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BACKGROUND: Sodium fluctuations in very preterm neonates and their neurodevelopmental consequences are not well described. METHODS: We assessed the changes in plasma sodium and glucose in the first days of life in very preterm neonates and studied the association of glucose-corrected plasma sodium fluctuations on neurodevelopmental outcomes. We included 147 consecutive neonates born before 29 weeks of gestation in our center and retrospectively obtained plasma sodium, glucose, and glucose-corrected sodium levels. Neurodevelopmental assessment was obtained from the Canadian Neonatal Follow-Up Network. RESULTS: Mean ± standard deviation of plasma sodium changes within the first 10 days of life were 16.2 ± 6.0, 14.8 ± 5.3, and 11.1 ± 5.2 mmol/l in neonates born ≤25, 25-26, and 26-27 weeks of gestation, respectively (p < 0.001). Non-steroidal anti-inflammatory drug administration was associated with larger plasma sodium fluctuation. Eighty-six percent had a known neurological status at 18 months. Higher fluctuations in glucose-corrected plasma sodium were associated with death or neurodevelopmental impairment at 18 months corrected age (B = 3.19, 95% CI [1.24, 5.14]), and this association remained after adjustment for gestational age (B = 2.1, 95% CI [0.16, 4.04]). CONCLUSIONS: Neonates born very preterm show fluctuations in glucose-corrected plasma sodium during the first days of life, which may increase the risk of death or developmental impairment. IMPACT: Risk factors and neurodevelopmental consequences of plasma sodium changes in early neonatal life of preterm infants are not well characterized. This study shows for the first time that glucose-corrected plasma sodium fluctuations within the first days of life are more severe in preterm infants receiving non-steroidal anti-inflammatory drugs (NSAIDs) and are associated with death or neurodevelopmental impairment at 18 months corrected age. Large plasma sodium and glucose fluctuations should be expected more often in preterm infants receiving NSAIDs and should be avoided.
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Doenças do Prematuro , Transtornos do Neurodesenvolvimento , Lactente , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Estudos Retrospectivos , Canadá , Idade Gestacional , Retardo do Crescimento Fetal , Anti-Inflamatórios , Sódio , Glucose , Anti-Inflamatórios não Esteroides , Transtornos do Neurodesenvolvimento/etiologiaRESUMO
PURPOSE: Over the last few decades, several articles have examined the feasibility of attempting primary reduction and closure of gastroschisis without general anesthesia (GA). We aimed to systematically evaluate the impact of forgoing routine intubation and GA during primary bedside reduction and closure of gastroschisis. METHODS: The primary outcome was closure success. Secondary outcomes were mortality, time to enteral feeding, and length of hospital stay. RESULTS: 12 studies were included: 5 comparative studies totalling 192 patients and 7 descriptive case studies totalling 56 patients. Primary closure success was statistically equivalent between the two groups, but trended toward improved success with GA/intubation (RR = 0.86, CI 0.70-1.03, p = 0.08). Mortality was equivalent between groups (RR = 1.26, CI 0.26-6.08, p = 0.65). With respect to time to enteral feeds and length of hospital stay, outcomes were either equivalent between the two groups or favored the group that underwent primary closure without intubation and GA. CONCLUSION: There are few comparative studies examining the impact of performing primary bedside closure of gastroschisis without GA. A meta-analysis of the available data found no statistically significant difference when forgoing intubation and GA. Foregoing GA also did not negatively impact time to enteral feeds, length of hospital stay, or mortality.
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Gastrosquise , Anestesia Geral , Gastrosquise/cirurgia , Humanos , Intubação Intratraqueal , Tempo de Internação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. METHODS: HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. RESULTS: At baseline, median age of the study population (Nâ =â 1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12), prior CVD (HR 8.48; 95% CI, 3.14-22.91), high total cholesterol (HR 1.43; 95% CI, 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08-0.63), statin use (HR 3.31; 95% CI, 1.31-8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35-7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18-0.96) was associated with coronary and/or cerebral events. CONCLUSIONS: HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.
