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Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary Although subepithelial lipomatous lesions of the GI tract remain largely asymptomatic and are incidentally found during endoscopy, these lesions may lead to bowel obstruction and GI bleeding if larger than 2 centimeters. Historically, a surgical approach has been the first treatment modality because of high concern for bleeding and perforation associated with endoscopic resection. Advances in endoscopic resection techniques such as EMR and endoscopic submucosal dissection (ESD) have enabled safe resection of these lesions. The wide-base stalks of pedunculated lipomatous lesions contain the major feeding vessel; thus, preventative coagulation and tamponade of the vessel would facilitate endoscopic resection and minimize the risk of postpolypectomy bleeding. This can be achieved by placement of either a detachable snare or a hemostatic clip to “strangulate” the stalk. Blanching of the polyp is a clue for optimal placement of the detachable snare or clips at the base of the stalk. Bleeding prevention can be reinforced with epinephrine injection at the base of the lipoma. The only caveat with removing such large lesions by EMR is uncertainty with regard to en bloc resection arising from an often challenging position and limited visualization. By contrast, ESD ensures dissection of the lesion from the stalk within the submucosa, the surface capsule being kept intact. It is worth noting that the majority of lipomatous lesions are benign lipomas, but rarely liposarcoma or pleomorphic lipoma/liposarcoma can be seen. It has been hypothesized that a larger size of the subepithelial fat could lead to superficial pressure necrosis of the mucosal surface and result in ulceration and bleeding. As demonstrated in these cases, the superficial mucosa is grossly intact except areas with small ulcerations and erosions, usually toward the tip of the lesion or at the point affected the most by the bowel peristalsis. Tara Keihanian, MD, MPH, Assistant Professor, Division of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

An outbreak of hepatitis A is ongoing in Portugal, with 71 confirmed cases from 7 October 2023 to 24 April 2024. Most cases are male, aged 18-44 years, with many identifying as men who have sex with men (MSM) and reported as suspected sexual transmission. Phylogenetic analysis identified the subgenotype IA, VRD 521-2016 strain, last observed in an MSM-associated multi-country outbreak in 2016 to 2018. We wish to alert colleagues in other countries to investigate potential similar spread.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019., Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = π rec ρ rec  + π ex ρ ex  + π non ρ non ; π rec , π ex , and π non represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρ rec , ρ ex , and ρ non represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature., Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs., Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID., Funding: ECDC., Competing Interests: IG: He is currently an employee of MSD Greece. He joined MSD after his post-doctoral work at the University of Cyprus. TV: He has received grants from Gilead Sciences and Bristol Myers Squibb; he has served as a consultant for Janssen Pharmaceuticals, Gilead Sciences, AbbVie, Bristol Myers Squibb; and he has served as a sponsored lecturer for Gilead Sciences and Abbvie. PBC: He has received unrestricted research grants for other studies from Abbvie, Gilead, and MSD. MG: He has received consultancy and speaker’s fees from Gilead Sciences. LAK: She has received personal lecturer fee from Abbvie and Gilead Sciences and an institutional grant from Gilead Italy Fellowship 2022. LJ: She has received honorarium for lectures from AbbVie and MSD; offered consultancy to AbbVie, MSD, Tamro; and received conference attending fee from AbbVie, MSD, Pfizer, Swixx Biopharma. CSD: She has received educational and research grants for other studies from Abbvie and Gilead Sciences. MV: He participated in advisory boards (ViiV, Gilead, and MSD–fees paid to his institution); he has received independent research grants from ViiV and Gilead (paid to his institution). CV: She has received honorarium for lectures and consultancy from AbbVie, Gilead, MSD, and ViiV Healthcare. AD: She has received a grant for another study and speaker fee at a conference about HIV from Gilead Sciences. AB: He has received speaker's fees from Gilead Sciences. GN: He has received an ASKLEPIOS grant (HIV-related competitive grant) from Gilead Sciences (Greece). All other authors declare no conflict of interest., (© 2023 The Author(s).)

Background: Hepatitis B virus (HBV) vaccination is recommended for non-immunised patients with rheumatic diseases starting biological disease-modifying antirheumatic drugs (bDMARDs). There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), but it is currently unclear whether this also applies to bDMARDs., Objectives: To assess the efficacy and safety of HBV vaccination in patients with inflammatory arthritides treated with bDMARDs., Methods: A prospective cohort with inflammatory arthritides treated with bDMARDs, negative for anti-HBs and anti-HBc and never vaccinated for HBV was recruited. Engerix B was administered at 0, 1 and 6 months and anti-HBs was reassessed ≥1 month after last dose. Response was defined as anti-HBs≥10 IU/L and compared against vaccinated healthy controls. Disease flare, serious adverse events and immune-related disorders not previously present were recorded., Results: 62 patients, most treated with TNF inhibitors (TNFi), and 38 controls were recruited. Most patients were taking csDMARDs (67.7%) and were in remission/low disease activity (59.4%). Only 20/62 patients (32.3%) had a positive response to vaccination, in comparison to 36/38 age-matched controls (94.7%, p<0.001). Response was seen in 19/51 patients treated with TNFi (37.3%) and in 1/11 (9.1%) patients treated with non-TNFi (p=0.07), including 1/6 treated with tocilizumab (16.7%). Among TNFi, response rates ranged from 4/22 (18.2%) for infliximab to 8/14 (57.1%) for etanercept. No relevant safety issues were identified., Conclusions: HBV vaccination response in patients with rheumatic diseases treated with bDMARDs was poorer than expected. Our data reinforce the recommendation for vaccination prior to starting bDMARDs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

