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1.
Gut ; 70(4): 707-716, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32723845

RESUMEN

OBJECTIVES: Existing scores are not accurate at predicting mortality in upper (UGIB) and lower (LGIB) gastrointestinal bleeding. We aimed to develop and validate a new pre-endoscopy score for predicting mortality in both UGIB and LGIB. DESIGN AND SETTING: International cohort study. Patients presenting to hospital with UGIB at six international centres were used to develop a risk score for predicting mortality using regression analyses. The score's performance in UGIB and LGIB was externally validated and compared with existing scores using four international datasets. We calculated areas under receiver operating characteristics curves (AUROCs), sensitivities, specificities and outcome among patients classified as low risk and high risk. PARTICIPANTS AND RESULTS: We included 3012 UGIB patients in the development cohort, and 4019 UGIB and 2336 LGIB patients in the validation cohorts. Age, Blood tests and Comorbidities (ABC) score was closer associated with mortality in UGIB and LGIB (AUROCs: 0.81-84) than existing scores (AUROCs: 0.65-0.75; p≤0.02). In UGIB, patients with low ABC score (≤3), medium ABC score (4-7) and high ABC score (≥8) had 30-day mortality rates of 1.0%, 7.0% and 25%, respectively. Patients classified low risk using ABC score had lower mortality than those classified low risk with AIMS65 (threshold ≤1) (1.0 vs 4.5%; p<0.001). In LGIB, patients with low, medium and high ABC scores had in-hospital mortality rates of 0.6%, 6.3% and 18%, respectively. CONCLUSIONS: In contrast to previous scores, ABC score has good performance for predicting mortality in both UGIB and LGIB, allowing early identification and targeted management of patients at high or low risk of death.


Asunto(s)
Hemorragia Gastrointestinal/mortalidad , Medición de Riesgo/métodos , Factores de Edad , Anciano , Comorbilidad , Femenino , Pruebas Hematológicas , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Sensibilidad y Especificidad
2.
Gastroenterology ; 158(1): 160-167, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31562847

RESUMEN

BACKGROUND & AIMS: Scoring systems are suboptimal for determining risk in patients with upper gastrointestinal bleeding (UGIB); these might be improved by a machine learning model. We used machine learning to develop a model to calculate the risk of hospital-based intervention or death in patients with UGIB and compared its performance with other scoring systems. METHODS: We analyzed data collected from consecutive unselected patients with UGIB from medical centers in 4 countries (the United States, Scotland, England, and Denmark; n = 1958) from March 2014 through March 2015. We used the data to derive and internally validate a gradient-boosting machine learning model to identify patients who met a composite endpoint of hospital-based intervention (transfusion or hemostatic intervention) or death within 30 days. We compared the performance of the machine learning prediction model with validated pre-endoscopic clinical risk scoring systems (the Glasgow-Blatchford score [GBS], admission Rockall score, and AIMS65). We externally validated the machine learning model using data from 2 Asia-Pacific sites (Singapore and New Zealand; n = 399). Performance was measured by area under receiver operating characteristic curve (AUC) analysis. RESULTS: The machine learning model identified patients who met the composite endpoint with an AUC of 0.91 in the internal validation set; the clinical scoring systems identified patients who met the composite endpoint with AUC values of 0.88 for the GBS (P = .001), 0.73 for Rockall score (P < .001), and 0.78 for AIMS65 score (P < .001). In the external validation cohort, the machine learning model identified patients who met the composite endpoint with an AUC of 0.90, the GBS with an AUC of 0.87 (P = .004), the Rockall score with an AUC of 0.66 (P < .001), and the AIMS65 with an AUC of 0.64 (P < .001). At cutoff scores at which the machine learning model and GBS identified patients who met the composite endpoint with 100% sensitivity, the specificity values were 26% with the machine learning model versus 12% with GBS (P < .001). CONCLUSIONS: We developed a machine learning model that identifies patients with UGIB who met a composite endpoint of hospital-based intervention or death within 30 days with a greater AUC and higher levels of specificity, at 100% sensitivity, than validated clinical risk scoring systems. This model could increase identification of low-risk patients who can be safely discharged from the emergency department for outpatient management.


