Clinical epidemiology of non-alcoholic fatty liver disease in children and adolescents. The LiverKids: Study protocol.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is rapidly increasing alongside overweight and obesity, not only in adults but also in children and adolescents. It is unknown what impact the development of NAFLD in childhood may have in later life. The importance of early detection and treatment lies in its potential for progression to cirrhosis, liver cancer and liver-related death, as well as its associated extrahepatic comorbidities. Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP) is an effective, non-invasive and safe diagnostic method to estimate the degree of fibrosis and steatosis in the liver, but little is known about its applicability in the paediatric population. AIMS: 1) To assess the prevalence of significant liver fibrosis (Liver Stiffness Measurement (LSM) ≥6.5 kPa) using VCTE, and that of non-alcoholic fatty liver disease (≥225 dB/m) using CAP in children and adolescents. 2) To determine the optimal cut-off points of the CAP to achieve maximum concordance with the Magnetic Resonance Imaging (MRI) findings in the diagnosis of mild, moderate and severe NAFLD in children and adolescents. METHODS: Cross-sectional population-based study which will include 2,866 subjects aged between 9 and 16 years. Participants will undergo: anamnesis, physical examination, blood extraction, VCTE, MRI and questionnaires on socio-demographic data, personal and family medical history and lifestyle assessment. APPLICABILITY AND RELEVANCE: The study aims to establish the foundations for the use of VCTE in children and adolescents in order to achieve early diagnosis of NAFLD. Moreover, it will serve to understand in further detail the disease and to identify the risk groups of children and adolescents who may be at risk of developing it. Ultimately, this will help determine to which subgroups of the population we need to target resources for prevention and early detection of this entity, as well as possible intervention for its treatment. TRIAL REGISTRATION: The LiverKids study is registered on Clinicaltrials.gov (NCT05526274).

Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study.

BACKGROUND: Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. METHODS: We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). FINDINGS: We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. INTERPRETATION: The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. FUNDING: European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).

Dysglycemia in young women attenuates the protective effect against fatty liver disease.

Introduction: Sexual dimorphism has been reported in non-alcoholic fatty liver disease (NAFLD), similar to the sex differences evident with cardiovascular disease. Type 2 diabetes mellitus (T2D) significantly increases the risk and severity of NAFLD, but there is scarce information on whether T2D or altered glucose metabolism can modify the prevalence of NAFLD in men and women of reproductive age. Purpose: To investigate the relationship between age, sex and NAFLD in subjects with and without dysglycemia. Materials and methods: We analyzed 2,790 patients. NAFLD was characterized using established diagnostic criteria: one or more positive results on the fatty liver index and hepatic ultrasound. Liver fibrosis (liver stiffness measurement [LSM] ≥8.0 kPa) was assessed by Fibroscan®. For analysis purposes, we included both T2D and prediabetes under the predefined condition of dysglycemia. Results: The global prevalence of NAFLD was higher in men than in women (50% and 34%; P<0.001), and the prevalence increased with age in both sexes. Older women (≥ 50 years) had a higher prevalence than younger women (<50 years), both in the overall cohort and in non-dysglycemic subjects. In dysglycemic subjects, the prevalence of NAFLD was slightly higher in men (68% vs 61%, p=0.021); in younger subjects, there were no differences in the prevalence of NAFLD between men and women (68% vs 64%, respectively; p=0.635). We found an interaction between dysglycemia and female sex (odds ratio [OR] 1.6 95% confidence interval [CI] 1.0-2.4, p=0.030), and between and age ≥50 years (OR 0.6, 95% CI 0.3-1.0, p=0.046). The global prevalence of LSM ≥8.0 kPa was higher in men compared with women (8% vs 4%; p< 0.001). This prevalence increased with age, mainly in men. We did not find any association between liver fibrosis and age and gender. Conclusions: While the global prevalence of NAFLD is higher in men than in women across all ages, younger women with dysglycemia have a similar risk of developing NAFLD as men of a similar age. Therefore, the presence of dysglycemia may erase the protective effect of female sex against fatty liver disease.

Abdominal obesity and dsyglycemia are risk factors for liver fibrosis progression in NAFLD subjects: A population-based study.

Objective: To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia. Material and Methods: A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively. Results: Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa. Conclusions: In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD.

Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population.