An 83-year-old male with a history of Whipple procedure (pancreatoduodenectomy) due to pancreatic cancer, underwent endoscopic retrograde colangiopancreatography (ERCP) for acute cholangitis. Because of the altered anatomy, an upper gastrointestinal endoscope was used. Severe stricture of the hepaticojejunal anastomosis was found. The anastomotic stricture was dilated with a 12mm through-the-scope (TTS) balloon under fluoroscopy and direct visualization. Right and left ducts were explored with Dormia basket and balloon, with extraction of bile duct stones and pus. Cholangioscopy with upper gastrointestinal endoscope was performed and residual cholesterol stones were identified in branches of the left hepatic duct and these were removed with the stone extraction balloon under endoscopic visualization. Ciprofloxacin was administered for 5 days and post interventional course was uneventful. Direct peroral colangioscopy using a conventional endoscope provides high quality endoscopic imaging, enabling access to virtual chromoendoscopy and the 2.8 mm diameter working channel allows for interventional procedures. This strategy is useful and economical, helping confirm clearance of common bile duct stones, while allowing extraction of any residual stones. New, cost effective scopes for peroral cholangioscopy are needed to improve the safety and success rate.

Background and Objectives: Endoscopic band ligation (EBL) plays a critical role in patients with clinically significant portal hypertension, as variceal eradication (VE) is essential to prevent further variceal upper gastrointestinal bleeding (GI). The emergence of COVID-19 has led to a dramatic reduction in endoscopic activity. Our study aimed to evaluate the effect of COVID-19 on VE, GI, and 6-month mortality of patients treated with prophylactic EBL therapy. In addition, our goal was to identify the risk factors for our proposed outcomes., Methods: A single-center retrospective cohort study included patients with esophageal varices treated with prophylactic EBL therapy between 2017 and 2021. To demonstrate the impact of COVID-19 on two independent groups on prophylactic EBL therapy with 1 year of follow-up, March 2019 was selected as the cut-off date. Clinical, laboratory, and endoscopic data were recovered from electronic reports., Results: Ninety-seven patients underwent 398 prophylactic EBL sessions, 75 men (77.3%) with mean age 59 ± 12 years. Most achieved VE (60.8%), 14.4% had GI bleeding post-therapy, and 15.5% died at 6 months. The rate of variceal obliteration was significantly lower in the pandemic group (40.9% vs. 77.4% in the pre-pandemic group, p = 0.001). Mean number of EBL sessions and pandemic group were independently associated with incomplete VE, while MELD-Na, portal vein thrombosis and failed VE were identified as risk factors associated with mortality at 6 months., Conclusions: Almost 60% of patients in the pandemic group failed to eradicate esophageal varices. Failure to achieve this result conferred a higher risk of GI bleeding and death at 6 months, the latter also significantly associated with the MELD-Na score and portal vein thrombosis. Our study is among the first to demonstrate the impact of COVID-19 in patients receiving prophylactic EBL therapy., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Author(s).Published by S. Karger AG, Basel.)

A 67-year-old male patient with long term gastroesophageal reflux disease (GERD) on double dose proton pump inhibitors, presented with dysphagia for soft foods. He underwent upper gastrointestinal (UGI) endoscopy which revealed a severe regular stricture at the level of the esophagogastric junction with a residual luminal orifice measuring 2 mm. Biopsies at the site of the stricture ruled out malignancy and were suggestive of peptic etiology. The patient underwent twelve endoscopic dilatation sessions, 11 of them with Savary-Guillard bougies and 1 with TTS balloon, up to a maximal diameter of 18 mm, with only partial relief of dysphagia symptoms. Due to the persistence of the stricture and dysphagia symptoms, incisional therapy was performed in two endoscopic sessions at the site of the stricture was performed with a Mori´s knife parallel to the longitudinal axis of the esophagus in a radial manner in all of the quadrants. There were no adverse events. On follow-up, 2 months later after the last session, the patient had a significant improvement and did not have any dysphagia symptoms. UGI endoscopy revealed minimal residual narrowing at the site of the previous stricture in the distal esophagus. He remains asymptomatic after 6 months follow-up.

