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Aims: to describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations.Methods and results: we studied 39,095 (51.5% women, mean age: 63.9±7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals (CIs), and p-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control.Conclusions: hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control.

Since the emergence of convolutional neural networks (CNNs), and later vision transformers (ViTs), the common paradigm for model development has always been using a set of identical block types with varying parameters/hyper-parameters. To leverage the benefits of different architectural designs (e.g. CNNs and ViTs), we propose to alternate structurally different types of blocks to generate a new architecture, mimicking how Lego blocks can be assembled together. Using two CNN-based and one SwinViT-based blocks, we investigate three variations to the so-called LegoNet that applies the new concept of block alternation for the segmentation task in medical imaging. We also study a new clinical problem which has not been investigated before, namely the right internal mammary artery (RIMA) and perivascular space segmentation from computed tomography angiography (CTA) which has demonstrated a prognostic value to major cardiovascular outcomes. We compare the model performance against popular CNN and ViT architectures using two large datasets (e.g. achieving 0.749 dice similarity coefficient (DSC) on the larger dataset). We evaluate the performance of the model on three external testing cohorts as well, where an expert clinician made corrections to the model segmented results (DSC>0.90 for the three cohorts). To assess our proposed model for suitability in clinical use, we perform intra- and inter-observer variability analysis. Finally, we investigate a joint self-supervised learning approach to assess its impact on model performance. The code and the pretrained model weights will be available upon acceptance., 12 pages, 5 figures, 4 tables

BACKGROUND: Epicardial adipose tissue volume (EAT) is a marker of visceral obesity that can be measured in coronary CT angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented.OBJECTIVE: To develop a deep-learning network (DLN) for automated quantification of EAT from CCTA, test it in technically challenging patients, and validate its prognostic value in routine clinical care.METHODS: The DLN was trained and validated to auto-segment EAT in 3720 CCTA scans from the Oxford Risk Factors And Non-invasive imaging cohort. The model was tested in patients with challenging anatomy and scan artefacts and applied to a longitudinal cohort of 253 post-cardiac surgery patients and 1558 patients from the SCOT-HEART trial, to investigate its prognostic value.RESULTS: External validation of the DLN yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT was associated with coronary artery disease (OR[95%CI] per SD increase in EAT 1.13[1.04-1.30] p=0.01), and atrial fibrillation (AF) (1.25[1.08-1.40], p=0.03), after correction for risk factors (including BMI). EAT predicted all-cause mortality (HR[95%CI] per SD = 1.28[1.10-1.37], p=0.02), myocardial infarction (1.26[1.09-1.38] p=0.001) and stroke (1.20[1.09-1.38] p=0.02) independently of risk factors in SCOT-HEART (5y follow-up). It also predicted in-hospital (HR[95%CI] = 2.67[1.26-3.73], p=< 0.01) and long-term post-cardiac surgery AF (7y follow-up; HR[95%CI] = 2.14[1.19-2.97], p=< 0.01).5CONCLUSIONS: Automated assessment of EAT is possible in CCTA, including in challenging patients; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification.

Angiotensin receptor blockers; Marfan syndrome Bloquejadors dels receptors d'angiotensina; Síndrome de Marfan Bloqueadores de los receptores de angiotensina; Síndrome de Marfan Background Angiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments. Methods In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus β blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus β blocker; and indirectly, β blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva. Findings We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference –0·07 [95% CI –0·12 to –0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with β-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with β blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase –0·08 [SE 0·03] in ARB groups vs –0·11 [SE 0·02] in β-blocker groups; absolute difference 0·03 [95% CI –0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between β blockers and control was –0·09 (95% CI –0·18 to 0·00; p=0·042). Interpretation In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a β blocker. The effects of β blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and β blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery. Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.

BACKGROUND: Angiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments. METHODS: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus β blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus β blocker; and indirectly, β blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva. FINDINGS: We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference -0·07 [95% CI -0·12 to -0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with β-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with β blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0·08 [SE 0·03] in ARB groups vs -0·11 [SE 0·02] in β-blocker groups; absolute difference 0·03 [95% CI -0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between β blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042). INTERPRETATION: In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a β blocker. The effects of β blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and β blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery. FUNDING: Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.

AIMS: We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy. METHODS AND RESULTS: Sixteen normal weight participants with dilated cardiomyopathy (DCMNW), and 27 with DCM and obesity (DCMOB), were compared to 26 normal weight controls (CTLNW). All underwent cardiac magnetic resonance imaging and 31P spectroscopy to assess function and energetics. Nineteen DCMOB underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCMNW than in CTLNW (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCMOB 41 ± 7%, DCMNW 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCMOB (P < 0.001), due to higher rate through CK [median kf 0.21 (0.14) vs. 0.11 (0.12) s-1, P = 0.002]. During increased workload, the CTLNW heart increased CK flux by 97% (P < 0.001). In contrast, CK flux was unchanged in DCMNW and fell in DCMOB (by >50%, P < 0.001). Intentional weight loss was associated with positive left ventricular remodelling, with reduced left ventricular end-diastolic volume (by 8%, P < 0.001) and a change in LVEF (40 ± 9% vs. 45 ± 10%, P = 0.002). This occurred alongside a fall in ATP delivery rate with weight loss (by 7%, P = 0.049). CONCLUSIONS: In normal weight, DCM is associated with reduced resting ATP delivery. In obese DCM, ATP demand through CK is greater, suggesting reduced efficiency of energy utilization. Dietary weight loss is associated with significant improvement in myocardial contractility, and a fall in ATP delivery, suggesting improved metabolic efficiency. This highlights distinct energetic pathways in obesity cardiomyopathy, which are both different from dilated cardiomyopathy, and may be reversible with weight loss.

Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.

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Introduction: Abnormal cardiac mitochondrial function and energetics may be a unifying feature in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), while transient pulmonary congestion during exercise is an important determinant of reduced exercise capacity and symptoms. Hypothesis: We hypothesized that a gradient of myocardial energetic impairment exists across the spectrum of HFpEF and limits cardiac reserve during exercise, leading to transient pulmonary congestion. Methods: 43 patients across the spectrum of diastolic dysfunction and HFpEF (age-matched controls n=11; type 2 diabetes (T2DM) n=9; HFpEF n=14; severe diastolic dysfunction due to cardiac amyloid n=9) underwent assessment of cardiac energetics (myocardial phosphocreatine to ATP ratio, PCr/ATP) and function using CMR, and lung water using a novel MR proton density mapping sequence. Studies were performed at rest and during exercise (20 W for 6 minutes). Results: Paralleling the stepwise decline in diastolic function across the groups (E/e’ ratio p Conclusion: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF, leading to impaired cardiac functional reserve and transient exercise-induced pulmonary congestion.

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.

