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Fístula Esofágica , Esofagectomía , Stents , Humanos , Esofagectomía/efectos adversos , Stents/efectos adversos , Masculino , Fístula Esofágica/etiología , Fístula Esofágica/cirugía , Fístula Esofágica/terapia , Neoplasias Esofágicas/cirugía , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/cirugía , Fuga Anastomótica/etiología , Fuga Anastomótica/terapia , Persona de Mediana Edad , Esofagoscopía/métodosRESUMEN
Chronic hepatitis B (CHB) is a major global health challenge. CHB can be controlled by antivirals but a therapeutic cure is lacking. CHB is characterized by limited HBV-specific T cell reactivity and functionality and expression of inhibitory receptors. The mechanisms driving these T cell phenotypes are only partially understood. Here, we created a single-cell RNA-sequencing dataset of HBV immune responses in patients to contribute to a better understanding of the dysregulated immunity. Blood samples of a well-defined cohort of 21 CHB and 10 healthy controls, including a subset of 5 matched liver biopsies, were collected. scRNA-seq data of total immune cells (55,825) plus sorted HBV-specific (1,963), non-naive (32,773) and PD1+ T cells (96,631) was generated using the 10X Genomics platform (186,123 cells) or the full-length Smart-seq2 protocol (1,069 cells). The shared transcript count matrices of single-cells serve as a valuable resource describing transcriptional changes underlying dysfunctional HBV-related T cell responses in blood and liver tissue and offers the opportunity to identify targets or biomarkers for HBV-related immune exhaustion.
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Hepatitis B Crónica , Inmunidad Celular , Humanos , Virus de la Hepatitis B , Hepatitis B Crónica/genética , Hepatitis B Crónica/inmunología , ARN , Análisis de la Célula Individual , Análisis de Secuencia de ARN , Linfocitos T/inmunología , Hígado/virologíaAsunto(s)
Colestasis , Trasplante de Hígado , Humanos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Constricción Patológica/etiología , Constricción Patológica/cirugía , Colestasis/diagnóstico por imagen , Colestasis/etiología , Colestasis/cirugía , Resultado del Tratamiento , Estudios Retrospectivos , Complicaciones Posoperatorias/cirugía , Anastomosis Quirúrgica/efectos adversosRESUMEN
BACKGROUND: Hepatitis Delta virus (HDV) infection is a major cause of liver-related morbidity and mortality in patients infected with HBV, with a global HDV prevalence uncertain. In France, 2 to 5 % of HBs antigen (HBsAg) carriers present anti-HDV antibodies (anti-HDV). The EASL recommends testing for anti-HDV in all HBsAg-positive patients. Since January 2022, we have systematically carried out anti-HDV serology when a positive HBsAg is discovered (new HBsAg carriers). OBJECTIVES: We evaluated the benefit of anti-HDV reflex testing after one year of practice by comparing anti-HDV and HBsAg serology data over the last six years, among the new HBsAg carriers and all the HBsAg carriers. STUDY DESIGN: HBsAg and anti-HDV were screened using the Abbott Architect HBsAg quanti kit and the DIA.PRO HDVAb kit. Serological, demographic, virological, and clinical data were analyzed. RESULTS: Implementing anti-HDV reflex testing leads to more than a 2-fold increase in diagnoses of HDV infection among all HBsAg carriers. If the anti-HDV positive rate remains stable among the new HBsAg carriers, a significant increase in the anti-HDV positive rate from 6.8 % to 10.3 % was observed considering all HBsAg carriers. Interestingly, the discovery of anti-HDV carriage increased from 3.9 % to 6.5 % in 2022, allowing earlier identification of HBV-HDV-infected patients and a fast referral to hepatologists for adequate clinical management and, in some cases, the introduction of bulevirtide-based therapy. CONCLUSIONS: Our preliminary results at one year seem promising and evaluating the cost-effectiveness of reflex tests in real life with feedback would be helpful.