Introduction: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term., Methods: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR)., Results: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR., Conclusions: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Backround: In acute severe autoimmune hepatitis (AS-AIH), the early identification of predictors of non-response to corticosteroids and the optimal timing for liver transplantation (LT) remains controversial., Aims: To determine early predictors of non-response to corticosteroids and to assess the usefulness of severity scores, namely the recently developed SURFASA., Methods: Retrospective multicentre cohort study including consecutive patients admitted for AS-AIH between 2016 and 2020. Definitions- response to corticosteroids: LT-free survival at 90 days (D90); SURFASA score: -6.8 + 1.92x(D0-INR)+1.94xINR[(D3-D0)/D0]+1.64xbilirubin[(D3-D0)/D0]., Results: We included 26 patients [median age 56 (45-69) years; 22 (84.6%) women]. All patients underwent corticosteroid therapy. Overall survival reached 73%. amongst the non-responders, 2 (7.8%) underwent LT and 5 (19.2%) died. The interval between admission and initiation of corticosteroids was not different between responders and non- responders [13 (7-23) vs. 8 (3-10), P:0.06], respectively. SURFASA and MELD-Na + (D3) scores showed an AUROC of 0.96 (0.87-1) and 0.92 (0.82-0.99), respectively, for prediction of non-response. SURFASA >-2.5 had a sensitivity of 85.7% and a specificity of 100% and MELD-Na + (D3) >26 had sensitivity of 85.7% and a specificity of 78% for the prediction of non-response., Conclusions: SURFASA and MELD-Na + at D3 scores are useful in early identification of non-responders to corticosteroids., Competing Interests: Conflict of interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Current evidence suggests vedolizumab (VDZ) may be as effective as Infliximab (IFX) in inflammatory bowel disease. It is unknown if proactive therapeutic drug monitoring (PTDM) of IFX may improve these results., Methods: Case-control study including consecutive patients with primary response to conventional IFX ( n  = 70), proactive IFX ( n  = 148), and VDZ ( n  = 95). PTDM was performed at week 14 and every other infusion, aiming at a trough level between 5 and 10 µg/ml. The primary outcome was fecal calprotectin (Fc) remission (<250 µg/g) at 1 year of treatment. Secondary outcomes included Fc remission at week 14 (proactive IFX/VDZ), clinical remission, treatment discontinuation, hospitalization, and surgery at 1-year of follow-up., Results: Proactive IFX was superior to conventional IFX and VDZ in inducing Fc remission at 1-year (69.4% vs 47.1% vs 37.9%, p  = .003 and p  < .001). Results remained significant in biologic naïve patients (70.8% vs 44.4% vs 51.4%, p  = .001 and p  = .043) but comparisons between conventional IFX and VDZ were not significant ( p  = .265 and p  = .664). In multivariate analysis correcting for prior biologic exposure, proactive IFX was more effective than conventional IFX (OR 2.480 95%CI [1.367-4.499], p  = .003) and VDZ (OR 3.467 95%CI [1.578-7.617], p  = .002) in inducing Fc remission. Amongst secondary outcomes, only clinical remission was significant between proactive IFX and VDZ in the overall cohort (80.4% vs 55.8%, p  < .001) and in biologic naïve patients (80.2% vs 62.9%, p  = .043). Fc remission at 1-year was associated with better results in most secondary outcomes., Conclusion: Proactive IFX was superior to VDZ in inducing Fc remission at 1-year, which was associated with improved clinical outcomes.SUMMARYCurrent evidence suggests that vedolizumab may be as effective as Infliximab in the treatment of patients with inflammatory bowel disease.There have been no studies comparing vedolizumab with proactively optimized Infliximab based on trough levels.We confirm that conventional IFX is as effective as vedolizumab but proactive IFX appears superior to vedolizumab in inducing fecal calprotectin remission.Fecal calprotectin remission associates with better clinical outcomes.

In this review, we would like to focus on risk stratification and quality indicators of diagnostic upper gastrointestinal endoscopy in the detection and characterization of early gastric cancer. Preparation of the upper gastrointestinal tract with mucolytic agents or simethicone is often overlooked in the west, and this inexpensive step prior to endoscopy can greatly improve the quality of imaging of the upper digestive tract. Risk stratification based on epidemiological features including family history, Helicobacter pylori infection status, and tobacco smoking is often overlooked but may be useful to identify a subgroup of patients at higher risk of developing gastric cancer. Quality indicators of diagnostic upper gastrointestinal endoscopy are now well defined and include: minimal inspection time of 3 min, adequate photographic documentation of upper gastrointestinal landmarks, utilization of advanced endoscopic imaging technology including narrow band imaging and blue laser imaging to detect intestinal metaplasia and characterize early gastric cancer; and standardized biopsy protocols allow for histological evaluation of gastric mucosa and detection of atrophic gastritis and intestinal metaplasia. Finally, endoscopic and histologic classifications such as the Kimura-Takemoto Classification of atrophic gastritis and the OLGA-OLGIM classifications may help stratify patients at a higher risk of developing early gastric cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferreira, Serrazina and Marinho.)

