under chemotherapy, are at a significant risk of HBV infection. The co-existence of anti-HBs with HBsAg and/or HBV-DNA may represent a possible residual transfusion-transmission risk with mutant HBV strains.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Neoplasias Hematológicas/terapia , Vacinas contra Hepatite B/efeitos adversos , Vírus da Hepatite B/isolamento & purificação , Hepatite B/epidemiologia , Reação Transfusional/epidemiologia , Estudos de Casos e Controles , Criança , DNA Viral/análise , Egito/epidemiologia , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Masculino , Prognóstico , Reação Transfusional/virologia
5.
J Pediatr Hematol Oncol ; 43(8): e1077-e1081, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33290293

RESUMO

BACKGROUND: Coronavirus disease-2019 (COVID-19) could be associated with morbidity and mortality in immunocompromised children. OBJECTIVE: The objective of this study was to measure the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among hospitalized children with cancer and to detect the associated clinical manifestations and outcomes. METHODOLOGY: A prospective noninterventional study including all hospitalized children with cancer conducted between mid-April and mid-June 2020 in Ain Shams University Hospital, Egypt. Clinical, laboratory, and radiologic data were collected. SARS-CoV-2 infection was diagnosed by reverse transcription polymerase chain reaction tests in nasopharyngeal swabs. RESULTS: Fifteen of 61 hospitalized children with cancer were diagnosed with SARS-CoV-2. Their mean age was 8.3±3.5 years. Initially, 10 (66.7%) were asymptomatic and 5 (33.3%) were symptomatic with fever and/or cough. Baseline laboratory tests other than SARS-CoV-2 reverse transcription polymerase chain reaction were not diagnostic; the mean absolute lymphocyte count was 8.7±2.4×109/L. C-reactive protein was mildly elevated in most of the patients. Imaging was performed in 10 (66.7%) patients with significant radiologic findings detected in 4 (40%) patients. Treatment was mainly supportive with antibiotics as per the febrile neutropenia protocol and local Children Hospital guidance for management of COVID-19 in children. CONCLUSIONS: Pediatric cancer patients with COVID-19 were mainly asymptomatic or with mild symptoms. A high index of suspicion and regular screening with nasopharyngeal swab in asymptomatic hospitalized cancer patients is recommended.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , COVID-19/complicações , Neoplasias/virologia , SARS-CoV-2/isolamento & purificação , COVID-19/transmissão , COVID-19/virologia , Criança , Países em Desenvolvimento , Egito/epidemiologia , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/economia , Neoplasias/epidemiologia , Prognóstico , Estudos Prospectivos
6.
BMC Public Health ; 21(1): 1243, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182960

RESUMO

BACKGROUND: Smoking negatively impacts COVID-19 severity and adverse outcomes. Evidence on whether smoking is associated with SARS-Co-V2 infection and having a positive test is scarce, particularly from low-and middle-income countries, where most of the world's billion smokers live. The inconsistency in relevant findings calls for study designs and analyses to account for possible confounders including background characteristics and pre-existing co-morbidities, to disentangle the specific effect of smoking. In healthcare workers (HCWs) the frequency of exposure to COVID-19 cases adds another layer of risk that was not factored in previous studies. We examined the association of HCWs' tobacco/nicotine use (never, former, and current use) with having a positive SARS-Co-V2 test result and symptoms suggestive of infection, accounting for demographics, exposures, and co-morbidities. METHODS: A prospective cohort study of 4040 healthcare workers with baseline and follow-up screening took place during April-June 2020 in 12 healthcare facilities in Cairo, Egypt. Data on demographics, tobacco/nicotine use (manufactured or roll-your-own cigarettes, waterpipe tobacco, and electronic devices), co-morbidities, symptoms, exposures, and SARS-Co-V2 investigations were analyzed. Multinomial and multivariable logistic regression analyses were performed. RESULTS: Overall, 270/4040 (6.7, 95%CI: 5.9-7.5) had positive SARS-CoV-2 tests, 479 (11.9%) were current and 79 (2.0%) were former tobacco/nicotine users. The proportion of positive tests was 7.0% (243/3482, 95%CI: 6.1-7.8) among never, 5.1% (4/79, 95%CI: 0.1-10.0) among former, and 4.8% (23/479, 95%CI: 2.9-6.7) among current users. HCWs' SARS-CoV-2 test results did not vary significantly by single/multiple or daily/non-daily tobacco/nicotine use. Compared to never users, former users were more likely to self-report a pre-existing medical condition (ORadjusted1.87, 95%CI: 1.05-3.33, p = 0.033), and to experience symptoms suggestive of COVID-19 (ORadjusted1.76, 95%CI: 1.07-2.90, p = 0.027). After adjustment, former (ORadjusted0.45, 95%CI: 0.11-1.89, p = 0.273) and current (ORadjusted0.65, 95%CI: 0.38-1.09, p = 0.101) tobacco/nicotine use was not associated with HCWs' SARS-CoV-2 positive test results. CONCLUSIONS: This is the first report on this association from low- and middle-income countries with high tobacco/nicotine use prevalence. In this HCW cohort, having a positive SARS-CoV-2 test was not associated with tobacco/nicotine use after accounting for demographics, exposures, and co-morbidities. Additional population-based studies could use such preliminary evidence to investigate this controversial association.


