Recommendations for the integral diagnosis of chronic viral hepatitis in a single analytical extraction. / Recomendaciones para el diagnóstico integral de las hepatitis virales crónicas en una única extracción analítica.

The Spanish Society of Digestive Pathology (SEPD), the Spanish Association for the Study of the Liver (AEEH), the Spanish Society of Infections and Clinical Microbiology (SEIMC) and its Viral Hepatitis Study Group (GEHEP), and with the endorsement of the Alliance for the Elimination of Viral Hepatitis in Spain (AEHVE), have agreed on a document to carry out a comprehensive diagnosis of viral hepatitis (B, C and D), from a single blood sample; that is, a comprehensive diagnosis, in the hospital and/or at the point of care of the patient. We propose an algorithm, so that the positive result in a viral hepatitis serology (B, C and D), as well as human immunodeficiency virus (HIV), would trigger the analysis of the rest of the virus, including the viral load when necessary, in the same blood draw. In addition, we make two additional recommendations. First, the need to rule out a previous hepatitis A virus (VHA) infection, to proceed with its vaccination in cases where IgG-type studies against this virus are negative and the vaccine is indicated. Second, the determination of the HIV serology. Finally, in case of a positive result for any of the viruses analyzed, there must be an automated alerts and initiate epidemiological monitoring.

Current state of telemedicine in the field of Hepatology in Spain: challenges, threats and next steps to follow for an intelligent digital transformation.

Medicine and technology are constantly evolving. The COVID-19 pandemic has accelerated the development of the digitalization of the health sector and specifically of telemedicine. Through a structured bibliographic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology, in this work the concepts related to telemedicine, its application and the legal regulatory context are defined. With this information, some recommendations and codes of good practice are proposed for their effective implementation in the field of hepatology.

Protective measures against Omicron could be more effective than Evusheld in liver transplant recipients.

Evusheld (the combination of cilgavimab and tixagevimab, two long-lasting monoclonal antibodies against SARS-CoV-2) has been approved by the FDA as a pre-exposure treatment for COVID-19 in immunocompromised patients older than 12 years. However, this monoclonal antibody has been developed from SARS-CoV-2 variants that were predominant at the beginning of the pandemic, when Ómicron was not prevalent. Compared with other solid organ transplant recipients, liver transplant recipients have shown an excellent immune response to standard vaccination with three doses of the SARS-CoV-2 vaccine. In addition, this population has shown very good adherence to protective measures for the transmission of COVID-19 infection. Several studies have shown that the use of Evusheld is less effective against Ómicron than against other variants of SARS-CoV-2. In addition, in the post-hoc analysis, it appears to be a drug that increases cardiovascular risk. For these reasons, we believe that in liver transplant recipients is essential to prioritize vaccination and protective measures, rather than the use of Evusheld as pre-exposure prophylaxis.

Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B.

BACKGROUND AND AIMS: HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). METHODS: Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. RESULTS: Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04-0.67, p = 0.01). CONCLUSION: Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.

Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients.

The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although vaccines clearly have had a beneficial effect, there is still a high percentage of unprotected patients that develop the pathology, due to an ineffective immune response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in the activation of the immune system and its implications in viral infection. In this context, the present study postulates Neddylation, a reversible ubiquitin-like post-translational modification of proteins that control their stability, localization and activity, as a key regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase in global neddylation levels in COVID-19 in the serum of patients, which is particularly associated with the early response to infection. In addition, the results showed that overactivation of neddylation controls activation, proliferation, and response of peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Inhibition of neddylation, and the subsequent avoidance of activated PBMCs, reduces cytokine production, mainly IL-6 and MCP-1 and induce proteome modulation, being a critical mechanism and a potential approach to immunomodulate COVID-19 patients.

SARS-CoV-2 and Liver Transplant: How Has It Behaved in This Sixth Wave?