Background and Aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), two-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) are proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).Methods: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model.Results: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and four 2DSWE studies, and for diagnosing NASH in four MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs.Conclusions: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking.Lay summary:Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy in assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants., Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

Objective: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM- VCTE), Fibrosis-4 index (FIB-4) and NAFLD Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.Design: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individu-ally and in sequential combinations.Results: Data were included from 37 primary studies (n=5735; 45% female; median age: 54 years; median BMI: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (

Introduction Hepatits A is a worldwide occurring disease with approximately 1,5 million cases par year. The aim of the study The role of cell-mediated immunity in HAV infection, correlation with clinical course, biochemical features and cellular immune responses. Material and methods HAV-infected 36 patients hospitalized in the Warsaw Medical University were aged between 17 and 40 years. Laboratory examination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin levels. All results were compared to normal healthy controls. The analysis of CD4+T-cells, CD8+T-cells of AHA patients, CD4+/CD8+ and NK lymphocyte populations. Additionally in acute period of disease was made the allergy skin testing with 7 recall antigens. Results Among 36 patients with persistent symptoms, elevation of aminotransferase and total bilirubin for at least 5 months was present in 3 patients (P-AHA). In P-AHA the number and percentage of CD4+T-cells to remaining acute hepatitis (AHA) were significantly decreased, but CD*+T-cells for both groups AHA and P-AHA was normal, the CD4+/CD8+ ratio in P-AHA were lower as compared to AHA, NK lymphocyte in P-AHA were higher as compared to AHA. Considering smaller than 10 mm reactions against recall antigens was corresponded to higher AspAT levels, but not to the persistently time course of AHA. Conclusions the higher AspAT levels might be due to diminished cellular immunity responses. Higher levels of NK lymphocyte in persistent cases suggest that they play an important role in the pathogenesis of HAV infection. The allergy skin testing is reliable index of disorders reactivity of CD4+ T-cells., Introduction West-central Poland seems to be an area of common exposure to hepatitis E virus (HEV) [Bura et al., Int J Infect Dis 2017; Grabarczyk et al., Transfusion 2018]. As HEV-3 infections most often go asymptomatically or with non-characteristic symptoms, it is difficult to identify patients in the acute phase of hepatitis. Anti-HEV IgG seroconversion may prove exposure to the virus. The aim of the study To determine the incidence of HEV infections in the group of people from Greater Poland living with HIV using a new automated assay for anti-HEV IgG. Material and methods From each of 50 HIV-positive patients (46 men) aged 22-55 years (median age – 38 years) two sera were obtained at intervals of 5-18 months (median – 12 months). Both samples were tested for the presence of anti-HEV IgG by the VIDAS Anti-IgG assay (BioMérieux, France). Results At baseline, HEV seroprevalence was 32% (16/50). The average age of seropositive patients (37.4 years) was not higher in comparison to those who were anti-HEV IgG-negative (39.1 years). In 31 patients (62%) both results were negative and in 14 persons (28%) both results were positive. Of the 34 initially seronegative patients, seroconversion was demonstrated in 3 persons (8.82%). None of the seroconverters reported any symptoms of hepatitis. The observation of these patients lasted a total of 377 patient-months, an average of 11.1 months (median 12 months). This corresponds to the seroconversion rate of 9.62% per year. In 2 cases (2/16 = 12.5%) the seroreversion was found. Conclusions Preliminary data obtained with the VIDAS Anti-IgG assay indicate that HEV seroconversion occurs annually in almost 10% of HEV-seronegative HIV-infected patients from Greater Poland. These HEV infections are subclinical., Introduction Autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) tend to have similar clinical presentation. The overlap of these features, together with biochemical, immunological and histological features can be considered as autoimmune sclerosing cholangitis (ASC). Additionally PSC is sometimes associated with inflammatory bowel disease (IBD), which can occur even in 75% of overlap syndromes. We present a 13 years old patient with these three conditions treated in the Children’s Memorial Health Institute. Material and methods In 2011, a five years old girl was admitted to the hospital because of the cholestasis, elevated transaminases: gamma globulins, GGTP and autoantibodies (ASMA 1 : 320, ANCA 1 : 1280), after exclusion of Wilson disease and viral hepatitis. During the treatment with Ursofalk (UDCA), the normalization of biochemical parameters was observed, and first after the recurrence of the disease, in 2013 (abnormal biochemical parameters and cholangiographic findings) liver biopsy showed histopathological changes characteristic for AIH/PSC (interface hepatits/fibrous obliterative cholangitis in small ducts). The patient followed Encorton with Immuran and Ursofalk treatment. Consecutive liver biopsies showed the remission of microscopical changes (in 2016 only mild inflammation and periductal fibrosis, in 2019 absence of inflammation, minimal fibrosis). However the endoscopic examination from 2017 revealed the presence of epithelioid granulomas, cryptitis and crypt abscesses in the sigmoidal and rectal region, which also disappeared after two years of treatment (Encorton, Immuran, Ursofalk, Pentase). Despite of the remission of the biochemical and microscopical parameters, the magnetic resonance cholangiopancreatography (MRCP) still show features of PSC (strictures and dilatations of the biliary three). Conclusions After nine years of the therapeutic modalities, the treatment of AIH/PSC/IBD, contributed to the remission of the clinical, biochemical and histopathological changes, which led us to discontinue immunosupression. MRCP features characteristic for PSC are present and the UDCA treatment should be continued., The aim of the study To analyzed the efficacy and clinical outcomes in hepatitis C (HCV) patients after direct acting antiviral therapy (DAA) based on selected blood and elastography parameters. Material and methods A total of 41 hepatitis C patients with compensated cirrhosis after successful DAA treatment were included. Selected blood parameters: platelets (PLT), alanine aminotransferase (ALT), prothrombin time (PT), glucose and elastography measurements: dynamic liver stiffness (LS) and controlled attenuation parameter (CAP) were performed 18-30 months after end of treatment and compared with baseline. Results We assessed blood and elastography parameters before and after HCV eradication. Mean follow-up period was 18-30 months after therapy. Our collecting data revealed that in long-term observation PLTs were higher by 26.8% (p < 0.001) [145.20 vs. 181.78 tys/ul] and glucose increased by 12.82% (p < 0.001) [109.46 vs. 118.58 mg/dl]. However, ALT decreased by 46.41% (p < 0.001) [80.84 vs. 25.32 IU]. The differences in PT was not significant. Elastography results revealed that liver stiffness decreased by 39.34% (p < 0.001) [20.57 vs. 14.54 kPa] while steatosis (measured by CAP) increased by 27.83% (p < 0.05) [261.41 vs. 288.03 dB/m]. Conclusions Our research showed that HCV eradication improves clinical liver parameters in patients with compensated cirrhosis. We also observed regression of liver stiffness in elastography however, noticeable increased liver steatosis and level of glucose are matters of concern and require further investigation., Introduction The is a need for an alternative to biopsy in paediatric liver disease. MRI-derived iron corrected T1 (cT1) and proton density fat fraction (PDFF) are emerging techniques that have demonstrated utility in stratifying adults with liver disease. We explored the potential discriminative value in paediatric patients. Material and methods Sixty patients (28 male; mean age 13.0 [6-17 yrs]; AIH (n = 43), PSC (n = 9), Wilson’s disease (n = 6), NAFLD (n = 2)) and 21 controls (9 male; mean age 13.8 yrs [9-17 yrs]) underwent multi-parametric MRI with LiverMultiScan™. cT1 and PDFF values were compared across groups using two-sided Kolmogorov-Smirnov (KS) tests and then combined into a probability risk score with multivariate logistic analysis with discriminative ability evaluated using ROC curves. Results Mean cT1 was significantly higher in AIH (763 ±87 ms) than controls (708 ±41 ms; p < 0.01) and elevated further in NAFLD and WD (883 ±38 ms; 890 ±60 ms, respectively, p < 0.01), but was not significantly elevated in PSC (734 ±66 ms). Mean PDFF was significantly elevated in NAFLD (18.3 ±6%, p, Management of autoimmune hepatitis (AIH) is highly variable in practice, with lack of consensus on optimal follow up strategies for patients, including the utility of on-treatment liver biopsy. LiverMultiScan™ is a multiparametric MRI method which measures iron-corrected T1 (cT1). This has been shown to correlate with the key histological features of liver disease (ballooning, inflammation and fibrosis), and to predict clinical outcomes. Here, we evaluate the utility of cT1 in AIH, in combination with circulating biomarkers, for the stratification patients experiencing flares of liver inflammation. Forty-six AIH patients (19 male; mean age 13.8 [6-18 yrs]; underwent LiverMultiScan™, with comparison to liver biopsy and liver enzymes (ALT, AST, GGT and bilirubin). Correlation with the imaging and blood biomarkers against biopsy was explored using Spearman’s Rho. The ability of these biomarkers to identify individuals with histologically confirmed portal inflammation was evaluated using AUROC analysis, with step-wise logistic regression used to combine biomarkers into a risk score. All biomarkers correlated with Ishak fibrosis and all except total bilirubin correlated with portal inflammation. Pairwise comparisons identified different patterns for cT1 compared to blood biomarkers, with stronger separation between Ishak scare 2-3 and 5-6 (p < 0.001) and equally a more stepwise pattern with portal inflammation. Independently, both cT1 and ALT were the best predictors of portal inflammation ≥ 2 (cT1 AUROC: 0.70 (0.55-0.85, se: 39%, sp: 100%, NPV: 61%, PPV: 100%)); ALT AUROC 0.73 (ci: 0.58-0.88), se: 61%, sp: 77%, NPV: 56%, PPV: 81%). Interestingly, the superior model with the strongest predictor of those with current portal inflammation ≥ 2 was a risk score combining cT1, total bilirubin and AST (AUROC of 0.84 (0.7-0.94)) that was able rule-in those currently experiencing a ‘flare’ with 100% specificity (PPV: 100%, NPV: 57%, sensitivity: 50%). Both ALT and cT1 are effective biomarkers for identifying portal inflammation. This performance for identifying low level inflammation however is further enhanced when cT1 is used in composite with AST and total bilirubin, highlighting the potential of multiparametric MRI when used in conjunction with circulating markers of disease for monitoring paediatric patients with AIH. Further research is warranted. Study funded by NCBiR, InnovateUK-EUREKA/Eurostars project E!10124-Kids4LIFe., Magnetic resonance cholangiopancreatography (MRCP) is commonly used for the evaluation of biliary disease but has significant limitations, including variable quality bile duct depiction and subjective assessment. This is particularly true in paediatric assessment, where biliary changes may be less advanced. We sought to understand the potential utility of quantitative MRCP (MRCP+™) in paediatric patients, particularly those with overlapping autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Recruited patients (6-18 yrs; AIH (51), AIH/PSC (10), Wilson’s disease (6), other (7)) and 21 healthy controls underwent multi-parametric MRI with LiverMultiScan™ and heavily T2-weighted three-dimensional MRCP imaging for MRCP+ processing to enhance and quantify the tubular biliary structures and assess liver parenchyma. The underlying algorithms combine multi-scale Hessian analysis, gradient vector flow analysis, an intelligent path search algorithm and novel duct modelling algorithms. PSC patients had an increased number of candidate strictures and dilatations (defined as a change in diameter > 30%) than healthy controls (p = 0.007) and AIH patients (p = 0.019). Furthermore, the percentage severity of strictures and total length of dilated and strictured regions were greater in PSC patients than healthy controls (p = 0.019; p = 0.008) and AIH patients (p = 0.045; p = 0.035). AUROCs of 0.80-0.95 were observed for a range of quantitative biliary metrics assessing AIH/PSC against Health or AIH patient groups. Increases in MRI-derived iron corrected T1 (cT1) whole liver inter-quartile range (which can reflect heterogeneity of fibro-inflammation) was associated with increases in the total length of dilated and strictured regions (Pearson’s correlation R = 0.88; p = 0.05), suggesting parenchymal disease association with biliary metrics. We report findings demonstrating that quantitative MRCP (MRCP+) provides measures that could objectively differentiate patients with PSC from healthy or other liver disease patients, with potential for monitoring and severity assessment applications. This study was funded by NCBiR and InnovateUK under EUREKA/Eurostars project E!10124 “Kids4LIFe – Assessing Kids for Liver Inflammation and Fibrosis using noninvasive MRI”., Introduction Majority of HCV-infected in Poland remain undiagnosed and screening campaigns are urgently needed. Previous hospitalizations and medical procedures are leading risk factors of anti-HCV positivity. Precise risk of nosocomial exposure is largely unknown. HCV is also regarded as modifier of morbidity and mortality of cardiovascular disorders (CVD). We aimed to assess the prevalence and risk factors of anti-HCV and HBsAg risk factors and possible influence of viral hepatitis on CVD mortality. Material and methods The analysis included 8,646 patients tested for anti-HCV and 47,831 for HBsAg in Silesian Center for Heart Diseases between 2014-2017. Anti-HCV and HBsAg were tested with immunoenzymatic assays according to current guideline. Analyses included comorbidities and previous hospitalizations (ICD-10), previous medical procedures (ICD-9), liver function tests and follow-up data including mortality based on Silesian CVD Registry. Results The prevalence of anti-HCV was 1.1% (94/8,646) and HBsAg 0.3% (141/47,831) among patients with available hepatitis testing. Anti-HCV+ subjects were younger then HBsAg+ (60.0 ±14.4 vs. 56.4 ±14.4 yo, p = 0.02) but gender distribution was comparable. Heart transplant rejection (10.6% vs. 2.1%, p = 0.01) and heart insufficiency (54.3% vs. 39.0%, p = 0.03) was diagnosed more often in anti-HCV+ vs. HBsAg+. Subjects with anti-HCV+ had higher median number of previous hospitalizations (9.3 vs. 6.7, p < 0.002), blood transfusions (5.8 vs. 0.6, p = 0.001) and CVD-surgeries (16.6 vs. 4.8) comparing HBsAg+. Moreover, trends towards higher number of previous invasive diagnostic procedures (3.3 vs. 2.1, p = 0.06) and history of abdominal surgery (52 vs. 39%, p = 0.06) were observed in anti-HCV+. In Cox-regression model the highest hazard ratio for anti-HCV+ vs HBsAg+ was for history of liver disease HR 5.32 (p < 0.001), previous invasive diagnostics HR 2.99 (p = 0.01) and chronic kidney disease HR 1.95 (p = 0.017). Kaplan-Meier analysis showed higher mortality in anti-HCV(+) subjects vs. HBsAg+ in follow-up (p = 0.009). Conclusions History of liver disease, previous invasive diagnostic procedures and chronic kidney disease constitute of the most important risk factors of anti-HCV(+) in patients with CVD. Importantly, anti-HCV(+) was associated with higher mortality. Results of the study underline the necessity of HCV-screening and prompt therapy in patients with CVD to improve their prognosis., HBV reactivations during direct acting antivirals (DAA) for HCV were described in both HBsAg(+) and HBsAg(–)/anti-HBcIgG(+) patients. The rate of HBV-reactivation in HBV/HCV coinfection is poorly defined. The aim was to characterize HBV/HCV coinfection and the prevalence HBV-reactivation during DAA. Analyzed population consisted of 6228 chronic hepatitis C patients (52% female, mean age 54 yo, 82% HCV-GT1b, 34% with liver cirrhosis) receiving DAAs in 2016-2017 included in EpiTer-2. DAA combinations consisted mainly of OBV/PTV/r ± DSV ± RBV (53%) and LDV/SOF ± RBV (28%). Prior to the DAA all subjects had HBsAg testing and ALT-activity evaluated every 4 weeks during DAA. Anti-HBc IgG was available in 742 patients without HBsAg. 70 of 6228 patients (1.1%) had detectable HBsAg. HBV/HCV patients were younger and more often infected with HCV-GT3-4 than HCV-group. They were also less often diagnosed with arterial hypertension (26% vs. 38%, p = 0.04), diabetes (6% vs. 15%, p = 0.03) and had lower BMI (24.5 vs. 26.0, p < 0.01). Prior to DAA only 21 of HBV/HCV required NA-therapy. DAA-therapy was continued according to plan in 96% (HBV/HCV) vs. 95% (HCV) of cases. Sustained virologic response (SVR) rates were similar in HBV/HCV and HCV-monoinfection (mITT 97% vs. 95%, p = 0.7). In HBsAg(+) subjects only 3 (4.3%) HBV reactivations were observed, while none occurred in HBsAg(–)/anti-HBc(+) group. All subjects with reactivation were HBeAg(–), infected with HCV-GT1 and had advanced liver disease. One reactivation was clinically significant with HBV-DNA increase at wk5 and ALT-flare (1337 IU/m) requiring DAA discontinuation, while 2 remaining were subclinical with HBV-DNA increase form negative to 1.3 (wk12) and 3.2 log10 IU/ml (wk8). Interestingly, one case of HBV-reactivation occurred during LAM-therapy. During next phase of Epiter-2 study additional reactivation in subject with HBsAg(–)/anti-HBc(+) was diagnosed, which suggests that occult hepatitis B should be taken into consideration before DAA. Data form a large cohort suggest that the risk of HBV-reactivation during therapy with DAA seems to be low in HBsAg(+) HBV/HCV subjects (< 5%), while probably minimal although existent in HBsAg(–)/anti-HBc IgG(+). Interestingly, subjects with HBV/HCV coinfection seem to less often present symptoms and complication of metabolic syndrome., Introduction The new direct acting antivirals (DAA) have opened access to treatment also for patients with liver cirrhosis infected with hepatitis C virus (HCV). In this group of patients, the beneficial effect of viral eradication on the further clinical outcome is relatively assessed. The aim of this clinical, retrospective study was to analyse the potential influence of HCV eradication with DAA on liver function in patients with decompensated liver cirrhosis. Material and methods Twenty eight patients (16 M/13 F, mean age 59 ±14 years) with liver cirrhosis (median