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1.
Medicine (Baltimore) ; 99(12): e19500, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195950

RESUMO

BACKGROUND: Lesions of herpes labialis are caused by the herpes simplex virus type 1 and cause pain and aesthetic compromise. It is characterized by the formation of small vesicles that coalesce and rupture forming extremely painful ulcers, that evolve to crusts, dry desquamations until their complete remission. Currently the treatment of these lesions is done with acyclovir. Although it diminishes the symptomatology, it causes viral resistance and does not prevent the recurrence of the lesions. It is known that antimicrobial photodynamic therapy (aPDT) has numerous advantages, among them: the reduction of the time of remission, and does not cause resistance. This protocol will determine the effectiveness of PDT in lesions of herpes labialis. MATERIALS AND METHODS: A total of 30 patients with herpes labialis in the prodromal stage of vesicles, ulcers, and crusts will be selected to participate in the study and randomized into 2 groups: G1 control and G2 experimental. After signing Research Ethics Committee and TA, patients in group G1 will undergo the standard gold treatment for herpes labialis with acyclovir and simulated PDT treatment. Patients in the experimental G2 group will be treated simulating the gold standard treatment of herpes labialis (placebo) and PDT. In all patients, saliva samples will be collected for analysis of cytokines, and will be performed exfoliative cytology in the lesions. The pain will be assessed through a pain scale and a questionnaire of quality of life related to oral health (OHIP-14) will be given to them. Patients will continue to be followed up after 7 days, 1 month, 3 months, and 6 months; if there is a recurrence of the lesion, they will contact the researchers.Clinical registration: clinicaltrials.gov - NCT04037475. Registered on July 2019.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Herpes Labial/terapia , Fotoquimioterapia/métodos , Aciclovir/efeitos adversos , Adulto , Antivirais/efeitos adversos , Feminino , Herpes Labial/patologia , Herpes Labial/virologia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 1/efeitos da radiação , Humanos , Masculino , Dor/etiologia , Estudos Prospectivos , Qualidade de Vida , Recidiva , Úlcera/patologia , Escala Visual Analógica , Adulto Jovem
2.
Drug Discov Ther ; 14(1): 50-53, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32101820

RESUMO

Our earlier study investigated the incidence of severe abnormal behavior associated with neuraminidase inhibitors (NIs), but some studies have specifically examined the association of oseltamivir use and moderately abnormal behavior. Therefore, this study was undertaken to assess associations between moderately abnormal behavior and administered drugs. All cases of patients with influenza who exhibited moderately abnormal behavior were reported to us by physicians of all sentinel clinics and hospitals for influenza throughout Japan. Open Data of the National Database of Electronic Medical Claims include the numbers of patients diagnosed as having influenza who were prescribed NI. Incidence by NI was tested using Fisher's exact test. We received 518 moderately abnormal cases in 5-9-year-olds and 207 moderately abnormal behavior cases in 10-19-year-olds. The incidence among NI ranged from 193 per one million influenza patients in laninamivir among 10-19-year-olds to 1021 for peramivir among 5-9-year-olds. Estimation results revealed the order of risk among NIs as peramivir, oseltamivir, zanamivir and laninamivir in moderate abnormal behavior. Because of data limitations, risk among patients with and without NI cannot be compared.


Assuntos
Inibidores Enzimáticos/efeitos adversos , Comportamento de Doença/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Influenza Humana/psicologia , Neuraminidase/antagonistas & inibidores , Adolescente , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Criança , Ciclopentanos/administração & dosagem , Ciclopentanos/efeitos adversos , Inibidores Enzimáticos/administração & dosagem , Guanidinas/administração & dosagem , Guanidinas/efeitos adversos , Humanos , Japão , Oseltamivir/administração & dosagem , Oseltamivir/efeitos adversos , Adulto Jovem , Zanamivir/administração & dosagem , Zanamivir/efeitos adversos , Zanamivir/análogos & derivados
4.
Medicine (Baltimore) ; 98(50): e18351, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852136