Asunto(s)
Hemorragia Gastrointestinal/diagnóstico , Aprendizaje Automático , Modelos Biológicos , Adulto , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hemorragia Gastrointestinal/terapia , Técnicas Hemostáticas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Medición de Riesgo/métodos
3.
J Gastroenterol Hepatol ; 35(1): 82-89, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31359521

RESUMEN

BACKGROUND AND AIM: Risk stratification for upper gastrointestinal bleeding (UGIB) is recommended. However, scoring system accuracy is suboptimal, and score calculation can be complex. Our aim was to develop a new score, the MAP(ASH) score, with information available in the emergency room and to validate it. METHODS: The score was built from a prospective database of patients with UGIB and validated in an international database of 3012 patients from six hospitals. Outcomes were 30-day mortality, endoscopic intervention, any intervention (red blood transfusion, endoscopic treatment, interventional radiology, surgery, or death), and rebleeding. Accuracy to predict outcomes was assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Five hundred forty-seven patients were included in the development cohort. Impaired mental status, albumin < 2.5 g/dL, pulse > 100, American Society of Anesthesiologists score > 2, systolic blood pressure < 90 mmHg, and hemoglobin < 10 g/dL were included in the score. The model had a good predictive accuracy for intervention (AUROC = 0.83; 95% confidence interval [CI]: 0.79-0.88) and fair for mortality (AUROC = 0.74; 95% CI: 0.68-0.81). Regarding endoscopic intervention, AUROC was 0.61 (95% CI: 0.56-0.66) in the original cohort and 0.69 (95% CI: 0.66-0.71) in the validation cohort, showing a poor performance, similar to other scores. For rebleeding, the MAP(ASH) (AUROC 0.73; 95% CI: 0.69-0.77) was similar to Glasgow Blatchford score (AUROC = 0.72; 95% CI: 0.67-0.76) but superior to AIMS65 (AUROC = 0.64; 95% CI: 0.59-0.68). CONCLUSION: MAP(ASH) is a simple pre-endoscopy risk score to predict intervention after UGIB, with fair discrimination at predicting mortality. Because of its applicability, it could be an option in clinical practice.


Asunto(s)
Hemorragia Gastrointestinal , Proyectos de Investigación , Anciano , Anciano de 80 o más Años , Bases de Datos como Asunto , Servicio de Urgencia en Hospital , Endoscopía , Femenino , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Riesgo
4.
Clin Microbiol Newsl ; 42(21): 171-179, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33110280

RESUMEN

Hepatitis A and E are both ancient diseases but have only been properly recognized as being caused by distinct pathogens in modern times. Despite significantly different genomic structures, both viruses employ remarkably similar strategies to avoid host detection and increase environmental transmission. There are millions of cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) each year, resulting in tens of thousands of deaths. The presentations can be clinically indistinguishable, but each virus also has a range of less common but more specific phenotypes. The epidemiology of HAV is complex, and is shifting in countries that are making improvements to public health and sanitation. HEV presents a significant public health challenge in resource-limited settings but has historically been incorrectly regarded as having little clinical relevance in industrialized countries.

5.
Clin Gastroenterol Hepatol ; 17(3): 440-447.e2, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29705263

RESUMEN

BACKGROUND & AIMS: Anti-thrombotic agents are risk factors for upper gastrointestinal bleeding (UGIB). However, few studies have evaluated their effects on patient outcomes. We assessed the effects of anti-thrombotic agents on outcomes of patients with high-risk UGIB. METHODS: We performed a prospective study of 619 patients with acute UGIB (defined by hematemesis, coffee-ground vomit or melena) who required intervention and underwent endoscopy at 8 centers in North America, Asia, and Europe, from March 2014 through March 2015. We collected data recorded on use of anti-thrombotic agents, clinical features, and laboratory test results to calculate AIMS65, Glasgow-Blatchford Score, and full Rockall scores. We also collected and analyzed data on co-morbidities, endoscopic findings, blood transfusion, interventional radiology results, surgeries, length of hospital stay, rebleeding, and mortality. RESULTS: Of the 619 patients who required endoscopic therapy, data on use of anti-thrombotic agents was available for 568; 253 of these patients (44%) used anti-thrombotic agents. Compared to patients not taking anti-thrombotic agents, patients treated with anti-thrombotics were older (P < .001), had a higher mean American Society of Anesthesiologists classification score (P < .0001), had a higher mean Rockall score (P < .0001), a higher mean AIMS65 score (P < .0001), and more frequently bled from ulcers (P < .001). There were no differences between groups in sex, systolic blood pressure, level of hemoglobin at hospital admission, frequency of malignancies, Glasgow-Blatchford Score, need for surgery or interventional radiology, number of rebleeding events, or requirement for transfusion. All-cause mortality was lower in patients who took anti-thrombotic drugs (11 deaths, 4%) than in patients who did not (37 deaths, 12%) (P = .002); this was due to lower bleeding-related mortality in patients taking anti-thrombotic drugs (3 deaths, 1%) than in patients who were not (19 deaths, 6%) (P = .003). Patients taking anti-thrombotic drugs had mean hospital stays of 6.9 days (95% CI, 2-23 days) compared to 7.9 days for non-users of anti-thrombotic agents (95% CI, 2-26 days) (P = .04). CONCLUSIONS: Despite being older, with higher American Society of Anesthesiologists classification, AIMS65, and Rockall scores, patients who have UGIB that requires endoscopic therapy and take anti-thrombotic drugs have lower mortality due to GI bleeding and shorter hospital stays, with similar rates of rebleeding, surgery, and transfusions, compared with those not taking anti-thrombotic drugs.