liver stiffness measurement (LSM) 29.1 kPa [21.30-4.30] evaluated with transient elastography) after successful therapy of HCV infection were analysed. Liver function tests, including alanine (ALT) and aspartate (AST) aminotransferase and gamma-glutamyltranspeptidase (GGT) serum activities, serum albumin and bilirubin levels as well as prothrombin time, were estimated before and at the end of treatment (EOT), 24 and 48 weeks after EOT. Severity of liver cirrhosis was estimated using Child-Turcotte-Pugh (CTP) classification in the same control points. LSM were conducted at baseline, 6 and 12 months after the end of therapy. Results During DAA therapy, serum activities of ALT, AST and GGT decreased significantly (p < 0.001, for each). Up to 48 weeks after EOT, albumin serum concentration increased significantly (p < 0.001) and bilirubin serum concentration decreased (p < 0.05) resulted in decreasing the CTP score (p < 0.01). LSM decreased in EOT24, but not significantly (p < 0.07). In EOT48, in 75% of patients LSM decreased significantly (p < 0.01) but in 25% increased. Conclusions Resolution of HCV-induced inflammation as a result of effective antiviral therapy caused gradual improvement in liver function and severity of cirrhosis during the one year after EOT. Longer observation is needed in order to assess the sustainability of this recovery. LSM improvement is not universal and further observation of liver stiffness is necessary., Echinococcosis is a parasitic disease caused by larval tapeworms of the Taeniidae family. There are four species known, however only Echinococcus granulosus and Echinococcus multilocular are of significant epidemiological and clinical significance. There are several new cases of echinococcosis in Poland annually, mainly in the Warmian-Masurian, Sub-Carpathian and Lesser Poland Voivodships. Spatial analysis of patients with echinococcosis is a complex and time-consuming task. It requires the doctor to not only maintain a detailed history of the disease of many patients, but also to analyze them and to manually apply selected cases to the map. This approach is not efficient and results in a high probability of making a mistake. Presented system answers above challenges by combining in one tool a comprehensive module for creating, editing and viewing disease history with a module for dynamically mapping selected aspects of the disease in a geographical context. It allows not only to store detailed data about patients but also to create summaries in terms of age, disease severity or hospitalization time. The system also provides an opportunity for visual representation of data in the form of thematic layers containing density of patients in various stages of the disease or statistical analysis of the number of cases in each city. Due to its high versatility, the system can also be used to analyze patients with a different disease entity. It is an innovative solution that supports physicians in their daily work as well as in scientific research in a comprehensive way., Introduction Drug-induced liver injury (DILI) is a growing clinical problem resulting from the widespread use of drugs, dietary supplements and herbal products (HDS). The aim of the study To assess the agreement between clinical diagnosis and selected methods for DILI causality assessment (CAM). The agreement between CAMs was described using Cohen’s kappa (κ) test. The κappa value ranges from −1 (perfect disagreement) to +1 (perfect agreement). Material and methods For each patient hospitalised between 2009 and 2018 who met criteria of DILI the causal relationship between the liver injury and the implicated drug/HDS was evaluated using selected CAMs: RUCAM (Russel Uclaf CAM), M & V (Maria & Victorino CAM), Naranjo (Naranjo Adverse Reaction Scale), WHO-UMC (World Health Organization-Russel Uclaf Monitoring Center). The agreement among scales was assessed using weighted coefficient Cohen’s kappa (κ). Results The agreement between clinical diagnosis and Naranjo (κ = 0.178), WHO-UMC (κ = 0.157) and RUCAM (κ =0.021) scale was described as slight, and as “disagreement” for the M&V scale (κ = –0.012). The highest values of kappa coefficient: κ = 0.373 (95% CI: 0.305-0.441), κ = 0.368 (95% CI: 0.197-0.538) were found in the group of acute cholestatic and mixed hepatitis, in the Naranjo scale. Causality assessment by means of WHO-UMC scale correlated with clinical diagnosis in all analyzed sub-groups with exclusion of: mild course of DILI κ = –0.086 (95% CI: 0.257-0.309) and acute hepatocellular hepatitis κ = –0.039 (95% CI: –0.070 to –0.007). Conclusions Despite wide recommendations on importance of causality assessments in DILI diagnosis we found their limited application in clinical practice when used retrospectively. The Naranjo and WHO-UMC scales showed better correlation with clinical diagnosis than DILI-specific CAMs: RUCAM and Maria & Victorino., Introduction Drug-induced liver injury (DILI) is a growing clinical problem. DILI can be caused by any drug either due to its dose-dependent direct hepatotoxic effect or as a result of idiosyncrasy. The diagnosis of DILI is based on the exclusion of other causes of liver disease. The aim of the study To analyze the causes and clinical picture of DILI in patients hospitalized in the Clinic of Infectious Diseases, Tropical Medicine and Hepatology in Warsaw (CIDTM&H) between 2009 and 2018. Material and methods Relevant clinical data was abstracted from medical records of patients hospitalized in CIDTM&H between 2009 and 2018. Liver injury type, disease severity and Hy’s rule were assessed for each patient. Logistic regression multivariant analysis was used to analyze factors associated with type of liver injury and severity of disease outcome. Results In the analyzed period, DILI was diagnosed in 79 patients: in 68 (86.1%) was caused by drugs, in 11 (13.9%) by herbs and dietary supplements (HDS). More than one drug contributed to DILI in 16 (20.3%) patients. 91.2% of patients presented with idiosyncratic DILI and 7 (8.8%) had intrinsic DILI. Leading causative agents were: amoxycillin/clavulanic acid – 13 (13.1%), anabolic steroids – 9 (9.2%), acetaminophen, estradiol – 6 each (6.1%). Antimicrobials were the most common class of causative drugs: 31 (35.6%). Based on multivariate analysis, the age ≥ 55 years and prolongation of the latency period were related to cholestatic/mixed type of liver injury. Moderate/severe DILI correlated with AST and GGTP values (p = 0.047 and p = 0.0196, respectively). Women compared to men and patients ≥ 55 years used a larger mean number of causative and associated drugs (p = 0.018 and p = 0.015, respectively). Conclusions Diagnosis of DILI in clinical practice requires assessment of disease-specific parameters which allow targeted diagnostic approach and predict disease outcome. Older age and prolonged latency period predispose to cholestatic and mixed liver injury., Introduction Amoxicillin with clavulanic acid (AC) is one of the most commonly prescribed antibiotics and a leading cause of idiosyncratic drug-induced liver injury (DILI) worldwide. Liver injury appears primarily due to the clavulanate component. The aim of the study To analyse clinical course of AC-related DILI in patients hospitalized in the Clinic of Infectious Diseases, Tropical Medicine and Hepatology in Warsaw (CIDTM&H), between 2009-2018. Material and methods Cases of DILI related to AC were selected from the electronic data base of the CIDTM&H. Relevant demographic, laboratory and other clinical data were collected for each patient. Results Between 2009 and 2018, 13 cases of AC-related DILI were diagnosed. AC was the main cause of all DILI cases reported within this period (13/79, 16.4%). The mean age of patients was 56.8 years (SD 13.9), 77% were women, mean latency period was 8.3 days (SD 7.6). Six patients had hepatocellular type of liver injury, 7 – mixed and cholestatic. In 8 cases disease had moderate severity. All patients had symptoms of DILI: jaundice (77%), itching (46%). All but one patient had concomitant diseases, 10/13 took other than offending drugs. Laboratory mean values were: ALT 664, 7 IU/l ±SD 514.4; FA 274.7 ±SD 137.3; total bilirubin 70.9 μmol/l ±SD 22.9; AST 371 IU/l ±SD 450.7; GGTP 457.7 IU/l ±SD 345.1. One patient had DILI due to re-exposure to AC. Conclusions Amoxycillin and clavulanic acid was the most common cause of DILI in the analysed period. AC-related DILI was predominately in women and manifested as hepatocellular and mixed/cholestatic type of liver injury., Introduction Sarcoidosis (Besnier-Boeck-Schaumann disease) is a systemic disease. Main clinical manifestations, include lungs (90%), eyes and skin. Diagnosis of sarcoidosis is still a challenge, frequently remaining a diagnosis of exclusion. It is important to mention, that other conditions, with similar symptomatology must be consider in the differential diagnosis such as, tuberculosis, Wegener’s granulomatosis, cancer or lymphoma. Case presentation We report a 34-year-old man with a 3 months history of acute kidney injury of unknown etiology with enlarged peripheral lymph nodes. Laboratory tests revealed hypercalcemia, increased activity of liver enzymes and elevated serum kappa/lambda ratio. Multiple hypoechoic nodules in the liver, kidney, spleen and pulmonary parenchyma as well as hepatosplenomegaly and concomitant lymphadenopathy in thorax and abdominal computed tomography were found. Result of bone marrow biopsy did not confirm multiple myeloma and histological examination of the external axillar lymph node and liver parenchyma demonstrated the presence of nonceasing granulomas, typical for sarcoidosis. Gluocorticosteroid therapy caused rapid reduction