BACKGROUND & AIMS: Fibrosis-4 (FIB-4) and the nonalcoholic fatty liver disease fibrosis score (NFS) are the 2 most popular noninvasive blood-based serum tests proposed for widespread fibrosis screening. We therefore aimed to describe the accuracy of FIB-4 and NFS to detect elevated liver stiffness as an indicator of hepatic fibrosis in low-prevalence populations. METHODS: This study included a total of 5129 patients with concomitant measurement of FIB-4, NFS, and liver stiffness measurement (LSM) by Fibroscan (Echosens, France) from 5 independent population-based cohorts from Spain, Hong Kong, Denmark, England, and France; 3979 participants from the general population and 1150 from at-risk cohorts due to alcohol, diabetes, or obesity. We correlated LSM with FIB-4 and NFS, and calculated pre- and post-test predictive values of FIB-4 and NFS to detect elevated LSM at 8 kPa and 12 kPa cutoffs. The mean age was 53 ± 12 years, the mean body mass index was 27 ± 5 kg/m2, and 2439 (57%) were women. One in 10 patients (552; 11%) had liver stiffness ≥8 kPa, but 239 of those (43%) had a normal FIB-4, and 171 (31%) had normal NFS. The proportion of false-negatives was higher in at-risk patients than the general population. FIB-4 was false-negative in 11% of diabetic subjects, compared with 2.5% false-negatives with NFS. Waist circumference outperformed FIB-4 and NFS for detecting LSM ≥8 kPa in the general population. Almost one-third (28%-29%) of elevated FIB-4/NFS were false-positive in both the general population and at-risk cohorts. CONCLUSIONS: FIB-4 and NFS are suboptimal for screening purposes due to a high risk of overdiagnosis and a non-negligible percentage of false-negatives, especially in patients with risk factors for chronic liver disease. Waist circumference emerged as a potential first step to identify patients at risk for liver fibrosis in the general population.

Atherogenic dyslipidemia, but not hyperglycemia, is an independent factor associated with liver fibrosis in subjects with type 2 diabetes and NAFLD: a population-based study.

OBJECTIVE: To investigate the prevalence and risks factors associated with the presence of liver fibrosis in subjects with nonalcoholic fatty liver disease (NAFLD) with and without type 2 diabetes mellitus (T2D). DESIGN AND METHODS: This study was part of a population-based study conducted in the Barcelona metropolitan area among subjects aged 18-75 years old. Secondary causes of steatosis were excluded. Moderate-to-advanced liver fibrosis was defined as a liver stiffness measurement (LSM) ≥ 8.0 kPa assessed by transient elastography. RESULTS: Among 930 subjects with NAFLD, the prevalence of moderate-to-advanced liver fibrosis was higher in subjects with T2D compared those without (30.8% vs 8.7%). By multivariable analysis, one of the main factors independently associated with increased LSM in subjects with NAFLD was atherogenic dyslipidemia but only in those with T2D. The percentage of subjects with LSM ≥ 8.0 kPa was higher in subjects with T2D and atherogenic dyslipidemia than in those with T2D without atherogenic dyslipidemia both for the cut-off point of LSM ≥8.0 kPa (45% vs 24% P = 0.002) and ≥13 kPa (13% vs 4% P = 0.020). No differences were observed in the prevalence of LSM ≥8.0 kPa regarding glycemic control among NAFLD-diabetic subjects. CONCLUSIONS: Factors associated with moderate-to-advanced liver fibrosis in NAFLD are different in subjects with and without T2D. Atherogenic dyslipidemia was associated with the presence of moderate-to-advanced liver fibrosis in T2D with NAFLD but not in non-diabetic subjects. These findings highlight the need for an active search for liver fibrosis in subjects with T2D NAFLD and atherogenic dyslipidemia.

Interaction between metabolic syndrome and alcohol consumption, risk factors of liver fibrosis: A population-based study.

BACKGROUND AND AIMS: Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort. METHODS: The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE). RESULTS: Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers. CONCLUSION: MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.

Relación entre el hipotiroidismo y el hígado graso no alcohólico en una población española / Relationship between hypothyroidism and non-alcoholic fatty liver disease in the Spanish population