Assuntos
COVID-19 , Nicotina , Estudos de Coortes , Egito , Pessoal de Saúde , Humanos , Nicotina/efeitos adversos , Estudos Prospectivos , SARS-CoV-2 , Fumar/epidemiologia , Nicotiana
7.
Int J Clin Pract ; 75(6): e14104, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33617679

RESUMO

BACKGROUND: Iron overload-induced oxidative stress and transfusion-acquired hepatitis C virus (HCV) infection are the main reasons of liver damage in beta thalassemia major (ß-TM). OBJECTIVES: Based on metformin's hepatic benefits in nondiabetic populations, the study aims to investigate the safety and the potential hepatoprotective effect of metformin in HCV-infected ß-TM adolescent patients. METHODS: This was a prospective, randomised, parallel, controlled, open-label study in which 60 HCV-infected ß-TM adolescent patients aged 11 to 18 years and receiving no antiviral therapy were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving ß-TM standard-of-care regimen, whereas metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for 6 months with assessment of liver biochemical profile, oxidative stress markers, liver fibrosis, clinical symptom improvement and metformin's adverse effects. RESULTS: Aspartate aminotransferase serum level decreased significantly over time in the treatment group only (P = .013). However, improvement was not clinically significant and did not attain normality. Change in total antioxidant capacity and malondialdehyde serum levels indicated significantly improved oxidative stress status in the treatment group versus significant deterioration in the control group (P < .001). Fibrosis grade improvement was observed in 14 patients in the treatment group versus one improved case in the control group. CONCLUSION: The use of metformin in HCV-infected ß-TM adolescent patients as an adjuvant antioxidant hepatoprotective agent is promising and can improve liver damage.


Assuntos
Hepatite C , Metformina , Talassemia beta , Adolescente , Criança , Hepacivirus , Humanos , Metformina/uso terapêutico , Estudos Prospectivos , Talassemia beta/complicações , Talassemia beta/tratamento farmacológico
8.
Semin Liver Dis ; 40(3): 213-224, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32526785

RESUMO

Hepatitis C is a global public health threat. The introduction of direct-acting antivirals (DAAs) brings the prospect of curing the 71 million people living with the disease, dramatically changing the landscape of hepatitis C. The World Health Organization developed a roadmap for the elimination and cure of hepatitis C by 2030 with a clear goal with measurable targets. However, there is a lack of a well-defined strategy to tackle the hepatitis C virus (HCV) problem in children and adolescents vis-à-vis the adult population. Hepatitis C in children and adolescents can be addressed as part of a national policy for elimination in the whole population, namely macroelimination, or could be fragmented into a microelimination approach targeting the high-risk population groups. Children born to HCV-infected mothers, adolescents who are injecting drugs, migrants, and those suffering from inherited blood diseases are important target populations. After the U.S. Food and Drug Administration approval for the use of DAAs in children aged 3 years and above, evidence from clinical trials and real-world experience was accumulated using brand and generic medicines, with sustained virological response rates exceeding 95%. The evidence created should guide policies on the management of hepatitis C in children and adolescents. There are many challenges in managing HCV in this left-behind marginalized population. The lack of awareness and epidemiological data, consent age, prohibitive prices of medicines, and absence of policies on access to diagnostics, treatment, and linkage to care are among the many barriers to service delivery that should be addressed to achieve the elimination goal by 2030.