of the lymph nodes dimensions as well as improvement of kidney function. Despite the treatment, supplemented by ursodeoxycholic acid, activity of liver enzymes was still elevated, however patient remained asymptomatic. Conclusions Hepatomegaly and liver dysfunction are found in ca. 10% of a patients and hepatitic sarcoidosis represents only a small percentage of causative hypercalcemia. Increased risk for cancer or lymphoma in affected organs in patients with sarcoidosis should be taken into consideration, however longer follow up is needed., Hepatocellular carcinoma is a primary liver tumor. The risk factors to develop this cancer are infection with hepatitis virus, alcoholism and liver diseases. The prognosis of this disease is poor. In the last years, the resistance of tumors against therapeutic procedures is increasing. So many new oncologic drugs obtain from plants. Well known are also dietary supplements which showed already antineoplastic potential such as trans-resveratrol and a pine bark extract. In the literature are described in-vitro studies with both agents with HT1080 fibrosarcoma cell line. It was already showed that trans-resveratrol modulates sphingolipid metabolism in hepatocellular carcinoma cells, inhibits the progression of human hepatocellular carcinoma via regulating p53 and the phosphoinositide 3-kinase/protein kinase B pathway. Trans-resveratrol also modulates PI3K/AKT Signalling through SIRT1 modification. Also hepatic stellate cells play a crucial role in resveratrol-induced inhibition of hepatocellular carcinoma cell growth. Resveratrol showed also anti-metastatic activity in hepatocellular carcinoma through SP-1 modulation. Oxyresveratrol inhibits hepatocellular carcinoma growth via modulation of angiogenesis and lymphangiogenesis. Pine bark extract showed already an inhibitory effect on hepatitis C virus replication so on one of risk factors of hepatocellular carcinoma. In the literature was also described a synergistic effect of piperine and curcumin in vitro and in vivo on the suppression of hepatocellular carcinoma cells. Nowadays already many natural compounds showed in in vitro but also in vivo study antineoplastic activity against hepatocellular carcinoma cells. It is possible that such agents could in the future be used as supportive therapy in hepato-oncology., The aim of this study was to analyze the clinical course of acute hepatitis A in children. Retrospective analysis of medical records of 25 children hospitalized due to hepatitis A from the March 2017 to the March 2019 was taken. Among analyzed group there were 12 girls and 13 boys in the age of 1-17 years (mean 10 years). In 21/25 (84%) the infection was transmitted via household contact. None of children were earlier vaccinated against hepatitis A. The most frequent symptoms were abdominal pain in 12/25 (48%), fever – 11/25 (44%), change in the color of urine and/or stool – 10/25 (40%), diarrhea – 9/25 (36%), nausea and vomiting – 8/25 (32%), loss of appetite – 6/25 (24%) and itching – 4/25 (16%). Hypertransaminasemia (17-2932 U/l) was reported in 22/25 (88%) children, with mean ALT activity 1109 U/l, ALT > 30× normal in 13/25 (52%) and mean AST level 908 U/l (34-2918 U/l). Increased GGTP level was observed in 21/25 (84%) patients (8-498 U/l, mean 145 U/l, in 6/25 (24%) > 4× normal). Jaundice was observed in 16/25 (64%) patients with mean total bilirubin level 3.76 mg/dl (0.77-8.94 mg/dl) and a predominance of direct bilirubin. Splenomegaly was found in 12/25 (48%) patients and hepatomegaly in 11/25 (44%). In 8/25 (32%) children cholecystitis was described. None long-term sequels were observed. Hepatitis A infection is a self-limiting disease, with a diversified clinical manifestation and usually complete recovery. It is necessary to promoting pre- and postexposure vaccinations, especially among household of children with hepatitis A., Introduction The decision of treatment in HD patients is slightly more complicated. Apart from DDIs and renal insufficiency, the pharmacokinetics and distribution of antiviral medications had to be considered. Material and methods EpiTer-2 project is a real-world, investigator-initiated study. The group that was analyzed started HCV treatment before January the 1st 2018. Among 6229 patients in EpiTer-2 database we identified 334 patients with any kidney disease. Among 77 patients with eGFR < 30 ml/min/1.73 m2 53 patients were on dialysis – 21 women (39.6%) and 32 men (60.4%). The mean age was 50.28 ±12.80 years. Females were younger (47.3 ±10.88 years) than males (52.4 ±13.67 years). Results Predominant genotype was 1b – 45 pts (84.9%). Three pts were infected with genotype 1a (5.7%) and 5 with genotype 4 (9.4%). Advanced liver fibrosis was found in 14 pts – F4 (26.4%) and in 9 pts – F3 (17.0%). In 19 pts (35.8%) F1 and in 11 pts F2 (20.8%) were diagnosed. At the baseline in 3 cases there was a history of liver decompensation. In group of HD patients 10 underwent kidney transplantation and 4 of 10 had acute graft rejection. The explanation for 40% graft rejection in this group is obvious, due to transplantation failure they continued replacement therapy. The most often regimen was OBV/PTV/r ± DSV – in 30 pts (56.6%). GZR/EBR was used in 15 pts (28.3%), ASV/DCV in 4 pts (7.5%), GLE/PIB in 1 (1.9%) and aLDV/SOF in 3 pts (5.7%). In 1 patient with genotype 1a physician decide to add reduced dose of RBV (200 mg) to OBV/PTV/r ± DSV for 12 weeks. Two patients with G1a were treated with GZR/EBR for 16 weeks and OBV/PTV/r ± DSV for 24 weeks without RBV. There was 1 episode of ascites, but the patient continued the treatment. In 4 patients anemia occurred, 2 had pruritus and 2 jaundince. All adverse events did not lead to therapy modification. All HD patients achieved SVR 12 and/or SVR24. Conclusions HD patients require close monitoring but they can be treated with efficacy and safety comparable to general population., The aim of the study The aim of the study was to determine if primary care practitioners (PCPs) take care of non-alcoholic fatty liver disease (NAFLD) patients and properly manage patients with suspected non-alcoholic steatohepatitis (NASH). Material and methods The tool used to carry out the research was a questionnaire consisting of 19 questions. General practitioners worked in Lublin Voivodeship participated in this research. Our study had been accepted by the Bioethics Committee. Results 64 PCPs in Lublin Voivodeship responded to the questionnaire. The age of the respondents ranged from 28 to 75. Twenty one percent of PCPs took care of patients with diagnosed NAFLD, while only 7% of them treated patients in everyday medical practice in primary care units. Twenty eight percent of respondents referred patients with fatty liver to further specialist evaluation. Forty percent considered screening for NAFLD, i.e. level of liver enzymes or ultrasonography examination, as important in a group of patients with obesity or metabolic syndrome. Twenty four percent of PCPs knew transient elastography e.g. FibroScan system and 26% were aware of diagnostic possibilities offered by this technique. Conclusions Although PHC is thought to be the first step in diagnosing NAFLD, only few doctors were aware of treating patients with this disease. Less than half of respondents paid attention to introduce screening tests. Improving the level of knowledge about NAFLD in general practitioners should be the necessary activity for the near future., Introduction HCV infection is considered a significant epidemiological problem in Polish population. Considering wide use of direct acting antiviral (DAA), we can expect increasing number of patients after oral therapy of HCV infection that are under control of Primary Health Care (PHC) providers. The aim of the study To gain information on the extent of knowledge the primary health care doctors have about DAA therapy of HCV infection. Enhancing awareness of general practitioners on the basis of current guidelines of Polish Association of Study of the Liver (PASL). Material and methods We distributed paper questionnaire to 64 primary health care doctors aged between 28 and 75 years working in Lublin and surrounding area. Survey was focused on HCV infection diagnostics and DAA treatment in Poland. After responding the questionnaire we provided doctors with a brochure with basic information about HCV diagnosis and DAA therapy. Results The results indicate that diagnostics, treatment and supervision of HCV-infected patients is not currently considered common knowledge for PHC doctors. Even though four out of five doctors knew how to interpret laboratory tests for HCV infection, one in three does not realize that infection can be effectively cured using oral therapy and half of them never heard about DAA therapy. 