RESUMO
The 2019 novel coronavirus (COVID-19) pandemic has placed a significant strain on hepatitis programs and interventions (screening, diagnosis, and treatment) at a critical moment in the context of hepatitis C virus (HCV) elimination. We sought to quantify changes in Direct Acting Antiviral (DAA) utilization among different countries during the pandemic. We conducted a cross-sectional time series analysis between 1 September 2018 and 31 August 2020, using the IQVIA MIDAS database, which contains DAA purchase data for 54 countries. We examined the percent change in DAA units dispensed (e.g., pills and capsules) from March to August 2019 to the same period of time in 2020 across the 54 countries. Interrupted time-series analysis was used to examine the impact of COVID-19 on monthly rates of DAA utilization across each of the major developed economies (G7 nations). Overall, 46 of 54 (85%) jurisdictions experienced a decline in DAA utilization during the pandemic, with an average of -43% (range: -1% in Finland to -93% in Brazil). All high HCV prevalence (HCV prevalence > 2%) countries in the database experienced a decline in utilization, average -49% (range: -17% in Kazakhstan to -90% in Egypt). Across the G7 nations, we also observed a decreased trend in DAA utilization during the early months of the pandemic, with significant declines (p < 0.01) for Canada, Germany, the United Kingdom, and the United States of America. The global response to COVID-19 led to a large decrease in DAA utilization globally. Deliberate efforts to counteract the impact of COVID-19 on treatment delivery are needed to support the goal of HCV elimination.
Assuntos
Antivirais/administração & dosagem , Tratamento Farmacológico da COVID-19 , Antivirais/normas , Brasil/epidemiologia , COVID-19/epidemiologia , Canadá/epidemiologia , Estudos Transversais , Egito/epidemiologia , Finlândia/epidemiologia , Alemanha/epidemiologia , Hepacivirus/isolamento & purificação , Hepatite C , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Cazaquistão/epidemiologia , Pandemias , Prevalência , SARS-CoV-2/isolamento & purificação , Reino Unido/epidemiologia , Estados UnidosRESUMO
BACKGROUND: Ontario is 1 of 5 provinces that immunize adolescents for hepatitis B virus (HBV), despite the World Health Organization recommendation for universal birth dose vaccination. One rationale for not vaccinating at birth is that universal prenatal screening and related interventions prevent vertical transmission. The aims of our study were to evaluate the uptake and epidemiology of prenatal HBV screening, and to determine the number of children in Ontario with a diagnosis of HBV before adolescent vaccination. METHODS: We extracted data from ICES, Public Health Ontario and Better Outcomes & Registry Network (BORN) Ontario databases. We assessed prenatal screening uptake and prevalence of prenatal hepatitis B surface antigen (HBsAg) from 2012 to 2016, as well as subsequent hepatitis B e-antigen (HBeAg) and HBV DNA testing and percent positivity. We used age and region to subcategorize the results. In a separate unlinked analysis, we evaluated the number of children positive for HBV aged 0-11 years who were born in Ontario from 2003 to 2013. RESULTS: From 2012 to 2016, 93% of pregnant women were screened for HBV, with an HBsAg prevalence of 0.6%. Prevalence of HBsAg increased with age, peaking at older than 45 years at 3%. North Toronto had the highest overall prevalence of 1.5%, whereas northern Ontario had the lowest. Of women who were HBsAg positive, HBeAg and HBV DNA tests were subsequently ordered in 13% and 38%, respectively. Of children born in Ontario between 2003 and 2013, 139 of 23 759 tested positive for HBV. INTERPRETATION: Prenatal HBV screening is not universal and subsequent evaluation is poor, limiting optimal intervention and possibly contributing to some Ontario-born children being given a diagnosis of HBV before age 12 years. These findings underscore the limitations of the province's adolescent vaccination strategy.
