The effect of COVID-19 on vascular elasticity and liver function in overweight patients.

Objective. To study the changes in the vascular wall, vascular age and metabolic parameters in polymorbid COVID-19 conva-lescents. Material and methods. The study included 62 patients with hypertension who reached the target blood pressure (BP) with dual an-tihypertensive therapy after severe and extremely severe COVID-19. The following examinations were performed: laboratory tests of metabolic parameters, assessment of changes in the vessel elasticity indices (pulse-wave velocity (PWV), augmentation index (AI), central systolic BP (cSBP), 24-hour BP monitoring, and non-invasive markers of liver fibrosis. Results. According to office BP measurements, after the coronavirus infection, an increase in systolic BP (SBP) by 29.6% and di-astolic BP (DBP) by 23.6%, as well as heart rate (HR) by 11.8% (p<0.05) was reported during regular antihypertensive therapy. In addition, 24-hour BP monitoring data indicated an increase in the average daily SBP, DBP, and heart rate. After the coronavirus infection, an increase in PWV by 35.4% (p<0.05), AI by 24.4% (p<0.05), cSBP by 22.1% were reported. Carbohydrate and lipid metabolism parameters deteriorated. A pronounced adverse effect of coronavirus infection on liver function was observed. The vascular age (according to the modified SCORE scale) increased by 6 years (p<0.05). Conclusion. Our study showed that patients after severe and extremely severe COVID-19 have a high risk of liver fibrosis, hypertension and lipid metabolism control worsening and accelerating vascular aging.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

The effect of COVID-19 on vascular elasticity and liver function in overweight patients.

Objective. To study the changes in the vascular wall, vascular age and metabolic parameters in polymorbid COVID-19 conva-lescents. Material and methods. The study included 62 patients with hypertension who reached the target blood pressure (BP) with dual an-tihypertensive therapy after severe and extremely severe COVID-19. The following examinations were performed: laboratory tests of metabolic parameters, assessment of changes in the vessel elasticity indices (pulse-wave velocity (PWV), augmentation index (AI), central systolic BP (cSBP), 24-hour BP monitoring, and non-invasive markers of liver fibrosis. Results. According to office BP measurements, after the coronavirus infection, an increase in systolic BP (SBP) by 29.6% and di-astolic BP (DBP) by 23.6%, as well as heart rate (HR) by 11.8% (p<0.05) was reported during regular antihypertensive therapy. In addition, 24-hour BP monitoring data indicated an increase in the average daily SBP, DBP, and heart rate. After the coronavirus infection, an increase in PWV by 35.4% (p<0.05), AI by 24.4% (p<0.05), cSBP by 22.1% were reported. Carbohydrate and lipid metabolism parameters deteriorated. A pronounced adverse effect of coronavirus infection on liver function was observed. The vascular age (according to the modified SCORE scale) increased by 6 years (p<0.05). Conclusion. Our study showed that patients after severe and extremely severe COVID-19 have a high risk of liver fibrosis, hypertension and lipid metabolism control worsening and accelerating vascular aging.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

The effect of COVID-19 on vascular elasticity and liver function in overweight patients.

Objective. To study the changes in the vascular wall, vascular age and metabolic parameters in polymorbid COVID-19 conva-lescents. Material and methods. The study included 62 patients with hypertension who reached the target blood pressure (BP) with dual an-tihypertensive therapy after severe and extremely severe COVID-19. The following examinations were performed: laboratory tests of metabolic parameters, assessment of changes in the vessel elasticity indices (pulse-wave velocity (PWV), augmentation index (AI), central systolic BP (cSBP), 24-hour BP monitoring, and non-invasive markers of liver fibrosis. Results. According to office BP measurements, after the coronavirus infection, an increase in systolic BP (SBP) by 29.6% and di-astolic BP (DBP) by 23.6%, as well as heart rate (HR) by 11.8% (p<0.05) was reported during regular antihypertensive therapy. In addition, 24-hour BP monitoring data indicated an increase in the average daily SBP, DBP, and heart rate. After the coronavirus infection, an increase in PWV by 35.4% (p<0.05), AI by 24.4% (p<0.05), cSBP by 22.1% were reported. Carbohydrate and lipid metabolism parameters deteriorated. A pronounced adverse effect of coronavirus infection on liver function was observed. The vascular age (according to the modified SCORE scale) increased by 6 years (p<0.05). Conclusion. Our study showed that patients after severe and extremely severe COVID-19 have a high risk of liver fibrosis, hypertension and lipid metabolism control worsening and accelerating vascular aging.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Abstracts for the British Association of Dermatologists 102nd Annual Meeting