Asunto(s)
Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Hemorragia Gastrointestinal/mortalidad , Tiempo de Internación/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Asia , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Estudios Prospectivos , Factores de Riesgo , Análisis de Supervivencia
6.
Am J Gastroenterol ; 113(3): 358-366, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29380820

RESUMEN

OBJECTIVES: Numerous reviews indicate bloody hematemesis signifies more severe bleeding than coffee-grounds hematemesis. We assessed severity and outcomes related to bleeding symptoms in a prospective study. METHODS: Consecutive patients presenting with hematemesis or melena were categorized as bloody emesis (N=1209), coffee-grounds emesis without bloody emesis (N=701), or melena without hematemesis (N=1069). We assessed bleeding severity (pulse, blood pressure) and predictors of outcome (hemoglobin, risk stratification scores) at presentation, and outcomes of bleeding episodes. The primary outcome was a composite of transfusion, intervention, or mortality. RESULTS: Bloody and coffee-grounds emesis were similar in pulse ≥100 beats/min (35 vs. 37%), systolic blood pressure ≤100 mm Hg (12 vs. 12%), and hemoglobin ≤100 g/l (25 vs. 27%). Risk stratification scores were lower with bloody emesis. The composite end point was 34.7 vs. 38.2% for bloody vs. coffee-grounds emesis; mortality was 6.6 vs. 9.3%. Hemostatic intervention was more common (19.4 vs. 14.4%) with bloody emesis (due to a higher frequency of varices necessitating endoscopic therapy), as was rebleeding (7.8 vs. 4.5%). Outcomes were worse with hematemesis plus melena vs. isolated hematemesis for bloody (composite: 62.4 vs. 25.6%; hemostatic intervention: 36.5 vs. 13.8%) and coffee-grounds emesis (composite: 59.1 vs. 27.1%; hemostatic intervention: 26.4 vs. 8.1%). CONCLUSIONS: Bloody emesis is not associated with more severe bleeding episodes at presentation or higher mortality than coffee-grounds emesis, but is associated with modestly higher rates of hemostatic intervention and rebleeding. Outcomes with hematemesis are worsened with concurrent melena. The presence of bloody emesis plus melena potentially could be considered in decisions regarding timing of endoscopy.


Asunto(s)
Hematemesis/fisiopatología , Melena/fisiopatología , Tracto Gastrointestinal Superior , Anciano , Conservación de la Sangre , Transfusión Sanguínea/estadística & datos numéricos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/fisiopatología , Hemorragia Gastrointestinal/terapia , Frecuencia Cardíaca , Hematemesis/etiología , Hematemesis/mortalidad , Hematemesis/terapia , Hemoglobinas/metabolismo , Hemostasis Endoscópica/estadística & datos numéricos , Humanos , Masculino , Melena/etiología , Melena/mortalidad , Melena/terapia , Persona de Mediana Edad , Mortalidad , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Índice de Severidad de la Enfermedad
7.
Liver Int ; 38(11): 1951-1964, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29660259

