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1.
BMC Infect Dis ; 20(1): 30, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924172

RESUMO

BACKGROUND: Georgia has one of the highest HCV prevalence in the world and launched the world's first national HCV elimination programs in 2015. Georgia set the ambitious target of diagnosing 90% of people living with HCV, treating 95% of those diagnosed and curing 95% of treated patients by 2020. We report outcomes of Sofosbuvir (SOF) based treatment regimens in patients with chronic HCV infection in Georgia. METHODS: Patients with cirrhosis, advanced liver fibrosis and severe extrahepatic manifestations were enrolled in the treatment program. Initial treatment consisted of SOF plus ribavirin (RBV) with or without pegylated interferon (INF). Sustained virologic response (SVR) was defined as undetectable HCV RNA at least 12 weeks after the end of treatment. SVR were calculated using both per-protocol and modified intent-to-treat (mITT) analysis. Results for patients who completed treatment through 31 October 2018 were analyzed. RESULTS: Of the 7342 patients who initiated treatment with SOF-based regimens, 5079 patients were tested for SVR. Total SVR rate was 82.1% in per-protocol analysis and 74.5% in mITT analysis. The lowest response rate was observed among genotype 1 patients (69.5%), intermediate response rate was achieved in genotype 2 patients (81.4%), while the highest response rate was among genotype 3 patients (91.8%). Overall, SOF/RBV regimens achieved lower response rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P < 0.0001). In multivariate analysis being infected with HCV genotype 2 (RR =1.10, CI [1.05-1.15]) and genotype 3 (RR = 1.14, CI [1.11-1.18]) were associated with higher SVR. Patients with cirrhosis (RR = 0.95, CI [0.93-0.98]), receiving treatment regimens of SOF/RBV 12 weeks, SOF/RBV 20 weeks, SOF/RBV 24 weeks and SOF/RBV 48 weeks (RR = 0.85, CI [0.81-0.91]; RR = 0.86, CI [0.82-0.92]; RR = 0.88, CI [0.85-0.91] and RR = 0.92, CI [0.87-0.98], respectively) were less likely to achieve SVR. CONCLUSIONS: Georgia's real world experience resulted in high overall response rates given that most patients had severe liver damage. Our results provide clear evidence that SOF plus IFN and RBV for 12 weeks can be considered a treatment option for eligible patients with all three HCV genotypes. With introduction of next generation DAAs, significantly improved response rates are expected, paving the way for Georgia to achieve HCV elimination goals.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Interferons/uso terapêutico , Programas Nacionais de Saúde , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Seguimentos , Genótipo , República da Geórgia/epidemiologia , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Resposta Viral Sustentada , Adulto Jovem
2.
BMC Infect Dis ; 19(1): 870, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640578

RESUMO

BACKGROUND: Mortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients. METHODS: We reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses. RESULTS: The mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality. CONCLUSION: Hospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Mortalidade Hospitalar , Adulto , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Infecções por Coronavirus/complicações , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Interferon-alfa/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Pneumonia/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Reação em Cadeia da Polimerase , Ribavirina/uso terapêutico , Arábia Saudita/epidemiologia , Resultado do Tratamento
3.
BMC Infect Dis ; 19(1): 875, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640596

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease globally. Direct acting antivirals (DAAs) have proven effective in curing HCV. However, the current standard of care (SOC) in Botswana remains PEGylated interferon-α (IFN-α) with ribavirin. Several mutations have been reported to confer resistance to interferon-based treatments. Therefore, there is a need to determine HCV genotypes in Botswana, as these data will guide new treatment guidelines and understanding of HCV epidemiology in Botswana. METHODS: This was a retrospective cross-sectional pilot study utilizing plasma obtained from 55 participants from Princess Marina Hospital in Gaborone, Botswana. The partial core region of HCV was amplified, and genotypes were determined using phylogenetic analysis. RESULTS: Four genotype 5a and two genotype 4v sequences were identified. Two significant mutations - K10Q and R70Q - were observed in genotype 5a sequences and have been associated with increased risk of hepatocellular carcinoma (HCC), while R70Q confers resistance to interferon-based treatments. CONCLUSION: Genotypes 5a and 4v are circulating in Botswana. The presence of mutations in genotype 5 suggests that some patients may not respond to IFN-based regimens. The information obtained in this study, in addition to the World health organization (WHO) recommendations, can be utilized by policy makers to implement DAAs as the new SOC for HCV treatment in Botswana.