RESUMO

Tenofovir disoproxil fumarate (TDF) is thought to cause varying degrees of hypophosphatemia in patients with chronic hepatitis B (CHB). Therefore, we investigated factors that cause hypophosphatemia in patients treated with TDF and methods to increase serum phosphorus concentrations in clinical practice.We completed a retrospective review of patients with CHB treated with TDF initially at Kosin University Gospel Hospital, Busan, Korea from January 2012 to January 2017. Subclinical hypophosphatemia and hypophosphatemia were defined as serum phosphorus below 3.0 mg/dL and 2.5 mg/dL, respectively.We screened 206 patients with CHB treated with TDF, among which 135 were excluded for the following reasons: baseline malignancy (59), limited data (50), co-administered other antivirals (14), hypophosphatemia at baseline (7), and other reasons (5). The final study population comprised 71 patients. Subclinical hypophosphatemia developed in 43 (60.5%) patients. Hypophosphatemia occurred in 18 patients (25.3%). Liver cirrhosis was the most significant predictor of hypophosphatemia (P = .038, OR = 3.440, CI = 1.082-10.937) Patients diagnosed with subclinical hypophosphatemia were encouraged to increase their intake of nuts and dairy products (25 patients) or reduce their alcohol intake (2), dose reduction of TDF (4) or placed under observation (4). Among patients with subclinical hypophosphatemia, serum phosphorus concentrations were elevated (>3.0 mg/dL) in 23 of 36 patients (63.8%). Increased nut and dairy intake increased phosphorus concentrations to more than 3.0 mg/dl in 16 of 25 patients (64.0%).Entecavir or tenofovir alafenamide fumarate (TAF) should be considered rather than TDF in patients with liver cirrhosis because of the risk of hypophosphatemia. Instead of stopping TDF treatment, encouraging increased intake of phosphorus-rich foods could increase serum phosphorus concentrations in clinical practice.


Assuntos
Antivirais/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Hipofosfatemia/induzido quimicamente , Tenofovir/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
5.
PLoS Negl Trop Dis ; 13(11): e0007890, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31751347

RESUMO

Recent outbreaks of the Ebola virus (EBOV) have focused attention on the dire need for antivirals to treat these patients. We identified pyronaridine tetraphosphate as a potential candidate as it is an approved drug in the European Union which is currently used in combination with artesunate as a treatment for malaria (EC50 between 420 nM-1.14 µM against EBOV in HeLa cells). Range-finding studies in mice directed us to a single 75 mg/kg i.p. dose 1 hr after infection which resulted in 100% survival and statistically significantly reduced viremia at study day 3 from a lethal challenge with mouse-adapted EBOV (maEBOV). Further, an EBOV window study suggested we could dose pyronaridine 2 or 24 hrs post-exposure to result in similar efficacy. Analysis of cytokine and chemokine panels suggests that pyronaridine may act as an immunomodulator during an EBOV infection. Our studies with pyronaridine clearly demonstrate potential utility for its repurposing as an antiviral against EBOV and merits further study in larger animal models with the added benefit of already being used as a treatment against malaria.


Assuntos
Antimaláricos/administração & dosagem , Antivirais/administração & dosagem , Doença pelo Vírus Ebola/prevenção & controle , Naftiridinas/administração & dosagem , Animais , Antimaláricos/efeitos adversos , Antimaláricos/farmacocinética , Antivirais/efeitos adversos , Antivirais/farmacocinética , Citocinas/imunologia , Reposicionamento de Medicamentos , Ebolavirus/efeitos dos fármacos , Ebolavirus/genética , Ebolavirus/fisiologia , Feminino , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Naftiridinas/efeitos adversos , Naftiridinas/farmacocinética
6.
N Engl J Med ; 381(24): 2293-2303, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31774950

RESUMO

BACKGROUND: Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. METHODS: We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase-polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. RESULTS: A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. CONCLUSIONS: Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.).


Assuntos
Alanina/análogos & derivados , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Doença pelo Vírus Ebola/tratamento farmacológico , Ribonucleotídeos/uso terapêutico , Adolescente , Adulto , Alanina/efeitos adversos , Alanina/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Antivirais/efeitos adversos , Criança , Pré-Escolar , República Democrática do Congo/epidemiologia , Surtos de Doenças , Ebolavirus/genética , Feminino , Doença pelo Vírus Ebola/mortalidade , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , RNA Viral/sangue , Ribonucleotídeos/efeitos adversos , Método Simples-Cego , Adulto Jovem
7.
BMC Infect Dis ; 19(1): 882, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640579

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. CASES PRESENTATION: In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. CONCLUSIONS: We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.


