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Chronic liver disease; Fibrosis 4 score Malaltia hepàtica crònica; Puntuació de fibrosi 4 Enfermedad crónica del hígado; Puntuación de fibrosis 4 Liver disease is frequently asymptomatic, challenging early identification in the primary care setting. The fibrosis 4 (FIB4) index is a liver fibrosis biomarker that is a potential alternative to liver biopsy for diagnosing and managing liver disease. This study aimed to calculate the FIB4 index for screening individuals at high risk of liver disease at the community level. This was a retrospective real-world study analyzing blood and serum test results from a central laboratory. The primary outcome was the number of individuals within each risk category for hepatic fibrosis: high risk (FIB4 ≥ 3.25) and low risk (FIB4 < 1.3). The analysis included samples from 31,753 patients, of which 18,102 were aged 40 to 75 years. In these patients, the FIB4 index had been explicitly requested in 1852 (10.2%) cases and estimated ad hoc in the rest. Of the 263 (1.5%) cases with FIB4 ≥ 3.25, the FIB4 index was requested in 46 (17.5%), and 52 (19.8%) showed evidence of liver fibrosis in their medical records, while the rest did not report any data regarding liver fibrosis. FIB4 is a simple score that can play a role as a “red flag” for early identification of patients at high risk of advanced liver fibrosis and their referral to specialized care.

Background and objectives Psoriasis is a chronic immunoinflammatory skin disease very frequent in the western world. Several authors have tried to calculate its prevalence in different regions, although most of them obtained the data from surveys and there are few publications from Mediterranean areas. The objective of our study was to analyze the prevalence and severity of psoriasis in Lleida (a northeastern region in Spain), identify age and sex specific differences and compare our results with other European series. Materials and methods A joint database of primary care medicine and the dermatology department was obtained from the entire province of Lleida with epidemiological data and psoriasis diagnosis and treatment codification. Results A corrected database was obtained with 398,701 individuals and 6,868 of them (1.72%) were coded with the diagnosis of psoriasis. The prevalence was significantly higher in men than in women (1.88% vs 1.56%, OR = 1.21, 95% CI: 1.15-1.27). The highest prevalence of psoriasis was found in the 61-70 years group (2.90%) and psoriasis in population under 18 years of age was 0.30%. In our sample, 7.27% of the patients were classified as moderate-severe psoriasis (499/6,868). Conclusion This study reports the prevalence and severity of psoriasis in a large Mediterranean region sample, obtaining the information through a electronic database. This study reveals a lower prevalence of psoriasis compared to other European countries, and the proportion of severe psoriasis (based on treatment criteria) is lower than in other studies. We emphasize that these differences could probably due to genetic background, life style and diet.

Resumen Antecedentes y objetivo La psoriasis es una enfermedad inmunoinflamatoria cronica de la piel muy frecuente en el mundo occidental. Muchos autores han intentado calcular su prevalencia en diversas regiones, aunque en la mayoria de los casos esta se ha obtenido mediante encuestas y existen escasas publicaciones procedentes del area mediterranea. El objetivo de nuestro estudio era analizar la prevalencia y severidad de la psoriasis en Lleida (region del noreste de Espana), identificar diferencias en edad y sexo, y comparar nuestros resultados con otras series europeas. Materiales y metodos Se obtuvo una base de datos conjunta entre medicina primaria y el departamento de dermatologia de toda la provincia de Lleida con datos epidemiologicos, diagnostico de psoriasis y codificacion de tratamiento. Resultados La base de datos final comprendia a 398.701 individuos y 6.868 de ellos (1,72%) fueron codificados con el diagnostico de psoriasis. La prevalencia de psoriasis fue significativamente mayor en hombres que en mujeres (1,88 vs. 1,56%; OR = 1,21; IC 95%: 1,15-1,27). La prevalencia mas alta de psoriasis se encontro en el grupo de edad de los 61-70 anos (2,90%) y la prevalencia de psoriasis en menores de 18 anos fue del 0,30%. En nuestra poblacion, el 7,27% de los pacientes fueron clasificados como psoriasis moderada-severa (499/6.868). Conclusiones Este estudio reporta la prevalencia y severidad de la psoriasis en una muestra amplia de una region mediterranea, obteniendo la informacion mediante una base de datos electronica. Ademas, se evidencia una prevalencia menor de psoriasis comparada con otros paises europeos y una proporcion de psoriasis severa (basado en criterios de tratamiento) menor que en otros estudios. Estas diferencias podrian deberse a factores geneticos, estilo de vida y dieta.