Assuntos
Hepacivirus/genética , Hepatite C/virologia , Mutação , Filogenia , Adulto , Antivirais/uso terapêutico , Botsuana , Carcinoma Hepatocelular/virologia , Estudos Transversais , Farmacorresistência Viral , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Ribavirina/uso terapêutico
4.
BMJ ; 366: l5021, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506273

RESUMO

Human respiratory syncytial virus (RSV) belongs to the recently defined Pneumoviridae family, Orthopneumovirus genus. It is a negative sense, single stranded RNA virus that results in epidemics of respiratory infections that typically peak in the winter in temperate climates and during the rainy season in tropical climates. Generally, one of the two genotypes (A and B) predominates in a single season, alternating annually, although regional variation occurs. RSV is a cause of disease and death in children, older people, and immunocompromised patients, and its clinical effect on adults admitted to hospital is clarified with expanded use of multiplex molecular assays. Among adults, RSV produces a wide range of clinical symptoms including upper respiratory tract infections, severe lower respiratory tract infections, and exacerbations of underlying disease. Here we discuss the latest evidence on the burden of RSV related disease in adults, especially in those with immunocompromise or other comorbidities. We review current therapeutic and prevention options, as well as those in development.


Assuntos
Carga Global da Doença , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios/genética , Infecções Respiratórias/epidemiologia , Adulto , Antivirais/uso terapêutico , Epidemias , Genótipo , Humanos , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/uso terapêutico , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/terapia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/patogenicidade , Infecções Respiratórias/imunologia , Infecções Respiratórias/terapia , Infecções Respiratórias/virologia , Ribavirina/uso terapêutico , Estações do Ano
5.
J Immunol Res ; 2019: 5878960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485460

RESUMO

Chemokine (C-X-C motif) ligand (CXCL)10 and other CXCR3 chemokines are involved in the pathogenesis of acute and "chronic hepatitis C virus (HCV) infection" (CHC). Here, we review the scientific literature about HCV and CXCL10. The combination of circulating CXCL10 and single nucleotide polymorphisms (SNPs) in IL-28B can identify patients with acute HCV infection most likely to undergo spontaneous HCV clearance and those in need of early antiviral therapy. In CHC, the HCV and intrahepatic interferon- (IFN-) γ drive a raised CXCL10 expression by sinusoidal endothelium and hepatocytes, thereby inducing the recruitment of CXCR3-expressing T cells into the liver; thus, CXCL10 plays an important role in the development of necroinflammation and fibrosis. Increased CXCL10 was significantly associated with the presence of active vasculitis in HCV-associated cryoglobulinemia, or with autoimmune thyroiditis in CHC. Pretreatment CXCL10 levels are predictive of early virological response and sustained virological response (SVR) to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy. The occurrence of SNPs adjacent to IL-28B (rs12979860, rs12980275, and rs8099917), and CXCL10 below 150 pg/mL, independently predicted the first phase viral decline and rapid virological response, which in turn independently predicted SVR. Directly acting antiviral agents-mediated clearance of HCV is associated with the loss of intrahepatic immune activation by IFN-α, associated by decreased levels of CXCL10. In conclusion, CXCL10 is an important marker of HCV clearance and successful therapy in CHC patients. Whether CXCL10 is a novel therapeutic target in CHC will be evaluated.