RESUMEN

BACKGROUND & AIMS: While hepatitis E virus infections are a relevant topic in Europe, knowledge about epidemiology of hepatitis E virus infections in the USA and Latin America is still limited. Aim of this study was to estimate anti-hepatitis E virus IgG seroprevalence in the Americas and to assess whether low socioeconomic status is associated with hepatitis E virus exposure. METHODS: We performed a systematic review and meta-analysis. Literature search was performed in PubMed for articles published 01/1994-12/2016. Prevalence was estimated using a mixed-effects model and reported in line with PRISMA reporting guidelines. RESULTS: Seroprevalence was significantly higher in the USA than in Latin America, independently of assay, patient cohort, methodological quality or study year (OR: 1.82 (1.06-3.08), P = .03). Patients in the USA had a more than doubled estimated seroprevalence (up to 9%, confidence interval 5%-15.6%) than those in Brazil (up to 4.2%, confidence interval 2.4%-7.1%; OR: 2.27 (1.25-4.13); P = .007) and Mixed Caribbean (up to 1%, OR: 8.33 (1.15-81.61); P = .04). A comparison with published data from Europe demonstrated that anti-hepatitis E virus seroprevalence in the USA and Europe did not differ significantly (OR: 1.33 (0.81-2.19), P = .25), while rate in South America was significantly lower than that in Europe (OR: 0.67 (0.45-0.98), P = .04). CONCLUSIONS: Hepatitis E virus is common in the USA. Surprisingly, the risk of hepatitis E virus exposure was low in many South American countries. Seroprevalence did not differ significantly between Europe and the USA. Hence, hepatitis E virus is not limited to countries with low sanitary standards, and a higher socioeconomic status does not protect populations from hepatitis E virus exposure.


Asunto(s)
Anticuerpos Antihepatitis/sangre , Hepatitis E/epidemiología , Inmunoglobulina G/sangre , Humanos , América Latina/epidemiología , Prevalencia , Factores de Riesgo , Estudios Seroepidemiológicos , Estados Unidos/epidemiología
8.
Euro Surveill ; 23(12)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29589577

RESUMEN

BackgroundPrevious studies showed low levels of circulating hepatitis E virus (HEV) in Scotland. We aimed to reassess current Scottish HEV epidemiology. Methods: Blood donor samples from five Scottish blood centres, the minipools for routine HEV screening and liver transplant recipients were tested for HEV antibodies and RNA to determine seroprevalence and viraemia. Blood donor data were compared with results from previous studies covering 2004-08. Notified laboratory-confirmed hepatitis E cases (2009-16) were extracted from national surveillance data. Viraemic samples from blood donors (2016) and chronic hepatitis E transplant patients (2014-16) were sequenced. Results: Anti-HEV IgG seroprevalence varied geographically and was highest in Edinburgh where it increased from 4.5% in 2004-08) to 9.3% in 2014-15 (p = 0.001). It was most marked in donors < 35 years. HEV RNA was found in 1:2,481 donors, compared with 1:14,520 in 2011. Notified laboratory-confirmed cases increased by a factor of 15 between 2011 and 2016, from 13 to 206. In 2011-13, 1 of 329 transplant recipients tested positive for acute HEV, compared with six cases of chronic infection during 2014-16. Of 10 sequenced viraemic donors eight and all six patients were infected with genotype 3 clade 1 virus, common in European pigs. Conclusions: The seroprevalence, number of viraemic donors and numbers of notified laboratory-confirmed cases of HEV in Scotland have all recently increased. The causes of this change are unknown, but need further investigation. Clinicians in Scotland, particularly those caring for immunocompromised patients, should have a low threshold for testing for HEV.


Asunto(s)
Donantes de Sangre , Virus de la Hepatitis E/aislamiento & purificación , Hepatitis E/epidemiología , Hepatitis E/virología , Inmunoglobulina G/sangre , ARN Viral/sangre , Viremia/virología , Adolescente , Adulto , Femenino , Genotipo , Anticuerpos Antihepatitis/sangre , Hepatitis E/sangre , Hepatitis E/transmisión , Virus de la Hepatitis E/genética , Virus de la Hepatitis E/inmunología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Filogenia , ARN Viral/análisis , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Escocia/epidemiología , Estudios Seroepidemiológicos , Viremia/epidemiología , Adulto Joven
9.
J Infect Dis ; 215(8): 1197-1206, 2017 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-28199701

RESUMEN

Hepatitis E virus (HEV), as a hepatotropic virus, is supposed to exclusively infect the liver and only cause hepatitis. However, a broad range of extrahepatic manifestations (in particular, idiopathic neurological disorders) have been recently reported in association with its infection. In this study, we have demonstrated that various human neural cell lines (embryonic stem cell-derived neural lineage cells) induced pluripotent stem cell-derived human neurons and primary mouse neurons are highly susceptible to HEV infection. Treatment with interferon-α or ribavirin, the off-label antiviral drugs for chronic hepatitis E, exerted potent antiviral activities against HEV infection in neural cells. More importantly, in mice and monkey peripherally inoculated with HEV particles, viral RNA and protein were detected in brain tissues. Finally, patients with HEV-associated neurological disorders shed the virus into cerebrospinal fluid, indicating a direct infection of their nervous system. Thus, HEV is neurotropic in vitro, and in mice, monkeys, and possibly humans. These results challenge the dogma of HEV as a pure hepatotropic virus and suggest that HEV infection should be considered in the differential diagnosis of idiopathic neurological disorders.