Introducción: El hígado graso no alcohólico (HGNA) es la enfermedad hepática más prevalente en los países desarrollados y se considera el componente hepático del síndrome metabólico (SM). Últimamente el hipotiroidismo se ha asociado al HGNA, pero nunca se ha estudiado en nuestro entorno. Objetivos: Analizar la relación entre hipotiroidismo (clínico y subclínico) y HGNA. Conocer la asociación de SM con HGNA e hipotiroidismo. Metodología: Estudio transversal, retrospectivo, poblacional en sujetos ≥45 años procedentes de centros de atención primaria de Cataluña e incluidos en la base de datos SIDIAP. Los datos fueron recogidos entre 2009 y 2013. Variables: datos sociodemográficos, comorbilidades, hábitos tóxicos, exploración física, analítica y diagnóstico de SM. Se llevó a cabo un análisis descriptivo y la aplicación de pruebas estadísticas para la comparación de variables. Resultados: Muestra de 10.116 individuos con edad media de 61 (10) años y predominio del sexo femenino (63,6%). La prevalencia de hipotiroidismo fue del 9,1%, sin encontrar diferencias significativas según la presencia de HGNA (p=0,631). El hipotiroidismo se asoció a niveles más elevados de triglicéridos y mayor prevalencia de obesidad (p=0,003). Se detectó mayor alteración de la AST en los individuos con valores incrementados de TSH (p=0,012) y disminuidos de T4L (p=0,037). Las alteraciones en los niveles de hormonas tiroideas no se vincularon con mayor prevalencia de HGNA (TSH p=0,072 y T4L p=0,447). El hipotiroidismo no se asoció como factor de riesgo para el desarrollo de HGNA (OR 0,75; IC 95%: 0,39-1,44; p=0,38). Conclusiones: No se ha demostrado asociación entre el hipotiroidismo y el HGNA. Se necesitan estudios prospectivos para esclarecer la relación entre ambas enfermedades

Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries and is considered the hepatic component of metabolic syndrome (MetS). Recently hypothyroidism has been associated with NAFLD but has never been studied in Spain. Objectives: To analyze the relationship between hypothyroidism (clinical and subclinical) and NAFLD. To determine the association between MetS with NAFLD and hypothyroidism. Methods: Cross-sectional, retrospective, population study in subjects ≥45 years from primary care centres in Catalonia included in the SIDIAP database. The data was collected between 2009 and 2013. Variables: socio-demographic data, comorbidities, toxic habits, physical examination, analytical tests and diagnosis of MetS. Descriptive analysis and application of statistical tests for the comparison of variables. Results: Sample of 10,116 individuals with a mean age of 61(10) and a predominance of females (63.6%). The prevalence of hypothyroidism was 9.1%, with no significant differences according to the presence of NAFLD (p=.631). Hypothyroidism was associated with higher triglyceride levels and a greater prevalence of obesity (p=.003). Greater alteration of AST was detected in individuals with elevated TSH (p=.012) and decreased levels of T4L (p=.037). Alterations in thyroid hormone levels were not associated with a higher prevalence of NAFLD (TSH p=.072 and T4L p=.447). Hypothyroidism was not considered a risk factor for the development of NAFLD (OR .75; 95% CI: .39-1.44; p=.38). Conclusions: No association was found between hypothyroidism and NAFLD. Prospective studies are needed to clarify a possible relationship between these two diseases

Relationship between hypothyroidism and non-alcoholic fatty liver disease in the Spanish population. / Relación entre el hipotiroidismo y el hígado graso no alcohólico en una población española.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries and is considered the hepatic component of metabolic syndrome (MetS). Recently hypothyroidism has been associated with NAFLD but has never been studied in Spain. OBJECTIVES: To analyze the relationship between hypothyroidism (clinical and subclinical) and NAFLD. To determine the association between MetS with NAFLD and hypothyroidism. METHODS: Cross-sectional, retrospective, population study in subjects ≥45 years from primary care centres in Catalonia included in the SIDIAP database. The data was collected between 2009 and 2013. VARIABLES: socio-demographic data, comorbidities, toxic habits, physical examination, analytical tests and diagnosis of MetS. Descriptive analysis and application of statistical tests for the comparison of variables. RESULTS: Sample of 10,116 individuals with a mean age of 61(10) and a predominance of females (63.6%). The prevalence of hypothyroidism was 9.1%, with no significant differences according to the presence of NAFLD (p=.631). Hypothyroidism was associated with higher triglyceride levels and a greater prevalence of obesity (p=.003). Greater alteration of AST was detected in individuals with elevated TSH (p=.012) and decreased levels of T4L (p=.037). Alterations in thyroid hormone levels were not associated with a higher prevalence of NAFLD (TSH p=.072 and T4L p=.447). Hypothyroidism was not considered a risk factor for the development of NAFLD (OR .75; 95% CI: .39-1.44; p=.38). CONCLUSIONS: No association was found between hypothyroidism and NAFLD. Prospective studies are needed to clarify a possible relationship between these two diseases.