BACKGROUND: Since the declaration of a new variant of concern (VOC), Omicron, by the World Health Organization in November 2021, a quick spread has been documented worldwide, being the main VOC in the sixth wave in Spain. The Omicron variant has more transmissibility, lower virulence, and less risk of severe disease than previously described VOC. Here we analyze the current wave of severe acute respiratory syndrome coronavirus 2 infection in liver transplant recipients (LTRs). METHODS: A retrospective observational study of 355 LTRs was conducted in La Rioja and Cantabria regions of Spain. Epidemiological and clinical parameters were gathered on the basis of clinical records and telephone interviews. RESULTS: In the current wave of infection, a higher number of LTRs have been found to be infected than the sum of the previous 5 waves (30 versus 16 LTRs). Of the 30 infected LTRs, 29 (96.6%) had received 3 vaccine doses (mRNA based), in a median of 93 d (interquartile range, 86-108) before infection. Eight of 30 LTRs (24.0%) were asymptomatic and 21 LTRs (67.8%) were with mild symptoms with a mean duration of 4.6 d (interquartile range, 2.5-7), whereas in the unvaccinated LTRs, the symptoms were fever, nausea, vomiting, and diarrhea. Moreover, in the sixth wave, intrafamiliar transmission was the main route of infection (17/30; 56.6%), and nosocomial transmission was confirmed in 2 LTRs (6.6%). CONCLUSIONS: In our series, increased transmissibility of the Omicron variant was confirmed, including nosocomial infection, with a lower risk of severe disease in LTRs. These findings could be supported by the universal vaccination of LTRs and less virulence of the Omicron variant.

Vaccinate fast but leave no one behind: a call to action for COVID-19 vaccination in Spain.

During the first five months of 2021, Spain's COVID-19 vaccination campaign progressed slowly and failed to reach marginalised populations. Here, we discuss how, despite recent improvements, it remains important to further engage key stakeholders to ensure nobody is left behind.

Antibody response to the messenger RNA-1273 vaccine (Moderna) in liver transplant recipients.

Different reports have shown the clinical and serologic response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in preventing coronavirus disease 2019 (COVID-19) in the general population, but few studies have examined these responses in transplant recipients. We assessed the vaccine immunogenicity of two doses (100 µg) of the mRNA-1273 vaccine (Moderna) administered with a 28-day interval in liver transplant recipients (LTRs) at follow-up at the Marques de Valdecilla University Hospital. LTRs without a history of COVID-19 infection were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies directed against the spike protein (S) a median of 43 days after receiving the second Moderna vaccine dose. Clinical data, including immunosuppressive regimen and routine laboratory data, were obtained from the medical record of each patient up to 3 months before the date of the first vaccination. Factors associated with serologic response were evaluated through logistic regression. In total, 129 LTRs who had anti-S results were included. Most patients were men (n = 99; 76.7%) with a median age of 63 years (interquartile range, 56-68). Alcohol (43.4%) and chronic hepatitis C (18.6%) were the most frequent causes of liver transplantation. A positive anti-S IgG response was observed in 113 LTRs (87.6%; 95% confidence interval [CI], 80.8-92.2). A strong inverse relationship between mycophenolate mofetil use and serologic response was found (odds ratio, 0.07; 95% CI, 0.02-0.26; p = 0.001). Conclusion: Most LTRs develop an immunological response to the Moderna SARS-CoV-2 mRNA-based vaccine. An immunosuppressive regimen that includes mycophenolate predicts a weak serologic response.

Telemedicine, time to change the paradigm of hepatitis C management: improve access and reduce costs In reference to: Chronic viral hepatitis C micro-elimination program using telemedicine. The Mexican experience, by Pérez Hernández et al.

Hepatitis C (HCV) management has dramatically changed with the advent of direct-acting antivirals. Their high efficacy and safety are changing the paradigm of detection and treatment of patients with an active HCV infection. Following the latest guidelines, the path to elimination of hepatitis C will be achieved by simplifying management.

Impact of the COVID-19 lockdown on liver transplant recipients. A single center observational study.

BACKGROUND: the impact of the COVID-19 outbreak and lockdown on liver transplant (LT) patients remains unknown. The aim of this cross-sectional study was to assess the consequences of the COVID-19 pandemic on the physical and mental health of LT patients during the lockdown period. METHODS: a web-based questionnaire was emailed to 238 LT patients undergoing regular follow-up at our unit between August and October 2020. This pseudonymized survey explored demographic and lifestyle variables (i.e., eating and physical habits), disruptions in routine medical care, different dimensions of mental health, COVID-19-related mood and coping (worries/anxiety, depression, insomnia, fear of COVID, resilience, etc.) and health perception using different validated instruments. RESULTS: altogether, 48.7 % (116 of 238) LT recipients accepted to participate in the study, 104 of whom gave their consent to publish the data. The median age was 63 years. Up to 39.4 % presented worrying scores indicating moderate/severe generalized anxiety disorder (GAD), whereas 25.5 % exhibited moderate/severe insomnia and only 10.5 % moderate/severe depression. Forty patients (38.5 %) gained weight, 24 % experienced a worsening in their eating habits and 63.4 % referred to practicing less or much less exercise during the lockdown. Only 25 % perceived a worsening in the control of their chronic comorbidities. Missed medical appointments (0.9 %) or poor adherence to therapy (1.9 %) were exceptional. CONCLUSIONS: COVID-19 lockdown has negatively impacted the mental and physical health of LT patients. Long-term consequences remain unclear.

Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG

The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them;in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: • To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. • To protect all healthcare professionals against the risks of infection with SARS-CoV-2. • To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2. Resumen El artículo recoge el conjunto de medidas propuestas por la SEPD, la AEEH, GETECCU y la AEG que pretenden servir de ayuda a los servicios en su reincorporación a la actividad habitual. Hemos confeccionado una serie de recomendaciones prácticas respecto al manejo y a la reintroducción progresiva de la actividad asistencial. Estas recomendaciones están guiadas por la escasa y cambiante evidencia disponible y serán objeto de futuras actualizaciones, en base a las necesidades diarias y la disponibilidad del material fungible para adecuarse a las mismas;y se podrán implementar en cada servicio en función de la incidencia acumulada de SARS-CoV-2 en cada región y de la carga que la epidemia ha ocasionado en cada uno de los hospitales. Los objetivos generales de estas recomendaciones son: • Proteger a nuestros pacientes de los riesgos de la infección por SARS-CoV-2 y prestarles una atención de calidad. • Proteger a todos los profesionales sanitarios de los riesgos de la infección por SARS-CoV-2. • Recuperar el normal funcionamiento de nuestros servicios en un entorno de riesgo continuado de infección por SARS-CoV-2.

Changes in the concentration and composition of urban aerosols during the COVID-19 lockdown.

This work investigates the impact of COVID-19 restrictive measures on the mass concentrations of PM1 and PM10, and their chemical components (water-soluble ions, organic and elemental carbon, and major and trace metals) at an urban site in the western Mediterranean. The evolution of gaseous pollutants (NOx, O3 and some volatile organic compounds) was also analyzed. The concentrations measured during the lockdown in 2020 were compared to those obtained during the same period over the preceding five years. The average decrease in the levels of NOx and traffic-related volatile organic compounds was higher than 50 %, while O3 concentrations did not exhibit significant variations during the study period. Our results show that temporal variations in PM1 and PM10 concentrations were strongly affected by the frequency of Saharan dust events. When these episodes were excluded from the analysis period, a 35 % decrease in PM1 and PM10 levels was observed. Traffic restrictions during the lockdown led to important reductions in the concentrations of elemental carbon and metals derived from road dust (e.g. Ca and Fe) and break wear (e.g. Cu). Regarding secondary inorganic aerosols, nitrate showed the largest reductions as a consequence of the drop in local emissions of NOx.

COVID-19 and the digestive system: protection and management during the SARS-CoV-2 pandemic.

The purpose of this rapid review is to provide an update on the impact of SARS-CoV-2 infection on Gastroenterology and Hepatology departments, our patients, and our new way of working. The gastrointestinal tract and the liver are affected by SARS-CoV-2, especially in patients with immunosuppressive therapies. Patients with liver transplantation should be followed closely. Digestive endoscopy is a high-risk procedure for the transmission of SARS-CoV-2. While the pandemic lasts, we must adapt its indications and promote protective measures for patients and healthcare professionals alike. The COVID-19 pandemic has changed our priorities and the way we work, although we do not know what the repercussions will be after normality is reinstated.

Feasibility of large-scale population testing for SARS-CoV-2 detection by self-testing at home.

The simplicity and low cost of rapid point-of-care tests greatly facilitate large-scale population testing, which can contribute to controlling the spread of the COVID-19 virus. We evaluated the applicability of a self-testing strategy for SARS-CoV2 in a population-based, cross-sectional study in Cantabria, Spain, between April and May 2020. For the self-testing strategy, participants received the necessary material for the self-collection of blood and performance of a rapid antibody test using lateral flow immunoassay at home without the supervision of healthcare personnel. A total of 1,022 participants were enrolled. Most participants correctly performed the COVID-19 self-test the first time (91.3% [95% CI 89.4-92.9]). Only a minority of the participants (0.7%) needed the help of healthcare personnel, while 6.9% required a second kit delivery, for a total valid test result in 96.9% of the participants. Incorrect use of the self-test was not associated with the educational level, age over 65, or housing area. Prevalence of IgG antibodies against SARS-CoV2 for subjects with a valid rapid test result was 3.1% (95% CI 2.2-4.4), similar to the seroprevalence result obtained using a conventional approach carried out by healthcare professionals. In conclusion, COVID-19 self-testing should be considered as a screening tool.