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Doenças Cardiovasculares , Infecções por HIV , Hepatite C , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Preterm birth has adverse consequences on the cardiovascular system. Whether premature birth is associated with conduction and repolarisation abnormalities past childhood and into adulthood still needs to be demonstrated. METHODS: We analyzed the ECG of young adults (23.9 ± 3.1 years) born term (≥37 weeks, n = 53) and preterm (<30 weeks, n = 49) at rest, peak exercise and 3 min into recovery during an exercise test on a cycle ergometer. We measured PR, QRS and QT intervals, calculated the corrected QT (QTc), and determined blood calcium, magnesium, potassium and fasting glucose. RESULTS: Mean gestational age was 39.7 ± 1.1 and 27.3 ± 1.3 weeks for the term and the preterm groups, respectively. Apart from an increased heart rate at rest in individuals born preterm, no significant difference was found between both groups for any other ECG parameters at rest. None of the participants had a severely prolonged QTc (>500 ms) at rest; exercise revealed severely prolonged QTc in two participants including one in the preterm group. The use of QT-prolonging medications did not influence ECG parameters in either groups. CONCLUSIONS: We observed no significant difference in electrocardiographic measurements between young adults born preterm and term. Current results do not support avoidance of QT-prolonging medications in individuals born preterm. IMPACT: Preterm birth is associated with adverse cardiovascular consequences in early adulthood, but controversial evidence exists regarding differences in electrocardiographic features between young individuals born term and preterm.This study aims to assess the differences in electrocardiographic features between young adults born term and preterm, at rest and during exercise training.In contrast with previously published data, we observed no significant difference in electrocardiographic measurements between young adults born preterm and term.Our study does not support that preterm birth itself exposes young adults to a higher risk of QT prolongation.Current results do not support avoidance of QT-prolonging medications in individuals born preterm.
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Aptidão Cardiorrespiratória , Eletrocardiografia , Exercício Físico , Frequência Cardíaca , Recém-Nascido Prematuro , Síndrome do QT Longo/etiologia , Nascimento Prematuro , Adulto , Teste de Esforço , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Nascimento a Termo , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND & AIMS: There is little data available on the use of new oral direct-acting antiviral (DAA) regimens to treat human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients in real-life settings. Here, the efficacy and safety of all-oral DAA-based regimens in HIV/HCV-co-infected patients enrolled in the French nationwide ANRS CO13 HEPAVIH observational cohort are reported. METHODS: HIV/HCV-co-infected patients enrolled in the ANRS CO13 HEPAVIH observational cohort were included if they began an all-oral DAA-based regimen before 1st May 2015 (12-week regimens) or 1st February 2015 (24-week regimens). Treatment success (SVR12) was defined by undetectable HCV-RNA 12weeks after treatment cessation. Exact logistic regression analysis was used to identify factors associated with SVR12. RESULTS: A total of 323 patients (74% men) with a median age of 53years were included, 99% of whom were on combination antiretroviral therapy (cART). HIV RNA load was <50 copies/ml in 88% of patients; median CD4 cell count was 540/mm3; 60% of patients were cirrhotic; 68% had previously received unsuccessful anti-HCV treatment. cART was protease inhibitor (PI)-based in 23%, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based in 15%, and integrase inhibitor (II)-based in 38%, while 24% of patients received other regimens. The SVR12 rate was 93.5% overall (95% confidence interval [CI]: 90.2-95.9), 93.3% (88.8-96.4) in patients with cirrhosis and 93.8% (88.1-97.3) in patients without cirrhosis. The SVR12 rates were 93.1% (84.5-97.7), 91.8% (80.4-97.7) and 95.8% (90.5-98.6) respectively, in patients receiving PI-based, NNRTI-based and II-based cART. In adjusted analysis, SVR12 was not associated with HIV RNA load, the cART regimen, cirrhosis, prior anti-HCV treatment, the duration of anti-HCV therapy, or ribavirin use. The most common adverse effects were fatigue and digestive disorders. CONCLUSIONS: New all-oral DAA regimens were well-tolerated and yielded high SVR12 rates in HIV/HCV-co-infected patients. LAY SUMMARY: We evaluated efficacy and safety of all-oral DAA regimens in a large French nationwide observational cohort study of HIV/HCV co-infected patients. Sustained virological response 12weeks after treatment cessation was 93.5% overall. The all-oral DAA regimens were well-tolerated and most common adverse effects were fatigue and digestive disorders.