Asunto(s)
Encéfalo/virología , Virus de la Hepatitis E/patogenicidad , Hepatitis E/patología , Neuronas/virología , Adulto , Anciano , Animales , Antivirales/farmacología , Encéfalo/patología , Línea Celular Tumoral , Líquido Cefalorraquídeo/virología , Femenino , Síndrome de Guillain-Barré/virología , Hepatitis E/tratamiento farmacológico , Humanos , Interferón-alfa/farmacología , Hígado/patología , Hígado/virología , Macaca mulatta , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Persona de Mediana Edad , Neuronas/patología , ARN Viral/análisis , Ribavirina/farmacología , Replicación Viral/efectos de los fármacos , Esparcimiento de Virus
10.
Emerg Infect Dis ; 23(2): 276-279, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28098527

RESUMEN

We compared the epidemiology of hepatitis A and hepatitis E cases in China from 1990-2014 to better inform policy and prevention efforts. The incidence of hepatitis A cases declined dramatically, while hepatitis E incidence increased. During 2004-2014, hepatitis E mortality rates surpassed those of hepatitis A.

11.
J Hepatol ; 67(5): 925-932, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28734938

RESUMEN

BACKGROUND & AIMS: Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury. METHODS: Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands. RESULTS: Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8-145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus. CONCLUSIONS: In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted. Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system.


Asunto(s)
Neuritis del Plexo Braquial , Isquemia Encefálica , Virus de la Hepatitis E , Hepatitis E , Convulsiones , Adulto , Neuritis del Plexo Braquial/diagnóstico , Neuritis del Plexo Braquial/epidemiología , Neuritis del Plexo Braquial/etiología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Isquemia Encefálica/etiología , Femenino , Francia/epidemiología , Anticuerpos Antihepatitis/sangre , Hepatitis E/complicaciones , Hepatitis E/epidemiología , Hepatitis E/inmunología , Hepatitis E/virología , Virus de la Hepatitis E/genética , Virus de la Hepatitis E/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Examen Neurológico/métodos , Proyectos Piloto , ARN Viral/análisis , Convulsiones/diagnóstico , Convulsiones/epidemiología , Convulsiones/etiología , Pruebas Serológicas/métodos , Estadística como Asunto , Reino Unido/epidemiología
12.
Hepatology ; 64(6): 1934-1950, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27631819

RESUMEN

The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel "Quantiferon" assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and 27 healthy volunteers. A genotype 3a peptide library (616 overlapping peptides spanning open reading frames [ORFs] 1-3) was used in interferon-gamma (IFN-γ) T-cell ELISpot assays. CD4+ /CD8+ T-cell subsets and polyfunctionality were defined using ICCS and SPICE analysis. Quantification of IFN-γ used whole-blood stimulation with recombinant HEV-capsid protein in the QuantiFERON kit. HEV-specific T-cell responses were detected in 41/44 immune-competent HEV exposed volunteers (median magnitude: 397 spot-forming units/106 peripheral blood mononuclear cells), most frequently targeting ORF2. High-magnitude, polyfunctional CD4 and CD8+ T cells were detected during acute disease and maintained to 12 years, but these declined over time, with CD8+ responses becoming more monofunctional. Low-level responses were detectable in immunosuppressed patients. Twenty-three novel HEV CD4+ and CD8+ T-cell targets were mapped predominantly to conserved genomic regions. QuantiFERON testing demonstrated an inverse correlation between IFN-γ production and the time from clinical presentation, providing 100% specificity, and 71% sensitivity (area under the receiver operator characteristic curve of 0.86) for HEV exposure at 0.3 IU/mL. CONCLUSION: Robust HEV-specific T-cell responses generated during acute disease predominantly target ORF2, but decline in magnitude and polyfunctionality over time. Defining HEV T-cell targets will be important for the investigation of HEV-associated autoimmune disease. (Hepatology 2016;64:1934-1950).


