Increased Prevalence of Antibodies to Hepatitis E Virus in Patients with Neurocysticercosis.

We explored the association between serological status for hepatitis E and neurocysticercosis (NCC) in neurologic patients attending a national neurological referral center in Lima, Perú, between the years 2008 and 2012. Anti-hepatitis E antibodies were evaluated in patients with and without NCC, and a control group of rural general population. Anti-hepatitis E IgG was found in 23.8% of patients with NCC, compared with 14.3% in subjects without NCC from a general rural population (P = 0.023) and 14.4% in subjects with neurological complaints without NCC (P = 0.027). Seropositive patients had a median age of 44 years compared with 30 years in seronegative patients (P <0.001). No significant differences in sex, region of residence, or liver enzyme values were found. Seropositivity to hepatitis E was frequent in this Peruvian population and higher in patients with NCC, suggesting shared common routes of infection.

International multicenter study comparing demographics, therapy and outcomes in bleeding from Mallory Weiss tears and peptic ulcers.

Background and study aims Mallory Weiss tears (MWTs) are relatively uncommon causes of upper gastrointestinal bleeding (UGIB), and patients are generally considered at low risk of poor outcome, although data are limited. There is uncertainty about use of endoscopic therapy. We aimed to describe and compare an international cohort of patients presenting with UGIB secondary to MWT and peptic ulcer bleeding (PUB). Patients and methods From an international dataset of patients undergoing endoscopy for acute UGIB at seven hospitals, we assessed patients with MWT bleeding, including the endoscopic stigmata and endoscopic therapy applied. We compared baseline parameters, rebleeding rate, and 30-day mortality between patients with MWT and PUB. Results A total of 3648 patients presented with UGIB, 125 of whom (3.4 %) had bleeding from a MWT. Those patients were younger (61 vs 69 years, P  < 0.0001) and more likely to be men (66 % vs 53 %, P  = 0.006) compared to the patients PUB. The most common endoscopic stigmata seen in MWTs were oozing blood (26 %) or clean base (26 %). Of the patients with MWT, 53 (42 %) received endoscopic therapy. Forty-eight of them (90 %) had epinephrine injections and 25 (48 %) had through-the-scope clips. The rebleeding rate was lower in MWT patients compared with PUB patients (4.9 % vs 12 %, P  = 0.016), but mortality was similar (5.7 vs 7.0 %, P  = 0.71). Conclusions Although patients presenting with MWT were younger, with a lower rebleeding rate, their mortality was similar to that of patients with PUB. Endoscopic therapy was applied to 42 % MWT patients, with epinephrine injection as the most common modality.

Serological evidence of hepatitis E virus infection in pigs from Northern Bulgaria.

The purpose of the present study was to investigate pigs in Northern Bulgaria for serological evidence of hepatitis E virus (HEV). Sera from 225 individuals from three industrial farms were tested for anti­HEV IgG antibodies. The overall HEV seroprevalence was 36% (81/225); weaners 6.8% (5/74); fattening pigs 38.7% (29/75) and in sows 61.8% (47/76). Compared to weaners, HEV positivity was higher in fattening pigs and sows: OR = 8.70 (95% CI: 3.14­24.12) and OR = 22.37 (95% CI: 8.07­61.96), respectively. These data confirm that HEV is endemic in pigs throughout Bulgaria, and can be a Public Health problem due to the transmission of HЕV to humans through the consumption of pork meat and pork products.

Control of Raw Pork Liver Sausage Production Can Reduce the Prevalence of HEV Infection.

After an acute hepatitis E (HEV) outbreak in Southern Switzerland, in January 2017 the local public health authorities started an active program of food chain control and public education. In this retrospective study, we analysed all laboratory-confirmed acute cases of HEV infection diagnosed between 2014 and 2020. In the period before the public health intervention, the number of cases increased steadily from 2014 (4 of 40 tests, 10%) reaching a peak in the last quarter of 2016 (42 of 285 tests, 14.7 %). Afterwards, the number of positive cases decreased steadily, reaching its lowest value (0.3%) in the second quarter of 2019. There was a statistically significant difference between the frequency of positive cases and period of testing, i.e., before and after the introduction of the public health interventions. Our study shows that active public health measures to control sausages containing raw pork liver can reduce the prevalence of HEV infection.

ABC score: a new risk score that accurately predicts mortality in acute upper and lower gastrointestinal bleeding: an international multicentre study.

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.

Hepatitis A and Hepatitis E: Clinical and Epidemiological Features, Diagnosis, Treatment, and Prevention.