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Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis Delta , Humanos , Anticuerpos Antihepatitis , Francia/epidemiología , Reflejo , Virus de la Hepatitis BRESUMEN
Left-sided or segmental portal hypertension (SPHT) is a rare entity, most often associated with pancreatic disease or antecedent pancreatic surgery. The starting point is splenic vein obstruction secondary to local inflammation or, less often, extrinsic compression. SPHT leads to splenomegaly and development of collateral porto-systemic venous circulation. SPHT should be suspected in patients with pancreatic history who present with episodic upper gastrointestinal bleeding and splenomegaly with normal liver function tests. The most common clinical presentation is major upper gastrointestinal bleeding secondary to rupture of esophageal and/or gastric varices. At the present time, there are no management recommendations for SPHT, particularly when the patient is asymptomatic. In patients with upper gastro-intestinal bleeding, hemostasis can be obtained either by medical or interventional means according to patient status and available resources. For symptomatic patients, splenectomy is the reference treatment. Recently, less invasive, radiologic procedures, such as splenic artery embolization, have been developed as an alternative to surgery. Additionally, sonography-guided endoscopic hemostasis can also be envisioned, leading to the diagnosis and treatment of the lesion by elastic band ligation or by glue injection into the varices during the same procedure. The goal of this article is to describe the pathophysiological mechanisms behind SPHT and its clinical manifestations and treatment, based on a review of the literature. Because of the absence of recommendations for the management of SPHT, we propose a decisional algorithm for the management of SPHT based on the literature.
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Hipertensión Portal , Hipertensión Portal Izquierda , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Esplenomegalia/diagnóstico por imagen , Esplenomegalia/etiología , Esplenomegalia/cirugía , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , AlgoritmosRESUMEN
BACKGROUND AND AIMS: EUS-guided radiofrequency ablation (EUS-RFA) has been described as a potentially curative option for solid and cystic pancreatic neoplasms. We aimed to assess the safety and efficacy of pancreatic EUS-RFA in a large study population. METHODS: A retrospective study retrieving all consecutive patients who underwent pancreatic EUS-RFA during 2019 and 2020 in France was conducted. Indication, procedural characteristics, early and late adverse events (AEs), and clinical outcomes were recorded. Risk factors for AEs and factors related to complete tumor ablation were assessed on univariate and multivariate analyses. RESULTS: One hundred patients (54% men, 64.8 ± 17.6 years old) affected by 104 neoplasms were included. Sixty-four neoplasms were neuroendocrine neoplasms (NENs), 23 were metastases, and 10 were intraductal papillary mucinous neoplasms with mural nodules. No procedure-related mortality was observed, and 22 AEs were reported. Proximity of pancreatic neoplasms (≤1 mm) to the main pancreatic duct was the only independent risk factor for AEs (odds ratio [OR), 4.10; 95% confidence interval [CI), 1.02-15.22; P = .04). Fifty-nine patients (60.2%) achieved a complete tumor response, 31 (31.6%) a partial response, and 9 (9.2%) achieved no response. On multivariate analysis, NENs (OR, 7.95; 95% CI, 1.66-51.79; P < .001) and neoplasm size <20 mm (OR, 5.26; 95% CI, 2.17-14.29; P < .001) were independently related to complete tumor ablation. CONCLUSIONS: The results of this large study confirm an overall acceptable safety profile for pancreatic EUS-RFA. Close proximity (≤1 mm) to the main pancreatic duct represents an independent risk factor for AEs. Good clinical outcomes in terms of tumor ablation were observed, especially for small NENs.