Asunto(s)
Virus de la Hepatitis E/inmunología , Hepatitis E/inmunología , Hepatitis E/virología , Especificidad del Receptor de Antígeno de Linfocitos T , Linfocitos T/inmunología , Linfocitos T/virología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hepatitis E/sangre , Hepatitis E/diagnóstico , Humanos , Interferón gamma/sangre , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto Joven
13.
Histopathology ; 71(4): 580-590, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28543644

RESUMEN

AIMS: To determine the relative utility of in-situ testing for hepatitis E virus (HEV) RNA and paraffin-section polymerase chain reaction (PCR) to diagnose HEV infection in paraffin-embedded clinical liver biopsies, and to correlate with clinicopathological characteristics. METHODS AND RESULTS: We evaluated in-situ and quantitative PCR (qPCR)-based approaches to identifying HEV in clinical liver biopsies from infected patients from multiple centres, correlating with clinical setting (immunocompetent, allograft or immunosuppressed native liver) and histological findings. Thirty-six biopsies from 29 patients had histological data, 27 and 23 of which had satisfactory material for in-situ RNA testing and tissue qPCR, respectively. Both approaches specifically identified HEV infection, but tissue qPCR was significantly more sensitive than RNAscope in-situ testing (P = 0.035). In immunocompetent but not immunosuppressed patients the tissue qPCR yield correlated with the severity of lobular hepatitis (rho = 0.94, P < 0.001). qPCR viral yield was comparably high in allografts and immunosuppressed native livers and significantly greater than with native liver infection. Immunosuppressed patients showed reduced severity of hepatitis and cholestatic changes, compared with immunocompetent patients. Indeed, HEV-infected liver allografts could show minimal hepatitis for many months. In individual cases each technique was useful when serum was not available to identify chronic infection retrospectively (in biopsies taken 4-31 months before diagnosis), to identify persistent/residual infection when contemporary serum PCR was negative and to identify cleared infection. CONCLUSIONS: qPCR is more effective than in-situ RNA testing to identify HEV infection in paraffin-embedded liver biopsies and has diagnostic utility in selected settings.


Asunto(s)
Virus de la Hepatitis E/aislamiento & purificación , Hepatitis E/diagnóstico , Aloinjertos , Biopsia , Hepatitis E/virología , Virus de la Hepatitis E/genética , Humanos , Huésped Inmunocomprometido , Hígado/patología , Hígado/virología , Trasplante de Hígado , ARN Viral/genética , Estudios Retrospectivos
14.
Gastrointest Endosc ; 86(6): 1028-1037, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28396275

RESUMEN

BACKGROUND AND AIMS: We performed a prospective multi-national study of patients presenting to the emergency department with upper GI bleeding (UGIB) and assessed the relationship of time to presentation after onset of UGIB symptoms with patient characteristics and outcomes. METHODS: Consecutive patients presenting with overt UGIB (red-blood emesis, coffee-ground emesis, and/or melena) from March 2014 to March 2015 at 6 hospitals were included. Multiple predefined patient characteristics and outcomes were collected. Rapid presentation was defined as ≤6 hours. RESULTS: Among 2944 patients, 1068 (36%) presented within 6 hours and 576 (20%) beyond 48 hours. Significant independent factors associated with presentation ≤6 hours versus >6 hours on logistic regression included melena (odds ratio [OR], 0.22; 95% CI, 0.18-0.28), hemoglobin ≤80 g/L (OR, 0.47; 95% CI, 0.36-0.61), altered mental status (OR, 2.06; 95% CI, 1.55-2.73), albumin ≤30 g/L (OR, 1.43; 95% CI, 1.14-1.78), and red-blood emesis (OR, 1.29; 95% CI, 1.06-1.59). Patients presenting ≤6 hours versus >6 hours required transfusion less often (286 [27%] vs 791 [42%]; difference, -15%; 95% CI, -19% to -12%) because of a smaller proportion with low hemoglobin levels, but were similar with regard to hemostatic intervention (189 [18%] vs 371 [20%]), 30-day mortality (80 [7%] vs 121 [6%]), and hospital days (5.0 ± 0.2 vs 5.0 ± 0.2). CONCLUSIONS: Patients with melena alone delay their presentation to the hospital. A delayed presentation is associated with a decreased hemoglobin level and increases the likelihood of transfusion. Other outcomes are similar with rapid versus delayed presentation. Time to presentation should not be used as an indicator for poor outcome. Patients with delayed presentation should be managed with the same degree of care as those with rapid presentation.