Background & Aims: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers’ knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally. Methods: NAFLD knowledge surveys containing 54 and 59 questions covering 3 domains (epidemiology/pathogenesis, diagnostics, and treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs), and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% high-income Global Burden of Disease super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). Results: Hepatologists saw the greatest number of NAFLD patients annually: median 150 (interquartile range, 60–300) vs 100 (interquartile range, 35–200) for GEs, 100 (interquartile range, 30–200) for ENDOs, and 10 (interquartile range, 4–50) for PCPs (all P

Background Alzheimer’s disease (AD) is the main cause of dementia in developed countries. Sleep disturbances have been shown to increase the risk of AD, however, benzodiazepine (BZD) consumption has also been shown to increase this risk in some cohort studies. Purpose The objective of the study was to assess the risk of AD incidence in a cohort of patients exposed to BZD. Material and methods Community-based retrospective cohort study from 1 January 2002 to 31 December 2015. Consumption was expressed in defined daily doses (DDD) accumulated by individuals. Three DDD intervals were established (1–90, 90–180 and >180). All approved BZD were included in the Medicines Catalogue of the Spanish Medicines Agency, as well as the BZD analogues (zoplicona, zolpidem). The patients treated with BZD during the 5 years immediately prior to diagnosis were excluded. The relationship between the BZD consumption categories and the development of AD was analysed by the Chi2 test and adjusted logistic regression models. Cox proportional hazards models were also used to consider the time to AD development. Results The cohort included 84 543 individuals consuming BZD and similar, with an average age in 2002 of 65 years. During follow-up, 584 new cases of AD were diagnosed. In the Cox models adjusted for year of birth, sex and comorbidities, taking as a reference the first category of BZD consumption (1–90 DDD), there was a 12-fold increase in the risk of developing AD in participants with cumulative consumption from 90 to 180 DDD (Hazard ratio (95% CI): 11.6 (3.8–35.7), P-value 180 DDD) of BZD of intermediate-long action 1.20% with respect to those of short-intermediate action 1.11%. Conclusion The long-term use of BZD increases the risk of developing AD. The establishment of new treatments with BZD should be restricted to the most serious cases and programmes of deprescription should be developed. References and/or acknowledgements https://www.bmj.com/content/352/bmj.i90 https://www.bmj.com/content/349/bmj.g5205 https://www.ncbi.nlm.nih.gov/pubmed/29273607 https://www.karger.com/Article/FullText/454881 No conflict of interest.

Psoriasis is a chronic immunoinflammatory skin disease very frequent in the western world. Several authors have tried to calculate its prevalence in different regions, although most of them obtained the data from surveys and there are few publications from Mediterranean areas. The objective of our study was to analyze the prevalence and severity of psoriasis in Lleida (a northeastern region in Spain), identify age and sex specific differences and compare our results with other European series.A joint database of primary care medicine and the dermatology department was obtained from the entire province of Lleida with epidemiological data and psoriasis diagnosis and treatment codification.A corrected database was obtained with 398,701 individuals and 6,868 of them (1.72%) were coded with the diagnosis of psoriasis. The prevalence was significantly higher in men than in women (1.88% vs 1.56%, OR=1.21, 95% CI: 1.15-1.27). The highest prevalence of psoriasis was found in the 61-70 years group (2.90%) and psoriasis in population under 18 years of age was 0.30%. In our sample, 7.27% of the patients were classified as moderate-severe psoriasis (499/6,868).This study reports the prevalence and severity of psoriasis in a large Mediterranean region sample, obtaining the information through a electronic database. This study reveals a lower prevalence of psoriasis compared to other European countries, and the proportion of severe psoriasis (based on treatment criteria) is lower than in other studies. We emphasize that these differences could probably due to genetic background, life style and diet.

Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. Methods: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. Findings: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4–4·6), corresponding to 291 992 000 (251 513 000–341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6–2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2–1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. Interpretation: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets. Funding: John C Martin Foundation. © 2018 Elsevier Ltd

SummaryBackground Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis. Aim The Phase III, open-label, single-arm PLUTO study evaluated the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naive and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis. Methods Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed. Results Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91–100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients. Conclusions Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naive and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807]