Assuntos
Antituberculosos/uso terapêutico , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Idoso , Antituberculosos/efeitos adversos , Antivirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Hepacivirus/genética , Humanos , Itália , Masculino , RNA Viral/sangue , Retratamento , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/virologia , Tuberculose Pulmonar/virologia
8.
West Afr J Med ; 36(3): 280-282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622492

RESUMO

The advent of direct-acting anti-virals revolutionized the treatment and prognosis of patients infected with hepatitis C. The interest of this presentation is to draw attention to the issue of therapeutic management posed by the hepatitis C virus in a kidney graft in Côte d'Ivoire, a resource-limited country where all the direct-acting anti-virals are not yet available. We report the case of a kidney transplant of 52 years old, chronic carrier of viral hepatitis C who presented after his kidney transplant in decompensated active cirrhosis. A treatment based on Sofosbuvir 400 mg/Ledipasvir 90 mg in this patient with genotype 2 for 12 weeks was initiated. Sustained virologic response 12 weeks and 24 weeks off therapy was observed. This is the first documented case of successful treatment of a genotype 2 viral C infection based on Sofosbuvir/Ledipasvir in a black African cirrhotic kidney transplant patient undergoing immunosuppressive therapy.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Transplante de Rim , Sofosbuvir/uso terapêutico , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Quimioterapia Combinada , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Sofosbuvir/efeitos adversos , Resultado do Tratamento
9.
Medicine (Baltimore) ; 98(39): e17343, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574875

RESUMO

RATIONALE: Glecaprevir/pibrentasvir, a pan-genotypic and ribavirin-free direct acting antiviral agent regimen, has shown significant efficacy and very few serious complications. However, as the drug metabolizes in the liver, it is not recommended in patients with decompensated liver cirrhosis. Herein, we report the case of a patient with compensated liver cirrhosis who developed severe jaundice after glecaprevir/pibrentasvir medication. PATIENT CONCERNS: A 77-year-old man diagnosed with chronic hepatitis C-related compensated liver cirrhosis visited hospital due to severe jaundice after 12 weeks of glecaprevir/pibrentasvir medication. DIAGNOSES: On the laboratory work-up, the total/direct bilirubin level was markedly elevated to 21.56/11.68 from 1.81 mg/dL; the alanine aminotransferase and aspartate aminotransferase levels were within the normal range. We checked the plasma drug concentration level of glecaprevir, and 18,500 ng/mL was detected, which was more than 15 times higher than the drug concentration level verified in normal healthy adults. INTERVENTIONS: Glecaprevir/pibrentasvir was abruptly stopped and after 6 days, the drug concentration level decreased to 35 ng/mL and the serum total/direct bilirubin decreased to 7.49/4.06 mg/dL. OUTCOMES: Three months after drug cessation, the serum total bilirubin level normalized to 1.21 mg/dL and HCV RNA was not detected. LESSONS: We report what is likely the first known case of severe jaundice after medication with glecaprevir/pibrentasvir in a patient with compensated liver cirrhosis. Clinicians should bear potential hyperbilirubinemia in mind when treating chronic hepatitis C with this regimen and should monitor the patient closely during follow-up laboratory exams, especially in elderly cirrhotic patients.


Assuntos
Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite C Crônica/tratamento farmacológico , Hiperbilirrubinemia/induzido quimicamente , Cirrose Hepática/induzido quimicamente , Pirrolidinas/efeitos adversos , Quinoxalinas/efeitos adversos , Sulfonamidas/efeitos adversos , Idoso , Doença Hepática Induzida por Substâncias e Drogas/virologia , Combinação de Medicamentos , Humanos , Hiperbilirrubinemia/virologia , Fígado/efeitos dos fármacos , Fígado/virologia , Cirrose Hepática/virologia , Masculino
10.
Rinsho Shinkeigaku ; 59(10): 641-645, 2019 Oct 26.
Artigo em Japonês | MEDLINE | ID: mdl-31564701

RESUMO

A 76-year-old Japanese female who was treated with long-term use of prednisolone at 10 mg/day for interstitial pneumonia developed acute right-dominant lower limb paralysis and then upper limb paralysis with herpes zoster eruptions on the right C7-Th1 dermatomes. On admission, right predominant quadriplegia was observed with sensory symptoms; Hughes functional grade was level 4; the hand grip power was right, 0, and left, 7 kg, the deep tendon reflexes were abolished throughout without pathologic reflexes. Twenty days after the onset of the symptoms, the cerebrospinal fluid (CSF) revealed mild increases of lymphocytes (13 cells/µl) and protein content (73 mg/dl). Varicella-zoster virus (VZV) PCR was negative in the CSF, but an enzyme immunoassay for VZV was positive in her serum and CSF, and the high titers were prolonged. Peripheral nerve conduction and F wave studies suggested right-dominant demyelinating polyradiculoneuropathy. A T1-weighted MR contrast image exhibited right-dominant high-intensity lesions on the C7-Th1 spinal roots and similar lesions on the L4-5 spinal roots. We compared with several similar cases from the literature and proposed that VZV itself involves the pathogenesis of the polyradiculoneuritis in immunocompromised hosts.