Assuntos
Quimiocina CXCL10/sangue , Hepatite C Crônica/imunologia , Doença Aguda , Antivirais/uso terapêutico , Quimiocina CXCL10/genética , Hepatite C/imunologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Imunomodulação , Interferon-alfa/uso terapêutico , Interferon gama/uso terapêutico , Interferons/genética , Fígado/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptores CXCR3/imunologia , Ribavirina/uso terapêutico
6.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(7. Vyp. 2): 40-51, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532590

RESUMO

OBJECTIVE: To evaluate the efficacy of different methods of antivirus therapy of tick-borne encephalitis (TBE) in children in the acute period and during chronic infections. MATERIAL AND METHODS: During 1 year, 130 children, aged 7-17 years, with TBEV received therapy in the acute period (an average in 3.5±1.3 days) in groups 1 (n=84) and 2 (n=20), and in the chronic infection in groups 3 (n=15) and 4 (n=11). Ribavirin orally, recombinant interferon-α2 (IFN-α2) i/m or in suppositories and anaferon orally were prescribed to children of groups 1 and 3. Children of groups 2 and 4 received tick-borne immunoglobulin (IgG)i/m and ribonuclease i/m. At admission, all patients received infusions of cytoflavin in the drip at the rate of 0.6 ml/kg per day. Etiological diagnosis included ELISA (IgM, G, viral antigen), and virus RNA by PCR in the blood and CSF. MRI of the brain and cervical spinal cord using standard programs was performed. All studies were performed prior to and in the course of treatment. RESULTS AND CONCLUSION: In patients of group 1, the period of increase in symptoms was reduced by ~ 4 days, and the duration of impairment of consciousness and pleocytosis in CSF ~ by 5 days, which was accompanied by a faster clearance of the virus in CSF, compared with group 2. In group 1, recovery without neurological deficit was observed in 83.3% (n=70), all patients had no progression of infection. In group 2, 30% of children (n=6) acquired TBEV chronic infection, and in 55% (n=11) there was a neurological deficit without progression. In patients of group 3 with chronic TBEV, the improvement was observed in 86.7% of cases, and complete regression of symptoms occurred in 1 patient, and replication of the virus was arrested in all of them. In group 4, symptoms increased in 72.7%, while virus replication was preserved and atrophic changes in the CNS increased on MRI. Antiviral therapy (ribavirin, IFN-α2 and release of active antibodies to gamma interferon -anaferon children) has the highest efficacy when prescribed for the first 5 days, while IgG and ribonuclease have insufficient efficacy in TBEV.


Assuntos
Antivirais , Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Imunização Passiva , Adolescente , Antivirais/uso terapêutico , Criança , Encefalite Transmitida por Carrapatos/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Humanos , Ribavirina/uso terapêutico
7.
Acta Med Indones ; 51(2): 128-136, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31383827

RESUMO

BACKGROUND: HIV infection in HCV-infected patients accelerates disease progression and reduces the success rate of Peg-IFN/RBV treatment. HCV mutation in NS5A-ISDR/PKR-BD region improved the outcome in HCV monoinfection treated with Peg-IFN/RBV. SNP-IL28B polymorphism is predicted to have an effect on HCV quasispecies evolution. However, the role of NS5A mutation and SNP IL-28B in HIV-HCV coinfection is still unclear. The aim of the study is to determine the role of HCV NS5A-ISDR/PKR-BD mutation and SNP IL-28 polymorphism on the successfulness of Peg-IFN/RBV therapy in HCV-HIV coinfection. METHODS: prospective cohort was performed in this study. Plasma sample were obtained from 30 and 8 patients with HCV-HIV coinfection and HCV monoinfection, respectively. PCR nucleotide sequencing was performed after RNA virus extraction and cDNA synthesis. Protein secondary structure and prediction of mutation function were analyzed using PredictProtein (PP) program. RESULTS: sixteen HCV-HIV coinfected patients and none from eight HCV patients achieved sustained virological response (SVR). ≥1 non-neutral mutation was found in 24/30 HCV-HIV coinfection and more frequent in SVR group (14 patients). ≥1 non-neutral mutation were found statistically significant for overall SVR achievement (p<0.05) in all patients regardless of coinfection or monoinfection status. Of the 27 HCV-HIV coinfected patients with CC-gene, 21 subjects had non-neutral mutation. The structure which was expected as NS5A binding site structure was different from consensus (wild type) in SVR group, while the structure was similar to consensus in non-SVR group. CONCLUSION: having ≥1 non-neutral mutation was associated with SVR achievement in Peg-IFN/RBV therapy, regardless of monoinfection and coinfection status.