Resultados en España de la encuesta de la Sociedad Europea de Cardiología sobre terapia de resincronización cardiaca (CRT-Survey II) / Spanish results of the Second European Cardiac resynchronization therapy survey (CRT-Survey II)

Introducción y objetivos: Se describen los resultados en España de la segunda encuesta de la Sociedad Europea de Cardiología sobre terapia de resincronización cardiaca (CRT-Survey II) y se comparan con los de los demás países participantes. Métodos: Pacientes a los que se implantó un dispositivo de terapia de resincronización cardiaca entre octubre de 2015 y diciembre de 2016 en 36 centros participantes. Se recogieron datos sobre las características basales de los pacientes y del implante, y un seguimiento a corto plazo hasta el alta hospitalaria. Resultados: La tasa de éxito del implante fue del 95,9%. La mediana [intervalo intercuartílico] de implantes anuales/centro en España fue significativamente menor que en los demás países participantes: 30 [21-50] frente a 55 [33-100] implantes/año (p=0,00003). En los centros españoles hubo una menor proporción de pacientes de edad ≥ 75 años (el 27,9 frente al 32,4%; p=0,0071), una mayor proporción de pacientes en clase funcional II de la New York Heart Association (el 46,9 frente al 36,9%; p <0,00001) y un mayor porcentaje de pacientes con criterios electrocardiográficos de bloqueo de rama izquierda (el 82,9 frente al 74,6%; p <0,00001). La media de la estancia hospitalaria fue menor en los centros españoles (5,8+/-8,5 frente a 6,4+/-11,6; p <0,00001) y una mayor proporción de pacientes recibieron un cable de ventrículo izquierdo cuadripolar (el 74 frente al 56%; p <0,00001) y fueron seguidos a distancia (el 55,8 frente al 27,7%; p <0,00001). Conclusiones: La encuesta CRT-Survey II muestra que en España hay una menor proporción de pacientes de 75 o más años que reciben un dispositivo de terapia de resincronización cardiaca, una mayor proporción de pacientes en clase funcional II de la New York Heart Association, con bloqueo completo de la rama izquierda del haz de His y con seguimiento a distancia, con estancias hospitalarias significativamente menores

Introduction and objectives: We describe the results for Spain of the Second European Cardiac Resynchronization Therapy Survey (CRT-Survey II) and compare them with those of the other participating countries. Methods: We included patients undergoing CRT device implantation between October 2015 and December 2016 in 36 participating Spanish centers. We registered the patients' baseline characteristics, implant procedure data, and short-term follow-up information until hospital discharge. Results: Implant success was achieved in 95.9%. The median [interquartile range] annual implantation rate by center was significantly lower in Spain than in the other participating countries: 30 implants/y [21-50] vs 55 implants/y [33-100]; P=.00003. In Spanish centers, there was a lower proportion of patients ≥ 75 years (27.9% vs 32.4%; P=.0071), a higher proportion in NYHA class II (46.9% vs 36.9%, P <.00001), and a higher percentage with electrocardiographic criteria of left bundle branch block (82.9% vs 74.6%; P <.00001). The mean length of hospital stay was significantly lower in Spanish centers (5.8+/-8.5 days vs 6.4+/-11.6; P <.00001). Spanish patients were more likely to receive a quadripolar LV lead (74% vs 56%, P <.00001) and to be followed up by remote monitoring (55.8% vs 27.7%; P <.00001). Conclusions: The CRT-Survey II shows that, compared with other participating countries, fewer patients in Spain aged ≥ 75 years received a CRT device, while more patients were in New York Heart Association functional class II and had left bundle branch block. In addition, the length of hospital stay was shorter, and there was greater use of quadripolar LV leads and remote CRT monitoring

Prevalence of Early Chronic Kidney Disease and Main Associated Factors in Spanish Population: Populational Study.

The aim of this study was to determine the prevalence of early chronic kidney disease (EKD) (stages 1 and 2) and the factors associated. This was a populational study including individuals from 18-75 years randomly selected from 18 Primary Healthcare centers in the area of Barcelonès Nord and Maresme (Catalunya, Spain). Variables: anamnesis, physical examination, blood pressure, and analysis. EKD was defined with by a glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 and albumin/creatinine ratio (ACR) ≥17 mg/g in men and ≥25 mg/g in women confirmed with two determinations. 2871 individuals: 43% men, mean age 55 years (19-75), 32.2% obese, 50.5% abdominal obesity, 21.1% hypertensive, and 10.6% diabetic. Prevalence of EKD: With one determination 157 individuals (5.5%), 110 men (9%) and 47 women (2.8%); with two determinations 109 individuals (3.8%), 85 men (7%), and 24 women (1.5%). Factors independently associated with the multivariate logistic regression model: Man (OR 3.35), blood pressure ≥ 135/85 mmHg (OR 2.29), BMI ≥ 30 kg/m2 (OR 2.48), glycemia ≥ 100 mg/dL (OR 1.73), smoker (OR 1.67) and age (OR 1.04). The prevalence varies if the diagnosis is established based on one or two analytical determinations, overestimated if only one determination is made and depends on the value chosen to define urine albumin excretion.