Assuntos
Hepatite B/epidemiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Diagnóstico Pré-Natal , Adolescente , Adulto , Fatores Etários , Criança , Serviços de Saúde da Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Feminino , Hepatite B/prevenção & controle , Vacinas contra Hepatite B , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Prevalência , Sistema de Registros , Adulto JovemRESUMO
Neurological symptoms can be one of the over-riding symptoms in patients with liver cirrhosis. Patients can present with subtle changes in mood or neurological function due to hepatic encephalopathy (HE), to more severe presentations including stupor and coma. While HE, in its severe form, can be clinically easy to diagnose, more subtle forms may be more difficult to recognize. Other neurological diseases may indeed be overlooked in the context of cirrhosis or confuse the physician regarding the diagnosis. Chronic acquired hepatocerebral degeneration (CAHD) is an uncommon problem occurring in patients with cirrhosis characterised by a Parkinsonian-like neurological presentation with damage to the brain secondary to manganese (Mn) deposition. Here we describe a case of a patient with a neurological presentation of liver disease with a review of the current CAHD literature. In conclusion, CAHD is a rare condition occurring in liver cirrhosis that should always be considered in patients with neurological manifestations of chronic liver disease.
Assuntos
Encéfalo/metabolismo , Degeneração Hepatolenticular/metabolismo , Cirrose Hepática/complicações , Manganês/metabolismo , Doença Crônica , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/etiologia , Humanos , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Liver regeneration is a normal response to liver injury. The aim of this study was to determine the molecular basis of liver regeneration, through an integrative analysis of high-throughput gene expression datasets. METHODS: We identified and curated datasets pertaining to liver regeneration from the Gene Expression Omnibus, where regenerating liver tissue was compared to healthy liver samples. The key dysregulated genes and pathways were identified using Ingenuity Pathway Analysis software. There were three eligible datasets in total. RESULTS: In the early phase after hepatectomy, inflammatory pathways such as Nrf2 oxidative stress-mediated response and cytokine signaling were significantly upregulated. At peak regeneration, we discovered that cell cycle genes were predominantly expressed to promote cell proliferation. Using the Betweenness centrality algorithm, we discovered that Jun is the key central gene in liver regeneration. Calcineurin inhibitors may inhibit liver regeneration, based on predictive modeling. CONCLUSION: There is a paucity of human literature in defining the molecular mechanisms of liver regeneration along a time continuum. Nonetheless, using an integrative computational analysis approach to the available high-throughput data, we determine that the oxidative stress response and cytokine signaling are key early after hepatectomy, whereas cell cycle control is important at peak regeneration. The transcription factor Jun is central to liver regeneration and a potential therapeutic target. Future studies of regeneration in humans along a time continuum are needed to better define the underlying mechanisms, and ultimately enhance care of patients with acute and chronic liver failure while awaiting transplant.
Assuntos
Regulação da Expressão Gênica , Hepatectomia , Regeneração Hepática/genética , Transdução de Sinais/genética , Biologia de Sistemas/métodos , Animais , Coleta de Dados , Conjuntos de Dados como Assunto , Fator de Crescimento Epidérmico/genética , Feminino , Fatores de Crescimento de Fibroblastos/genética , Humanos , Transplante de Fígado/métodos , Masculino , Valores de Referência , Fator de Necrose Tumoral alfa/genéticaRESUMO
INTRODUCTION: Radiofrequency ablation (RFA) is a recommended curative intent treatment option for patients with early stage hepatocellular carcinoma (HCC). We investigated if wait times for RFA were associated with residual tumor, tumor recurrence, need for liver transplantation, or death. MATERIAL AND METHODS: We conducted a retrospective study of patients diagnosed with HCC between January 2010 and December 2013 presenting to University Health Network (UHN) in Toronto, Canada. All patients receiving curative intent RFA for HCC were included. Multivariable Cox regression was used to determine if wait times were associated with clinical outcomes. RESULTS: 219 patients were included in the study. 72.6% were male and the median age was 62.7 years (IQR 55.6-71). Median tumor size at diagnosis was 21.5 mm (IQR 17-26); median MELD was 8.7 (IQR 7.2-11.4) and 57.1% were Barcelona stage 0. The cause of liver disease was viral hepatitis in 73.5% (Hepatitis B and C). The median time from HCC diagnosis to RFA treatment was 96 days (IQR 75-139). In multivariate analysis, wait time was not associated with requiring liver transplant or tumor recurrence, however, each incremental 30-day wait time was associated with an increased risk of residual tumor (HR = 1.09; 95% CI 1.01-1.19; p = 0.033) as well as death (HR = 1.23; 95% CI 1.11-1.36; p ≤ 0.001). CONCLUSION: Incremental 30-day wait times are associated with a 9% increased risk of residual tumor and a 23% increased risk of death. We have identified system gaps where quality improvement measures can be implemented to reduce wait times and allocate resources for future RFA treatment, which may improve both quality and efficiency of HCC care.
Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/mortalidade , Neoplasias Hepáticas/cirurgia , Tempo para o Tratamento , Listas de Espera/mortalidade , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ablação por Cateter/efeitos adversos , Distribuição de Qui-Quadrado , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Ontário , Modelos de Riscos Proporcionais , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
UNLABELLED: Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon-free regimens of direct-acting antiviral agents, making it difficult to optimize therapy. We performed a post-hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed-dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment-naïve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV-SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had failed previous treatment with a protease-inhibitor regimen. Overall, 493 patients (96%; 95% confidence interval [CI]: 94%-98%) achieved SVR12, 98% of treatment-naïve and 95% of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95% of patients receiving 12 weeks and 98% of patients receiving 24 weeks of treatment), nor by addition of RBV (95% of patients receiving LDV-SOF alone and 97% of those who received LDV-SOF plus RBV), although previously treated patients receiving 12 weeks of LDV-SOF without RBV had an SVR12 rate of 90%. One patient discontinued LDV-SOF because of an adverse event (AE). The most common AEs were headache (23%), fatigue (16%-19%), and asthenia (14%-16%). One patient (<1%) of those receiving LDV-SOF alone, and 4 (2%) of those receiving LDV-SOF plus RBV had treatment-related serious AEs. CONCLUSIONS: This analysis suggests that 12 weeks of LDV-SOF is safe and effective for treatment-naïve patients with HCV genotype 1 and compensated cirrhosis. The relatively lower SVR in treatment-experienced patients treated with 12 weeks of LDV-SOF raises the question of whether these patients would benefit from adding RBV or extending treatment duration to 24 weeks.
Assuntos
Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Fluorenos/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Ribavirina/efeitos adversos , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Sofosbuvir , Resultado do Tratamento , Uridina Monofosfato/efeitos adversos , Adulto JovemRESUMO
Noninvasive markers of fibrosis have emerged as an alternative to the staging of fibrosis by means of liver biopsy. Apart from being noninvasive and thus lacking the adverse effects of liver biopsy, they offer some advantages such as reduced risk of sampling error, objectiveness in the interpretation of the result, appropriateness for repeated measurements and lower cost. Many studies have validated different panels of blood markers and imaging/transient elastography for the estimation of fibrosis with acceptable accuracy. Clinical scenarios leading to inacurate or failed estimation must be acknowledged, as well as the fact that performance of blood markers and transient elastography, and their diagnostic cut-off values vary among specific liver diseases. The combination of two blood markers or of a blood marker and transient elastography has been shown to increase accuracy of the estimation. Further, unlike liver biopsy the noninvasive markers of fibrosis are not associated with a ceiling effect after cirrhosis is identified, but can discriminate early from advanced stages of cirrhosis. Longitudinal studies have shown their utility as predictors of complications from portal hypertension and mortality, outperforming liver biopsy. In conclusion, noninvasive markers of fibrosis provide major advantages over liver biopsy. The reported performance of some of the available tests particularly when used in combination make them a reliable tool, very attractive for daily clinical practice.