95% of responders think that knowledge about modern HCV therapy should be widened in the group of general practitioners. Conclusions Recent developments in HCV therapy made specialists to place particular emphasis on the role of primary health care doctors in screening of HCV infection and after treatment management. In the age of effective antiviral treatment, significant decrease in number of infected people can be reached mostly by education of health care workers, including general practitioners., The aim of the study Residual HCV-RNA can persist in liver tissue and peripheral blood mononuclear cells (PBMCs) long after antiviral therapy of chronic hepatitis C in patients repeatedly negative for viral RNA in serum. This occult infection associates with impaired immune response and the risk of lymphoproliferative disorders or progressive liver disease. There are currently no monitoring strategies for patients after treatment. We investigated if serum inflammation markers and interferon lambda (IFNL) genotype can be predictors of the presence of HCV-RNA and the replicative, HCV-RNA(–) strand in patients who reached sustained virological response after interferon-free therapy. Material and methods Forty two consecutive patients who remained HCV-RNA negative in serum 24 weeks after end of treatment (EOT) and during the follow-up were enrolled. Total HCV-RNA and HCV-RNA(–) strand were detected using ultrasensitive RT-PCR in PBMCs collected 12-15 months after EOT. Polymorphisms within IFNL3-IFNL4 region (rs12979860 and ss469415590) were genotyped with allele-specific PCR. Results Viral RNA was found in PBMCs from 31 (74%) patients, and of those 29 (69%) were also positive for HCV-RNA(–). Neither normalization of alanine aminotransferase nor IFNL genotype predicted the presence of residual HCV-RNA. Significantly higher neutrocyte to lymphocyte ratio (NLR) 24 weeks after start of treatment, predicted elimination of replicative HCV-RNA strand (OR = 0.23; 95% CI: 0.10-0.86; p = 0.019). Patients with no HCV-RNA(–) in PBMCs showed greater increase in neutrocyte count between EOT and baseline (p = 0.028). Conclusions Lack of significant elevation of NLR after therapy with directly acting antivirals could predict the presence of residual replicative HCV-RNA strand in PBMCs., The development of interferon free regimens improved efficacy of antiviral treatment for HCV, but failures still occur. The aim of our study was to evaluate the efficacy of retreatment with genotype specific direct acting antivirals based regimens in non-responders to previous IFN-free therapy. Studied population consisted of 31 non-responders to interferon-free regimen, which received second interferon-free rescue therapy, selected from 6228 patients from a large database EpiTer-2. Age, gender and genotype in this group were similar to whole population, but included patients demonstrated more advanced fibrosis. Primary therapy was discontinued in 12 patients recognized as non-virologic failures, whereas virologic failure was recognized in 19 patients which completed therapy. Overall SVR rate was 81% and 86% in intent-to-treat (ITT) and modified ITT analysis, respectively (74% and 78% in virologic failures, 92% and 100% in non-virologic failures). There were no significant differences in SVR rate after the rescue therapy related to the type of administered primary or rescue regimen. All non-responders to rescue therapy were cirrhotics. SVR in cirrhotic virologic failures was 62%, whereas vs. non-virologic failures and non-cirrhotics achieved 100%. Resistance associated substitutions testing was carried out in 8 virologic non-responders, three of them had risk for failure related to NS5A, but two of them achieved SVR. Concluding, rescue therapy with genotype specific regimens can be considered in non-virologic failures related to discontinuation of primary therapy and in non-cirrhotics, but should be avoided in cirrhotics after virologic failure. RAS testing is not essential after the first failure of treatment., Introduction and aims Since 2016 treatment-naïve patients with chronic hepatitis C virus genotype 1b infection with minimal or moderate fibrosis can be treated with ombitasvir/paritaprevir/ritonavir and dasabuvir (OprD) for 8 weeks according to Summary of Product Characteristics updated based on results of Garnet trial. The aim of our study was to assess the comparative efficacy of 8 and 12-week treatment duration of OPrD in patients with none, minimal or moderate fibrosis (F0-F2) treated in real-world setting. Material and methods We analysed data of 3067 HCV genotype 1b infected patients treated with OPrD between 2015 and 2017 obtained from EpiTer-2 database. Results A total of 800 patients with not advanced fibrosis were enrolled to the study, that included 223 (29%) treated for 8 weeks and 577 patients fulfilling criteria for shorter treatment but assigned to 12-week regimen. Majority of patients had no or minimal fibrosis, and they were more frequently treated for 8 weeks (80%) than 12 weeks (61%). Longer treatment duration was more often administered in patients with comorbidities (56% vs. 31%), concomitant medications (45% vs. 30%), HIV coinfected (0.7% vs. 0%) and HBV coinfected (11.6% vs. 7.2%). SVR was achieved in 211 (95%) patients treated for 8 weeks and 561 (97%) for 12 weeks (p = 0.09). After exclusion of lost to follow up patients, SVR rate reached 96% and 98%, respectively, and the difference was statistically significant according to the Fischer analysis (p = 0.02). All 10 non-responders from the 8 weeks group were naïve to DAA and demonstrated viral load below 6 million U/l. All except one demonstrated minimal fibrosis (F1) and 9 were males. We were not able to identify factors associated with non-response in this group. Conclusions We confirmed high effectiveness of 8 and 12-weeks regimens of OPrD in genotype 1b HCV infected patients with non-advanced fibrosis and supported no need of 12-weeks therapy in large majority of such patients. Further analysis of growing population treated for 8 weeks is necessary to identify possible factors responsible for non-response., Introduction and aims Non-cirrhotic treatment-naive hepatitis C patients infected with genotype 1 can be treated with ledipasvir/sofosbuvir (LDV/SOF) for 8 weeks according to Summary of Product Characteristics, but in real world practice this regimen is frequently extended up to 12 weeks. The aim of our study was efficacy comparison of 8 and 12-weeks regimens in patients eligible for 8 weeks therapy. Material and methods Data of HCV genotype 1 infected patients treated with LDV/SOF between 2015 and 2017 and included into the EpiTer-2 database were analysed in respect to patients characteristics and length of treatment. Results Among total of 1718 patients treated with LDV/SOF, 679 were included in the analysis and 238 (35%) received 8-weeks regimen, whereas 441 patients were treated for 12-weeks although fulfilled criteria for a shorter LDV/SOF course. Majority of patients were infected with genotype 1b (89%) and demonstrated minimal fibrosis (55%). Twelve weeks regimen was assigned significantly more frequently to patients with comorbidities (71% vs. 45%), concomitant medications (69% vs. 39%), advanced liver fibrosis (32% vs. 1%), HIV coinfected (7.9% vs. 2.5%) and HBV coinfected (13.4% vs. 4.6%). Sustained virologic response rate was similar after 8 (98%) and 12 (97%) weeks of therapy according to intent-to-treat analysis and reached 99% in both groups after exclusion of patients lost to follow-up. Conclusions We confirmed high and the same efficacy of 8 and 12-weeks regimens of LDV/SOF in non-cirrhotic chronic hepatitis C patients infected with genotype 1 which fulfilled criteria for 8 regimens according to current label and expert guidelines. This real-world study confirmed no need of 12-weeks therapy with LDV/SOF in this population., In 2008 analysis of SHARP trial showed that sorafenib improved overall survival (OS) of patients with advanced HCC (aHCC) in comparison with placebo (median OS: 10.7 months vs. 7.9 months, HR = 0.69, p < 0.001). Since then sorafenib has become a new standard for the treatment of aHCC, and has served as a reference regimen for future trials. In 2017, the results of REFLECT trial were released and showed that lenvatinib in comparison to sorafenib was a non-inferior first-line treatment option for patients with aHCC. The median OS with lenvatinib was 13.6 months compared with 12.3 months for sorafenib (HR = 0.92, 95% CI: 0.79-1.06). Until 2016 there were no accepted second-line treatment options for patients with aHCC. The first positive was the RESOURCE trial, which demonstrated regorafenib efficacy compared with placebo in second-line therapy. The median OS for regorafenib group was 10.6 months, and for placebo group was 7.8 months, and 38% reduction in the risk of death for patients treated with regorafenib (HR = 0.62, 95% CI: 0.50-0.78, p < 0.001). The second positive trial was the CELESTIAL trial. This trial, conducted in patients with aHCC who had progressed following at least one prior systemic therapy including sorafenib, showed that cabozantinib significantly improved median OS over placebo (10.2 months vs. 8.0 months, HR = 0.76, 95% CI: 0.63-0.92, p = 0.0049). Molecules that inhibit the PD-1/PD-L1 receptor seems to be valuable treatment option in advanced HCC. A phase I/II CHECKMATE 040 trial with nivolumab confirmed characteristic feature of anti-PD-1 molecules i.e. the persistence of a long-lasting clinical response (ORR) with a median of 17 months, and the long OS of 28.6 months for first-line therapy and 15.6 months for patients who progressed on sorafenib. In the phase II KEYNOTE-224 trial pembrolizumab induced ORR of 17% among patients previously treated with sorafenib, with median OS 12.9 months. Although, the KEYNOTE-240 confirmatory trial showed that the pembrolizumab improved OS vs. placebo (HR = 0.78, 95% CI: 0.611-0.998, p = 0.0238), it was not deemed statistically significant. Combination therapy using targeted agents with immune checkpoint inhibitors is expected to yield even better effects, and many trials are ongoing., Interferon-free regimens based on direct acting antivirals (DAA) became available in Poland since mid 2015. Untill the end of 2018 10 166 patients were included in the EpiTer-2 study. Analysis of this database resulted with five already published articles. This real world experience provide huge source of informations about Polish HCV infected patients and changes in their profile between 2015 and 2018. Comparison of patients characteristics did not demonstrate changes in gender distribution, but significant reduction of age, as well as prevalence of overweight, accompanying diseases and concomitant medications were observed. Genotype 1b was predominant, but decreasing tendency from 87% in 2015/2016 to 78% in 2018 was observed. Increasing proportion of treatment naïve and non-cirrhotics were noticed. Despite of significantly reduced number of cirrhotics (from 44% to 15%) less patients have decompensation history, Child-Pugh > A, MELD > 15 and history of liver transplantation. In 2017 and 2018 propotion of HIV coinfected patients increased from 1.4% to 3.9%. Ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OPrDR) was the most frequent regimen till 2017, followed by ledipasvir/sofosbuvir ± ribavirin (LSR), but in 2018 the leading became grazoprevir/elbasvir ± ribavirin (GER). SVR rate after OPrDR was higher (97%) than LSR (95%) and GER (95%). SVR of 96% in non-cirrhotics was significantly higher than in cirrhotics (92%). Among 83 patients treated with pangenotypic regimens (available from mid 2018) with available efficacy data at the moment of the abstract submission, SVR was achieved in 93% only. It was due to administration to cirrhotic non-responders to previous DAA based therapies mostly., The lecture discusses the hepatology presentation of nonhepatotropic viruses infections. The literature search shows that wide group of viruses can cause liver disease including CMV, EBV, adenovirus, parvovirus B19, TTV and VZV. Most of the viruses listed above are common in population. In immunocompromised patients they may induce serious clinical course leading to severe hepatitis with acute liver failure. Nonhepatotropic infections in immunocompetent subjects are usually asymptomatic however increase of ALT and bilirubin may be present. In rare cases the infection may be the reason for acute liver failure and death. Nonhepatotropic viruses infection do not have specific clinical signs or symptoms allowing for easy differentiation from other causes of liver disease. Thus these infections should be taken into account in subjects with unexplained liver pathology. Detection of viral etiology of liver disease allows to modify the therapy with the limitation of the use of surgery or antibiotics., Epstein-Barr infections in children are usually asymptomatic. If the infection occured at a later age, in adolescents and adults, it can lead to infectoius mononuckleosis (IM). Over 95% of adults worldwide are infected with this virus and about half of the population has primary Epstein-Barr virus (EBV) infection until 5 years of age in developed countries. In the acute phase of primary EBV infections, hepatic involvement is common. Mild to moderate elevations of liver enzymes concern up to 80-90% of patients. Cholestatic EBV hepatitis is a rare presentation and severe cholestasis is seen in 5% of cases. Hepatic failure has rarely been reported. An atypical presentation of primary EBV infection is also acute acalculous cholecystitis, isolated gallbladder wall thickening or hydrops. In light of the sporadic presentation of AAC, the etiologic pattern and clinical spectrum of the disease in childhood have not been well established. The presence of Gilbert’s syndrome in patients with cholestasis of infectious origin (EBV-infection) could also play a role in the development of gallbladder abnormalities. The incidence of Gilbert’s syndrome may contribute in the pathogenesis of ACC in children with EBV infection. Infection-induced acute hepatitis complicated with acute pancreatitis is associated with hepatitis A virus, hepatitis B virus or hepatitis E virus. Although rare, EBV infection should be considered also in the differential diagnosis if the patient has acute hepatitis combined with pancreatitis. The mechanism of the relation with development of pancreatitis associated to infectious hepatitis are unknown and likely multifactorial. The reliable confirmation of infectious mononucleosis, as primary EBV infection, is detection of specific IgM antibodies or heterophile antibodies tests. There is also the possibility of false negative results, mainly in children. In these case real-time PCR is a reliable tool for diagnosis of primary EBV infection early in the course of disease. In addition, EBV DNA detection may serve as a useful diagnostic supplement in serologically indeterminate EBV infections., Long-term therapy with nucleos(t)ide analogues is a corner stone of chronic hepatitis B management due to effective control of HBV replication and favourable safety profile. It reduces risk of liver related complications such as cirrhosis and hepatocellular carcinoma. The accepted endpoint for treatment discontinuation is hepatitis B antigen seroclearance but whether analogue therapy can safely be stopped before HBsAg loss is a subject of debate. The arguments for therapy cessation are: cost reduction, safety issues in the elderly, in patients with co-morbidities and HIV coinfection, procreation plans in young patients, risk of poor adherence over time, and chance for HBsAg seroclearance. The arguments against treatment discontinuation are: high probability of virological relapse, biochemical and clinical rebound with risk of hepatic decompensation and the frequent need for retreatment., Coinfection and particularly superinfection with hepatitis D virus (HDV) of HBV-infected patients is considered important threat for their liver condition. It may cause the most severe form of chronic viral hepatitis with earlier development of liver cirrhosis, significant risk of hepatocellular carcinoma development and increased liver-related and overall mortality. Additional problem is lack of standardized diagnostic methods and poor correlation between anti-HDV positivity and HDV-RNA presence. In addition, treatment options for hepatitis D are currently limited. So far the standard of care might be pegylated interferon alpha treatment that was proved to suppress HDV replication in about 25% of patients but only a minority of patients can be treated with interferon-based therapies. Altogether is a reason of doubtful real diseases burden assessment and difficulties in management standards development. We have assessed the prevalence of anti-HDV in HBsAg-positive patients using different tests (both quantitative and qualitative) with PCR diagnosis of HDV replication in anti-HDV positive patients. The lack of repeatability of results with the use of different tests makes us look very critically at the usefulness of particular tests in the diagnosis of active HDV infection. The accurate diagnosis is important also because of expected new therapies within next a few years. The key problems that have to be answered: Choosing a serological test.What test for HDV-RNA determination, as many of used in labs are home-made.In whom anti-HDV testing should be obligatory (in all HBsAg+?).In whom HDV-RNA testing as there are reports of HDV-RNA positive results in seronegative patients.What HBV treatment and when (since the low/negative HBV-DNA viral load is not a sign of inactivity).The role PEG-IFN and upcoming new therapies awaiting approval., The knowledge about the epidemiology of hepatotropic viruses in blood donors in Poland is based on the results of obligatory serological (HBsAg, anti-HCV) and molecular (HBV DNA, HCV RNA) screening, additional testing of plasma for fractionation (RNA HAV) and emerging pathogens monitoring in blood donors (anti-HEV and RNA HEV). During the presentation epidemiological trends will be discussed (number of infections/100,000 donors, 95% confidence interval, CI) in years 2005-2018, and for HEV in 2015. The frequency of confirmed anti-HCV results decreased significantly from 368 (342-394) in 2010 to 105 (89-121) in 2018 in first-time donors and from 12.9 (8.7-17.1) in 2006 to 5.2 (3.1-7.3) in 2018 in repeat donors. In first-time donors, a significant decrease was noted in the age groups below 50 years-old. The frequency drop for seropositive HBV infections was found among both, first-time: from 601 (567-635) in 2005 to 126 (109-145) in 2018 and repeat blood donors: from 7.6 (4.9-11.7) in 2005 to 0.2 (0-1.2) in 2018, RR 0.21 (0.18-0.24) and 0.03 (0-0.21) respectively. So far, 2017 was the first and the only one year without HBsAg-positive infections in repeat donors. The most significant decrease of HBsAg detection among first-time donors was recorded in the age group up to 20 years (RR = 0.01 (0-0.03)), significant changes were not noticed in donors over 50 years old. For 14 years, the majority seronegative infections were detected for HBV: 184 occult infections (OBI) (frequency/1 million donors, 95% CI: 22.7, 19.7-26.3) and 47 in serological window period (WP) (5.8, 4.4-7.7). During this period 75 HCV WP (9.3, 7.4-11, 6) were identified. HAV infections were not detected until the outbreak. In 2017-18, 17 infected donors (2.6/100,000 donors, 1.4-3.7) and two likely transmissions via transfusion were identified. In 2015, the frequency of HEV RNA was 47.4 (21.7-103.3)/100,000 first-time donors, and anti-HEV IgG antibodies were found in 43.5% (41.8-45.3) donors. Currently, the highest risk of transfusion-transmitted infection (TTI) concerns HEV, following HAV during the epidemic period (up to several cases per year). The risk of HBV transmission is mainly associated with OBI. For HCV, TTI is estimated to may occur no more frequently than once every few years., Ciliopathies, the defects of organ microstructure with cystic phenotype, include renal damage among several organs. The presence of renal cysts has several phenotypic patterns and those which are of genetic background are divided, in terms of localisation, volume and clinical consequences, to recessive and dominant