Background and Aims: Sorafenib, used for advanced-stage hepatocellular carcinoma (HCC), has an overall survival (OS) of 10 months. However, some patients have better response and long-term survival (LTS). Aims to assess predictive factors for LTS., Methods: Retrospectively reviewed 77 advanced HCC patients, starting sorafenib treatment between 2007 and 2016, with LTS (OS ≥24 months) as primary endpoint. Univariate and multivariable analysis of clinical variables were performed in order to identify predictive factors for LTS., Results: Patients: seventy (90.9%) males; median age: 65 years (39-82). All had cirrhosis mostly HCV infection (n = 32, 41.6%). Majority were Child-Pugh class A (n = 50, 64.9%); median MELD-Na: 11 (6-30). Multinodular HCC: 74% (n = 57); portal vein invasion (PVI): 50.6% (n = 39); extrahepatic spread: 18.2% (n = 14). Median time between HCC diagnosis and sorafenib start: 3.3 months (0-37.6). Median OS: 13 months [95% confidence interval (CI) 8.2-17.8]. Twenty-five (32.5%) patients were considered LTS, with amedian OS: 52.3 months (95% CI 17.1-87.4). Multivariable analysis identified Child-Pugh class A [odds ratio (OR) 11.1, 95% CI 1.78-69.54] and absence of PVI (OR 7.88, 95% CI 1.56-39.8) as independent predictors of LTS. Sub-analysis of Child-Pugh class A: absence of PVI (OR 7.13, 95% CI 1.69-30.2) and alpha-fetoprotein <400 ng/ml (OR 5.82, 95% CI 1.18-28.75) independently related to LTS., Conclusion: Despite global short median OS, sorafenib treatment is associated with longer than 2-year survival in a sub-group, more likely in compensated liver disease and absence of PVI., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The 3-DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) has shown high sustained virologic response rates (~95%) in phase 3 clinical trials including >2300 HCV genotype 1-infected patients. Real-world evidence studies have confirmed the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with chronic HCV genotype 1 infection and are consistent with clinical trial results. TOPAZ-I and TOPAZ-II are ongoing phase 3b trials, assessing safety, efficacy and long-term progression of liver disease and clinical outcomes for up to 5 years post-treatment in patients treated with OBV/PTV/r + DSV ± RBV. High rates of sustained virologic response (SVR) were achieved regardless of presence or absence of cirrhosis.In this report, we assessed the long-term progression of liver disease and incidence of clinical outcomes up to 3 years of post-treatment follow-up in patients with chronic HCV GT1 infection who were treated with (OBV/PTV/r + DSV) ± RBV in the TOPAZ-I and TOPAZ-II studies. Improvements were observed in liver disease markers including FIB-4, METAVIR and Child-Pugh scores as well as platelet counts. Clinical outcomes related to long-term progression of liver disease such as liver decompensation were infrequent (<1%). Hepatocellular carcinoma (HCC) occurred in 1.4% of cirrhotic patients., (© 2020 John Wiley & Sons Ltd.)

Introduction: In Sao Tome and Principe there are no studies on alcohol and drug use among students, who could be potential allies in preventive interventions. The objectives of the present study are 1) to determine the frequency of alcohol and drug consumption in the school population, and 2) to identify the main characteristics associated with this behaviour., Material and Methods: We applied a biographical, demographic and socioeconomic questionnaire on the use of licit and illicit substances to a sample of 2064 students. Demographic and social characteristics are presented based on observed frequencies and comparisons between groups were made using chi-square tests. Significance was assessed at α = 0.05., Results: More than half of the students reported consumed alcohol at least once in their lifetime, and 32% consumed in the last 30 days. Older students were more likely to consume alcohol (p < 0.0001), but even in students under 16 years, 17% consumed in the last 30 days. We also found that 7% consumed one or more times per week in the last 30 days. The reasons presented for frequent consumption were different for boys ("participation in their group of friends") and girls ("decrease anxiety") (p = 0.005). Less than 1% of respondents admitted to having used marijuana, cocaine, crack or ecstasy., Discussion: Despite some limitations, such as self-reporting, we provide a first overview showing high consumption of alcohol by young people and the existence of illegal drugs circulating in the schools., Conclusion: It is urgent to implement preventive interventions, namely in the context of public health communication.

Introduction: Sao Tome and Principe is an African low-and-middle-income country, where extreme poverty causes major health inequalities. No systematic research has been done on the consumption of alcohol and drugs in Sao Tome and Principe, and only overall statistics are available based on the importation of alcoholic drinks and their distribution among the population. There are also no studies on consumption of alcohol and illicit substances in children and youth and no preventive measures being undertaken. Besides that, manual databases present significant limitations, considering the lack of causes associated with mortality rates (0 - 5 years and > 5), and the difficulty to establish a cause/effect relation between diseases, deaths and life expectancy. No relevant data with burden of life was found in the reports of Centro Nacional de Endemias or the non-governmental, organization Instituto Marques de Valle Flor, a facilitator on healthcare clinical specialties selected on a voluntary basis by doctors from Portuguese hospitals. So, we proposed to provide a first overview of family and housing conditions, and above all, the consumption of alcohol and illegal drugs in young people. Thus, a project, the National Survey on Harmful Consumption of Alcohol and Drugs in Schools of Sao Tome and Principe, will be realized in order to better characterize the situation among children and young students and test public health communication strategies and preventive interventions aimed at this target-population. Interventions were designed taking into consideration local sociocultural realities of target audiences. We considered dialect language, single-parent families (matriarchal structure) and polygamy (mostly) in men and a country and governments led by men (patriarchal structure) and, in which the woman's role, as Food and Agriculture Organization of the United Nations reports, remains overlooked. Subsequently, we will collect traditional alcohols samples from the two main islands for analysis (at Laboratório de Estudos Farmacêuticos and Laboratório Nacional de Engenharia Civil - Portugal) and to determine heavy metals in the production process and impact on burden of life., Material and Methods: In order to characterise the country's situation in terms of alcohol and illicit substances consumption a literature review was carried out through a search in several international electronic databases, such as those of the World Health Organization, World Health Organization Africa, United Nation, The Lancet and Lancet Global Health, etc. Available data of the following institutions of Sao Tome and Príncipe was also analyzed: National Institute of Statistics, Ministry of Education, Culture and Training and Ministry of Health and Social Affairs. Several interviews with community and church leaders as well as with members of catholic missions were carried out to better understand the local situation. Following this, a nationwide cross-sectional survey of a sample of 2064 students will be carried out. This will include a questionnaire on socio-demographic characteristics, lifestyles, health behaviors/attitudes, alcohol and illicit substances consumption. Finally, based on the overall diagnosis obtained, some edutainment health communication preventive interventions will be tested in the primary schools of three districts (EDUCA&#95;TURTLE) and on the radio journalists (EDUCA&#95;PRESS). These were evaluated by primary school teachers and by radio journalists.