Assuntos
Antivirais/administração & dosagem , Erradicação de Doenças/métodos , Hepatite C Crônica/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Saúde Global , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/transmissão , Humanos
9.
Trop Med Int Health ; 25(7): 850-860, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32306545

RESUMO

OBJECTIVES: Despite the high burden of hepatitis C virus (HCV) infection in Egypt, screening of pregnant women is not yet universal, making national and global elimination unlikely. This study assessed the proportion of pregnant women who were screened for HCV infection at delivery, the prevalence and risk factors for HCV infection, the associated adverse neonatal outcomes, and the real-life linkage to care of infected women and follow-up of their infants' HCV status and timing of testing. METHODS: Data were collected from medical records of a retrospective cohort of all pregnant women who were admitted to a university hospital in Cairo for delivery between January and June 2018 (n = 6734). HCV antibody- and RNA-positive women and their infants were prospectively followed-up by phone interviews till September 2019. RESULTS: 2177 (32.3%) pregnant women were screened for HCV infection. 19 (0.9%) tested HCV antibody- and RNA-positive. Being ≥ 30 years old (ORa 3.6, 95% CI: 1.4-9.2; P = 0.009), history of abortion (ORa 3.5, 95% CI: 1.2-10.3; P = 0.022) and blood transfusion (ORa 29.1, 95% CI: 9.6-88.4; P < 0.001) were independent risk factors for infection. Adverse neonatal outcomes did not vary significantly among HCV antibody-positive and antibody-negative women. Only 13 (68.4%) HCV antibody- and RNA-positive women started treatment with direct-acting antivirals (DAAs) post-breastfeeding (two completed the treatment course and were cured). Four (21.1%) did not start treatment, and two (10.5%) were lost to follow-up. All infants of the 13 HCV antibody- and RNA-positive women who started DAA therapy tested HCV RNA-negative within their first year of life. CONCLUSION: Extending screening services to all pregnant women and better linkage to care are essential for the national elimination of HCV infection.


OBJECTIFS: Malgré la charge élevée de l'infection par le virus de l'hépatite C (VHC) en Egypte, le dépistage des femmes enceintes n'est pas encore universel, ce qui rend peu probable l'élimination nationale et mondiale. Cette étude a évalué la proportion de femmes enceintes qui ont été dépistées pour l'infection par le VHC à l'accouchement, la prévalence et les facteurs de risque d'infection par le VHC, les résultats néonatals indésirables associés et le ralliement réel avec les soins aux femmes infectées et le suivi du statut VHC de leurs nourrissons et le calendrier des tests. MÉTHODES: Les données ont été collectées à partir des dossiers médicaux d'une cohorte rétrospective de toutes les femmes enceintes admises dans un hôpital universitaire du Caire pour un accouchement entre janvier et juin 2018 (n = 6734). Les femmes testées positives pour les anticorps et l'ARN du VHC et leurs nourrissons ont fait l'objet d'un suivi prospectif par des entretiens téléphoniques jusqu'en septembre 2019. RÉSULTATS: 2.155 (32,3%) femmes enceintes ont été dépistées pour l'infection au VHC. 19 (0,9%) ont été testées positives pour les anticorps et l'ARN du VHC. Avoir ≥30 ans (ORa: 3,6 ; IC95%: 1,4-9,2; p = 0,009), les antécédents d'avortement (ORa : 3,5 ; IC 95%: 1,2-10,3; p = 0,022) et la transfusion sanguine (ORa: 29,1 ; IC95%: 9,6-88,4; p <0,001) étaient des facteurs de risque indépendants d'infection. Les résultats néonatals défavorables ne variaient pas de manière significative entre les femmes positives et négatives aux anticorps anti-VHC. Seules 13 (68,4%) femmes positives pour les anticorps et l'ARN du VHC ont commencé un traitement avec des antiviraux à action directe (AAD) après l'allaitement (deux ont terminé le traitement et ont été guéries). Quatre (21,1%) n'ont pas commencé le traitement et deux (10,5%) ont été perdus de vue. Tous les nourrissons des 13 femmes positives pour l'anticorps et l'ARN du VHC qui ont commencé un traitement par AAD ont été testés négatifs pour l'ARN du VHC au cours de leur première année de vie. CONCLUSION: L'extension des services de dépistage à toutes les femmes enceintes et un meilleur lien avec les soins sont essentiels pour l'élimination nationale de l'infection par le VHC.