Aliment Pharmacol Ther 2010; 32: 97–104 Summary Background Some patients continue to have detectable HBV-DNA levels with liver disease progression after hepatitis B e antigen (HBeAg) loss. It is important to identify these patients, candidates for long-term treatment. Aims To evaluate hepatitis B virus (HBV) genotype and the main mutations in the basic core promoter (BCP, A1762T/G1764A) and precore (G1896A) sequences as markers of persistent HBV-DNA after HBeAg loss. Methods We analysed 60 serum samples from 20 Caucasian, HBeAg-positive, chronic hepatitis B patients, who lost HBeAg and were followed-up longitudinally. HBV genotype and precore and BCP mutations were determined before, at the time of, and after HBeAg loss. Results After HBeAg loss, eight (40%) patients continued to have undetectable HBV-DNA and 12 (60%) had persistent HBV-DNA (median level 4.7 log10 copies/mL). The presence of BCP mutations prior to therapy was the only variable associated with persistently detectable viraemia (P = 0.017). Four patients with genotype A and no mutations in the BCP region experienced hepatitis B surface antigen (HBsAg) loss after a mean period of 35 months from baseline. Conclusions Main BCP mutations in HBeAg-positive patients are useful markers to identify patients who will not have sustained virological suppression after HBeAg loss and therapy discontinuation and could benefit from long-term treatment.

Summary. This study aims to determine the prevalence of hepatitis B virus (HBV) genotypes (A–F) and their association with the G1896A precore mutation in 486 patients positive for HBV surface antigen. Genotypes were determined by RFLP and precore mutation by real-time PCR. Genotypes D (48.1%) and A (39.5%) were the most common, followed by F (4.1%) and B, C and E (

Objective: To perform a budget impact analysis (BIA) of the treatment with pegylated interferon (pegIFN), alfa-2a or alfa-2b, plus ribavirin in patients with chronic hepatitis C (CHC). Method: An interactive model has been designed from the inputs obtained from hospital databases. Prices for pegIFN and RIB have been taken from the hospitals considering their respective discounts. Only pharmacological costs (euros 2005 values) for the options have been considered. Both strategies have been considered as therapeutic equivalents. Results: The number of patients with CHC evaluated in the model has been of 117, with an average age of 42 years and an average weight of 75 kg. The genotypes of the patients were: G1/4, 85% and; G2/3, 15%. Discontinuation of the treatment at week 12 took place in 26% of the patients. The average duration of treatment has been of 37 weeks. Total cost of the 117 evaluated patients ranged between 942,632-952,109 and 861,646- 880,751 euros for the treatment with pegIFN alfa-2a + RIB and pegIFN alfa-2b + RIB, respectively. Conclusions: BIA models can be useful for the inclusion or reassessment of drugs in formularies. In this case, the treatment with pegIFN alfa-2b + RIB (in comparison with pegIFN alfa-2a + RIB) is an efficient strategy although it depends on acquisition prices, and so, it would be rarely useful in other centres. In our hospital it would produce a budgetary saving that would range from 71,358 to 80,986 euros, which would represent a 7,5-8,6% of the total cost of the pharmacological treatment of the CHC

Summary Background : Lamivudine therapy for chronic hepatitis B has been associated with changes in different regions of the hepatitis B virus nucleotide sequence. Aim : To study changes in the sequences of polymerase and precore/core promoter regions of hepatitis B virus, before and during 5 years of therapy with lamivudine. Methods : Eighty consecutive samples were taken from 10 chronic hepatitis B ‘e’ antigen-negative patients. Results : Nine patients carried hepatitis B virus precore mutations during the study. Before therapy, wild type was replaced by A1896 in two (20%) cases. During treatment, A1896 reverted transitory to wild type in five cases (50%) and in one case wild type was replaced by A1896. The continuous detection of precore mutations during therapy was associated with a lower response rate. YMDD mutations were observed in nine cases and both, L180M and M204V/I mutations were simultaneously detected in six cases. About 75% of the patients with M204V mutations were responders and none with M204I or mixed pattern sustained response. Conclusion : Hepatitis B ‘e’ antigen-negative patients exhibit changes in the precore regions both spontaneously and under lamivudine therapy, the transitory reversion to wild type being most frequently witnessed. Patients carrying M204V mutations are more likely to respond to therapy. If, in further studies, these results are confirmed some patients with YMDD mutations could benefit from prolonging the duration of lamivudine therapy.