The proceedings contain 388 papers. The topics discussed include: vitiligo diagnosis is associated with an increase in new-onset depression and anxiety: a population-based cohort study in the UK;effect modification of biologic survival by patient characteristics: a prospective cohort study from the British Association of Dermatologists Biologics And Immunomodulators Register;'a raised P3NP is a matter of time': replacing P3NP with FIB-4 for monitoring of methotrexate-related liver fibrosis;a randomized controlled trial assessing the effectiveness and safety of ciclosporin vs. methotrexate in the treatment of severe atopic eczema in children and young people: the treatment of severe atopic eczema trial (TREAT);carbonylated proteins as markers of oxidative stress and their association with filaggrin genotype in atopic eczema;skin tumors in England 2013-2019: in-depth reporting of a new consensus classification to improve prospective data extraction and clinical interpretation;a national review of porocarcinoma epidemiology in England 2013-2018;national Merkel cell carcinoma epidemiology and mortality-related risk factors in England 2004-2018;and hospitalization from COVID-19 is most frequently observed in patients with atopic dermatitis treated with systemic corticosteroids, and in particular when systemic corticosteroids are used in combination with another immunomodulatory treatment: lessons from the global SECURE-AD registry.

Expression and Function of BMP and Activin Membrane-Bound Inhibitor (BAMBI) in Chronic Liver Diseases and Hepatocellular Carcinoma.

BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) is a transmembrane pseudoreceptor structurally related to transforming growth factor (TGF)-ß type 1 receptors (TGF-ß1Rs). BAMBI lacks a kinase domain and functions as a TGF-ß1R antagonist. Essential processes such as cell differentiation and proliferation are regulated by TGF-ß1R signaling. TGF-ß is the best-studied ligand of TGF-ßRs and has an eminent role in inflammation and fibrogenesis. Liver fibrosis is the end stage of almost all chronic liver diseases, such as non-alcoholic fatty liver disease, and at the moment, there is no effective anti-fibrotic therapy available. Hepatic BAMBI is downregulated in rodent models of liver injury and in the fibrotic liver of patients, suggesting that low BAMBI has a role in liver fibrosis. Experimental evidence convincingly demonstrated that BAMBI overexpression is able to protect against liver fibrosis. Chronic liver diseases have a high risk of hepatocellular carcinoma (HCC), and BAMBI was shown to exert tumor-promoting as well as tumor-protective functions. This review article aims to summarize relevant studies on hepatic BAMBI expression and its role in chronic liver diseases and HCC.

Nonalcoholic fatty liver disease and diabetes.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression. The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance; thus the association between diabetes and NAFLD is widely recognized in the literature. Since NAFLD is the hepatic manifestation of a metabolic disease, it is also associated with a higher cardio-vascular risk. Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis, although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients. Treatment of NAFLD patients depends on the disease severity, ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis. Abstinence from alcohol, a Mediterranean diet, and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events, as per all diabetic patients. In addition, weight loss induced by bariatric surgery seems to also be effective in improving liver features, together with the benefits for diabetes control or resolution, dyslipidemia, and hypertension. Finally, liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries. This review offers a comprehensive multidisciplinary approach to NAFLD, highlighting its connection with diabetes.

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited;35 females;median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition. © 2022 The Author(s)

Ivermectin Attenuates CCl4-Induced Liver Fibrosis in Mice by Suppressing Hepatic Stellate Cell Activation.