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Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Estudos de Coortes , Feminino , Hepatite C Crônica/virologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce. METHODS: Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome. RESULTS: We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/8%/1%; 87% with HIV RNA <50 copies/mL; 99% on antiretrovirals; median CD4 count: 489 cells/µL; HCV treatment naive 29%; HCV genotype 1/2/3/4: 58%/4%/17%/21%. Sofosbuvir (SOF) + daclatasvir ± ribavirin (RBV) was used in 123 patients, SOF + RBV in 30, SOF + simeprevir in 11, and SOF + ledipasvir in 23. An SVR12 was reported in 93.1% of the patients (95% confidence interval, 88.5%-96.3%). In adjusted analyses, no difference was found between 12 or 24 weeks of treatment, in patients receiving RBV or not, and in treatment-naive vs experienced patients. Premature stop of DAA was reported for 8 patients. One patient died during treatment (unknown cause), and 12 other patients developed liver-related events. CONCLUSIONS: In this prospective real-life cohort, all-oral DAA regimens were well tolerated and associated with a high virologic efficacy in cirrhotic HIV/HCV-coinfected patients. This should not alleviate the surveillance for liver-related events in these patients.
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Antivirais/uso terapêutico , Infecções por HIV , Hepatite C , Cirrose Hepática/complicações , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ribavirina , Sofosbuvir , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is an independent risk factor for chronic kidney disease and leads to faster liver disease progression in patients requiring hemodialysis than in those with normal renal function. Little is known about the use of a sofosbuvir-containing regimen for infected patients on hemodialysis. We aimed to describe the pharmacokinetics, safety and efficacy of sofosbuvir in 2 dosing regimens and associated antiviral agents in HCV-infected patients requiring hemodialysis. METHODS: Multicenter, prospective and observational study of patients receiving sofosbuvir, 400mg once daily (n=7) or 3 times a week (n=5), after hemodialysis with simeprevir, daclatasvir, ledipasvir or ribavirin was conducted. Drug plasma concentrations were determined by liquid chromatography-tandem mass spectrometry before and after a 4h hemodialysis and 1.5h after last drug intake at the end of hemodialysis. RESULTS: Plasma concentrations of sofosbuvir or its inactive metabolite sofosbuvir-007 did not accumulate with either regimen between hemodialysis sessions or throughout the treatment course. Sofosbuvir-007 extraction ratio (52%) was consistent with historical data. In one patient receiving the once daily regimen, sofosbuvir-007 half-life was slightly higher (38h) than for patients with normal renal function receiving a full dose. Hemodialysis did not remove any other associated anti-HCV agents. Clinical and biological tolerance was good for all patients. Two relapses occurred with the 3 times a week regimen and none with the once daily. CONCLUSIONS: A regimen including sofosbuvir, 400mg once daily, could be proposed for HCV-infected patients requiring hemodialysis and should be associated with close clinical, biological, cardiovascular, and therapeutic drug monitoring. LAY SUMMARY: Hepatitis C Virus (HCV) infection in hemodialysis patients is prevalent and aggressive. Effective anti-HCV treatment in these patients may stabilize their renal disease. However, sofosbuvir, the cornerstone of most anti-HCV-containing regimens, should not be administered to these patients until more data is available. In this pharmacokinetic study, sofosbuvir full dose (400mg once daily) administered every day with another direct antiviral agent did not accumulate in hemodialysis patients and was safe and effective.