Assuntos
Herpes Zoster/complicações , Polirradiculoneuropatia/complicações , Polirradiculoneuropatia/virologia , Infecção pelo Vírus da Varicela-Zoster , Aciclovir/administração & dosagem , Aciclovir/efeitos adversos , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Imagem de Difusão por Ressonância Magnética , Feminino , Síndrome de Guillain-Barré , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/administração & dosagem , Oxidiazóis/administração & dosagem , Polirradiculoneuropatia/diagnóstico , Polirradiculoneuropatia/tratamento farmacológico , Quadriplegia/etiologia
11.
AIDS Rev ; 21(3): 126-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532397

RESUMO

Persistent coinfection with the hepatitis B/D viruses (HDV) represents the most severe form of viral hepatitis. Hepatitis D often leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. The current treatment options are limited as only pegylated interferon-alpha (PEG-IFNa) has efficacy against HDV. However, treatment response is still unsatisfactory with 25-40% HDV RNA suppression after 1-2 years. In addition, late HDV RNA relapses have been described during long-term follow-up. Fortunately, new treatment options for patients with chronic hepatitis delta are now on the horizon. The hepatocyte entry inhibitor bulevirtide (formerly myrcludex B) and the farnesyl transferase inhibitor lonafarnib are currently explored in patients with chronic hepatitis delta in Phase 3 clinical studies. The nucleic acid inhibitor REP-2139-Ca and PEG-IFN-lambda are studied in Phase 2 trials. We here summarize data on the efficacy of these new antiviral drugs and the existing safety data on the treatment of HDV infection.


Assuntos
Antivirais/administração & dosagem , Hepatite D/tratamento farmacológico , Interferon-alfa/administração & dosagem , Lipopeptídeos/administração & dosagem , Ácidos Nucleicos/administração & dosagem , Piperidinas/administração & dosagem , Polímeros/administração & dosagem , Piridinas/administração & dosagem , Antivirais/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Coinfecção/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Hepatite B Crônica/tratamento farmacológico , Vírus Delta da Hepatite/efeitos dos fármacos , Humanos , Interferon-alfa/efeitos adversos , Lipopeptídeos/efeitos adversos , Ácidos Nucleicos/efeitos adversos , Piperidinas/efeitos adversos , Polímeros/efeitos adversos , Piridinas/efeitos adversos , Recidiva , Resultado do Tratamento
12.
BMC Complement Altern Med ; 19(1): 253, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510997

RESUMO

BACKGROUND: General antiviral agents such as oseltamivir are associated with certain adverse effects and the emergence of resistance. This study investigated the phytochemical properties, antiviral activities, and safety of three herbs used in traditional Korean medicine. METHODS: Extracts of three medicinal herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) were prepared using ethanol or water. The total phenolic, flavonoid, and saponin content, condensed tannin content, and reducing sugar content of the herb extracts were determined via phytochemical screening. Tandem mass analysis was performed using an ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-Q/Orbitrap instrument. Virus titrations were determined via tissue culture infective dose (TCID50) and cytotoxicity assays. Hemolysis and hepatotoxicity were measured to determine safety. RESULTS: Among the three medicinal herbs, F. suspensa showed the highest concentration of phenolic compounds, flavonoids, and saponins. The number of phytochemical compounds detected via tandem mass analysis of B. juncea, F. suspensa, and I. britannica was 5 (including sinigrin, m/z [M-H] = 358.02), 14 (including forsythoside A, m/z [M-H] = 623.19), and 18 (including chlorogenic acid, m/z [M-H] = 353.20), respectively. The antiviral effects of the B. juncea extracts (ethanol and water) and I. britannica extract (ethanol) were further investigated. The ethanol extract of B. juncea showed a 3 Log TCID50/25 µL virus titration reduction and the water extract showed a selectivity index of 13.668 against infected influenza H1N1 virus A/NWS/33. The B. juncea extracts did not show hemolysis activities and hepatotoxicity (< 20%). The ethanol extract of I. britannica showed the most effective virus titration decrease, whereas its hemolytic and hepatotoxicity values were the most significantly different compared to the control. Despite the high concentration of phytochemicals detected in F. suspensa, the extract showed approximately 1 Log TCID50/25 µL at the highest concentration. CONCLUSION: B. juncea may show antiviral effects against H1N1 in a host. In addition, B. juncea may also show decreased disadvantages compared to other antiviral agents.