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.

Mortality and morbidity of locally acquired hepatitis E in the national Scottish cohort: a multicentre retrospective study.

BACKGROUND: Hepatitis E virus (HEV) is the most common acute viral hepatitis in Scotland. Little is known about the burden of morbidity and mortality, which can be high in chronic liver disease or immunocompromised states. AIMS: To record the morbidity and mortality of HEV in Scotland. METHODS: Demographic, clinical and laboratory data were collected retrospectively from all cases of HEV reported to virology departments across nine NHS health boards, between January 2013 and January 2018. RESULTS: Five hundred and eleven cases were included (Mean age 62, 64% male). 58 (11%) cases had pre-existing cirrhosis and 110 (21%) had diabetes. Three hundred and three patients required admission (59%), totalling 2747 inpatient bed days. Seventeen (3.3%) HEV-related deaths were recorded. Factors that predicted mortality included haematological malignancy (OR 51.56, 95% CI 3.40-782.83, P = 0.005), cirrhosis (OR 41.85, 95% CI 2.85-594.16, P = 0.006), higher serum bilirubin (OR 1.01, 95% CI 1.01-1.02, P = 0.011) and chronic HEV infection (OR 0.02, 95% CI 0.02-0.28, P < 0.001). HEV infection affected 35 transplant patients of 106 total immunosuppressed patients (21%). Of these, 25 patients received Ribavirin therapy with a sustained virological remission of 76%. Thirty-five (6.7%) patients developed acute or acute-on-chronic liver failure with two requiring transplant. Thirty-seven (7.2%) patients reported neurological complications with 10 developing neuralgic amyotrophy, 6 Guillain-Barré and 2 encephalitis. Forty-four (8.6%) patients developed acute kidney injury. CONCLUSION: In Scotland, HEV causes a significant burden of inpatient admissions, organ failure and death. Cirrhosis and haematological malignancy are significant predictors of mortality. Neurological and renal complications occur in a significant minority.

MAP(ASH): A new scoring system for the prediction of intervention and mortality in upper gastrointestinal bleeding.

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.

The Shock Index is not accurate at predicting outcomes in patients with upper gastrointestinal bleeding.

BACKGROUND: Acute upper gastrointestinal bleeding (UGIB) remains a major cause of hospital admission worldwide. The recent UK National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report on severe gastrointestinal bleeding used the Shock Index to assess bleeding severity and found an association between Shock Index and mortality. However, this has never been prospectively validated as a predictor of outcome in UGIB. AIMS: To compare the Shock Index with existing pre-endoscopic UGIB risk scores in predicting outcomes after UGIB METHODS: In an international, prospective study of 3012 consecutive patients with UGIB, we compared the Shock Index with existing scores including the Glasgow Blatchford score (GBS), admission Rockall score, AIMS65, and the newly described "ABC" score. Pre-determined endpoints were need for major (≥4 units red cells) transfusion, need for endoscopic therapy and 30-day mortality. RESULTS: The Shock Index was inferior to the GBS in predicting need for major transfusion (area under the receiver operator characteristic curve [AUROC] 0.655 vs 0.836, P < 0.001) and need for endotherapy (AUROC 0.606 vs 0.747, P < 0.001). The Shock Index was inferior to all other scores for 30-day mortality: for example, AUROC 0.611 vs 0.863 for ABC score (P < 0.001). Adding the Shock Index to the ABC score did not improve accuracy of the ABC score in predicting mortality (AUROC 0.864 vs 0.863, P = 0.95). CONCLUSION: The Shock Index performed poorly with AUROCs <0.66 and was inferior to existing pre-endoscopy scores at predicting major clinical endpoints after UGIB. We found no clear evidence that the Shock Index is clinically useful at predicting outcomes in UGIB. [Correction added on 20 December 2019, after first online publication: Summary section has been changed for clarification.].

Locally acquired hepatitis E virus in Marche Italy: Clinical/laboratory features and outcome.