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Hepatite C Crônica , Antivirais , Quimioterapia Combinada , Genótipo , Hepacivirus , Humanos , Estudos Prospectivos , Diálise Renal , Ribavirina , Simeprevir , SofosbuvirRESUMO
BACKGROUND: Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. METHODS: HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). RESULTS: Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. CONCLUSIONS: Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
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Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To improve neonatal outcomes through the implementation of an eat, sleep, console (ESC) assessment and change in hospital policy regarding the monitoring requirements for pharmacologic treatment of neonates with neonatal abstinence syndrome (NAS). DESIGN: Retrospective chart review and descriptive survey design. SETTING/LOCAL PROBLEM: A hospital in Northwestern Ontario decided to implement an evidence-informed practice change to better care for neonates with NAS. PARTICIPANTS: Neonates being screened for NAS during the Modified Finnegan Neonatal Abstinence Syndrome Scoring System (MFNASSS) protocol (n = 75) and ESC protocol (n = 40). Nurses working in the departments after the implementation of ESC were surveyed. MEASUREMENTS: Length of stay (LOS) and morphine administration by intervention status using unadjusted hazard and risk ratios, respectively. Descriptive statistics are also presented. A one-sample t test was completed for the nurses' perspectives survey questions. RESULTS: Reduced rate of LOS (HR = 1.66, 95% confidence interval [1.1, 2.51]) was observed for participants receiving the ESC intervention (4.53, SD = 1.94), compared to the MFNASSS control (7.45, SD = 6.35). Although the ESC group appeared to have a greater proportion of neonates administered morphine (42.5% ESC vs. 26.7% MFNASSS), the relative risk was not statistically significant (RR = 1.28, 95% confidence interval [0.95, 1.72]). Morphine doses per day were reduced in the ESC group (0.37, SD = 1.50) compared to the MFNASSS group (5.16, SD = 1.02). Overall, the nurses had a positive perspective on the policy change. CONCLUSION: ESC was successfully implemented in a Northwestern Ontario hospital. The overall LOS of neonates with NAS decreased. Nurses found the policy change to be safe and attainable.
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Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection. Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician's decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log10 IU/ml from baseline. Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30-65) copies/ml and 566 ± 307/mm3, respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNÉ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNÉ group had a combined response (virological response and normal alanine aminotransferase level). Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNÉ showed a strong virological response. Impact and implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported.
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INTRODUCTION: Hepatitis B is a major cause of death in patients with HIV who usually receive drugs active against hepatitis B virus (HBV). The variability of HBV DNA over time has been little studied. Recombination between different HBV genotypes has been described in many cross-sectional studies, but the frequency of intergenotypic and intragenotypic recombinations in individual patients is unknown. METHODS: 32 HIV-positive and 11 HIV-negative patients who remained HBV viraemic despite antiviral therapy for at least 1 year were studied. Genotyping was based on line probe assays and genotype-specific PCR. The variability of HBV DNA over time was examined with restriction length and single-strand conformational polymorphism (RFLP-SSCP). HBV DNA sequences obtained by cloning a 2800 bp PCR fragment were analysed for phylogenetic parameters (diversity and selection pressure) and recombination was detected with RDP3 software. RESULTS: Large fragments of HBV DNA could be amplified at two different time points in 33 patients. Marked quasi-species modifications occurred in 14 patients. In seven of these patients and in one patient with no change detectable by RFLP-SSCP, the 2800 bp fragment was cloned at two time points at least. In four (57%) of these seven patients, various intergenotypic or intragenotypic recombination events were detected between subvariants present in the initial quasi-species. Recombinant fragments mostly harboured antiviral resistance determinants and reflected a large increase in diversity and in positive selection pressure on the entire HBV quasi-species. CONCLUSIONS: In coinfected patients, HBV DNA recombination events are frequent during antiviral therapy, corresponding to increased positive selection pressure on the HBV quasi-species and to conservation of antiviral resistance mutations. In this population and at the individual level, recombination is a significant source of HBV genetic variability.