Asunto(s)
Enfermedades Duodenales/sangre , Enfermedades del Esófago/sangre , Hematemesis/sangre , Melena/sangre , Aceptación de la Atención de Salud/estadística & datos numéricos , Gastropatías/sangre , Anciano , Transfusión Sanguínea/estadística & datos numéricos , Confusión/etiología , Enfermedades Duodenales/mortalidad , Enfermedades Duodenales/terapia , Enfermedades del Esófago/mortalidad , Enfermedades del Esófago/terapia , Femenino , Escala de Coma de Glasgow , Hematemesis/mortalidad , Hematemesis/terapia , Hemoglobinas/metabolismo , Hemostasis Endoscópica/estadística & datos numéricos , Humanos , Tiempo de Internación/estadística & datos numéricos , Letargia/etiología , Masculino , Melena/mortalidad , Melena/terapia , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Albúmina Sérica/metabolismo , Gastropatías/mortalidad , Gastropatías/terapia , Estupor/etiología , Tiempo de Tratamiento
15.
Pract Neurol ; 17(4): 282-288, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28647707

RESUMEN

Hepatitis E is the most common cause of hepatitis worldwide. While originally considered a disease of developing countries, it is increasingly recognised in developed countries, probably related to contaminated pork meat, and where infection is often asymptomatic. However, several non-liver manifestations have become apparent, the most important of which are neurological, including Guillain-Barré syndrome (acute inflammatory demyelinating polyradiculoneuropathy (AIDP)), neuralgic amyotrophy and meningoencephalitis. We recommend testing all patients with AIDP and neuralgic amyotrophy for hepatitis E and consider testing any patient with an unexplained neurological illness and abnormal liver function tests for the virus.


Asunto(s)
Neuritis del Plexo Braquial/virología , Encefalitis Viral/virología , Síndrome de Guillain-Barré/virología , Hepatitis E/complicaciones , Meningitis Viral/virología , Virus de la Hepatitis E , Humanos , Enfermedades del Sistema Nervioso/virología
16.
Curr Opin Infect Dis ; 29(6): 639-644, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27607911

RESUMEN

PURPOSE OF REVIEW: Over the last 10 years, it has become apparent that hepatitis E virus (HEV) is a pathogen of global significance. In contrast to HEV in the developing world, HEV in developed countries is caused by HEV genotypes 3 and 4, which are enzoonotic with a porcine primary host and cause both acute and chronic infection. Chronic infection occurs in the immunosuppressed, including transplant recipients, and untreated can cause rapidly progressive cirrhosis. RECENT FINDINGS: Ribavirin has been used successfully to treat acute hepatitis E in high-risk patients. Ribavirin monotherapy is the treatment of choice for patients chronically infected with HEV, with sustained virological response (SVR) of approximately 85%. A minority of chronically infected patients fail to achieve SVR with ribavirin monotherapy, possibly because of viral mutants. The treatment of patients who fail to achieve SVR with ribavirin monotherapy is problematic. SUMMARY: Ribavirin is an effective treatment for hepatitis E, but further studies are required to determine which other antiviral agents are of clinical utility in treating HEV in the minority of patients who do not respond to ribavirin.


Asunto(s)
Antivirales/uso terapéutico , Virus de la Hepatitis E , Hepatitis E/tratamiento farmacológico , Ribavirina/uso terapéutico , Animales , Genotipo , Virus de la Hepatitis E/genética , Humanos , Huésped Inmunocomprometido , Porcinos
17.
Liver Int ; 36(4): 467-72, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27005692

RESUMEN

Hepatitis E virus can cause acute, fulminant and chronic hepatitis and has been associated with a range of extrahepatic manifestations. Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis are the main neurological manifestations associated with acute and chronic hepatitis E virus infection. Renal injuries have been also reported, including membranoproliferative glomerulonephritis with or without cryoglobulinemia and membranous glomerulonephritis. Acute pancreatitis, haematological disorders and other autoimmune extrahepatic manifestations of hepatitis E virus, such as myocarditis and thyroiditis, have been also reported. In this comprehensive article, we review all published reports describing hepatitis E virus-associated extrahepatic manifestations.