Assuntos
Infecções por HIV/complicações , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferons/genética , Proteínas não Estruturais Virais/genética , Adulto , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Polietilenoglicóis , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Ribavirina/uso terapêutico , Resposta Viral Sustentada
8.
BMC Infect Dis ; 19(1): 675, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362697

RESUMO

BACKGROUND: Hepatitis E virus (HEV) infection is now recognized as a major cause of acute hepatitis worldwide. HEV specific antibodies develop shortly after infection and are thought to confer protection. CASE PRESENTATION: We report an immunocompromised patient who developed chronic HEV infection despite the presence of high level antibodies. HEV infection was detected using RT-PCR upon diagnostic evaluation due to increased liver enzymes. Upon retrospective analysis of stored serum samples we found that the patient was HEV RNA positive since 7 months. Chronic HEV infection was successfully treated with ribavirin. CONCLUSIONS: In conclusion, the patient suffered from a chronic course of HEV infection, which was successfully treated with ribavirin. Our case underlines the importance of RT-PCR for HEV diagnostics in immunosuppressed patients and supports the notion that HEV antibodies do not confer universal protection. Counseling patients at risk for chronic HEV infection seems advisable. The role of the humoral and T-cell mediated immune response in cases of HEV reinfection deserves further study.


Assuntos
Hepatite E/etiologia , Hepatite Crônica/etiologia , Transplante de Rim/efeitos adversos , RNA Viral/sangue , Formação de Anticorpos , Antivirais/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Anticorpos Anti-Hepatite/sangue , Anticorpos Anti-Hepatite/imunologia , Hepatite E/diagnóstico , Hepatite E/tratamento farmacológico , Hepatite Crônica/diagnóstico , Hepatite Crônica/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ribavirina/uso terapêutico
9.
Gastroenterology ; 157(6): 1506-1517.e1, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31401140

RESUMO

BACKGROUND & AIMS: Treatment options are limited for patients with hepatitis C (HCV) infection with treatment failure after sofosbuvir plus an NS5A inhibitor. There are some data for the efficacy of glecaprevir/pibrentasvir (G/P) in these patients. We performed a randomized trial of the safety and efficacy of 12 and 16 weeks of G/P, with or without ribavirin, in patients with HCV genotype 1 infection with treatment failure after sofosbuvir and an NS5A inhibitor. METHODS: We performed a phase 3b, open-label study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor. Patients without cirrhosis were randomly assigned to groups that received G/P for 12 weeks (n = 78, group A) or 16 weeks (n = 49, group B). Patients with compensated cirrhosis were randomly assigned to groups that received G/P and ribavirin for 12 weeks (n = 21, group C) or G/P for 16 weeks (n = 29, group D). The primary end point was a sustained virologic response 12 weeks after treatment. Samples collected at baseline and at time of treatment failure were sequenced for resistance-associated substitutions in NS3 and NS5A. RESULTS: Of the 177 patients in the 4 groups, 81% were men, 79% had HCV genotype 1a infection, and 44% were black. Proportions of patients with sustained virologic response 12 weeks after treatment in groups A, B, C, and D were 90%, 94%, 86%, and 97%, respectively. The treatment failed in 13 (7.3%) patients with HCV genotype 1a infection, 6 (7.9%) in group A, 3 (6.1%) in group B, 3 (6.1%) in group C (6.1%), and 1 (3.4%) in group D. Most patients had baseline resistance-associated substitutions in NS5A. Treatment-emergent resistance-associated substitutions in NS3 and NS5A were observed in 9 and 10 patients with treatment failure, respectively. G/P was well tolerated. Ribavirin increased adverse events but did not increase efficacy. CONCLUSIONS: In a randomized study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor, 16 weeks treatment with G/P produced sustained virologic response 12 weeks after treatment in >90% of patients, including those with compensated cirrhosis. ClinicalTrials.gov, Number: NCT03092375.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/farmacologia , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Combinação de Medicamentos , Farmacorresistência Viral Múltipla/genética , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas/farmacologia , Pirrolidinas/uso terapêutico , Quinoxalinas/farmacologia , Quinoxalinas/uso terapêutico , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Sofosbuvir/farmacologia , Sofosbuvir/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Falha de Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética
10.
Hepatol Int ; 13(5): 587-598, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31463665