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DNA Viral/genética , Infecções por HIV/genética , HIV/genética , Vírus da Hepatite B/genética , Hepatite B/genética , Mutação , Recombinação Genética , Adulto , Estudos Transversais , Feminino , Genótipo , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepatite B/complicações , Hepatite B/virologia , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
BACKGROUND & AIMS: Compared to HCV-mono-infected patients, hepatocellular carcinoma (HCC) occurs at younger age in HIV/HCV-co-infected patients, is markedly more advanced at diagnosis, is less amenable to curative treatment, and has a more severe outcome. The aim of this study was to identify factors predictive of HCC occurrence in a large cohort of HIV/HCV-co-infected patients with cirrhosis. METHODS: This study involved 244 HIV/HCV-co-infected patients included in the ANRS CO13 HEPAVIH cohort, who had HCV-related cirrhosis (clinically or histologically proven cirrhosis, or liver stiffness ≥12.5 kPa) and no signs of HCC at baseline. Cox proportional hazards models were used to identify factors associated with HCC occurrence. RESULTS: During a median follow-up of 2.6 (IQR, 1.8-3.5) years, 21 patients (8.6%) developed HCC. Diagnosis of HCC was based on histology in 5 patients (24%) and non-invasive criteria in 16 patients (76%). In univariate analyses, the following factors were related to HCC occurrence: age, previous cirrhosis decompensation, a HOMA value >3.8 (patients with treated diabetes were excluded from the HOMA calculation), a lower platelet count, a lower prothrombin level, and higher alpha-fetoprotein levels. The HOMA value was >3.8 at baseline in 66.7% of patients who developed HCC and in 35.3% of the remaining patients (p=0.016). In multivariate analysis, age over 50 years (adjusted RR 3.2, 95% CI 1.2-9.0; p=0.02) and a HOMA value >3.8 (adjusted RR 3.4, 95% CI 1.1-10.3; p=0.03) remained significantly associated with HCC occurrence. CONCLUSIONS: As in HCV-mono-infected patients with HCV-related cirrhosis, insulin resistance appears to play a key role in HCC occurrence in HCV/HIV-co-infected patients with cirrhosis. This finding calls for specific screening strategies for patients with a particularly high risk of developing HCC.
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Carcinoma Hepatocelular/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Resistência à Insulina/fisiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
AIM: To evaluate the early virological response (EVR) to combined tenofovir-lamivudine or emtricitabine regimen in HBV/HIV-co-infected patients and the long-term efficacy of tenofovir. METHODS: In this retrospective monocentric study, among the 166 HIV/HBV-co-infected patients regularly followed from 2003 to 2008 at Bichat Claude Bernard Hospital, 61 patients had received, either de novo combination therapy with tenofovir and lamivudine or emtricitabine (group I, n = 15) or add-on tenofovir to lamivudine therapy (group II, n = 46). The HBV polymerase region was sequenced and analysed for all patients with available samples. RESULTS: All 15 group I patients achieved EVR vs 32 (82%) of group II patients (P = 0.15). Seven adherent group II patients met criteria for primary non-response, but achieved delayed response (DR) to therapy. In these seven patients, when compared with the 39 group II patients, there was a trend to longer duration of lamivudine pre-treatment and to higher rate of lamivudine-resistant mutants; and HBV genotype-G proportion was higher (P = 0.026). No virological breakthrough occurred after a median of 46 months follow up. CONCLUSION: In these HBV/HIV-co-infected patients, first-line HBV therapy with tenofovir and emtricitabine or lamivudine was associated with EVR. However, DR to tenofovir was observed in 15% of patients who added tenofovir to lamivudine therapy, of whom four of seven (57%) had genotype G-HBV infection. No resistance was evidenced after 46 months of therapy even in patients with DR to tenofovir. At last, a good renal safety profile of TDF was observed after a median follow-up of 4 years of therapy.