Liver fibrosis, a common liver dysfunction with high morbidity and mortality rates, is the leading cause of cirrhosis and hepatocellular carcinoma, for which there are no effective therapies. Ivermectin is an antiparasitic drug that also has been showing therapeutic actions in many other diseases, including antiviral and anticancer actions, as well as treating metabolic diseases. Herein, we evaluated the function of ivermectin in regulating liver fibrosis. Firstly, carbon tetrachloride (CCl4)-injected Balb/c mice were used to assess the antifibrosis effects of ivermectin in vivo. Further, CFSC, a rat hepatic stellate cell (HSC) line, was used to explore the function of ivermectin in HSC activation in vitro. The in vivo data showed that ivermectin administration alleviated histopathological changes, improved liver function, reduced collagen deposition, and downregulated the expression of profibrotic genes. Mechanistically, the ivermectin treatment inhibited intrahepatic macrophage accumulation and suppressed the production of proinflammatory factors. Importantly, the ivermectin administration significantly decreased the protein levels of α-smooth muscle actin (α-SMA) both in vivo and in vitro, suggesting that the antifibrotic effects of ivermectin are mainly due to the promotion of HSC deactivation. The present study demonstrates that ivermectin may be a potential therapeutic agent for the prevention of hepatic fibrosis.

Features of respiratory tests (hydrogen + methane), indirect liver elastometry data in COVID-19 convalescents (pilot study)

Purpose of the work: to study liver elasticity indicators, hydrogen and methane levels in exhaled air, and their associations with clinical and biochemical parameters for patients who underwent COVID-19. Materials and methods. We examined 30 patients (mean age 51.8±2.91) who underwent COVID-19 (confirmed by SARSCoV-2 RNA test or SARS-CoV-2 antigen) 12-16 weeks after the onset of the first symptoms, of which 11 were diagnosed with pneumonia. 19 people (mean age 47.1±3.09) who did not have COVID-19 made up the comparison group. The patients underwent a clinical and biochemical study, the degree of liver fibrosis was determined (FibroScan® 502 Echosens, France), the levels of hydrogen (H2) and methane (CH4) in the exhaled air were measured (baseline and after taking lactulose solution) (GastroCheck Gastrolyzer, Bedfont Scientific Ltd., England). Results. Past COVID-19 infection was directly correlated with age (r=0.331, p=0.022), male gender (r=0.324, p=0.025), and presence of liver fibrosis (r=0.291, p=0.044). COVID-19 survivors were more likely to have liver fibrosis (p<0.001) and higher liver elasticity in kPa (p=0.018) with overweight and obesity (63.3%) and elevated body mass index (p= 0.03) compared with the control group. The presence of liver fibrosis was associated with moderate pneumonia (p<0.001). Among those who had COVID-19, there were significantly more non-producers of methane (p=0.02), fewer people with an average level of methane in exhaled air (p=0.016). In COVID-19 convalescents, bacterial overgrowth syndrome (BOS) was detected less frequently than in controls (p=0.04), but signs of delayed intestinal transit were more often recorded (p<0.05). The presence of liver fibrosis in survivors of COVID-19 is associated with BOS detection (23.3% vs. 5.2%, p<0.001), which probably contributes to the pathogenesis of liver damage. Hydrogen levels at 120 min and methane at 60 min after ingestion of lactulose solution distinguished between COVID-19 convalescents and COVID-19 survivors with an AUC of 0.683 and 0.660, respectively. The associations of the levels of gases in the exhaled air with clinical and biochemical parameters were revealed: the presence of overweight and obesity showed inverse associations with the level of methane production (r= -0.342, p<0.05), its concentration after taking lactulose at various time intervals, and also the basic level of hydrogen (r= -0.313, p<0.05);the degree of obesity was also inversely correlated with the level of methane emission (r= -0.368, p=0.038). Direct links were established between indicators of liver elasticity in kPa and the level of hydrogen production (r=0.275, p<0.05). Conclusions. Obtained indirect signs of pronounced changes in the intestinal microbiome, which obviously contribute to a more severe course of COVID-19, the development of liver fibrosis, so the impact on the intestinal microflora can be considered as a potential target in the treatment of patients with COVID-19. © 2022 Kola Science Centre of the Russian Academy of Sciences. All rights reserved.