Transient elastography for screening of liver fibrosis: Cost-effectiveness analysis from six prospective cohorts in Europe and Asia.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease and alcohol-related liver disease pose an important challenge to current clinical healthcare pathways because of the large number of at-risk patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography (TE) as a screening method to detect liver fibrosis in a primary care pathway. METHODS: Cost-effectiveness analysis was performed using real-life individual patient data from 6 independent prospective cohorts (5 from Europe and 1 from Asia). A diagnostic algorithm with conditional inference trees was developed to explore the relationships between liver stiffness, socio-demographics, comorbidities, and hepatic fibrosis, the latter assessed by fibrosis scores (FIB-4, NFS) and liver biopsies in a subset of 352 patients. We compared the incremental cost-effectiveness of a screening strategy against standard of care alongside the numbers needed to screen to diagnose a patient with fibrosis stage ≥F2. RESULTS: The data set encompassed 6,295 participants (mean age 55 ±â€¯12 years, BMI 27 ±â€¯5 kg/m2, liver stiffness 5.6 ±â€¯5.0 kPa). A 9.1 kPa TE cut-off provided the best accuracy for the diagnosis of significant fibrosis (≥F2) in general population settings, whereas a threshold of 9.5 kPa was optimal for populations at-risk of alcohol-related liver disease. TE with the proposed cut-offs outperformed fibrosis scores in terms of accuracy. Screening with TE was cost-effective with mean incremental cost-effectiveness ratios ranging from 2,570 €/QALY (95% CI 2,456-2,683) for a population at-risk of alcohol-related liver disease (age ≥45 years) to 6,217 €/QALY (95% CI 5,832-6,601) in the general population. Overall, there was a 12% chance of TE screening being cost saving across countries and populations. CONCLUSIONS: Screening for liver fibrosis with TE in primary care is a cost-effective intervention for European and Asian populations and may even be cost saving. LAY SUMMARY: The lack of optimized public health screening strategies for the detection of liver fibrosis in adults without known liver disease presents a major healthcare challenge. Analyses from 6 independent international cohorts, with transient elastography measurements, show that a community-based risk-stratification strategy for alcohol-related and non-alcoholic fatty liver diseases is cost-effective and potentially cost saving for our healthcare systems, as it leads to earlier identification of patients.

Spanish Results of the Second European Cardiac Resynchronization Therapy Survey (CRT-Survey II).

INTRODUCTION AND OBJECTIVES: We describe the results for Spain of the Second European Cardiac Resynchronization Therapy Survey (CRT-Survey II) and compare them with those of the other participating countries. METHODS: We included patients undergoing CRT device implantation between October 2015 and December 2016 in 36 participating Spanish centers. We registered the patients' baseline characteristics, implant procedure data, and short-term follow-up information until hospital discharge. RESULTS: Implant success was achieved in 95.9%. The median [interquartile range] annual implantation rate by center was significantly lower in Spain than in the other participating countries: 30 implants/y [21-50] vs 55 implants/y [33-100]; P=.00003. In Spanish centers, there was a lower proportion of patients ≥ 75 years (27.9% vs 32.4%; P=.0071), a higher proportion in New York Heart Association functional class II (46.9% vs 36.9%; P <.00001), and a higher percentage with electrocardiographic criteria of left bundle branch block (82.9% vs 74.6%; P <.00001). The mean length of hospital stay was significantly lower in Spanish centers (5.8±8.5 days vs 6.4±11.6; P <.00001). Spanish patients were more likely to receive a quadripolar LV lead (74% vs 56%; P <.00001) and to be followed up by remote monitoring (55.8% vs 27.7%; P <.00001). CONCLUSIONS: The CRT-Survey II shows that, compared with other participating countries, fewer patients in Spain aged ≥ 75 years received a CRT device, while more patients were in New York Heart Association functional class II and had left bundle branch block. In addition, the length of hospital stay was shorter, and there was greater use of quadripolar LV leads and remote CRT monitoring.

High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver Disease: A Population-Based Study.

