Hepatic Steatosis and Weight Gain During the Coronavirus Disease 2019 Pandemic Among People With Human Immunodeficiency Virus: Impact of Therapy With Tenofovir Alafenamide.

Background: Lockdown due to the coronavirus disease 2019 (COVID-19) pandemic led to increases in weight in part of the population. Weight gain leads to hepatic steatosis (HS). Antiretroviral treatment could also influence HS in people with human immunodeficiency virus (PWH). The impact of lockdown on HS in PWH is unknown. The aim of this study was to analyze the changes in HS, as measured by the controlled attenuation parameter (CAP), during the COVID-19 pandemic in PWH. Methods: This was a cohort study that included PWH who attended a tertiary care center in southern Spain from January 2018 to December 2021. The CAP was evaluated by transient elastography. Only those who had a valid CAP before and after March 2020 were included. HS was defined as CAP ≥248 dB/m. Results: Six hundred eighty PWH were attended and 488 (71.8%) were included. Two hundred and fourteen (43.9%) had HS at baseline and 239 (49%) at the end of the follow-up (P = .036). The median change in CAP among PWH taking tenofovir alafenamide (TAF) was 8.5 (interquartile range [IQR], -24 to 46.3) dB/m versus -4 (IQR, -35 to 27) dB/m among PWH receiving TAF-free regimens (P = .003). After multivariate analysis, adjusted by sex and age, weight gain (adjusted odds ratio [AOR], 1.09 [95% confidence interval {CI}, 1.05-1.14]; P < .001), TAF therapy (AOR, 1.59 [95% CI, 1.07-2.35]; P = .021), plasma triglycerides (AOR, 1.01 [95% CI, 1-1.01]; P < .001), and fasting blood glucose (AOR, 1.01 [95% CI, 1-1.02]; P = .027) were associated with HS at the end of follow-up. Conclusions: The frequency of HS increased during the COVID-19 pandemic among PWH. TAF is associated with HS development, regardless of metabolic factors.

Hepatic steatosis after switching to integrase inhibitor-based regimens does not parallel short-term weight gain.

We studied hepatic steatosis in people with HIV (PWH) who switched to an integrase inhibitor (INSTI)-based regimen. One hundred and fifty-four PWH were included. After 48 weeks, median (Q1-Q3) weight gain was 1.2 (-0.6 to 3.8) kg and median (Q1-Q3) controlled attenuation parameter (CAP) change was -4 (-33 to 27) dB/m. Weight gain was weakly correlated with CAP change [R2 95% confidence interval (CI) = 0.144 (-0.014 to 0.296); P = 0.074)]. Changes in hepatic steatosis after switching to INSTI-based regimens do not seem to parallel weight gain after 1 year.

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.

Oportunistic diagnosis based on age and hepatitis C virus clearance: an essential step to improve the overall health of the liver.

Back in January 2022, an EASL-Lancet Commission on the impact of liver disorders in the European region commissioned by the WHO demonstrated that this condition is, actually, the second leading cause of loss of labor years in Europe after ischemic heart disease (1). This is a very relevant piece of information since this is something that is going to impact the new generations of Europeans unless a significant change is made in public health policies. Despite the advances made over the last few years in hepatitis C virus clearance-understood as a significant reduction of morbidity and mortality associated with Hepatitis B and C viruses-there are still challenges ahead to improve liver health due to the high use of alcohol, and the inseparable triad obesity / diabetes mellitus / metabolic associated fatty liver disease. Also, access to healthcare for several population groups at risk of presenting higher rates of liver disease has become a problem.

Certification program of Addiction Centres for hepatitis C virus elimination in Spain. HepCelentes Project. / Programa de certificación de Centros de Adicciones para la eliminación del virus de la hepatitis C en España. Proyecto HepCelentes.

Microelimination strategies for the hepatitis C virus (HCV) in vulnerable populations, such as users of Addiction Centres (AC), are key for the elimination of hepatitis C. The aim of the HepCelentes project was to design a certification program for AC from the generation of a guide with the criteria to favour the prevention, diagnosis, control, and treatment of HCV in Spain. The project was structured in 4 phases: normalisation, implementation, certification, and communication. In the first phase, developed between July and December 2020, a Steering Committee was created (formed by representatives of scientific societies, healthcare professionals from AC, primary care centres and hospital units, and patient associations) that, from of an exhaustive bibliographic review, generated by consensus an accreditation guide for AC. The guide consists of 22 criteria (15 mandatory and 7 recommended) structured based on the requirements to be met by AC, justification for the selection, level of action (management, prevention, diagnosis and treatment/follow-up), measurement of the indicator, objective level to be achieved, evidence of compliance, clarifications to improve understanding, and mandatory / recommendation (depending on their relevance to achieve HCV elimination and its feasibility for implementation in real practice). The development of a certification system for the AC, based on consensus and coordination of multidisciplinary teams, is intended to favour the management of hepatitis C and its elimination in AC users, supporting the international, national, and regional elimination strategies.