The approach to the patient with gastrointestinal bleeding (GIB) can be very complex. A multidisciplinary panel of physicians with expertise in Gastroenterology, Anesthesiology, and Transfusion Medicine worked together to provide the best knowledge and guide clinical practitioners in the real setting of health institutions, characterized by disparate availability of human and technical resources. The authors propose a global and personalized approach according to different clinical scenarios to improve the outcomes of patients with GIB, for whom the reduction of inappropriate transfusions is crucial. The goal of this document is to provide clear and objective guidance through interventional algorithms toward a goal-directed approach according to the clinical situation and supported by the latest available scientific data on GIB management in different settings.

Background: The hepatitis C virus (HCV) is known to infect the brain, however, the findings based on associated neuropsychiatric syndrome are controversial and the association itself remains unclear. Gender research in HCV infection is limited, failing to integrate the role of gender differences in neurocognitive syndrome. The aim of this study was to characterize psychological and neurocognitive profiles in HCV-infected patients before treatment and to explore gender differences in those profiles, as well as the impact of disease severity., Methods: A total of 86 patients diagnosed with chronic hepatitis C were included. Depression and anxiety were assessed using Hamilton anxiety scale (HAM-A), Hamilton depression scale (HAM-D), Beck Depression Inventory (BDI). For cognition, a neuropsychological battery to measure attention, concentration and memory was used, and executive function components validated for the Portuguese population was also used before starting treatment. To identify the disease severity, platelet ratio index, and FibroScan ® were used., Results: A statistically significant gender effect was found on HAM-A ( B = 0.64, CI: 0.17-1.11) and HAM-D ( B = 0.62, CI: 0.14-1.09), with women scoring higher compared to men. Regarding neuropsychological scores, significant differences between gender were identified in executive functions measured by Trail Making Test (TMT B) ( B = 0.48, CI: 0.02-0.97), TMT B-A ( B = 0.26, CI: -39.2 to -3.7) and in digit span total ( B = -0.52, CI: -1.0 to -0.04), with women performing worse than men. Controlling for years of substance dependence, TMT-B and TMT B-A showed significant gender differences. Regarding the presence or absence of substance dependence, only HAM-A and HAM-D remained significant. For categorical variables, Digit Span Total was also influenced by gender, with women being more likely to be impaired: odds ratio (OR) = 7.07, CI: 2.04-24.45), and a trend was observed for Digit Span Backward (OR = 3.57, CI: 1.31-9.75). No significant differences were found between disease severity and neurocognitive performance., Conclusion: Data suggest that gender has an influence on depression, anxiety and cognitive functions with women showing greater impairment compared with men. This effect seems to be influenced by substance dependence., (Copyright © 2019 Barreira, Marinho, Bicho, Flores, Fialho and Ouakinin.)

Background and Aims: The role of portal vein thrombosis (PVT) in the natural history of cirrhosis is controversial. There are few prospective studies validating risk factors for development of PVT. We analysed the incidence, factors associated with PVT development and its influence on cirrhosis decompensations and orthotopic liver transplant (OLT)-free survival., Methods: In this prospective observational study between January 2014 and March 2019, 445 consecutive patients with chronic liver disease were screened and finally 241 with cirrhosis included. Factors associated with PVT development and its influence on cirrhosis decompensations and OLT-free survival by time dependent covariate coding were analysed., Results: Majority of patients belonged to Child-Pugh class A 184 (76.3%) and the average MELD score was 10 ± 5. Previous cirrhosis decompensations occurred in 125 (52.1%), 63 (26.1%) were on NSBB and 59 (27.2%) had undergone banding for bleeding prophylaxis. Median follow-up was 29 (1-58) months. Cumulative incidence of PVT was 3.7% and 7.6% at 1 and 3 years. Previous decompensation of cirrhosis and low platelet counts but not NSBB independently predicted the development of PVT. During follow-up, 82/236 (34.7%) patients developed cirrhosis decompensations. OLT-free survival was 100% and 82.8% at 3 years, with and without PVT respectively. MELD score, but not PVT, independently predicted cirrhosis decompensations (HR 1.14; 95%CI:1.09-1.19) and OLT-free survival (HR 1.16;95%CI:1.11-1.21)., Conclusion: Previous decompensations of cirrhosis and thrombocytopenia predict PVT development in cirrhosis suggesting a pathophysiologic role for severity of portal hypertension. PVT development did not independently predict cirrhosis decompensations or lower OLT-free survival., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Wilson's disease (WD) is an autosomal recessive disorder which is caused by poor excretion of copper in mammalian cells. In this review, various issues such as effective characterization of ATP7B genes, scope of gene network topology in genetic analysis, pattern recognition using different computing approaches and fusion possibilities in imaging and genetic dataset are discussed vividly. We categorized this study into three major sections: (A) WD genetics, (B) diagnosis guidelines and (3) treatment possibilities. We addressed the scope of advanced mathematical modelling paradigms for understanding common genetic sequences and dominating WD imaging biomarkers. We have also discussed current state-of-the-art software models for genetic sequencing. Further, we hypothesized that involvement of machine and deep learning techniques in the context of WD genetics and image processing for precise classification of WD. These computing procedures signify changing roles of various data transformation techniques with respect to supervised and unsupervised learning models.