Physical Activity of Obese Children and Adolescents with the Nonalcoholic Fatty Liver Disease during the Covid-19 Pandemic

Introduction: Social isolation due to the COVID-19 pandemic leads to changes in general physical activity in children with nonalcoholic fatty liver disease (NAFLD) which may aggravate the course of the disease and alleviate the efficacy of the treatment. Aims & Methods: The aim of our study was to investigate the physical activity (PA) in children and adolescents with NAFLD during the COVID-19 pandemic and its association with liver fibrosis. 40 obese patients with NAFLD aged from 10 to 17 years (average age was 12.15 +/- 2.51 years) were examined from September-October 2021. Obesity was established by body mass index (BMI) calculation and comparison with the sigma deviations of BMI values according to age and sex. The presence of liver fibrosis and steatosis was evaluated by transient elastography (Fibroscan502touch, France). Children were divided into 4 groups according to transient elastography and BMI: 1 group - 13 children with NAFLD and liver fibrosis, 2 group - 13 children with NAFLD without fibrosis, 3 group - 14 obese children without NAFLD and fibrosis. The 4 group (control) consisted of 10 children with normal weight without NAFLD and fibrosis. The assessment of physical activity was conducted with the Physical Activity Questionnaire for older children (PAQ-C) and adolescents (PAQ-A). Result(s): The final summary score of the PA amounted to 2.4+/-0.3 in the 1 group, 2.2+/-0.2 in the 2 group, 2.2+/-0.3 in the 3 group, 2.4+/-0.2 in the 4 group without significant differences between the groups. The level of PA in spare time was the lowest in all groups compared to other types of activity. The highest rate of the PA score was observed in all groups during physical education classes, but the number of children who attended these classes not regularly was 43.9% among whom do not attend physical education classes at all 9.8%, almost never - 2.4%, from time to time - 31.7% of children. Only 26.8% of patients were active at recess while 73.2% of children stood or walked within the classroom or sat down. The level of PA of chil dren right after school increased slightly, also without significant differences between groups, but children with liver fibrosis had the lowest PA level (2.1 +/-0.2). 24.4% of children did not have any PA right after school. Free time at the weekend was not accompanied by an increase in physical activity, on the contrary, the summary score decreased in almost all groups to 1.94 points, and the portion of children without physical activity remains stable (24.4%). According to self-reports children of the 1-3 groups had a lower level of physical activity score compared to children of the control group. Almost 73.2% of interviewed children understood that their level of physical activity was low. The total level of physical activity on each day of the week was the lowest in children with liver fibrosis (1 group). The highest percentage of PA absence was on weekends. The total PA score was negatively correlated with calf circumference (r = -0.582, p = 0.018), self-report PA tended to a negative correlation with the level of alaninaminotransferase (r = - 0.372, p = 0.056). Conclusion(s): Physical activity of obese NAFLD children during the COVID- 19 pandemic is low, especially in spare time, and does not rise at the weekends. The majority of children (73.2%) are inactive at recess as well as self-reported low level of PA. NAFLD children with liver fibrosis have the lowest total level of PA right after school and generally on each day of the week, which may reflect an insufficiency of adaptation.

Liver Fibrosis Indices Predict the Severity of SARS-CoV-2 Infection.

Discovering novel risk and prognostic factors for COVID-19 may help not only in reducing severity and mortality but also in creating targeted therapies considering patients' individual features. Liver fibrosis is considered a complication in Non-alcoholic Fatty Liver Disease (NAFLD), it is a feature of steatohepatitis (NASH), and it has already been related to an increased risk for a wide range of diseases. Here, we aimed to define if any parameter assessing metabolic status has predictive power in identifying inpatients at risk for poorer prognosis and an increased mortality from COVID-19. This retrospective study was conducted at the Sub-Intensive Medicine Care Unit of the Presidio Maxi-Emergenze Fiera del Levante, Azienda Ospedaliero-Universitaria Policlinico di Bari, Italy. We evaluated 271 inpatients with moderate-to-severe SARS-CoV-2-related respiratory failure by comparing biochemical features and non-invasive liver fibrosis scores among discharged, transferred to Intensive Care Units (ICU) and non-survivor patients. Moreover, by performing ROC curves, we defined cut-off values to predict mortality and disease severity for each score. We found that non-invasive scores of liver fibrosis, obtained at day of admission, such as AAR (p < 0.001), FIB-4 and mFIB-4, FORNS, and AARPRI (p < 0.05) strongly predict not only in-hospital mortality but also the length of hospitalization and eventual admission to ICU. FIB-4 was the best score to identify non-survivor patients (sensitivity of 80% and specificity of 63%) and predict the need for ICU or mortality (71% of sensitivity and 65% of specificity), with a cut-off value of 1.94. Therefore, we present the predictive power and the cut-off values of several liver fibrosis scores here for disease severity and mortality in SARS-CoV-2 in-patients and we proposed the use of the present scores to identify ab initio the clinical therapeutic and diagnostic protocols for high-risk patients.

Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia.

Familial combined hyperlipidemia (FCH) is a very common inherited lipid disorder, characterized by a high risk of developing cardiovascular (CV) disease and metabolic complications, including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The prevalence of non-alcoholic fatty liver disease (NAFLD) is increased in FCH patients, especially in those with IR or T2DM. However, it is unknown how precociously metabolic and cardiovascular complications appear in FCH patients. We aimed to evaluate the prevalence of NAFLD and to assess CV risk in newly diagnosed insulin-sensitive FCH patients. From a database including 16,504 patients, 110 insulin-sensitive FCH patients were selected by general practitioners and referred to the Lipid Center. Lipid profile, fasting plasma glucose and insulin were determined by standard methods. Based on the results of the hospital screening, 96 patients were finally included (mean age 52.2 ± 9.8 years; 44 males, 52 females). All participants underwent carotid ultrasound to assess carotid intima media thickness (cIMT), presence or absence of plaque, and pulse wave velocity (PWV). Liver steatosis was assessed by both hepatic steatosis index (HSI) and abdomen ultrasound (US). Liver fibrosis was non-invasively assessed by transient elastography (TE) and by fibrosis 4 score (FIB-4) index. Carotid plaque was found in 44 out of 96 (45.8%) patients, liver steatosis was found in 68 out of 96 (70.8%) and in 41 out of 96 (42.7%) patients by US examination and HSI, respectively. Overall, 72 subjects (75%) were diagnosed with steatosis by either ultrasound or HSI, while 24 (25%) had steatosis excluded (steatosis excluded by both US and HSI). Patients with liver steatosis had a significantly higher body mass index (BMI) compared to those without (p < 0.05). Steatosis correlated with fasting insulin (p < 0.05), liver stiffness (p < 0.05), BMI (p < 0.001), and inversely with high-density lipoprotein cholesterol (p < 0.05). Fibrosis assessed by TE was significantly associated with BMI (p < 0.001) and cIMT (p < 0.05); fibrosis assessed by FIB-4 was significantly associated with sex (p < 0.05), cIMT (p < 0.05), and atherosclerotic plaque (p < 0.05). The presence of any grade of liver fibrosis was significantly associated with atherosclerotic plaque in the multivariable model, independent of alcohol habit, sex, HSI score, and liver stiffness by TE (OR 6.863, p < 0.001). In our cohort of newly diagnosed, untreated, insulin-sensitive FCH patients we found a high prevalence of liver steatosis. Indeed, the risk of atherosclerotic plaque was significantly increased in patients with liver fibrosis, suggesting a possible connection between liver disease and CV damage in dyslipidemic patients beyond the insulin resistance hypothesis.

Enhanced liver fibrosis score as a noninvasive biomarker in hepatitis C virus patients after direct-acting antiviral agents.