Assuntos
Hepatite C/epidemiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Programas de Rastreamento/métodos , Adulto , Antivirais/uso terapêutico , Egito/epidemiologia , Feminino , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Anticorpos Anti-Hepatite C/sangue , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , Gravidez , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Liver Int ; 40(4): 797-805, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31858694

RESUMO

BACKGROUND AND AIMS: This study aimed to assess the safety and efficacy of sofosbuvir (SOF)-based regimens in patients with moderate to severe renal impairment; a subject which has been questioned by many investigators with conflicting results. METHODS: This is a real-life multicentre retrospective cohort study on 4944 chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m2 ) who received SOF-based therapy in specialized treatment centres affiliated to the National Committee for the Control of Viral Hepatitis in Egypt. The efficacy and safety of SOF-based regimens was assessed. RESULTS: Week 12 virological response rates were 97.5%, 96.7%, 85.7% and 80% in the total cohort, patients with eGFR <30 mL/min/1.73 m2 , patients with associated hepatic decompensation and patients on dialysis respectively. Various treatment regimens did not statistically affect the response rates. Treatment experience, cirrhosis and diabetes were predictors of treatment failure on multivariate analysis. Serious adverse events occurred in 0.1% of cases. Forty patients (0.8%) discontinued treatment. CONCLUSION: Sofosbuvir-based regimens are effective and safe for treating patients with chronic HCV and moderate to severe CKD, and in those with associated hepatic decompensation.


Assuntos
Hepatite C Crônica , Sofosbuvir , Antivirais/efeitos adversos , Quimioterapia Combinada , Egito , Genótipo , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento
11.
Semin Liver Dis ; 38(3): 181-192, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29986353

RESUMO

The introduction of efficacious new hepatitis C virus (HCV) treatments galvanized the World Health Organization to define ambitious targets for eliminating HCV as a public health threat by 2030. Formidable obstacles to reaching this goal can best be overcome through a micro-elimination approach, which entails pursuing elimination goals in discrete populations through multi-stakeholder initiatives that tailor interventions to the needs of these populations. Micro-elimination is less daunting, less complex, and less costly than full-scale, country-level initiatives to eliminate HCV, and it can build momentum by producing small victories that inspire more ambitious efforts. The micro-elimination approach encourages stakeholders who are most knowledgeable about specific populations to engage with each other and also promotes the uptake of new models of care. Examples of micro-elimination target populations include medical patients, people who inject drugs, migrants, and prisoners, although candidate populations can be expected to vary greatly in different countries and subnational areas.


Assuntos
Antivirais/uso terapêutico , Prestação Integrada de Cuidados de Saúde/organização & administração , Erradicação de Doenças/organização & administração , Saúde Global , Política de Saúde , Hepatite C/prevenção & controle , Modelos Organizacionais , Comportamento Cooperativo , Prestação Integrada de Cuidados de Saúde/legislação & jurisprudência , Erradicação de Doenças/legislação & jurisprudência , Saúde Global/legislação & jurisprudência , Política de Saúde/legislação & jurisprudência , Hepatite C/etnologia , Hepatite C/transmissão , Humanos , Comunicação Interdisciplinar , Cooperação Internacional , Formulação de Políticas , Prevalência , Fatores de Risco , Participação dos Interessados , Populações Vulneráveis
13.
N Engl J Med ; 382(12): 1166-1174, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32187475
15.
J Pediatr Gastroenterol Nutr ; 64(6): 851-854, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28362694