Background: Hepatitis C virus (HCV) infection involves changes not only from the point of view of physical health, but also emotional, and social that have a significant impact on the quality of life of these patients. According to the literature review, it seems that there is an important association between psychosocial factors, in particular on a cognitive level and disease progression. The aim of this mini-review is to summarize recent literature looking at the associations between psychosocial and neurocognitive factors and HCV. Methods: PubMed/Medline was systematically searched for psychosocial and neurocognitive factors associated with hepatitis C, treatment adherence, and patient wellbeing. Results: Patients present with a range of extrahepatic symptoms including fatigue, anxiety, depression, and neurocognitive dysfunction. HCV's impact on quality of life and wellbeing has serious clinical and social implications. Conclusion: Hepatitis C and its management continue to have a profound impact on health and psychologic wellbeing. Considering the serious extrahepatic implications for individuals, it is imperative that healthcare professionals pay close attention to psychosocial and neurocognitive factors. The focus on combined clinical approaches could enhance understanding about the health and social impacts of hepatitis C along the life course.

Background & Aims: Chronic liver disease is a major worldwide cause of morbidity and mortality. Palliative care policies are not clearly established in chronic liver disease. The NECPAL CCOMS-ICO© (NECesidades PALiativas/Palliative Needs) is a tool to identify palliative care needs, including a section for liver disease., Aim: The aim of this study was to identify palliative care needs in liver patients hospitalised in a tertiary referral Liver Unit., Methods: Single-centre prospective observational study. One hundred and twenty patients with cirrhosis were included and NECPAL questionnaire was applied to all patients in a 7-month period., Results: 84.2% of patients were considered as requiring palliative intervention; however, clinicians identified those needs only in 65.8% of the cases and caregivers in 6.7% of the cases; less than 8% of the patients were referred for palliative care consultation. An excessive use of healthcare resources (positive answer to question 3) was strongly associated with a positive need for palliative care (positive NECPAL): OR 7.305, CI 95% 2.54-20.995, P < .001). An excessive use of healthcare facilities has a sensitivity of 84.2% and a specificity of 42.1% for prediction of a positive NECPAL result (AUC 0.710, 95% CI 0.570-0.850, P = .004)., Conclusions: The NECPAL CCOMS-ICO© represents a feasible and easy-to-use tool to identify palliative care needs in patients with chronic liver disease., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Any successful strategy to prevent and control HCV infection requires an understanding of the epidemic behaviour among the different genotypes. Here, we performed the first characterization of the epidemic history and transmission dynamics of HCV subtypes in Portugal. Direct sequencing of NS5B was performed on 230 direct-acting antiviral drugs (DAA)-treatment naïve patients in Lisbon. Phylogenetic analysis was used for subtyping and transmission cluster identification. Bayesian methods were used to reconstruct the epidemic history of HCV subtypes. Sequences were analysed for resistance-associated substitutions (RAS). The majority of strains were HCV-GT1 (62.6%), GT3 (18.3%, all subtype 3a) and GT4 (16.1%). Among GT1, the most frequent were subtypes 1a (75.5%) and 1b (24.5%). Polyphyletic patterns were found in all but 12 lineages suggesting multiple introductions of the different subtypes in this population. Five distinct epidemics were identified. The first significant HCV epidemic in Portugal occurred between 1930s and 1960s, was caused almost exclusively by GT1b and was likely associated with blood transfusions. Rapid expansion of GT3a occurred in the 1960s and GT1a in the 1980s, associated with intravenous drug use. The most recent epidemics were caused by GT4a and GT4d and seem to be associated with the resurgence of opioid use. The C316N substitution was found in 31.4% of GT1b-patients. Close surveillance of patients bearing this mutation and undergoing dasabuvir-based regimens will be important to determine its impact on treatment outcome.

Introduction: Hepatobiliary disease is becoming a major public health problem, and recent data suggest that the burden of liver disease is higher than previously thought. Our aim was to quantify the mortality from hepatobiliary disease in Portugal and to compare this with the mortality related o other causes over a 7-year period (2006-2012)., Materials and Methods: A statistical analysis of mortality data according to cause, sex, age, and region from the National Statistics Institute in Portugal was carried out. The data related to 14 causes of death, the most frequent of which were alcoholic liver disease (ALD) (International Classification of Diseases code K70), unspecified cirrhosis of liver (UCL) (K74.6), hepatocellular carcinoma (HCC) (C22.0), unspecified malignant neoplasm of liver (C22.9), and cholangiocarcinoma (C22.1)., Results: Between 2006 and 2012, 18,279 deaths (24.5/100,000) from hepatobiliary disease were registered in Portugal, constituting the 8th leading cause of death. The main causes of death from hepatobiliary disease were ALD (7.1/100,000), UCL (5.5/100,000), and HCC (4.3/100,000), with a male predominance (72%). ALD was the main aetiology in younger age groups (40-65 years), while primary neoplasms of the liver and the intrahepatic bile ducts were predominant in the elderly (>80 years). The mortality related to HCC increased by 66% between 2006 and 2012., Conclusion: These data outline the burden of hepatobiliary disease in Portugal (8th cause of death) and highlight a potential impact on economic productivity.