RESUMO

BACKGROUND AND AIMS: One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia. METHODS: Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25 IU/mL 12 week post-therapy). RESULTS: A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5 years, p < 0.0001), had lower body mass indices (22.9 kg/m2 vs. 24.6 kg/m2, p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes. CONCLUSIONS: In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Idoso , Quimioterapia Combinada , Feminino , Hong Kong , Humanos , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Isoquinolinas/administração & dosagem , Isoquinolinas/uso terapêutico , Japão , Masculino , Pessoa de Meia-Idade , República da Coreia , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Sofosbuvir/administração & dosagem , Sofosbuvir/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Taiwan , Resultado do Tratamento
11.
Int J Infect Dis ; 89: 84-86, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31465848

RESUMO

BACKGROUND: The signs and symptoms of Lassa fever are initially indistinguishable from other febrile illnesses common in the tropics and complications of pregnancy. Surviving Lassa fever during pregnancy is rare. Only few cases have been documented. The antiviral drug of choice is ribavirin. CASE DESCRIPTION: A 25-year-old multigravida farmer with fever who was initially thought to have malaria in pregnancy at 29 weeks gestation. Further changes in her clinical state and laboratory tests led to a confirmation of Lassa fever. The Liver enzymes were markedly deranged and the packed cell volume was 27%. She commenced on ribavirin and subsequently was delivered of a live male neonate who was RT PCR negative for Lassa fever virus. Her clinical state improved, repeat RT PCR on day 15 was negative and she made full recovery. DISCUSSION: The case reported had similar clinical features of fever and abdominal pain and resulted in the initial diagnoses of Malaria in pregnancy. When she failed to respond to antimalarial and antibiotics treatments, a strong suspicion of viral hemorrhagic fever was made. At this time the patient was in advanced stage of the disease with bleeding from vagina and puncture sites. On the third day of admission she was delivered of a live male neonate who remained negative after 2 consecutive RT PCR tests for Lassa fever virus. Lassa fever carries a high risk of death to the fetus throughout pregnancy and to the mother in the third trimester. Mothers with Lassa fever improved rapidly after evacuation of the uterus by spontaneous abortion, or normal delivery. She was clinically stable following delivery. Her laboratory investigations were essentially normal. Throughout her management transmission based precautions were observed. None of the six close contacts developed symptoms after been followed up for 21 days. CONCLUSION: This report adds to the body of literature that individuals can survive Lassa fever during pregnancy with good maternal and fetal outcome.


Assuntos
Febre Lassa/virologia , Complicações na Gravidez/virologia , Adulto , Antivirais/uso terapêutico , Feminino , Febre/diagnóstico , Febre/tratamento farmacológico , Febre/fisiopatologia , Febre/virologia , Humanos , Recém-Nascido , Febre Lassa/diagnóstico , Febre Lassa/tratamento farmacológico , Febre Lassa/fisiopatologia , Vírus Lassa/efeitos dos fármacos , Vírus Lassa/genética , Vírus Lassa/isolamento & purificação , Masculino , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez , Ribavirina/uso terapêutico
12.
Anticancer Res ; 39(7): 3855-3862, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262913

RESUMO

BACKGROUND: We examined treatment the efficacy and data on long-term outcomes in real-world Japanese patients infected with hepatitis C virus (HCV) genotype 2 treated with 12-week sofosbuvir/ribavirin combination therapy. PATIENTS AND METHODS: In a total of 86 patients who were treated with sofosbuvir/ribavirin, sustained virological response (SVR) rates and long-term-outcomes were retrospectively analyzed. RESULTS: The adherence to this combination therapy was 98.8%. The rates of SVR at week 24 (SVR24) achieved with this treatment according to the 'intention-to-treat' and 'per-protocol' analyses were 89.5% and 96.2%, respectively. Two patients who experienced relapse did not have any previously reported resistance-associated substitutions in the HCV non-structural protein 5B (NS5B) polymerase region. We did not observe any patients who experienced late relapse but did observe that 50% and 1.3% of patients with and without a previous history of hepatocellular carcinoma (HCC), respectively, developed HCC after achieving SVR24 (with a mean follow-up period of 2.7±0.8 years). CONCLUSION: Patients with SVR should be carefully followed-up to screen for the occurrence of HCC, although it is infrequent.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Resultado do Tratamento
13.
Egypt J Immunol ; 26(1): 151-161, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31333005