BACKGROUND & AIMS: Liver fibrosis is the main determinant of long-term outcome in chronic liver diseases. Little is known about the prevalence of liver fibrosis in the general population. The aim of the study was to investigate the prevalence of liver fibrosis in the general adult population with unknown liver disease. METHODS: This was a population-based, cross-sectional study performed in the Barcelona metropolitan area. Subjects aged 18 to 75 years old were identified randomly from citizens included in the primary health care registry. Of 4866 subjects invited, 3076 participated (63.2%). Liver fibrosis was estimated by measuring liver stiffness (LS) with transient elastography (TE). Liver histology was assessed in 92 subjects with increased LS. RESULTS: Prevalence estimates of increased LS (≥6.8, ≥8.0, and ≥9.0 kPa) were 9.0%, 5.8%, and 3.6%, respectively. The etiology of liver disease was mainly nonalcoholic fatty liver disease (NAFLD), followed by alcohol risk consumption (consumption of ≥21 standard drinking units/wk in men and ≥14 standard drinking units/wk in women). Factors independently associated with increased LS were male sex, abdominal obesity, type 2 diabetes, serum glucose, high-density lipoprotein, and triglyceride levels. Subjects without risk factors for NAFLD or without alcohol risk consumption had a very low prevalence of increased LS. The best cut-off value of LS for significant liver fibrosis (F2-F4) was 9.2 kPa, with high sensitivity and specificity. TE was more accurate than alanine aminotransferase, NAFLD fibrosis score, or Fibrosis 4. An algorithm for screening for liver fibrosis using TE in the community setting is proposed. CONCLUSIONS: These findings show a high prevalence of silent liver disease with advanced fibrosis mainly related to NAFLD in adult European subjects without known liver disease. An LS value less than 9.2 kPa predicts the absence of significant liver fibrosis with high accuracy and could be used for screening purposes.

Adecuación y calidad de las ecografías abdominales solicitadas por los profesionales de medicina / Acceptability and quality of abdominal ultrasound studies requested by medical professionals

OBJETIVO: Evaluar la adecuación/calidad de las ecografías abdominales solicitadas por médicos de atención primaria de Barcelona, desarrollar una guía para la ecografía y evaluar su impacto en la adecuación. MÉTODOS: Diseño estudio en 2 fases, una descriptiva, retrospectiva, que evalúa la calidad/adecuación de las solicitudes (fase preintervención), y otra que evalúa el impacto en la calidad/adecuación gracias a la guía (fase postintervención). Sujetos: solicitudes de ecografías durante enero-junio del 2010 procedentes de 10 centros de AP y el mismo número de solicitudes provenientes de los mismos centros después de la intervención. Variables. Fase preintervención: motivo de la visita y petición; presencia de orientación diagnóstica; resultado de la ecografía; calidad/adecuación de la solicitud. Intervención: diseño de una guía mediante técnica grupo nominal y difusión de la guía en los mismos centros. Fase postintervención: 3 meses después de la difusión, analizar el mismo número de solicitudes evaluando las mismas variables que en la fase preintervención. RESULTADOS: Fase preintervención, 1.063 solicitudes, 52,4% mujeres, edad media 52±16 años (rango 11-94). Fase postintervención, 1.060 solicitudes, 57,6% mujeres, edad 54±17 años (rango 6-91). Principales motivos de petición: dolor abdominal/molestias 38,3% (preintervención) y 43,1% (postintervención). Orientación diagnóstica en el 14,5% (preintervención) y el 40,8% (postintervención). Resultado de ecografía normal en el 46,0% (preintervención) y el 42,3% (postintervención). Calidad de las solicitudes buena en el 42,7% (preintervención) y el 46,5% (postintervención). Adecuación de ecografía del 70,5% (preintervención) y del 94,1% (postintervención). A mayor calidad de la solicitud, mejor adecuación y mayor presencia de patología. CONCLUSIONES: La guía de la ecografía mejora la calidad de las solicitudes, la orientación diagnóstica y su adecuación

OBJECTIVE: To evaluate the acceptability/quality of abdominal ultrasound studies requested by primary care physicians in Barcelona; to develop ultrasound guidelines and assess their impact on acceptability. METHODS: Desing 2-phase study, one retrospective, descriptive phase evaluating the acceptability/quality of requests (pre-intervention phase) and another to assess the impact of guidelines on acceptability/quality (post-intervention phase). Subjects: Requests for ultrasound studies from January-June 2010 from 10 primary care centers and the same number of requests from the same centers after the intervention. Variables. Pre-intervention phase: reason for consultation and request; presence of diagnostic orientation; results of ultrasound; acceptability/quality of the request. Intervention: design guidelines using the nominal group technique, dissemination of guidelines in the same centers. Post-intervention phase: three months after dissemination analyze the same number of requests assessing the same variables included in the pre-intervention phase. RESULTS: Pre-intervention phase: 1,063 requests, 52.4% women, mean age 52±16 years (range 11-94). Post-intervention phase: 1,060 requests, 57.6% women, mean age 54±17 years (range 6-91). Main reasons for requests: abdominal pain/discomfort 38.3% (pre-intervention) and 43.1% (post-intervention). Diagnostic orientation in 14.5% (pre-intervention) and 40.8% (post-intervention). Normal ultrasound results in 46.0% (pre-intervention) and 42.3% (post-intervention). Good quality of requests in 42.7% (pre-intervention) and 46.5% (post-intervention). Acceptability of ultrasound: 70.5% (pre-intervention) and 94.1% (post-intervention). The better the quality of the request, the better the acceptability of the studies and the greater the number of pathological conditions identified. CONCLUSIONS: Guidelines for ultrasound improve the quality of requests, diagnostic orientation and acceptability of the studies