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Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Adulto , Coinfecção/tratamento farmacológico , Análise Mutacional de DNA , DNA Viral/análise , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Farmacorresistência Viral , Quimioterapia Combinada , Emtricitabina , Feminino , Genótipo , HIV/efeitos dos fármacos , Vírus da Hepatite B/classificação , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Tenofovir , Fatores de Tempo , Resultado do TratamentoRESUMO
Overweight is increasingly prevalent in people living with HIV (PLWH), and is a high risk factor for metabolic disorders in this population. PLWH co-infected with hepatitis C virus (HCV) have a higher risk of metabolic disorders than their mono-infected counterparts. The putative relationship between cannabis use and body weight found in the general population has never been documented in HIV-HCV co-infected people. We tested whether cannabis use is associated with body mass index (BMI), overweight, and underweight in HCV co-infected PLWH (N = 992). Mixed-effects linear and logistic regression models were used to study the association between cannabis use and the three outcomes over time. After multivariable adjustment, cannabis use was inversely associated with BMI. Cannabis use was associated with a lower and higher risk of overweight and underweight, respectively. Cannabis use should be assessed and taken into account in the clinical management of the HIV-HCV co-infected population.
Assuntos
Cannabis , Coinfecção , Infecções por HIV , Hepatite C , Coinfecção/complicações , Coinfecção/epidemiologia , Infecções por HIV/prevenção & controle , Hepacivirus , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Fatores de Proteção , Magreza/complicaçõesRESUMO
UNLABELLED: Acute hepatitis C continues to be a concern in men who have sex with men (MSM), and its optimal management has yet to be established. In this study, the clinical, biological, and therapeutic data of 53 human immunodeficiency virus (HIV)-infected MSM included in a multicenter prospective study on acute hepatitis C in 2006-2007 were retrospectively collected and analyzed. The mean hepatitis C virus (HCV) viral load at diagnosis was 5.8 ± 1.1 log(10) IU/mL (genotype 4, n = 28; genotype 1, n = 14, genotype 3, n = 7). The cumulative rates of spontaneous HCV clearance were 11.0% and 16.5% 3 and 6 months after diagnosis, respectively. Forty patients were treated, 38 of whom received pegylated interferon and ribavirin. The mean duration of HCV therapy was 39 ± 17 weeks (24 ± 4 weeks in 14 cases). On treatment, 18/36 (50.0%; 95% confidence interval 34.3-65.7) patients had undetectable HCV RNA at week 4 (RVR), and 32/39 (82.1%; 95 confidence interval 70.0-94.1) achieved sustained virological response (SVR). SVR did not correlate with pretreatment parameters, including HCV genotype, but correlated with RVR (predictive positive value of 94.4%) and with effective duration of HCV therapy (64.3% for 24 ± 4 weeks versus 92.0% for longer treatment; P = 0.03). CONCLUSION: The low rate of spontaneous clearance and the high SVR rates argue for early HCV therapy following diagnosis of acute hepatitis C in HIV-infected MSM. Pegylated interferon and ribavirin seem to be the best option. The duration of treatment should be modulated according to RVR, with a 24-week course for patients presenting RVR and a 48-week course for those who do not, irrespectively of HCV genotype.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Doença Aguda , Adulto , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Anticorpos Anti-Hepatite C/análise , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Estudos Retrospectivos , Carga Viral/efeitos dos fármacosRESUMO
The consequences of hepatitis B virus (HBV) infection for fertility are still unclear. Spermatozoa with decreased motility have been reported in HBV-infected patients. It has been demonstrated in vitro that HBV S protein has adverse effects on human sperm function with consequences for fertilization. In a case-control study design, 32 IVF cycles in couples with male HBV infection were compared with 64 cycles in non-infected couples, matched for age, time period, cycle rank and sperm parameters on the day of oocyte retrieval. Sperm motility before selection was significantly reduced in the HBV group (36.3 ± 11.6% versus 45.3 ± 14.4%,P = 0.003). A low fertilization rate (LFR) was more frequently observed in the HBV group (34.4% versus 15.6%, P = 0.036) and was associated with a decreased number of embryos available for transfer, although embryo quality on day 2 or 3 was not different.Implantation and pregnancy rates were comparable between groups. This study shows that HBV has a deleterious effect on sperm motility in vivo and that couples whose male partner is infected have a higher risk of LFR after IVF, a risk which is independent from the initial sperm motility.