RESUMO

Hepatitis C virus (HCV) is a major health problem all over the world with the highest prevalence reported in Egypt. Various treatment regimens have been developed over the last years. Interferon (IFN) based regimen was the standard of care regimen and then the IFN-free therapies were emerged. Host innate immunity through the activity of natural killer (NK) cell is one of the major players in competing infections and tumors, by producing perforin and granzymes that cause cytolysis of target cells, or by the production of various cytokines such as natural interferon gamma. Natural cytotoxicity receptors (NCRs), including Nkp30, Nkp44 and Nkp46, are a group of activating receptors that almost have restricted expression on the surface of NK cells and their density correlates with NK cytotoxicity. The role of these cells is not fully elucidated in patients with chronic HCV infection either treatment-naive or treatment experienced. Therefore, this study aimed to investigate the change that occurs in NK cell activity and cytotoxicity in response to successful elimination of HCV from blood after triple therapy with PEG-IFN-α, ribavirin and sofosbuvir. A total of 56 (50 male: 6 female) HCV patients with mean age of 41.6± 12.1 years were included in this study. They were divided into two groups: treatment naive group (20 patients) and the sustained virologic response (SVR) group (36 patients). All patients were investigated for their NK cell profile, NCRs, perforin and granzyme B expression by flow cytometry. Data was expressed as mean fluorescence intensity (MFI). Results revealed significant increase in MFI of granzyme B (P=0.001) and decrease in MFI of NKp30 (P=0.042) in the SVR group as compared to treatment naïve group. These findings indicated that triple therapy of HCV (IFN, Ribavirin and Sofosbuvir) effected NK activation and cytotoxicity.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Células Matadoras Naturais/efeitos dos fármacos , Adulto , Egito , Feminino , Hepacivirus , Humanos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Receptor 3 Desencadeador da Citotoxicidade Natural/análise , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada
14.
Orthop Nurs ; 38(4): 273-277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31343633

RESUMO

The treatment of hepatitis C virus (HCV) has evolved significantly, marked by the approval of combination, direct-acting antiviral medications, which have improved the tolerability and efficacy of therapy. As the number of patients engaged in HCV treatment increases, it is important that all members of the healthcare team remain current on treatment options and equipped with the knowledge to educate patients. Nursing staff play a critical role in understanding the role of new medications in treatment, significant drug interactions, and patient counseling points on administration, potential adverse reactions, and the importance of adherence.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Fluorenos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Educação de Pacientes como Assunto/métodos , Quinoxalinas/uso terapêutico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Resultado do Tratamento
15.
Medicine (Baltimore) ; 98(30): e16524, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348267