RESUMO

The development of oral hepatitis C virus (HCV) direct-acting antivirals (DAAs) has revolutionized the therapeutic field. Nowadays, multiple safe and highly effective antiviral regimens are commercially available to treat adults with hepatitis C infection. These new regimens for the first time genuinely raise the prospects of eradicating HCV. Many challenges, however, remain from identifying infected individuals to optimizing treatment and ensuring global access to antiviral therapy to all population groups, including children. Recently, in April 2017, the association of sofosbuvir with ribavirin and the fixed-dose combination sofosbuvir/ledipasvir have been approved by the Food and Drug Administration for treatment of children with chronic HCV infection 12 years of age and older. The only drugs currently approved for children younger than 12 years are pegylated interferon and ribavirin. There are 6 registered ongoing pediatric trials assessing safety and efficacy of DAAs, but their current completion timelines are years away. Herein, we summarize the state of the art of DAAs' development for adult and children and highlight the crucial importance of overcoming barriers to treating children with HCV.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Administração Oral , Adolescente , Benzimidazóis/uso terapêutico , Criança , Quimioterapia Combinada , Fluorenos/uso terapêutico , Humanos , Interferon Tipo I/uso terapêutico , Ribavirina/uso terapêutico , Sofosbuvir , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapêutico
16.
Pediatr Blood Cancer ; 63(9): 1539-45, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27163515

RESUMO

BACKGROUND: The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL). PROCEDURE: One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records. RESULTS: There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (P < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation was observed (P values <0.001, 0.02, and 0.001, respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases. CONCLUSIONS: The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens.


Assuntos
Hepacivirus/isolamento & purificação , Mercaptopurina/efeitos adversos , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Fígado/efeitos dos fármacos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metiltransferases/genética , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia
17.
Clin Ther ; 46(1): e12-e22, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37925363

RESUMO

PURPOSE: Children with hematological malignancies and chronic hepatitis C virus (HCV) infection are at a higher risk for rapid progression of liver disease and malignancy relapse due to multiple hepatitis flares and chemotherapy interruption. They are therefore potential candidates for microelimination of HCV infection. This study aimed to assess the effect of acute lymphoblastic leukemia (ALL) on the pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF) and the SOF major metabolite GS-331007. METHODS: This was a 24-week, prospective, controlled, open-label, 2-arm PK study of patients receiving 45/200 mg once-daily LDV/SOF orally for 12 weeks. Eligible patients were HCV-RNA-positive, treatment-naive children aged 6 to <12 years and/or weighing 17 to <35 kg with genotype 4 chronic HCV infection without cirrhosis. The primary efficacy and safety end points were the achievement of sustained virologic response for all patients with absence of any adverse events leading to permanent discontinuation of the study drug. Steady-state noncompartmental analysis was performed to determine the PK parameters of SOF, GS-331007, and LDV as the primary PK outcome. Dose suitability was based on the 90% CI of exposure geometric mean ratio percentage within 50% to 200% compared with adults. FINDINGS: Ten HCV-infected children with ALL (chemotherapy treatment group) and 12 eligible children with no malignancy (control group) were enrolled and completed the study period. All 22 patients achieved the sustained virologic response with no adverse events leading to interruption or permanent discontinuation of the study drug. Compared with the control group, the ALL group patients had similar SOF, GS-331007, and LDV exposure. Compared with adults, the AUCτ of GS-331007 was lower and the AUCτ and Cmax,ss of SOF and the Cmax,ss of LDV were modestly higher in the ALL group (acceptance limit, 50%-200%). However, the observed efficacy and favorable safety profile made these changes not clinically significant. IMPLICATIONS: Weight-based dosing of LDV/SOF (45/200 mg) is highly effective and safe among genotype 4 HCV-infected children weighing 17 to <35 kg and diagnosed with ALL undergoing maintenance chemotherapy. The similarity in the drug exposure, efficacy, and safety clinical end points between patients with and without hematological malignancy support their therapeutic equivalence. Further studies with a larger sample size may be required to confirm the safety of LDV/SOF in patients with ALL and to recommend appropriate dosing in children with hematological malignancies, if needed. CLINICALTRIALS: gov identifier: NCT03903185.