[Acceptability and quality of abdominal ultrasound studies requested by medical professionals]. / Adecuación y calidad de las ecografías abdominales solicitadas por los profesionales de medicina.

OBJECTIVE: To evaluate the acceptability/quality of abdominal ultrasound studies requested by primary care physicians in Barcelona; to develop ultrasound guidelines and assess their impact on acceptability. DESIGN: 2-phase study, one retrospective, descriptive phase evaluating the acceptability/quality of requests (pre-intervention phase) and another to assess the impact of guidelines on acceptability/quality (post-intervention phase). SUBJECTS: Requests for ultrasound studies from January-June 2010 from 10 primary care centers and the same number of requests from the same centers after the intervention. VARIABLES: Pre-intervention phase: reason for consultation and request; presence of diagnostic orientation; results of ultrasound; acceptability/quality of the request. INTERVENTION: design guidelines using the nominal group technique, dissemination of guidelines in the same centers. Post-intervention phase: three months after dissemination analyze the same number of requests assessing the same variables included in the pre-intervention phase. RESULTS: Pre-intervention phase: 1,063 requests, 52.4% women, mean age 52±16years (range 11-94). Post-intervention phase: 1,060 requests, 57.6% women, mean age 54±17years (range 6-91). Main reasons for requests: abdominal pain/discomfort 38.3% (pre-intervention) and 43.1% (post-intervention). Diagnostic orientation in 14.5% (pre-intervention) and 40.8% (post-intervention). Normal ultrasound results in 46.0% (pre-intervention) and 42.3% (post-intervention). Good quality of requests in 42.7% (pre-intervention) and 46.5% (post-intervention). Acceptability of ultrasound: 70.5% (pre-intervention) and 94.1% (post-intervention). The better the quality of the request, the better the acceptability of the studies and the greater the number of pathological conditions identified. CONCLUSIONS: Guidelines for ultrasound improve the quality of requests, diagnostic orientation and acceptability of the studies.

Marcadores no invasivos de fibrosis en el diagnóstico del hígado graso no alcohólico / Non-invasive markers of fibrosis in the diagnosis of non-alcoholic fatty liver disease

OBJETIVO: Analizar la utilidad de tres índices predictivos de fibrosis en la detección de hígado graso no alcohólico (HGNA) como método no invasivo en atención primaria. Diseño Estudio descriptivo de base poblacional, multicéntrico y transversal, procedentes de 25 Centros de Atención Primaria de la provincia de Barcelona. Participantes Individuos sanos entre 17-83 años seleccionados aleatoriamente a partir del Sistema Informático de Atención Primaria (SIAP).Método Anamnesis, exploración física, analítica para determinar los índices predictivos de fibrosis; HAIR (hipertensión arterial, resistencia a insulina, alaninaaminotransferas a); Fatty Liver Index (FLI) (índice de masa corporal, gammaglutamiltranspeptidasa, triglicéridos, perímetro abdominal) y Lipid Accumulation Product (LAP) (triglicéridos, perímetro abdominal), y ecografía abdominal. RESULTADOS: Setecientos dos individuos, 58% mujeres, edad media de 53±14 años. Un 30,8% tuvieron FLI positivo, 6,7% el HAIR y 15,5% el LAP, oscilando la concordancia entre los tres índices entre el 63,1% y el 84,9%, con índices kappa entre 0,18 y 0,50. Cumplían criterios ecográficos de HGNA 184 individuos representando una prevalencia de 26,29%. La prevalencia de HGNA en pacientes con índice FLI, HAIR y LAP positivo fue del 46,8%, 68,1% y 56,0% respectivamente. El índice con mayor sensibilidad para HGNA fue el FLI ≥ 60 con un 84%. La especificidad fue mayor para el HAIR y LAP con un 97% y 91% respectivamente. CONCLUSIONES: FLI, HAIR y LAP son muy prevalentes y se han mostrado como marcadores independientes para el diagnóstico de HGNA. La falta de concordancia entre estos índices, provoca la obtención de diferentes prevalencias siendo necesario unificar criterios para obtener un índice más útil para el diagnóstico de HGNA