Background & Aims: Hepatitis C virus (HCV) has high genotypic diversity and global distribution. Agents that are effective against all major HCV genotypes, with shorter treatment duration, are needed to reduce disease burden. Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) have a high barrier to resistance and synergistic antiviral activity. We evaluated the safety and efficacy of 8 and 12 weeks' treatment with glecaprevir/pibrentasvir in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis in 3 separate phase 3 trials., Methods: We performed 2 open label, single-arm studies (SURVEYOR-II, Part 4 and ENDURANCE-4) and a randomized, double-blind, placebo-controlled study (ENDURANCE-2). In the ENDURANCE-2 study, adult patients with untreated or previously treated HCV genotype 2 infection without cirrhosis were randomly assigned (2:1) to groups given once-daily oral glecaprevir/pibrentasvir (n = 202; 300 mg/120 mg) or placebo (n = 100) for 12 weeks. In the SURVEYOR-II, Part 4 and ENDURANCE-4 studies, adult patients with untreated or previously treated patients with HCV genotype 2, genotype 4, genotype 5, or genotype 6 infection, without cirrhosis, were given once-daily oral glecaprevir/pibrentasvir (n = 121 in ENDURANCE-4 and n = 145 in SURVEYOR-II) for 12 or 8 weeks, respectively. In all studies the primary endpoint was sustained virologic response at 12 weeks after treatment (SVR12) in the intention-to-treat population., Results: Among patients receiving glecaprevir/pibrentasvir for 8 weeks, rates of SVR12 were 98% (95% CI, 94.1-99.3) in those infected with HCV genotype 2 and 93% (95% CI, 83.6-97.3) in those infected with HCV genotypes 4, 5, or 6. Among patients receiving glecaprevir/pibrentasvir for 12 weeks, rates of SVR12 were 99.5% (95% CI, 98.5-100) in those infected with HCV genotype 2 and 99% (95% CI, 97.6-100) in those infected with HCV genotype 4, 5, or 6. No virologic failures occurred in patients with HCV genotype 4, 5, or 6 infections. The frequency and severity of adverse events in patients receiving glecaprevir/pibrentasvir were similar to those of patients who received placebo., Conclusion: In 3 Phase 3 studies, 8 weeks' treatment with glecaprevir/pibrentasivr produced an SVR12 in at least 93% of patients with chronic HCV genotype 2, 4, 5, or 6 infection without cirrhosis, with virologic failure in less than 1%. The drug combination had a safety profile comparable to 12 week's treatment with glecaprevir/pibrentasvir. ClinicalTrials.gov numbers: NCT02640482 (ENDURANCE-2), NCT02636595 (ENDURANCE-4), and NCT02243293 (SURVEYOR-II)., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The original version of this article unfortunately contained a mistake. The family name of Rui Tato Marinho was incorrectly spelled as Marinhoe.

Fatty Liver Disease (FLD) is caused by the deposition of fat in liver cells and leads to deadly diseases such as liver cancer. Several FLD detection and characterization systems using machine learning (ML) based on Support Vector Machines (SVM) have been applied. These ML systems utilize large number of ultrasonic grayscale features, pooling strategy for selecting the best features and several combinations of training/testing. As result, they are computationally intensive, slow and do not guarantee high performance due to mismatch between grayscale features and classifier type. This study proposes a reliable and fast Extreme Learning Machine (ELM)-based tissue characterization system (a class of Symtosis) for risk stratification of ultrasound liver images. ELM is used to train single layer feed forward neural network (SLFFNN). The input-to-hidden layer weights are randomly generated reducing computational cost. The only weights to be trained are hidden-to-output layer which is done in a single pass (without any iteration) making ELM faster than conventional ML methods. Adapting four types of K-fold cross-validation (K = 2, 3, 5 and 10) protocols on three kinds of data sizes: S0-original, S4-four splits, S8-sixty four splits (a total of 12 cases) and 46 types of grayscale features, we stratify the FLD US images using ELM and benchmark against SVM. Using the US liver database of 63 patients (27 normal/36 abnormal), our results demonstrate superior performance of ELM compared to SVM, for all cross-validation protocols (K2, K3, K5 and K10) and all types of US data sets (S0, S4, and S8) in terms of sensitivity, specificity, accuracy and area under the curve (AUC). Using the K10 cross-validation protocol on S8 data set, ELM showed an accuracy of 96.75% compared to 89.01% for SVM, and correspondingly, the AUC: 0.97 and 0.91, respectively. Further experiments also showed the mean reliability of 99% for ELM classifier, along with the mean speed improvement of 40% using ELM against SVM. We validated the symtosis system using two class biometric facial public data demonstrating an accuracy of 100%.