Las estrategias de microeliminación del virus de la hepatitis C (VHC) en poblaciones vulnerables, como los usuarios de los centros de adicciones (CA), son fundamentales para lograr la eliminación de la hepatitis C. El objetivo del proyecto HepCelentes fue diseñar un programa de certificación para los CA, a partir de la generación de una guía con los criterios para favorecer la prevención, diagnóstico, control y tratamiento del VHC en España. El proyecto se estructuró en 4 fases: normalización, implementación, certificación y comunicación. En la primera fase, desarrollada entre julio y diciembre de 2020, se creó un Comité de Normalización (formado por representantes de sociedades científicas, profesionales sanitarios de CA, centros de atención primaria, unidades hospitalarias, y asociaciones de pacientes) que, a partir de una revisión bibliográfica exhaustiva, generó por consenso una guía de certificación de los CA. La guía consta de 22 criterios (15 obligatorios y 7 recomendados) estructurados en base a la definición del criterio, justificación de su selección, nivel de actuación (gestión, prevención, diagnóstico y tratamiento/seguimiento), fórmula de medición, nivel objetivo a alcanzar, evidencias de su cumplimiento, aclaraciones para mejorar su comprensión y obligatoriedad/recomendación (en función de la relevancia en la eliminación y capacidad de implementación). El desarrollo de un sistema de certificación para los CA, a partir del consenso y la coordinación de equipos multidisciplinares, pretende favorecer el manejo de la hepatitis C y su eliminación en los usuarios de los CA, apoyando las estrategias de eliminación internacionales, nacionales y autonómicas.

Similar CD4/CD8 Ratio Recovery After Initiation of Dolutegravir Plus Lamivudine Versus Dolutegravir or Bictegravir-Based Three-Drug Regimens in Naive Adults With HIV.

Background: The initiation of antiretroviral treatment based on a 2-drug regimen (2DR) with dolutegravir plus lamivudine has demonstrated non-inferior efficacy than dolutegravir-based three-drug regimens (3DR). We aimed to assess whether the treatment initiation with this 2DR has a different impact on the CD4/CD8 ratio recovery than INSTI-based 3DR. Methods: We emulated a target trial using observational data from the Spanish HIV Research Network cohort (CoRIS). The outcomes of interest were the normalization of the CD4/CD8 ratio at 48 weeks using three different cutoffs: 0.5, 1.0, and 1.5. We matched each participant who started 2DR with up to four participants who received 3DR. Subsequently, we fitted generalized estimating equation (GEE) models and used the Kaplan-Meier method for survival curves. Results: We included 485, 805, and 924 participants for cutoffs of 0.5, 1.0, and 1.5, respectively. At 48 weeks, 45% of participants achieved a CD4/CD8 ratio >0.5, 15% achieved a ratio >1.0, and 6% achieved a ratio >1.5. GEE models yielded a similar risk of reaching a CD4/CD8 ratio >0.5 (OR 1.00, 95% CI 0.67 - 1.50), CD4/CD8 >1.0 (OR 1.03, 95% CI 0.68 - 1.58), and CD4/CD8 >1.5 (OR 0.86, 95% CI 0.48 - 1.54) between both treatment strategies. There were no differences between 2DR and 3DR in the incidence ratio of CD4/CD8 ratio normalization at 0.5, 1.0 and 1.5 cut-offs. Conclusions: In this large cohort study in people with HIV, ART initiation with dolutegravir plus lamivudine vs. dolutegravir or bictegravir-based triple antiretroviral therapy showed no difference in the rates of CD4/CD8 normalization at 48 weeks.

Orthohepevirus C infection as an emerging cause of acute hepatitis in Spain: First report in Europe.