Assuntos
Antivirais/farmacologia , Forsythia/química , Inula/química , Mostardeira/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Antivirais/efeitos adversos , Antivirais/química , Linhagem Celular , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Influenza Humana/virologia , Compostos Fitoquímicos/efeitos adversos , Compostos Fitoquímicos/química , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química
13.
J Med Case Rep ; 13(1): 299, 2019 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-31542053

RESUMO

BACKGROUND: Although several cases of hepatitis B virus reactivation have been described in patients with a history of hepatitis B virus infection while undergoing treatment for hepatitis C virus infection with direct acting antivirals, the question of whether hepatitis B virus surface antigen immune-escape mutations might play a role has not been addressed so far. CASE PRESENTATION: We report a case of hepatitis B virus reactivation in a Caucasian patient infected with hepatitis C virus during treatment with sofosbuvir and velpatasvir. A 50-year-old man with a genotype 1a hepatitis C virus infection was considered for therapy. His serological profile was hepatitis B virus surface antigen-negative, hepatitis B virus core antibody-positive, hepatitis B virus surface antibody-negative, and anti-hepatitis D virus-positive. The detection of hepatitis B virus deoxyribonucleic acid (DNA) indicated active viral replication during the direct acting antiviral treatment that spontaneously returned to undetectable levels after treatment completion. Starting from week 12 after the end of treatment, hepatitis B virus surface antibody titers and hepatitis B virus e antibody developed. Sequencing analysis revealed the hepatitis B virus genotype D3 and the presence of two relevant immune-escape mutations (P120S and T126I) in the major hydrophilic region by analyzing the S region. CONCLUSIONS: We speculate that the presence of the hepatitis B virus surface antigen mutations, endowed with the enhanced capability to elude the immune response, could play a role in hepatitis B virus reactivation. This observation confirms that occult hepatitis B infection should also be carefully monitored, through surveillance of the hepatitis B virus viral load before and during direct acting antiviral treatment of hepatitis C virus.


Assuntos
Antivirais/efeitos adversos , Vírus da Hepatite B/genética , Hepatite C Crônica/tratamento farmacológico , Mutação , Ativação Viral/efeitos dos fármacos , Antivirais/uso terapêutico , Carbamatos/efeitos adversos , Carbamatos/uso terapêutico , Coinfecção/virologia , Quimioterapia Combinada , Genótipo , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Sofosbuvir/efeitos adversos , Sofosbuvir/uso terapêutico
14.
Pediatrics ; 144(4)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31477606

RESUMO

This statement updates the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccines and antiviral medications in the prevention and treatment of influenza in children during the 2019-2020 season. The American Academy of Pediatrics continues to recommend routine influenza immunization of all children without medical contraindications, starting at 6 months of age. Any licensed, recommended, age-appropriate vaccine available can be administered, without preference of one product or formulation over another. Antiviral treatment of influenza with any licensed, recommended, age-appropriate influenza antiviral medication continues to be recommended for children with suspected or confirmed influenza, particularly those who are hospitalized, have severe or progressive disease, or have underlying conditions that increase their risk of complications of influenza.