OBJECTIVE: To analyze the utility of three indices to predict hepatic fibrosis in the detection of non-alcoholic fatty liver disease (NAFLD) as a non-invasive method in primary care. DESIGN: We performed a descriptive, cross-sectional, multicenter study with a populational base from 25 primary care centers in the province of Barcelona. PARTICIPANTS: Healthy individuals aged 17 to 83 years randomly selected from the Primary Care Computer System. METHODS: Medical history, physical examination, and blood analyses were used to determine the following predictive indices of fibrosis; HAIR (hypertension, alanine-aminotransferase, insulin resistance); Fatty Liver Index (FLI) (body mass index, gammaglutamyl-transpeptidase, triglycerides, abdominal perimeter) and Lipid Accumulation Product (LAP) (triglycerides, abdominal perimeter), and abdominal echography. RESULTS: We included 702 individuals; 58% were women and the mean age was 53±14 years. The FLI was positive in 30.8%, HAIR was positive in 6.7%, and LAP was positive in 15.5%. Agreement among the three indices ranged from 63.1% to 84.9%, with kappa indices between 0.18 and 0.50. A total of 184 individuals met the echographic criteria of NAFLD, representing a prevalence of 26.29%. The prevalence of NAFLD in patients with positive FLI, HAIR and LAP indices was 46.8%, 68.1% and 56%, respectively. The index with the greatest sensitivity for NAFLD was tFLI≥60 with 84%. Specificity was highest for HAIR and LAP with 97% and 91%, respectively. CONCLUSIONS: FLI, HAIR and LAP are highly prevalent and have been shown to be independent markers for the diagnosis of NAFLD. Because of the lack of concordance between the indices, different prevalences are obtained, thus requiring criteria to be unified in order to obtain a more useful index for the diagnosis of NAFLD. Because of the lack of concordance between the indices, different prevalences are obtained, thus requiring criteria to be unified in order to obtain a more useful index for the diagnosis of NAFLD

[Non-invasive markers of fibrosis in the diagnosis of non-alcoholic fatty liver disease]. / Marcadores no invasivos de fibrosis en el diagnóstico del hígado graso no alcohólico.

OBJECTIVE: To analyze the utility of three indices to predict hepatic fibrosis in the detection of non-alcoholic fatty liver disease (NAFLD) as a non-invasive method in primary care. DESIGN: We performed a descriptive, cross-sectional, multicenter study with a populational base from 25 primary care centers in the province of Barcelona. PARTICIPANTS: Healthy individuals aged 17 to 83 years randomly selected from the Primary Care Computer System. METHODS: Medical history, physical examination, and blood analyses were used to determine the following predictive indices of fibrosis; HAIR (hypertension, alanine-aminotransferase, insulin resistance); Fatty Liver Index (FLI) (body mass index, gammaglutamyl-transpeptidase, triglycerides, abdominal perimeter) and Lipid Accumulation Product (LAP) (triglycerides, abdominal perimeter), and abdominal echography. RESULTS: We included 702 individuals; 58% were women and the mean age was 53±14 years. The FLI was positive in 30.8%, HAIR was positive in 6.7%, and LAP was positive in 15.5%. Agreement among the three indices ranged from 63.1% to 84.9%, with kappa indices between 0.18 and 0.50. A total of 184 individuals met the echographic criteria of NAFLD, representing a prevalence of 26.29%. The prevalence of NAFLD in patients with positive FLI, HAIR and LAP indices was 46.8%, 68.1% and 56%, respectively. The index with the greatest sensitivity for NAFLD was tFLI≥60 with 84%. Specificity was highest for HAIR and LAP with 97% and 91%, respectively. CONCLUSIONS: FLI, HAIR and LAP are highly prevalent and have been shown to be independent markers for the diagnosis of NAFLD. Because of the lack of concordance between the indices, different prevalences are obtained, thus requiring criteria to be unified in order to obtain a more useful index for the diagnosis of NAFLD.

Radiofrequency catheter ablation of a right free-wall accessory pathway in dextrocardia with complete situs inversus.

An uncommon case of orthodromic atrioventricular reentrant tachycardia in a patient with dextrocardia and complete situs inversus is reported. There was no associated cardiac abnormality apart from the mirror image dextrocardia. An electrophysiological study and successful catheter ablation of a right free-wall concealed accessory pathway was performed. A simplified three-catheter technique from a femoral approach and monoplane fluoroscopy were used in a noncomplicated procedure of normal duration.