BACKGROUND & AIM: Hepatitis E virus (HEV) was considered the only member of the Hepeviridae family with zoonotic potential. Nevertheless, this consideration has been reassessed owing to several reported cases of acute and chronic hepatitis linked to the Orthohepevirus C genus. Because the circulation of Orthohepevirus C in rodents has been described worldwide, the risk of zoonotic transmission is plausibly global. METHODS: Orthohepevirus C RNA was retrospectively evaluated in 2 cohorts of patients in Spain. The first cohort included patients with acute hepatitis without etiological diagnosis after screening for hepatotropic virus infection. The second cohort included patients diagnosed with acute HEV infection, defined as positivity for anti-HEV-IgM antibodies and/or detectable HEV RNA in serum. RESULTS: Cohort 1 comprised 169 patients (64.4% male, median age 43 years) and cohort 2 comprised 98 individuals (68.3% male, median age 45 years). Of the individuals included in Cohort 1, two (1.18%; 95% CI 0.2-3.8) had detectable Orthohepevirus C RNA in serum. In Cohort 2, of the 98 included patients, 58 showed detectable HEV RNA, while 40 only showed positivity for IgM antibodies. Among those bearing only IgM antibodies, Orthohepevirus C RNA was detected in 1 (2.5%; 95% CI 0.06-13.1) individual. All strains were consistent with genotype C1. The infection resulted in mild self-limiting acute hepatitis in 2 patients. Infection caused severe acute hepatitis in the remaining patient who died as a result of liver and renal failure. CONCLUSIONS: We described 3 cases of Orthohepevirus C in patients with acute hepatitis, resulting in the first description of this infection in Europe. The prevalence obtained in our study suggests that Orthohepevirus C could be an emerging disease in Europe. LAY SUMMARY: We describe the first cases of acute hepatitis related to rat hepatitis E virus in Europe. The prevalence found in our study suggest that rat hepatitis E virus could be considered an emerging disease in Europe.

No association of a risk variant for severe COVID-19 with HIV protection in three cohorts of highly exposed individuals.

An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was inherited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection. We thus expected this allele to be over-represented in highly exposed individuals who remain uninfected (exposed seronegative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to detect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype status. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.

CD46 Genetic Variability and HIV-1 Infection Susceptibility.

CD46 is the main receptor for complement protein C3 and plays an important role in adaptive immune responses. CD46 genetic variants are associated with susceptibility to several infectious and autoimmune diseases. Additionally, CD46 function can be subverted by HIV-1 to evade attack by complement, a strategy shared by viruses of other families. We sought to determine the association between CD46 gene variants and HIV-1 acquired through intravenous drug use (IDU) and sexual routes (n = 823). Study subjects were of European ancestry and were HIV-1 infected (n = 438) or exposed but seronegative (n = 387). Genotyping of the rs2796265 SNP located in the CD46 gene region was done by allele-specific real-time PCR. A meta-analysis merging IDU and sexual cohorts indicates that the minor genotype (CC) was associated with increased resistance to HIV-1 infection OR = 0.2, 95% CI (0.07-0.61), p = 0.004. The HIV-1-protective genotype is correlated with reduced CD46 expression and alterations in the ratio of CD46 mRNA splicing isoforms.

Limited Value of Single Sampling for IgM Antibody Determination as a Diagnostic Approach for Acute Hepatitis E Virus Infection.

The objective was to evaluate the accuracy of a single determination of IgM antibodies for hepatitis E virus (HEV) diagnosis in patients with acute hepatitis. A prospective study included patients with suspicion of HEV infection, defined as individuals with acute hepatitis showing negative results for serological and molecular markers of other hepatitis viruses. All patients were evaluated for hepatitis E virus infection, including both IgM antibodies and viral RNA determinations. Hepatitis E virus infection was defined as positivity for any of these markers. A total of 182 patients were included in the study, of whom 68 (37.4%) were diagnosed with HEV infection. Of these, 29 (42.6%) were positive for both IgM and HEV RNA, 25 (36.8%) were positive only for IgM antibodies, and 14 (20.6%) were positive only for HEV RNA. Considering only those individuals who were positive for IgM antibodies, 54 of the 68 total cases (79.4%) could be identified, showing a percentage of false-negative individuals of 20.6%. The diagnostic algorithm of hepatitis E virus infection in patients with acute hepatitis should include the determination of both IgM antibodies and HEV RNA because single sampling for IgM antibody determination led to an important proportion of misdiagnosed cases. IMPORTANCE In immunocompetent patients with a suspicion of hepatitis E virus (HEV) infection, single IgM antibody testing is typically applied. In this prospective study, we aimed to evaluate the accuracy of three different HEV screening approaches in patients with acute hepatitis, including approaches based on IgM determination, HEV RNA detection, and the combination of both. Our study shows that any diagnostic algorithm for HEV infection in patients with acute hepatitis should be based on the determination of both markers (IgM antibodies and HEV RNA) because single sampling for IgM antibodies results in an unacceptable number of false-negative results (20%). According to our results, the determination of HEV RNA should not be limited to immunosuppressed individuals because a high proportion of cases could be misdiagnosed.