Asunto(s)
Anemia/virología , Crioglobulinemia/virología , Virus de la Hepatitis E/patogenicidad , Hepatitis E/virología , Enfermedades Renales/virología , Enfermedades del Sistema Nervioso/virología , Pancreatitis/virología , Trombocitopenia/virología , Enfermedad Aguda , Anemia/diagnóstico , Animales , Crioglobulinemia/diagnóstico , Hepatitis E/complicaciones , Hepatitis E/diagnóstico , Interacciones Huésped-Patógeno , Humanos , Enfermedades Renales/diagnóstico , Enfermedades del Sistema Nervioso/diagnóstico , Pancreatitis/diagnóstico , Factores de Riesgo , Trombocitopenia/diagnóstico
18.
Dig Dis ; 34(4): 308-16, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27170383

RESUMEN

Until recently, hepatitis E virus (HEV) was thought not to occur in developed countries. It is now clear that locally acquired HEV is common in such settings. HEV infection acquired in these areas differs from that in developing countries in a number of important aspects: it is caused by genotype 3 (and 4 in China and Japan), it mainly affects middle-aged/elderly males and it is zoonotic with a porcine primary host. Pig herds worldwide are infected with HEV genotype 3 and HEV has been found in the human food chain in a number of developed countries. However, the route of transmission is not fully understood, since most cases are not obviously associated with pigs/pig products. HEV can be transmitted by blood transfusion and surprisingly high numbers of asymptomatic blood donors are viremic at the time of donation: Germany 1:1,200, Netherlands 1:2,671, England 1:2,848. Our understanding of the clinical phenotype of HEV infection in humans has undergone a sea-change in recent years. Previously, HEV was thought to cause only acute self-limiting hepatitis. However, HEV may cause persistent disease in the immunocompromised. Patients with chronic HEV infection have no symptoms, but some develop rapidly progressive liver cirrhosis. The full clinical spectrum of HEV is still emerging. HEV has important extra-hepatic manifestations, which deserve further investigation. For example, HEV can cause a wide range of neurological illness. In particular, very recent data suggest that Guillain-Barré syndrome and neuralgic amyotrophy are associated with locally acquired HEV in approximately 5 and 10% of the cases, respectively.


Asunto(s)
Virus de la Hepatitis E/genética , Hepatitis E/transmisión , Anciano , Anciano de 80 o más Años , Animales , China , Inglaterra , Femenino , Enfermedades Transmitidas por los Alimentos/virología , Genotipo , Alemania , Hepatitis E/virología , Humanos , Japón , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Países Bajos , Porcinos , Enfermedades de los Porcinos/transmisión , Enfermedades de los Porcinos/virología
19.
Transfus Apher Sci ; 55(3): 271-274, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27843081

RESUMEN

Following the discovery of HEV in the 1980s, it became apparent that HEV is endemic in a number of developing countries in Asia, Africa and Mexico. In these geographical settings HEV is spread oral faecally by HEV genotypes (gt) 1 and 2, which are obligate human pathogens. Infection occurs oro-faecally, often as a result in the breakdown of fragile sanitary infrastructure allowing drinking water supplies to become contaminated with human sewage. Hepatitis E usually causes a self-limiting hepatitis in young adults with sporadic cases and occasional dramatic outbreaks involving hundreds or thousands of cases. Clinically the illness is indistinguishable from hepatitis A, except in pregnant women where the mortality is 20-25%. Death occurs in the third trimester from fulminant hepatic failure and obstetric complications such as eclampsia, with very high associated foetal loss. For the best part of 20 years hepatitis E was considered as an imported disease in developed countries, and was only seen in travellers returning from endemic developing countries. We got this very badly wrong: HEV gt3 was 'hiding in the shadows' in humans, pigs, and other animals.


Asunto(s)
Países Desarrollados , Virus de la Hepatitis E/fisiología , Animales , Donantes de Sangre , Transfusión Sanguínea , Hepatitis E/epidemiología , Hepatitis E/virología , Virus de la Hepatitis E/genética , Humanos
20.
Clin Microbiol Rev ; 27(1): 116-38, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24396139

RESUMEN

Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries.


Asunto(s)
Hepatitis E , Enfermedad Crónica , Países Desarrollados/estadística & datos numéricos , Países en Desarrollo/estadística & datos numéricos , Reservorios de Enfermedades/virología , Hepatitis E/diagnóstico , Hepatitis E/tratamiento farmacológico , Hepatitis E/epidemiología , Hepatitis E/microbiología , Hepatitis E/transmisión , Virus de la Hepatitis E/fisiología , Humanos
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