Assuntos
Fertilização in vitro/métodos , Hepatite B/complicações , Motilidade dos Espermatozoides , Adulto , Estudos de Casos e Controles , Feminino , Fertilização , Vírus da Hepatite B/metabolismo , Humanos , Infertilidade Masculina/complicações , Masculino , Oócitos/citologia , Indução da Ovulação , Gravidez , Taxa de Gravidez , Espermatozoides/virologia , Fatores de TempoRESUMO
Sorafenib prolongs survival of patients with unresectablehepatocellular carcinoma (HCC). It is likely to be used in human immunodeficiency virus (HIV) infected patients. Interactions between sorafenib and highly active antiretroviral therapy (HAART) have not been studied yet. We report a case of serious adverse effects in anHIV-1 patient co-infected with HBV.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzenossulfonatos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , HIV-1 , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Carcinoma Hepatocelular/virologia , Interações Medicamentosas , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , SorafenibeRESUMO
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is characterised by otherwise unexplained maternal pruritus, increased serum bile acid concentration over 10 µmol/L and spontaneous relief of symptoms and liver abnormalities after delivery. It occurs most frequently during the third trimester and is usually not induced by medication. Besides, azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel disease and is allowed during pregnancy, in order to stabilize maternal disease. METHODS: We reviewed all cases of ICP between 2010 and 2018 in two French perinatal centers. RESULTS: We encountered eight pregnancies complicated by atypical ICP among patients treated with azathioprine. ICP associated with azathioprine appears to be biologically more severe and to occur earlier than "standard" ICP. Furthermore, clinical and biochemical abnormalities related to ICP disappear when azathioprine is discontinued. Azathioprine safety should be reconsidered and practitioners advised to discuss discontinuing this drug as soon as ICP diagnosis is established.
Assuntos
Azatioprina/efeitos adversos , Colestase Intra-Hepática/induzido quimicamente , Imunossupressores/efeitos adversos , Complicações na Gravidez/induzido quimicamente , Prurido/induzido quimicamente , Adulto , Ácidos e Sais Biliares/sangue , Colagogos e Coleréticos/uso terapêutico , Colestase Intra-Hepática/sangue , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Substituição de Medicamentos , Feminino , França , Humanos , Mesalamina/uso terapêutico , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/tratamento farmacológico , Remissão Espontânea , Estudos Retrospectivos , Ácido Ursodesoxicólico/uso terapêutico , Suspensão de TratamentoRESUMO
Coronavirus disease 2019 (CoVID-19) is a viral disease. Although the predominant presentation is respiratory disease, other manifestations such as gastrointestinal manifestations are commonly reported. Nevertheless, it has not been associated with chronic cholangitis or hepatic injury. In this study, we report three cases of severe CoVID-19 infection that required ICU admission, intubation, and sedation with ketamine. All three patients had abnormal liver function despite recovery and were diagnosed with cholangitis in the context of CoVID-19.
RESUMO
Preterm birth increases risk of cardiovascular disease and early death. A body of evidence suggests left ventricle (LV) echocardiographic alterations in children and adults born preterm. We aimed to determine if neonatal characteristics were associated with alterations in LV structure and function in preterm adults. We evaluated a cohort of 86 young adults born preterm below 30 weeks of gestation, and 85 full-term controls. We determined LV dimensions and function using tissue Doppler imaging, conventional and speckle tracking echocardiography (STE). Adults born preterm had smaller LV dimensions, but these differences did not remain after adjustment for body surface area (BSA), which was smaller in the preterm group. Stroke volume and cardiac output were reduced even after adjustment for BSA. We found a smaller e' wave in the preterm group, but other markers of systolic and diastolic function did not differ. Use of antenatal steroids may be associated with a further reduced cardiac output in those born preterm. Adults born preterm show alterations in markers of LV dimensions and function. Identification of these markers may represent opportunities for early prevention of cardiovascular events in this at-risk population.