Background: In more than 90% of chronic viral hepatitis C (HCV) patients treated with direct-acting antiviral agents (DAAs), a sustained viral response (SVR) was observed. Unfortunately, there are subgroups of subjects who display enduring liver fibrosis and are at high risk of developing hepatocellular carcinoma (HCC). Thus, liver fibrosis evaluation during the follow-up of these patients plays a pivotal role. The gold standard to evaluate hepatic fibrosis is liver biopsy, which is an invasive procedure. Imaging techniques and serum biomarkers have been proposed as safer and cheaper procedures. Objectives: In this study, we evaluated the concordance of transient elastography (TE) with ELF score ( enhanced liver fibrosis) in a cohort of patients with HCV before and after direct-acting antiviral (DAAs) treatment. ELF score has been validated in other chronic liver diseases; the evidence is not available in HCV patients treated with DAAs. Study design: We prospectively recruited all consecutive HCV patient candidates for DAAs therapy at the University of Naples "Federico II" between April 2015 and July 2016. TE and ELF scores were assessed at baseline, at SVR24, and at SVR48. Results: One-hundred-nineteen patients were treated with DAAs, and 94.1% of them reached SVR. A total of 55.5% of patients were males with a mean age of 64.7 ± 9.6 years. TE results revealed that 12 patients (10%) had F1-2 mild/moderate fibrosis, and 107 (90%) had F3-4 advanced fibrosis. At baseline, SVR24, and SVR48, the concordance between ELF test and TE was poor: 0.11 (p = 0.086), 0.15 (p = 0.124), and 0.034 (p = 0.002), respectively. However, at SVR24 and SVR48, both methods showed a significant amelioration of liver fibrosis compared to baseline (p < 0.001). In addition, both ELF index and TE were significantly associated with portal hypertension at baseline, but not with varices and ascites. Conclusions: Our findings suggested that ELF test could predict changes in liver fibrosis, independently of TE. In case of TE unavailability, ELF score could represent an appropriate tool. Notably, in the context of the COVID-19 pandemic, ELF testing should be encouraged to reduce unnecessary access to the hospital and prolonged physical contact.

TWO-TIERED LIVER FIBROSIS ASSESSMENT IN PRIMARY CARE ANNUAL DIABETIC SCREENING - 3 YEAR FOLLOW UP

Introduction We previously presented the outcome of a pathway incorporating 2-tiered fibrosis assessment into annual diabetic reviews in primary care. This 3 year follow up study looks at: 1. Outcomes in patients referred into secondary care with moderate-advanced fibrosis Ongoing service delivery requirements after the first year of case finding Effectiveness of the pathway in detecting patients with advanced disease, by looking at the number of patients missed in the pathway presenting with advanced disease. Methods All patients aged >35 years with Type 2 Diabetes Mellitus (T2DM) attending annual review at two primary care practices in North East England between April 2018 and September 2019 (n=467) had a Fib-4 requested, followed by transient elastography (TE) if the Fib-4 was above the high sensitivity threshold. Those with a liver stiffness measurement (LSM) >8kPa were reviewed in secondary care. This pathway was continued in both practices after the end of the initial study period. We reviewed the outcomes of all patients referred to secondary care;the number of patients referred in the subsequent years with ongoing case-finding;and any patients missed from initial screening presenting with decompensated/ symptomatic disease. Results From the 467 patients in the initial study, 58 were referred for TE, 25 had a LSM>8kPa and 20 had advanced disease (on imaging/biopsy/endoscopy). 6/20 (30%) patients with advanced disease have died- 2/20 liver related deaths (hepatocellular carcinoma (HCC) and decompensated cirrhosis);1 patient diagnosed with HCC was treated with curative transarterial chemoembolisation;3 patients had varices on OGD (2 started on carvedilol for primary prophylaxis);12 remain under follow up. In all patients with LSM >8kPa (n=25): 8/25 (32%) died (3/8 from COVID-19);24% (6) LSM improved, 8% (2) LSM deteriorated;32% (8/25) lost weight. No patients missed by the pathway presented with decompensated disease. Serial FIB- 4 at annual screening 2019-2021: 4 patients new raised Fib-4 scores - 1 DNA, 1 TE is awaited, 1 LSM <8kPa (discharged), 1 advanced disease (LSM 17.1kPa). Conclusion Incorporation of a two-tiered liver fibrosis assessment into primary care annual diabetic screening significantly improves identification of advanced liver disease and no patients have presented with advanced disease out-with the pathway. It allows for early detection and interventions against the complications associated with advanced liver disease. Mortality in patients with advanced liver disease remains high. Referrals for TE and into secondary care dramatically reduce after the initial year of case finding.