RESUMO

Anti-hepatitis C virus (HCV) treatment for human immunodeficiency virus (HIV)/HCV co-positive patients with hemophilia A presents numerous problems in terms of safety and effectiveness. The emergence of direct-acting antiviral (DAA) regimens has led to tremendous changes in the management of HIV/HCV co-infection over the past few years, but the application of DAA in patients with hemophilia complicated with HIV/HCV co-infection has rarely been reported.We retrospectively analyzed the clinical course and outcome of hemophilia A patients with HIV/HCV co-infection receiving DAA with a focus on the virological response, changes in cluster of differentiation 4 lymphocyte (CD4) count, side effects, and impact on bleeding before and after DAA therapy.A total of 12 hemophilia A patients with HIV/HCV co-infection were included, 9 of which were severe. All the patients were in stable states with CD4 counts >200/mm and plasma HIV ribonucleic acid (RNA) suppressed (<40 IU/mL) while taking the antiretroviral regimen. Majority of the patients (n = 9, 75.0%) were infected with HCV genotype (GT) 1b, while 2 and 1 was infected with HCV GT 2i and HCV GT 3, respectively.After 12 weeks of DAA treatment, 11 patients (91.7%) obtained sustained virologic response within 24 weeks of discontinuation of treatment (SVR24), except 1 patient who was treated with sofosbuvir (SOF) + pegylated interferon + ribavirin (PR), which was then switched to daclatasvir (DCV) + asunaprevir (ASV) for 12 weeks; this patient then achieved SVR24. During DAA treatment, HIV RNA in all the patients was constantly suppressed, while CD4 counts showed no obvious change.The most common treatment-emergent adverse events were weakness and loss of appetite (generally mild). There was no evidence of an increased tendency of bleeding, and changes in response to replacement.DAA therapy offered a safe and well-tolerated management strategy for HIV/HCV co-infected patients with hemophilia A. An awareness of the potential drug-drug interactions (DDI) between DAA and combination antiretroviral therapy (cART) by clinicians is important for optimal management of co-infected patients.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hemofilia A/tratamento farmacológico , Hepatite C/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Coinfecção/imunologia , Coinfecção/virologia , Quimioterapia Combinada , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1 , Hemofilia A/imunologia , Hemofilia A/virologia , Hepacivirus , Hepatite C/imunologia , Hepatite C/virologia , Humanos , Imidazóis/uso terapêutico , Interferons/uso terapêutico , Isoquinolinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada
16.
Int J Infect Dis ; 87: 15-20, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357056

RESUMO

OBJECTIVES: Lassa fever (LF) causes annual outbreaks in endemic regions with high mortality of symptomatic patients. Ribavirin is recommended as standard treatment for LF in national and international guidelines but the evidence base for this recommendation has been questioned recently. METHODS: We conducted a systematic review and included 6 studies providing efficacy data of ribavirin treatment for LF (PROSPERO protocol CRD42018103994). RESULTS: Besides retrospective case series, the evidence mostly relies on a single prospective clinical trial with critical risk of bias. In this trial, LF associated mortality is reduced for patients with elevated aspartate aminotransferase (AST) when treated with ribavirin (OR 0.41, 95% CI 0.23-0.73), while mortality is higher for patients without elevated AST (OR 2.37, 95% CI 1.07-5.25). CONCLUSIONS: Based on the available data, current treatment guidelines may therefore put patients with mild LF at increased risk of death. The role of ribavirin in the treatment of LF requires urgent reassessment.


Assuntos
Febre Lassa/tratamento farmacológico , Vírus Lassa/efeitos dos fármacos , Ribavirina/uso terapêutico , Aspartato Aminotransferases/metabolismo , Ensaios Clínicos como Assunto , Humanos , Febre Lassa/enzimologia , Febre Lassa/mortalidade , Febre Lassa/virologia , Vírus Lassa/fisiologia , Estudos Prospectivos , Estudos Retrospectivos
17.
Enferm. glob ; 18(55): 157-169, jul. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-186239

RESUMO

Objetivo: describir la caracterización sociodemográfica y clínica de los pacientes portadores de hepatitis C crónica acompañados en el ambulatorio de un hospital de referencia en infectología. Método: estudio transversal, descriptivo, cuantitativo, con usuarios portadores de hepatitis C crónica asistidos en el ambulatorio de un hospital de referencia durante noviembre de 2015 a abril de 2016 con una muestra de 47 usuarios. Resultados: los participantes son de sexo masculino (76,6%) con rango de edad superior a 57 años (57,5%), pardo (38,3%), casado (55,3%), con grado de escolaridad (31,9%), y residente en la capital (61,7%), con tiempo de descubrimiento de hasta 6 años (68,1%), desconociendo la forma de contaminación (57,5%), inmunizado contra la hepatitis B (65,9%), realizando tratamiento medicamentoso (85,1%) con Ribavirina (55,6%); Y el 70,2% presentó efectos adversos. Conclusión: la caracterización sociodemográfica y clínica auxilian en la práctica clínica del equipo multiprofesional con los portadores de hepatitis C crónica