Assuntos
Antivirais/administração & dosagem , Vacinas contra Influenza/administração & dosagem , Influenza Humana/tratamento farmacológico , Influenza Humana/prevenção & controle , Adolescente , Fatores Etários , Antivirais/efeitos adversos , Aleitamento Materno , Causas de Morte , Criança , Criança Hospitalizada , Pré-Escolar , Contraindicações , Progressão da Doença , Farmacorresistência Viral , Hipersensibilidade a Ovo , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/efeitos adversos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Pediatria , Gravidez , Estados Unidos/epidemiologia , Vacinas de Produtos Inativados/administração & dosagem
15.
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
16.
J Dairy Sci ; 102(11): 9559-9569, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495632

RESUMO

Antiviral neuraminidase inhibitors, such as oseltamivir, zanamivir, and peramivir, are widely used for treatment of influenza virus infection. We reported previously that oseltamivir inhibits the viral growth cycle, ameliorates symptoms, and reduces viral antigen quantities. Suppressed viral antigen production, however, induces a reduction of acquired antiviral humoral immunity, and increases the incidence of re-infection rate in the following year. To achieve effective treatment of influenza virus infection, it is necessary to overcome these adverse effects of antiviral neuraminidase inhibitors. Feeding of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1 is reported to have immune-stimulatory effects on influenza virus infection in mice and humans. In the present study, we assessed the effect of feeding L. bulgaricus OLL1073R-1 yogurt cultures (YC) on local and systemic humoral immune responses, which were suppressed by oseltamivir treatment, in mice infected with influenza A virus. Yogurt culture (1.14 × 108 cfu/0.4 mL per mouse per day) or sterile water (vehicle) was administered by intragastric gavage for 35 d. At d 22, influenza A virus/Puerto Rico/8/34 (H1N1) (PR8; 0.5 pfu/15 µL per mouse) was instilled intranasally, followed immediately by oral administration of oseltamivir (50 µg/100 µL per mouse, twice daily) or 5% methylcellulose (100 µL/mouse) as a vehicle for 13 d. Titers of anti-PR8-specific IgG and IgA in serum and mucosal secretory IgA (S-IgA) and IgG in bronchoalveolar lavage fluid (BALF) were analyzed by ELISA at 14 d after infection. Oseltamivir significantly suppressed the induction of anti-PR8-specific IgG and IgA in serum and S-IgA and IgG in BALF after infection. Feeding YC mildly but significantly stimulated production of PR8-specific IgA in serum, S-IgA in BALF, and IgG in serum without changing the IgG2a:IgG1 ratio. We analyzed the neutralizing activities against PR8 in serum and BALF and found that oseltamivir also reduced protective immunity, and YC feeding abrogated this effect. The immune-stimulatory tendency of YC on anti-PR8-specific IgA and IgG titers in serum and BALF was also detected in mice re-infected with PR8, but the effect was insignificant, unlike the effect of YC in the initial infection.


Assuntos
Antivirais/uso terapêutico , Imunidade Humoral/efeitos dos fármacos , Lactobacillus delbrueckii , Neuraminidase/antagonistas & inibidores , Infecções por Orthomyxoviridae/imunologia , Oseltamivir/uso terapêutico , Probióticos/uso terapêutico , Proteínas Virais/antagonistas & inibidores , Ração Animal , Animais , Antivirais/efeitos adversos , Antivirais/antagonistas & inibidores , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Lactobacillus delbrueckii/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/dietoterapia , Infecções por Orthomyxoviridae/tratamento farmacológico , Oseltamivir/efeitos adversos , Oseltamivir/antagonistas & inibidores , Iogurte
17.
N Engl J Med ; 381(12): 1136-1147, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31532960

RESUMO

BACKGROUND: Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known. METHODS: In a phase 2, open-label, maribavir dose-blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment. RESULTS: Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available - 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir. CONCLUSIONS: Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events - notably dysgeusia - and a lower incidence of neutropenia were found in the maribavir group. (Funded by ViroPharma/Shire Development; EudraCT number, 2010-024247-32.).


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/fisiologia , Ribonucleosídeos/uso terapêutico , Valganciclovir/uso terapêutico , Viremia/tratamento farmacológico , Adulto , Idoso , Aloenxertos , Antivirais/efeitos adversos , Antivirais/farmacologia , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacologia , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/virologia , Disgeusia/induzido quimicamente , Feminino , Gastroenteropatias/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Transplante de Órgãos/efeitos adversos , Ribonucleosídeos/efeitos adversos , Ribonucleosídeos/farmacologia , Valganciclovir/efeitos adversos , Valganciclovir/farmacologia , Ativação Viral/efeitos dos fármacos
18.
Expert Rev Gastroenterol Hepatol ; 13(9): 839-848, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31392907