Drug-drug interactions between treatment specific pharmacotherapy and concomitant medication in patients with COVID-19 in the first wave in Spain.

Primary aim was to assess prevalence and severity of potential and real drug-drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) ('potential interactions') and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02-1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12-1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.

Long runs of homozygosity are associated with Alzheimer's disease.

Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer's disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [ßAVROH (CI 95%) = 0.070 (0.037-0.104); P = 3.91 × 10-5; ßFROH (CI95%) = 0.043 (0.009-0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10-16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (ß (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10-4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in whole-exome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability.

Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower Risk of Hepatocellular Carcinoma After Sustained Virological Response to Direct-acting Antivirals in Hepatitis C Infected Patients With Advanced Fibrosis.

BACKGROUND: The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). METHODS: Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. RESULTS: In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]: .08-.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5-24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01-1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01-1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11-.85). CONCLUSIONS: Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus / Efecto sobre la adherencia a medicaciones concomitantes tras el inicio del tratamiento con antivíricos de acción directa para el virus de la hepatitis C

INTRODUCTION: Many patients with hepatitis C virus (HCV) have associated comorbidities that require complex treatments. We sought to determine the impact of treatment with direct-acting antiviral agents (DAAs) for HCV on adherence to prescribed concomitant medications for associated comorbidities and to identify predictors of non-adherence to comedications. PATIENTS AND METHODS: HCV-infected patients treated with DAAs in a Spanish hospital between January 2015 and December 2016 and followed-up by the pharmacy unit were included in the study. Adherence to concomitant comedication prescribed before and during HCV therapy with DAAs was compared to adherence during the same number of weeks before DAA initiation. Demographic, clinical and pharmacotherapy variables were analyzed to determine factors associated with non-adherence. A multivariate regression model was created for prediction of non-adherence to concomitant medication. RESULTS: Data from 214 patients using prescribed concomitant therapies were analyzed. Significant reduction on adherence to comedications was observed after initiation of DAA treatment compared with a similar period before therapy initiation (29.9% vs. 36.9%, p = 0.032). The univariate analysis showed that polypharmacy and presence of vascular disease were associated negatively with adherence to concomitant medications (87.8%, p = 0.006 and 84.7%, p < 0.001, respectively). Multivariate analysis indicated that HIV/HBV coinfection was associated with adherence (OR 0.19; 95% CI 0.09-0.39), while polypharmacy was a predictor for non-adherence (OR 4.54; 95% CI 1.48-13.92). DISCUSSION: Adherence to concomitant medications decreases in HCV-infected patients when DAA therapy is initiated. Polypharmacy is a predictor for non-adherence, while HIV/HBV coinfection reduce non-adherence rates. Polymedicated patients on DAAs might benefit from close follow-up and educational programmes to improve their adherence

INTRODUCCIÓN: Muchos pacientes con virus de la hepatitis C (VHC) presentan comorbilidades que requieren tratamientos complejos. Queremos determinar el impacto del tratamiento con antivirales de acción directa (AAD) para el VHC en la adherencia a medicaciones concomitantes e identificar factores predictivos de no adherencia a comedicaciones. PACIENTES Y MÉTODOS: Pacientes tratados con AAD entre 2015 y 2016 se incluyeron en el estudio y se comparó su adherencia a medicaciones concomitantes antes y durante la terapia con AAD en un periodo de tiempo similar. Múltiples variables fueron analizadas para identificar factores asociados a la no-adherencia. Se creó un modelo de regresión multivariable para predecir la no adherencia a medicaciones concomitantes. RESULTADOS: Se analizaron datos de 214 pacientes en tratamientos concomitantes. Tras iniciar la terapia con AAD, la adherencia a las comedicaciones disminuyó respecto a la adherencia en ausencia de AAD (29,9% respecto al 36,9%; p = 0,032). El análisis univariante demostró que la polifarmacia y la enfermedad vascular estaban asociadas negativamente con la adherencia a las medicaciones concomitantes (87,8%, p = 0,006 y 84,7%, p < 0,001, respectivamente). El análisis multivariante indicó que la coinfección con VIH/VHB estaba asociada con la adherencia (OR: 0,19; IC 95%: 0,09-0,39), mientras que la polifarmacia era un predictor de no adherencia (OR: 4,54; IC 95%: 1,48-13,92). DISCUSIÓN: El inicio del tratamiento con AAD disminuye la adherencia a la comedicación en pacientes con VHC. La polifarmacia es predictor de no adherencia mientras que la coinfección con VIH/VHB la reduce. Aquellos pacientes polimedicados y en tratamiento con AAD podrían beneficiarse de un seguimiento estrecho para aumentar su adherencia

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus.