Background: HCV treatment among people who inject drugs (PWID) is low. Education programs may be suitable strategies to improve patients' knowledge about their condition and to overcome barriers to access treatment., Methods: The Health Educational Program (HEP) consisted of patient workshops and educational videos and leaflets, and healthcare professionals' workshops. HEP was implemented at seven substance dependence treatment centers (STDC) in Portugal. The study comprised two cross-sectional evaluations conducted before and after HEP. At both evaluations, adult patients with confirmed HCV diagnosis and registered in the STDC were consecutively included. For patients that completed both evaluations, the overall knowledge score were calculated and compared with McNemar test. Linear regression modelling was used to evaluate factors associated with baseline knowledge. Rates of referral and attendance to referral specialist, treatment proposal, initiation and retention at both evaluations were also compared with McNemar test., Results: Overall, 504 patients with chronic hepatitis C were included: 78 % male, mean age 42.3 ± 6.6 years, 14 % school education ≤ 4 years, disease duration 11.0 ± 6.0 years and 26 % HIV co-infected. A higher baseline knowledge was independently associated with educational level ≥ 10 years (regression coefficient [B] =15.13, p < 0.001), current use of intravenous drugs (B = 7.99, p = 0.038), previous referral for treatment (B = 4.26, p = 0.008) and previous HCV treatment (B = 5.40, p = 0.003). Following HEP, mean knowledge score increased from 69 % to 79 % (p < 0.001). The rate of patient referral to a liver specialist increased from 56.2 % to 67.5 % (p < 0.001)., Conclusions: An HEP conducted at STDCs improved significantly patient knowledge about hepatitis C, even among patients with a high baseline knowledge. The HEP has also increased the rate of referral to the liver specialist and showed a great potential to support healthcare professionals in managing HCV. Education programs may promote treatment access among PWID, a population that represents the majority of HCV infected patients.

Background: Liver disease, one of the most common causes of hospitalization worldwide, is particularly prevalent in Europe. This study aimed to determine the number of hospital discharges and admissions, mortality, premature death and costs associated with liver disease from the perspective of the National Health Service in Portugal., Methods: A descriptive, retrospective analysis of data from 97 hospitals between 2000 and 2008, and mortality data for 2011 collected from the Portuguese National Institute of Statistics. The 9th and 10th revisions of the international classification of diseases were used to establish diagnoses. National data on demographics, average length of stay, in-patient mortality and direct costs associated with hospital admissions and liver transplantation were compared for the most common liver diseases. Mortality and premature death were compared using the potential years of life lost (PYLL) index., Results: The annual mean number of discharges for liver disease was 11,503 between 2000 and 2008. Most cases of liver disease were diagnosed in men (70.4 %) and the prevalence of liver disease peaked in patients aged from 20 to 64 years (60.7 %). Alcoholic cirrhosis was the most frequent liver-disease diagnosis leading to discharge (38.6 %). In addition, alcoholic cirrhosis emerged as the main cost-driver, accounting for €26,818,930 (42.6 %) of the total cost imposed by liver disease. Overall, chronic hepatic disease was the 10th most common cause of mortality in Portugal in 2011, causing 21.8 deaths per 100,000. Chronic hepatic disease and hepatocellular carcinoma are even more important causes of premature death, ranking third based on PYLL., Conclusion: In 2011, liver disease was the 10th most common cause of death and the third most important cause of premature death in Portugal. Alcohol cirrhosis was the leading cause of liver-related hospital admissions between 2001 and 2008. It appears that liver disease imposes a considerable social and economic burden on Portugal. Our results suggest that educational, legislative and therapeutic interventions to prevent morbidity, mortality and premature death from liver disease are urgently required to minimise the economic and clinical burdens.

The statistics proved that approximately 25% of the patients with acute HCV present with jaundice, and only 10-20% develop gastrointestinal symptoms. We present the case of a 58 year-old woman, with prior antecedents of arterial hypertension and diabetes mellitus since 25 years old, hypercholesterolemia and hypertriglyceridemia, psoriasis, epilepsy and depressive syndrome. She clinically presents asthenia, anorexia, itching, jaundice and choluria. The objective examination showed an orientated patient, without flapping, hemorrhagic dyscrasia or signs of chronic hepatic disease, with icteric mucosa and skin, abdominal pain, with hepatomegaly and splenomegaly. The laboratory tests have been compatible with acute hepatitis with colestatic pattern: AST/ALT 969/798 UI/ml, FA 796 UI/ml, GGT 2476 UI/ml, BT/BD 7.39/6.10, INR 0.9. The abdominal echography showed: hepatomegaly, regular borders, hepatic steatosis, splenomegaly without ascitic fluid. The viral serological tests revealed protection for hepatitis A ( IgM neg/IgG pos), negative for HVB infection (AgHBs neg, anti-HBc neg), negative for HVE and other viruses (CMV Herpes virus, Epstein Barr, HIV), positive antibodies for HCV and positive RNA VHC (164200 UI/ml), HCV genotype 3a, IL-28B CT, negative autoimmunity. The previous HCV tests were negative, sustaining the recent infection. We assumed an acute hepatitis C. The patient was symptomatically treated with hydroxyzine for the skin itch, with vitamin K for INR correction and she was closely monitored. She had good clinical and laboratorial evolution and she was discharged after one week, maintaining hepatology consultation. She spontaneously cleared HCV infection after 3 months, maintaining negative RNA VHC 6 months after infection. The patient has cured the HCV infection with no need for antiviral treatment.