Assuntos
Neoplasias Hematológicas , Hepatite C Crônica , Hepatite C , Adulto , Criança , Humanos , Sofosbuvir/efeitos adversos , Hepacivirus/genética , Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Estudos Prospectivos , Uridina Monofosfato/efeitos adversos , Hepatite C/tratamento farmacológico , Quimioterapia Combinada , Neoplasias Hematológicas/tratamento farmacológico , Genótipo , Resultado do Tratamento
18.
Clin Liver Dis (Hoboken) ; 23(1): e0140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567091

RESUMO

Chronic hepatitis C (HCV) in women of childbearing age is a major public health concern with ∼15 million women aged 15-49 years living with HCV globally in 2019. Evidence suggests HCV in pregnancy is associated with adverse pregnancy and infant outcomes. This includes ∼6% risk of infants acquiring HCV vertically, and this is the leading cause of HCV in children globally. However, few countries offer routine universal antenatal HCV screening, and direct-acting antivirals (DAAs) are not approved for pregnant or breastfeeding women although small clinical trials are ongoing. We conducted a survey of pregnant and postpartum women in 3 high HCV burden lower-middle-income countries to assess the acceptability of universal antenatal HCV screening and DAA treatment in the scenario that DAAs are approved for use in pregnancy. Pregnant and postpartum women attending antenatal clinics in Egypt, Pakistan, and Ukraine were invited to complete a survey and provide demographic and clinical data on their HCV status. Among the 630 women included (n=210 per country), 73% were pregnant and 27% postpartum, 27% were ever HCV antibody or PCR positive. Overall, 586 (93%) reported acceptability of universal antenatal HCV screening and 544 (88%) would take DAAs in pregnancy (92%, 98%, and 73% in Egypt, Pakistan, and Ukraine, respectively). Most said they would take DAAs in pregnancy to prevent vertical acquisition and other risks for the baby, and a smaller proportion would take DAAs for maternal cure. Our findings suggest that should DAAs be approved for use in pregnancy, the uptake of both HCV screening and DAA treatment may be high in women living in lower-middle-income countries.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36901164

RESUMO

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger's test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3-9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.


Assuntos
Coinfecção , Infecções por HIV , Hepatite B , Humanos , Feminino , Criança , Recém-Nascido , Gravidez , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , HIV , Estudos Soroepidemiológicos , Hepatite B/epidemiologia , Infecções por HIV/epidemiologia , Côte d'Ivoire/epidemiologia , Prevalência , Coinfecção/epidemiologia
20.
Pediatr Hematol Oncol ; 29(7): 627-32, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22889151

RESUMO

Ursodeoxycholic acid (UDCA) possesses a hepatoprotective effect in drug-induced hepatotoxicity. In a prospective randomized parallel study, 39 children with acute lymphoblastic leukemia (ALL) were randomized to receive UDCA with chemotherapy for 6 months, then discontinued UDCA and were followed up for 3 months, (UDCA group) (N = 19) or receive chemotherapy without UDCA and followed up for 9 months (control group) (N = 20). In this pilot study, UDCA treatment was associated with a trend toward decreased levels of hepatic transaminases when concomitantly administered with chemotherapy and, therefore, safer outcome in children with ALL. Future studies with a larger sample size are needed to confirm the efficacy and safety of UDCA in this setting.


Assuntos
Antineoplásicos/efeitos adversos , Fígado/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Ácido Ursodesoxicólico/uso terapêutico , Administração Oral , Adolescente , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Seguimentos , Humanos , Fígado/patologia , Estudos Prospectivos , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Ácido Ursodesoxicólico/administração & dosagem , Ácido Ursodesoxicólico/farmacologia
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