BACKGROUND AND AIMS: Hepatitis E Virus is endemic in Europe with increasing numbers of cases in recent years, also in Italy where this phenomenon has hitherto been modest. The aim of this study was to document the clinical features/natural history of locally acquired hepatitis E in our territory and explore factors which determine adverse outcome. METHODS: Retrospective study of patients with locally-acquired HEV (hepatitis E virus) in Marche, Italy (2011-2019). RESULTS: 1189 patients were tested for HEV with 89 confirmed cases. 81 (6.8%) had locally acquired infection; 54 (66%) were male (mean age 55.5 years) and 32 (39.5%) had active co-morbidities. 41 cases were viraemic (all HEV-3 (HEV genotype 1,2,3,4)); acute infection was found in 79 and chronic infection in 2. Forty-five cases (55%) required admission to hospital, for a total of 785 days. 4 patients developed acute on-chronic liver failure, 6 developed acute kidney injury and 8 died: all had active comorbidities. Univariate analysis showed that bilirubin, INR, immunosuppression, cirrhosis and diabetes were associated with death. On multivariant analysis the only predictor of death was the presence of diabetes (p = 0.04). CONCLUSIONS: Hepatitis E in Marche Italy is mostly locally acquired and caused by HEV-3 that impacts on the morbidity and mortality particularly for fragile patients.

Validation of a Machine Learning Model That Outperforms Clinical Risk Scoring Systems for Upper Gastrointestinal Bleeding.

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.

Hepatitis E: an underestimated emerging threat.

Hepatitis E virus (HEV) is the most common cause of viral hepatitis in the world. It is estimated that millions of people are infected every year, resulting in tens of thousands of deaths. However, these estimates do not include industrialized regions and are based on studies which employ assays now known to have inferior sensitivity. As such, this is likely to represent a massive underestimate of the true global burden of disease. In the developing world, HEV causes large outbreaks and presents a significant public-health problem. Until recently HEV was thought to be uncommon in industrialized countries, and of little relevance to clinicians in these settings. We now know that this is incorrect, and that HEV is actually very common in developed regions. HEV has proved difficult to study in vitro, with reliable models only recently becoming available. Our understanding of the lifecycle of HEV is therefore incomplete. Routes of transmission vary by genotype and location: endemic regions experience large waterborne epidemics, while sporadic cases in industrialized regions are zoonotic infections likely spread via the food chain. Both acute and chronic infection has been observed, and a wide range of extrahepatic manifestations have been reported. This includes neurological, haematological and renal conditions. As the complete clinical phenotype of HEV infection is yet to be characterized, a large proportion of cases go unrecognized or misdiagnosed. In many cases HEV infection does not feature in the differential diagnosis due to a lack of knowledge and awareness of the disease amongst clinicians. In combination, these factors have contributed to an underestimation of the threat posed by HEV. Improvements are required in terms of recognition and diagnosis of HEV infection if we are to understand the natural history of the disease, improve management and reduce the burden of disease around the world.

Previous Use of Antithrombotic Agents Reduces Mortality and Length of Hospital Stay in Patients With High-risk Upper Gastrointestinal Bleeding.

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.

Hepatitis E seroprevalence in the Americas: A systematic review and meta-analysis.

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.

Transmission and Epidemiology of Hepatitis E Virus Genotype 3 and 4 Infections.

Following the introduction of robust serological and molecular tools, our understanding of the epidemiology of zoonotic hepatitis E virus (HEV) has improved considerably in recent years. Current thinking suggests that consumption of pork meat products is the key route of infection in humans, but it is certainly not the only one. Other routes of infection include environmental spread, contaminated water, and via the human blood supply. The epidemiology of HEV genotype (gt)3 and gt4 is complex, as there are several sources and routes of infection, and it is likely that these vary between and within countries and over time.

Hepatitis E virus (HEV) in Scotland: evidence of recent increase in viral circulation in humans.

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.

Seroprevalence of Hepatitis A Virus, Hepatitis E Virus, and Helicobacter pylori in Rural Communities of the Bolivian Chaco, 2013.

In the Bolivian Chaco, south-east of Bolivia, studies conducted over the past three decades reported hepatitis A virus (HAV) and Helicobacter pylori seroprevalences above 90% and 60%, respectively. Hepatitis E virus (HEV) prevalence was previously found to be 6-7% but is probably an underestimate because of the poor sensitivity of the assays used. In November 2013, we conducted a cross-sectional study of 263 healthy volunteers from two rural communities of the Bolivian Chaco, aiming to reassess HAV, HEV, and H. pylori seroprevalence 10-20 years following the previous surveys. Hepatitis A virus seroprevalence was 95%, with universal exposure after the first decade of life; HEV seroprevalence was considerably higher (31-35%) than that previously reported; H. pylori seroprevalence was 59%, with an age-dependent distribution. The high prevalence of these infections suggests that major efforts are still needed to reduce fecal-oral transmission and to improve human health in the Bolivian Chaco.