Hepatitis B Existen tres farmacos para el tratamiento de la hepatitis cronica B, los interferones, la lamivudina y el adefovir. Los interferones consiguen erradicar la infeccion en el 30% de los casos y la duracion del tratamiento es limitada. La lamivudina y el adefovir son analogos de los nucleosidos o nucleotidos de administracion oral que carecen de efectos adversos importantes. Actuan fundamentalmente inhibiendo la replicacion virica, siendo menos frecuente la erradicacion de la infeccion. Hepatitis C El interferon pegilado y ribavirina es el tratamiento de eleccion para los pacientes con hepatitis cronica C. Los pacientes infectados por genotipos 2 y 3 deben ser tratados durante 24 semanas mientras que los pacientes infectados por genotipo 1 durante 48

En pocos anos el uso de la tecnologia digital y de la videoconferencia sera algo habitual en nuestro trabajo asistencial. El hecho de usar la fotografia digital en las consultas de las areas rurales, aporta multiples ventajas asistenciales, representando una dificultad tecnica y economica baja, entre las que destacan la mejoria de la asistencia a nuestros pacientes, la eficiente mejoria entre los diversos profesionales y especialistas, disminuira el tiempo de demora asistencial, e incrementara la formacion medica continuada de aquellos medicos que se dedican al ejercicio de la medicina rural.

Introduccion La prevalencia de homocigosidad para C282Y en pacientes con hemocromatosis hereditaria (HH) originarios de algunos paises de la cuenca mediterranea puede ser sustancialmente inferior a la observada en el norte de Europa. Los datos referidos a Espana son contradictorios y basados en series pequenas de ambito regional. El objetivo de nuestro estudio es determinar la prevalencia de las 2 principales mutaciones del gen HFE en una serie de pacientes espanoles con HH, no relacionados y de diferente procedencia geografica. Pacientes y mEtodo Los criterios para el diagnostico de HH fueron: indice de saturacion de transferrina superior al 45% en 2 determinaciones y homocigosidad para C282Y y/o indice de hierro hepatico mayor de 1,9 de tejido hepatico seco en pacientes no cirroticos o superior a 4,1 en presencia de cirrosis. Se excluyeron los casos detectados en familiares. Se evaluaron los datos demograficos, la expresion clinica, los parametros del hierro y las mutaciones C282Y y H63D del gen HFE en un total de 222 pacientes. Resultados El 83,3% de los pacientes fueron homocigotos para C282Y y el 5% dobles heterocigotos (C282Y/H63D). No se observaron diferencias significativas en la expresion fenotipica ni en la frecuencia de homocigosidad para C282Y en los pacientes nacidos en el norte o en el sur de Espana. Conclusion El patron genotipico y la expresion fenotipica de la HH en Espana son muy similares a los observados en el norte de Europa. Por tanto, la heterogeneidad genetica descrita en algunas regiones del sur de Europa no puede considerarse una caracteristica comun a todos los paises de la cuenca mediterranea.

A PHASE 3 STUDY OF TENOFOVIR ALAFENAMIDE COMPARED WITH TENOFOVIR DISOPROXIL FUMARATE IN PATIENTS WITH HBEAGNEGATIVE, CHRONIC HEPATITIS B: WEEK 48 EFFICACYAND SAFETY RESULTS M. Buti1, E. Gane2, W.K. Seto3, H.L.Y. Chan4, W.-L. Chuang5, T. Stepanova6, A.J. Hui7, Y.-S. Lim8, R. Mehta9, H.L.A. Janssen10,11, S.K. Acharya12, J.F. Flaherty13, B. Massetto13, A. Cathcart13, P. Dinh13, G.M. Subramanian13, J.G. McHutchison13, C. Pan14, M. Brunetto15, N. Izumi16, P. Marcellin17. 1Hospital General Universitari Vall d’Hebron, Barcelona, Spain; 2Auckland Clinical Studies, Auckland, New Zealand; 3Queen Mary Hospital; 4The Chinese University of Hong Kong, Hong Kong, Hong Kong, China; 5Kaoshing Medical University Hospital, Kaoshing, Taiwan; 6Modern Medicine Clinic, Moscow, Russia; 7Alice Ho Miu Ling Nethersole Hospital, Hong Kong, Hong Kong, China; 8Asan Medical Center, Seoul, South Korea; 9Nirmal Hospital Private Limited, Surat, India; 10Toronto Western Hospital, Toronto, Canada; 11Erasmus Medical Center, Rotterdam, Netherlands; 12All India Institute of Medical Sciences, New Delhi, India; 13Gilead Sciences, Foster City; 14New Discovery, LLC, Flushing, United States; 15University Hospital of Pisa, Pisa, Italy; 16Musashino Red Cross Hospital, Tokyo, Japan; 17Hopital Beaujon, Clichy, France E-mail: John.Flaherty@gilead.com