INTRODUCTION: Many patients with hepatitis C virus (HCV) have associated comorbidities that require complex treatments. We sought to determine the impact of treatment with direct-acting antiviral agents (DAAs) for HCV on adherence to prescribed concomitant medications for associated comorbidities and to identify predictors of non-adherence to comedications. PATIENTS AND METHODS: HCV-infected patients treated with DAAs in a Spanish hospital between January 2015 and December 2016 and followed-up by the pharmacy unit were included in the study. Adherence to concomitant comedication prescribed before and during HCV therapy with DAAs was compared to adherence during the same number of weeks before DAA initiation. Demographic, clinical and pharmacotherapy variables were analyzed to determine factors associated with non-adherence. A multivariate regression model was created for prediction of non-adherence to concomitant medication. RESULTS: Data from 214 patients using prescribed concomitant therapies were analyzed. Significant reduction on adherence to comedications was observed after initiation of DAA treatment compared with a similar period before therapy initiation (29.9% vs. 36.9%, p=0.032). The univariate analysis showed that polypharmacy and presence of vascular disease were associated negatively with adherence to concomitant medications (87.8%, p=0.006 and 84.7%, p<0.001, respectively). Multivariate analysis indicated that HIV/HBV coinfection was associated with adherence (OR 0.19; 95% CI 0.09-0.39), while polypharmacy was a predictor for non-adherence (OR 4.54; 95% CI 1.48-13.92). DISCUSSION: Adherence to concomitant medications decreases in HCV-infected patients when DAA therapy is initiated. Polypharmacy is a predictor for non-adherence, while HIV/HBV coinfection reduce non-adherence rates. Polymedicated patients on DAAs might benefit from close follow-up and educational programmes to improve their adherence.

Executive summary: Consensus document of the diagnosis, management and prevention of infection with the hepatitis E virus: Study Group for Viral Hepatitis (GEHEP) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) / Resumen ejecutivo: Documento de consenso del Grupo de Estudio de las Hepatitis Víricas perteneciente a la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica sobre el diagnóstico, manejo y prevención de la infección por el virus de la hepatitis E

Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis in both developed and developing countries. This infectious disease has a high prevalence and incidence in Europe. HEV infection has a greater clinical impact in vulnerable populations, such as immunosuppressed patients, pregnant women and patients with underlying liver disease. Therefore, the Study Group for Viral Hepatitis (Grupo de Estudio de Hepatitis Víricas, GEHEP) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, SEIMC) believed it very important to prepare a consensus document to help in decision-making regarding diagnosis, clinical and therapeutic management, and prevention of HEV infection

La infección por el virus de la hepatitis E (VHE) es una de las principales causas de hepatitis aguda tanto en países desarrollados como en vías de desarrollo, situándose como una enfermedad infecciosa de alta prevalencia e incidencia en Europa. La infección por el VHE tiene mayor impacto clínico en poblaciones especialmente vulnerables, como pacientes inmunodeprimidos, mujeres embarazadas y pacientes con hepatopatía base. Por todo ello, desde el Grupo de Estudio de las Hepatitis Víricas (GeHEP) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) se considera de gran relevancia la elaboración de un Documento de Consenso que sirva de ayuda en la toma de decisiones sobre el diagnóstico, manejo clínico-terapéutico y la prevención de la infección por el VHE

Executive summary: Consensus document of the diagnosis, management and prevention of infection with the hepatitis E virus: Study Group for Viral Hepatitis (GEHEP) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis in both developed and developing countries. This infectious disease has a high prevalence and incidence in Europe. HEV infection has a greater clinical impact in vulnerable populations, such as immunosuppressed patients, pregnant women and patients with underlying liver disease. Therefore, the Study Group for Viral Hepatitis (Grupo de Estudio de Hepatitis Víricas, GEHEP) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, SEIMC) believed it very important to prepare a consensus document to help in decision-making regarding diagnosis, clinical and therapeutic management, and prevention of HEV infection.