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Neoplasias Quísticas, Mucinosas y Serosas , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Ablación por Radiofrecuencia , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios Retrospectivos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Ablación por Radiofrecuencia/métodos , Tumores Neuroendocrinos/cirugía , Factores de RiesgoAsunto(s)
Sistema Biliar , Hemobilia , Pancreatitis , Humanos , Hemobilia/complicaciones , Hallazgos Incidentales , Pancreatitis/etiologíaAsunto(s)
Várices Esofágicas y Gástricas , Hipertensión Portal , Humanos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Hipertensión Portal/diagnóstico , Hipertensión Portal/etiología , Hipertensión Portal/cirugía , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/cirugíaAsunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/cirugía , Páncreas , Conducto Colédoco , Drenaje , Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/cirugíaRESUMEN
INTRODUCTION: Significant hepatocellular carcinoma (HCC) risk persists after chronic hepatitis C (CHC) cure. Preclinical studies have shown that erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has an antiviral activity and HCC chemopreventive effect. Erlotinib is metabolized in the liver, and its safety in patients with CHC is unknown. This study aimed to assess the safety and antiviral activity of erlotinib in patients with CHC. METHODS: In this investigator-initiated dose-escalation phase Ib prospective randomized double-blind placebo-controlled study, noncirrhotic hepatitis C virus (HCV) patients received placebo or erlotinib (50 or 100 mg/d) for 14 days with a placebo-erlotinib ratio of 1:3. Primary end points were safety and viral load reduction at the end of treatment (EOT). The secondary end point was viral load reduction 14 days after EOT. RESULTS: This study analyzed data of 3 patients receiving placebo, 3 patients receiving erlotinib 50 mg/d, and 3 patients receiving erlotinib 100 mg/d. One grade 3 adverse event was reported in the placebo group (liver enzymes elevation), leading to treatment discontinuation and patient replacement, and 1 in the erlotinib 100 mg/d group (pericarditis), which was not considered to be treatment-related. Grade 2 skin rash was observed in 1 erlotinib 100 mg/d patient. No significant HCV-RNA level reduction was noted during treatment, but 2 of the 3 patients in the erlotinib 100 mg/d group showed a decrease of >0.5 log HCV-RNA 14 days after EOT. DISCUSSION: Erlotinib demonstrated to be safe in noncirrhotic CHC patients. An antiviral activity at 100 mg/d confirms a functional role of EGFR as an HCV host factor in patients. These results provide perspectives to further study erlotinib as an HCC chemopreventive agent in patients with CHC.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Antivirales/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Receptores ErbB/genética , Receptores ErbB/uso terapéutico , Clorhidrato de Erlotinib/efectos adversos , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Estudios Prospectivos , ARNRESUMEN
BACKGROUND AND AIMS: People who use drugs (PWUDs) are the main group at risk for hepatitis C virus (HCV) transmission and a key population for hepatitis C elimination. Multidisciplinary team (MDT) meetings were set up in France in December 2014 within regional reference centers to supervise the prescriptions and delivery of direct-acting antivirals (DAAs) to optimize the management of HCV infection. The aim of this retrospective study was to analyze the changes in the profile and therapeutic care of PWUDs with HCV mono-infection according to the evolution of MDT meetings in a regional tertiary reference center. METHODS: Between 2015 and 2019, overall 1912 HCV-infected patients presented at the MDT meetings, 547 were PWUDs with HCV mono-infection treated with DAAs. Five periods were defined according to the evolution of MDT meetings. The profile and management of PWUDs were compared among these five periods. RESULTS: Over time, the frequency of advanced stage of fibrosis decreased from 90.8 to 36.3% (P < 0.001), whereas the therapeutic care of the patients in primary addictology centers and networks of general practitioners increased from 17.4 to 55% (P < 0.001). The frequency of excessive alcohol consumption varied between 9.1 and 30% (P = 0.003) and that of opioid substitution therapy between 42.5 and 70% (P < 0.001). The Sustained virologic response assessed 12 weeks after the end of treatment rate was above 95% for the five periods. CONCLUSION: Between 2015 and 2019, the changes in the profile and management of PWUDs have followed the evolution of MDT meetings concerning patients with less advanced fibrosis and more therapeutic hepatitis C care made by the primary care centers.
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Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Fibrosis , Hepacivirus , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Preparaciones Farmacéuticas , Estudios Retrospectivos , Respuesta Virológica SostenidaAsunto(s)
Enfermedades de los Conductos Biliares , Colecistectomía Laparoscópica , Humanos , Colecistectomía Laparoscópica/efectos adversos , Esfinterotomía Endoscópica , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/cirugía , Conductos Biliares/cirugía , Conductos Biliares/lesiones , Colangiopancreatografia Retrógrada EndoscópicaRESUMEN
BACKGROUND: In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. METHODS: We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits. RESULTS: 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7-51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24-0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08-0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15-0.54, p < 0.0001), liver-related mortality (HR 0.40, 95% CI 0.17-0.96, p = 0.04), non-liver-related mortality (HR 0.17, 95% CI 0.06-0.49, p = 0.001), liver transplantation (HR 0.17, 95% CI 0.05-0.54, p = 0.003), and hepatocellular carcinoma (HR 0.52, 95% CI 0.29-0.93, p = 0.03). CONCLUSION: Treatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov registry number: NCT01953458.