Abstracts of the BSG Annual Meeting

The proceedings contain 374 papers. The topics discussed include: optical biopsy with linked color imaging accurately predicts inflammation in ulcerative colitis;predicting use of opiates in patients with inoperable pancreatic cancer: a retrospective cohort study;unbiased clustering of breath signature in NAFLD identifies disease progression high-risk patient phenotype - 5 year study;prevalence of malnutrition screening;the association between IBD and mental ill health: a retrospective primary care cohort study;the interleukin 22//neutrophil axis is associated with treatment resistance in ulcerative colitis;neuromuscular dysfunction in patients with nausea and vomiting syndrome defined by body surface gastric mapping;two-tiered liver fibrosis assessment in primary care annual diabetic screening 3 year follow up;can an algorithm help in the difficult dilemma of upper gastrointestinal bleed and anticoagulant COVID-19 pandemic and alcohol-specific hospital admissions;and upper gastrointestinal hemorrhages and COVID-19: a nationwide cohort study of the pandemic's impact on hospitalizations.

Temporal changes in patient-reported outcome measures stratified by liver fibrosis severity in large-duct primary sclerosing cholangitis

Background and aims: Patient-reported outcome measures (PROMs) are increasingly used as exploratory end points in clinical trials. The aim of this studywas to evaluate the temporal relationship between health-related quality of life (HrQoL) and liver fibrosis using generic (SF-36) and disease-specific (PSC-PRO) tools. Method: Patients with large-duct PSC were invited to complete HrQoL questionnaires in an outpatient setting at baseline (V1) and follow-up (V2) visits at least 12 months apart. Transient elastography liver stiffness (LS;Echosens, France) measurementswere recorded on the same day. SF-36 and PSC-PRO health domains were scored out of a maximum of 100% and 5, respectively. Mean scores were calculated for each domain with lower SF-36 and higher PSC-PRO scores representing poorer quality of life. Advanced fibrosis (F3-6) was defined based on published cutoff of LS >9.6kPa in PSC. Results: Fifty-five patients (64% male) with median age 45 years (range: 20–77) and median PSC duration 11 years (range: 2–26) attended both study visits. The median time between visits was 417 days (range: 362–582). The mean scores were numerically lower at V2 than V1 in all the SF-36 domains but only three domains showed statistically significant difference: bodily pain (74% vs 83%, p < 0.01), energy/fatigue (47% vs 57%, p < 0.0001), and mental summary score (66% vs 71%, p < 0.001). There were no differences in any of the PSCPRO domains between the visits. When stratified by baseline LS >9.6 kPa threshold (Figure 1), SF-36 physical functioning mean score dropped in the F3-6 group but increased slightly in the F0-2 group (−9.0 ± 17% vs 0.4 ± 21%, p = 0.01). In the PSC-PRO, the emotional impact mean score increased in the F3-6 group but decreased in the F0-2 group (0.6 ± 0.7 vs −0.1 ± 0.5, p < 0.01). Therewere no significant differences in mean scores in the other domains between the visits.(Figure Presented)Conclusion: Therewasworsening of bodily pain, levels of energy and mental health even within a year in patients with large-duct PSC. Patients with advanced fibrosis reported lower physical functioning and higher emotional impact of their disease compared to those without advanced fibrosis. Changes in PROMs are related to liver fibrosis and need to be considered in future antifibrotic drug trials. These findings, however, need to be interpreted in the context of imposed restrictions during the Covid-19 pandemic which may have had a significant psycho-social impact on patients.

Rationale for evaluation of PLN-74809 treatment in participants with primary sclerosing cholangitis in Phase 2a study INTEGRIS-PSC