Objetivo: descrever a caracterização sociodemográfica e clínica dos pacientes portadores de hepatite C crônica acompanhados no ambulatório de um hospital referência em infectologia. Método: estudo transversal, descritivo, quantitativo, com usuários portadores de hepatite C crônica assistidos no ambulatório de um hospital referência durante Novembro 2015 a Abril de 2016 com uma amostra de 47 usuários. Resultados: os participantes encontram-se no sexo masculino (76,6%) com faixa etária acima de 57 anos (57,5%), pardo (38,3%), casado (55,3%), com grau de escolaridade fundamental incompleto (31,9%), e residente na capital (61,7%), com tempo de descoberta de até 6 anos (68,1%), desconhecendo a forma de contaminação (57,5%), realizando tratamento medicamentoso (85,1%) com Ribavirina (55,6%); e 70,2% apresentaram efeitos adversos. Conclusões: a caracterização sociodemográfica e clínica auxiliam na prática clínica da equipe multiprofissional com os portadores de hepatite C crônica


Objective: to describe the sociodemographic and clinical characterization of patients with chronic hepatitis C followed at the outpatient clinic of a reference hospital in infectology. Method: a cross-sectional, descriptive, quantitative study with chronic hepatitis C patients attended at a referral hospital during November 2015 to April 2016 with a sample of 47 users. Results: the participants were male (76.6%), 57 years old (57.5%), brown (38.3%), married (55.3%), (61.7%), with a discovery time of up to 6 years (68.1%), not knowing the form of contamination (57.5%), immunized against hepatitis B (65.9%), undergoing drug therapy (85.1%) with Ribavirin (55.6%); And 70.2% had adverse effects. Conclusion: sociodemographic and clinical characterization assist the clinical practice of the multiprofessional team with patients with chronic hepatitis C


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hepatite C Crônica/epidemiologia , Hepacivirus/patogenicidade , Ribavirina/uso terapêutico , Estimativas de População , Continuidade da Assistência ao Paciente/tendências , Hepatite C Crônica/tratamento farmacológico
19.
Int Immunopharmacol ; 74: 105708, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254956

RESUMO

BACKGROUND AND AIMS: Soluble E-cadherin (sE-cadherin) has been observed elevated in patients with various diseases, and implicated in the occurrence and development of those diseases. The implications of sE-cadherin in chronic hepatitis C virus (HCV) infection are still unclear. The purpose of this study is to explore the significance of sE-cadherin in chronic hepatitis C infection and the correlation with treatment response. METHODS: 87 chronic HCV infected patients and 60 healthy subjects were enrolled in this study. Blood samples from patients receiving the combined treatment of pegylated interferon-a (Peg-IFN-α) with ribavirin (RBV) were collected before treatment, during 4th, 12th therapy weeks, end of the treatment, and 24 weeks post-therapy. Plasma sE-cadherin level was detected by enzyme-linked immunosorbent assay (ELISA) and the relationship between sE-cadherin and antiviral treatment outcome was analyzed. RESULTS: Plasma sE-cadherin concentrations of Chronic HCV infected patients were significantly higher than that of healthy controls. A strong correlation between sE-cadherin level and the HCV viral load, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and also glutamyl transpeptidase (GGT) level was detected. Chronic HCV infected patients achieving rapid virological response (RVR) and sustained virological response (SVR) had lower baseline sE-cadherin concentrations compared with the non-RVR and non-SVR groups respectively. Univariate and multivariate regression analyses suggested that baseline plasma sE-cadherin level was predictive of therapeutic effect in patients with chronic HCV infection. CONCLUSION: Baseline sE-cadherin level could be considered as an independent predictor of SVR with Peg-IFN-α plus ribavirin therapy in the Chinese Han population chronic HCV infection patients. Effective antiviral therapy might restore sE-cadherin at physiological levels.


Assuntos
Biomarcadores Farmacológicos/sangue , Caderinas/sangue , Hepacivirus/fisiologia , Hepatite C Crônica/diagnóstico , Imunoterapia/métodos , Adulto , Antivirais/uso terapêutico , China , Quimioterapia Combinada , Feminino , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Prognóstico , Ribavirina/uso terapêutico , Carga Viral
20.
Zhonghua Gan Zang Bing Za Zhi ; 27(5): 352-357, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31177659

RESUMO

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion: Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Antivirais/efeitos adversos , China , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Resultado do Tratamento
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