RESUMO

Introduction: Over 70 million people are infected with hepatitis C virus (HCV), increasing the risk of cirrhosis and hepatocellular carcinoma. Areas covered: Since the approval of the first interferon-free direct-acting antiviral (DAA) therapy in 2011, a number of DAAs have been approved, and HCV is now considered curable. Until recently, however, there were no clear guidelines on how to re-treat patients who fail DAA therapy. Current protease inhibitors (PIs) are generally unaffected by earlier resistance-associated variants (RAVs), but many NS5A inhibitors continue to have overlapping resistance profiles, and NS5A RAVs can persist even in the absence of DAAs. Expert opinion: Fortunately, RAVs affecting NS5B polymerase inhibitors are rare, making sofosbuvir a safe choice as the backbone of re-treatment therapies. Recent re-treatment guidelines that take into account genotype, fibrosis, treatment history, and RAV suggest that >90% of patients with prior treatment failures can be successfully re-treated with sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Humanos , Falha de Tratamento
19.
Gastroenterology ; 157(5): 1253-1263.e2, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31374215

RESUMO

BACKGROUND & AIMS: There is controversy regarding the benefits of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection for patients with a history of hepatocellular carcinoma (HCC). We performed a multicenter cohort study to compare overall survival between patients with HCV infection treated with DAAs and patients who did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC who achieved a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy, from January 2013 through December 2017 at 31 health care systems throughout the United States and Canada. We used Cox proportional hazards regression to determine the association between receipt of DAA therapy, modeled as a time-varying covariate, and all-cause mortality, accounting for informative censoring and confounding using inverse probability weighting. RESULTS: Of 797 patients with HCV-related HCC, 383 (48.1%) received DAA therapy and 414 (51.9%) did not receive treatment for their HCV infection after complete response to prior HCC therapy. Among DAA-treated patients, 43 deaths occurred during 941 person-years of follow-up, compared with 103 deaths during 526.6 person-years of follow-up among patients who did not receive DAA therapy (crude rate ratio, 0.23; 95% confidence interval [CI], 0.16-0.33). In inverse probability-weighted analyses, DAA therapy was associated with a significant reduction in risk of death (hazard ratio, 0.54; 95% CI, 0.33-0.90). This association differed by sustained virologic response to DAA therapy; risk of death was reduced in patients with sustained virologic response to DAA therapy (hazard ratio, 0.29; 95% CI, 0.18-0.47), but not in patients without a sustained virologic response (hazard ratio, 1.13; 95% CI, 0.55-2.33). CONCLUSIONS: In an analysis of nearly 800 patients with complete response to HCC treatment, DAA therapy was associated with a significant reduction in risk of death.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/terapia , Hepatite C/tratamento farmacológico , Neoplasias Hepáticas/terapia , Idoso , Antivirais/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Feminino , Hepatite C/complicações , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , América do Norte , Fatores de Proteção , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
World J Gastroenterol ; 25(29): 3929-3940, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31413528

RESUMO

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. The disease usually develops on a background of chronic liver disease. Until recently, the most common etiology was infection with the hepatitis C virus (HCV). The advent of direct-acting antiviral (DAA) therapies has been a major breakthrough in HCV treatment. Sustained virologic response can now be achieved in almost all treated patients, even in patients with a high risk for the development of HCC, such as the elderly or those with significant fibrosis. Early reports raised concerns of a high risk for HCC occurrence after DAA therapy both in patients with previous resection of tumors and those without previous tumors. As the World Health Organization's goals for eradication of HCV are being endorsed worldwide, the elimination of HCV seems feasible. Simultaneous to the decrease in the burden of cirrhosis from HCV, non-alcoholic fatty liver disease (NAFLD) incidence has been increasing dramatically including significant increased incidence of cirrhosis and HCC in these patients. Surprisingly, a substantial proportion of patients with NAFLD were shown to develop HCC even in the absence of cirrhosis. Furthermore, HCC treatment and potential complications are known to be influenced by liver steatosis. These changes in etiology and epidemiology of HCC suggest the beginning of a new era: The post-HCV era. Changes may eventually undermine current practices of early detection, surveillance and management of HCC. We focused on the risk of HCC occurrence and recurrence in the post-HCV era, the surveillance needed after DAA therapy and current studies in HCC patients with NAFLD.


Assuntos
Antivirais/efeitos adversos , Carcinoma Hepatocelular/etiologia , Detecção Precoce de Câncer/métodos , Neoplasias Hepáticas/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Progressão da Doença , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepacivirus/patogenicidade , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Incidência , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Transplante de Fígado/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Resposta Viral Sustentada
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