Background and aims: Transforming growth factor beta (TGF-beta) signalling is a key driver of liver fibrosis. In primary sclerosing cholangitis (PSC), integrins over-expressed on injured cholangiocytes (alpha-v/beta-6) and myofibroblasts (alpha-v/beta-1) regulate TGFbeta activity. PLN-74809 is an oral, once-daily, dual-selective inhibitor of integrins alpha-v/beta-6 and alpha-v/beta-1 in development for the treatment of PSC and idiopathic pulmonary fibrosis. It has shown favourable tolerability in over 280 healthy participants, reduced TGF-beta signalling and achieved high target engagement in human lungs. Pre-clinical evaluation of antifibrotic activity resulting from dual integrin inhibition was performed to support clinical evaluation. Method: PLN-74809 was administered orally for 6 weeks in BALBc. Mdr2-/- mice with established fibrosis. A tool alpha-v/beta-6 and alpha-v/beta-1 inhibitor compound, PLN-75068, was tested therapeutically in a diet-induced mouse model of biliary fibrosis using 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC). Hepatic collagen was quantified by hydroxyproline (OHP) and collagen proportionate area (CPA) and TGF-beta signalling by phosphorylated SMAD3 (pSMAD3) levels. An ex vivo study evaluated the effects of 2-day treatment with PLN-74809 on the expression of profibrotic genes, COL1A1 and COL1A2, in precision-cut liver slices (PCLivS) from tissue explants of participants with biliary fibrosis (n = 2 PSC;n = 2 primary biliary cholangitis [PBC]). A review of available blinded safety data from the enrolling Phase 2a study in participants with PSC was performed (NCT04480840). Results: PLN-74809 dose-dependently reduced OHP (up to ∼30%, p < 0.05), CPA (up to ∼50%, p < 0.05) and pSMAD3 (up to ∼40%, p < 0.001) in the BALBc.Mdr2-/- mouse model, as well as COL1A1 and COL1A2 gene expression (up to ∼30%, p = 0.0789) in PCLivS from tissue explants of participants with PSC and PBC. PLN-75068 reduced OHP (up to ∼20%, p < 0.05) in DDC-injured mice in a dose-dependent manner. PLN-74809waswell tolerated in participants with PSC. Most adverse events (AEs)were mild;nonewere severe. The most common AE was mild headache. One participant experienced serious AEs at least 20 days after the last dose of study drug, deemed not related by the investigator. One participant prematurely discontinued due to COVID-19. PLN-74809 pharmacokinetics in participants with PSC were consistent with those of healthy participants. Conclusion: Pharmacological inhibition of integrins alpha-v/beta-6 and alpha-v/beta-1 demonstrated antifibrotic activity in two models of biliary fibrosis and in PCLivS from participants with PSC or PBC. Available safety findings from participants with PSC enrolled in the ongoing Phase 2a INTEGRIS-PSC study, continue to support the favourable tolerability profile of PLN-74809.

Structured Early detection of Asymptomatic Liver Cirrhosis: Results of the population-based liver screening program SEAL.

BACKGROUND & AIMS: Detection of patients with early cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. The SEAL program aimed at evaluating the usefulness of a structured screening procedure to detect cirrhosis as early as possible. METHODS: SEAL was a prospective cohort study with a control cohort from routine care data. Individuals participating in the general German health check-up after the age of 35 ("Check-up 35") at their primary care physicians were offered a questionnaire, liver function tests (aspartate and alanine aminotransferase [AST and ALT]), and follow-up. If AST/ALT levels were elevated, the AST-to-platelet ratio index (APRI) score was calculated, and patients with a score >0.5 were referred to a liver expert in secondary and/or tertiary care. RESULTS: A total of 11,859 participants were enrolled and available for final analysis. The control group comprised 349,570 participants of the regular Check-up 35. SEAL detected 488 individuals with elevated APRI scores (4.12%) and 45 incident cases of advanced fibrosis/cirrhosis. The standardized incidence of advanced fibrosis/cirrhosis in the screening program was slightly higher than in controls (3.83‰ vs. 3.36‰). The comparison of the chance of fibrosis/cirrhosis diagnosis in SEAL vs. in standard care was inconclusive (marginal odds ratio 1.141, one-sided 95% CI 0.801, +Inf). Of note, when patients with decompensated cirrhosis at initial diagnosis were excluded from both cohorts in a post hoc analysis, SEAL was associated with a 59% higher chance of early cirrhosis detection on average than routine care (marginal odds ratio 1.590, one-sided 95% CI 1.080, +Inf; SEAL 3.51‰, controls: 2.21‰). CONCLUSIONS: The implementation of a structured screening program may increase the early detection rate of cirrhosis in the general population. In this context, the SEAL pathway represents a feasible and potentially cost-effective screening program. REGISTRATION: DRKS00013460 LAY SUMMARY: Detection of patients with early liver cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. This study demonstrates that the implementation of a structured screening program using easily obtainable measures of liver function may increase the early detection rate of cirrhosis in the general population. In this context, the 'SEAL' pathway represents a feasible and potentially cost-effective screening program.