polycystic kidney disease (ARPKD, ADPKD), various types of medullar cystic pathologies (nephronophtysis) and cystic disease accompanying tuberous sclerosis (TSC). Simple cysts as well as cysts present in some cases of renal cancer or congenital kidney diseases (CAKUT) are of separate pattern. Several ciliopathies are limited to the kidneys, while in remaining ones the several variable extrarenal symptoms, including hepatic, CNS, large vessels, pancreas and intestine pathologies accompany the presence of renal cysts. The diagnostic algorithm starts with detailed defining of phenotype and ends with genetic evaluation, which confirms final diagnosis (especially in syndromic cases), indicates the need for additional diagnostic procedures in cases when some potentially important clinical symptoms are not overt yet and determines the outcome, at least in terms of renal survival. The clinical diagnostic sequence starts with evaluation of renal function (filtration rate and tubular functions), then goes to the imaging procedures: renal USG, evaluating numer, size and localisation of the cysts; CT or MRI evaluating the volume of the cysts and it’s progression over time and presence/development of solid changes inside the cysts; and (upon additional indication) radiologic evaluation of pathology of great vessels and cerebral circulation (in ADPKD). The management is variable and may include ongoing correction of homeostasis disturbances (nephronophtysis), renoprotection with ACEi or blocking of vasopression receptors with tolvaptan (ADPKD), use of mTORi (sirolimus or everolimus) in TSC and finally the isolated kidney or combined/sequential liver-kidney transplantation in severe cases of ARPKD. Distinct management based on radiologic intervention or surgical treatment of arterial wall abnormalities (coarctation or aneurysms), secondary to the defect of polycystin (relevant both to cysts formation and arterial wall defects) is necessary in some cases in ADPKD., Non-alcoholic fatty liver disease (NAFLD) in people with normal body weight often remains unrecognized. Epidemiological studies, albeit few in number, suggest that this problem may affect from several to more than a dozen percent of people in the general population with a normal body mass index (BMI). The pathogenesis of lean NAFLD seems to differ from the disease in obese people, but the consequences in the form of cirrhosis, as well as the risk of developing hepatocellular carcinoma are analogous. In view of the few studies, it is difficult to unequivocally assess the specificity of metabolic disorders, as well as extrahepatic risk, the effectiveness of therapeutic treatment, including the essential for the treatment of NAFLD in obese people, weight reduction. It is emphasized in people with visceral obesity. Further research on therapies, including metabolic disorders disturbed by their distinctness and genetic determinants, are necessary to determine the proper algorithm of management. For the clinician, the most important issue is that people with normal BMI may be at risk of fatty liver disease and require diagnostic procedures similar to those with obesity and metabolic syndrome. Diagnosis of the disease, even in the absence of pharmacotherapy, allows the implementation of appropriate measures limiting the negative effects of the disease., Nonalcoholic steatohepatitis (NASH) is a disease that affects an increasing part of the population around the world and is associated primarily with environmental factors such as diet and its effect on metabolic changes in the body, which is a trigger mechanism for the induction of fatty liver. NASH is considered a type of chronic hepatitis reminiscent of the changes occurring in people who abuse alcohol, but the cause is completely different factors. It is regarded as a progression of non-alcoholic hepatitis and is a risk factor for the development of liver cirrhosis and hepatocellular carcinoma. According to the latest literature data, the most important in the development of the disease are carbohydrate-related disorders of insulin resistance type, resulting in the accumulation of fat in hepatocytes and their steatosis. As a result of chronic oxidative stress, lipid peroxidation occurs with the production of proinflammatory cytokines and the development of hepatitis (NASH). Numerous dietary factors leading to steatosis are primarily simple sugars found in food products, especially glucose-fructose syrup and a diet rich in carbohydrates and simple sugars, including natural (e.g., juices, fruits, honey, sweetened beverages). Hepatic metabolism disorders on this background concerning glycogenolysis, glyconeogenesis and fat metabolism favor the rapid development of hepatocyte reversal and steatosis, even in lean patients. Effective dietary intervention involving a long-term change in eating habits has a huge impact on the reduction of liver steatosis, is the only prophylactic action, and while maintaining dietary regimen, including liver regeneration capabilities, allows the retreat of even advanced NASH changes, confirmed in both laboratory and available non-invasive methods (e.g., fibroscan, ultrasound)., Liver steatosis is a common disorder in chronic HCV infection, affecting from 40% up to 80% patients. HCV-dependent fatty liver is linked to particular virus genotype. Metabolic steatosis prevails in infections due to viruses of not genotype 3, while in viral one viruses of genotype 3 are apparently responsible. In the latter some virus sequences were shown to induce lipid accumulation in hepatocytes. Moreover, fatty change in liver was found to be correlated with viral replication. Some liver proteins such as seipin participate in the formation of cellular large lipid droplets. HCV-dependent liver steatosis appears to be promoting factor for insulin resistance, leading to diabetes, liver fibrosis and hypo-beta lipoproteinemia. Blood laboratory findings show high triglyceride and insulin levels but low values of adipokines and especially adiponectin. It is of interest, that in patients treated by DAA new cases of insulin resistance and type II diabetes were practically not found. In HCV infection lipid accumulation affects also cardiovascular system manifested by arteriosclerosis, coronary arteries of heart, internal carotid arteries and brain ones, the latter often leading to a stroke. Thus, close attention to metabolic lesions during HCV+ liver disease seems to be mandatory., Ethanol is responsible for the development of diseases of many organs and it is the reason for the development of 3.6% of cancers. There is no safe dose of alcohol with respect to risk of cancer development. The carcinogenic activity of ethanol is based on the toxic effects of acetaldehyde, which has mutagenic effects on DNA. Ethanol is metabolized to acetaldehyde through three metabolic systems: cytochrome CYP2E1, alcohol dehydrogenase and catalase. Microbiota has a significant impact on the development of metabolic diseases and cancer. A significant change in microbiota composition leading to dysfunction of intestinal barrier is observed in patients chronically ingesting ethanol, obese and with diabetes. There is a clear relationship between chronic ethanol consumption and the development of tumors of the upper gastrointestinal tract and liver. More and more evidence points to an increase in the development of colon and pancreatic cancer for the people consuming ethanol. The role of alcohol in the development of pancreatic and gastric cancer is still not fully understood and can be modified by environmental, genetic and dietetic factors. Further studies are necessary to better explain and understand the role of ethanol in pathogenesis of cancer development and progression., Improved long-term survival after liver transplantation (LTx) has led to increased prevalence of late complications after LTx such as chronic kidney disease (CKD). CKD has become one of the leading causes of morbidity and mortality after LTx. The reported prevalence of CKD after LTx ranges between 10% and 45%. Although calcineurin inhibitor-toxicity is typically considered a major contributor, other risk factors for CKD include perioperative acute kidney injury, HRS, preexisting CKD, diabetes mellitus, hypertension and chronic hepatitis C infection, donor factors. Decreased GFR < 30 ml/min is a risk factor of mortality after LTx. Renal biopsy can be relatively safe population with liver failure, may help elucidate the etiology of renal failure, may predict post-LAT kidney function, and may be helpful in kidney allocation for liver transplant candidates, but little data exist to validate the usefulness of kidney biopsies in this patient population. Frequent diagnosis includes glomerulonephritis, ATN, thrombotic microangiopathy. Renal biopsy in patients with CKD after LT should be performed, it seems safe and may offer specific therapeutic options. Furthermore, unnecessary changes of immunosuppression can be avoided in a considerable number of patients. Recommendations of ILTS for immunosuppression modification are presented below. In the peri-operative period to optimize renal function induction therapy (interleukin-2 receptor antibodies or short-term of antilymphocyte/thymocyte antibody preparations) combined with cortiosteroids and MMF/MPA and reduced dose or delayed initiation of CNIs is associated with superior renal function and less need for renal replacement therapy than early initiation and standard dosing of CNIs. mTORis should be avoided in the first postoperative month. Early institution at one month of EVL in combination with low dose TAC (5 ng/ml) results in a significantly better renal function than is achieved with standard dosing of TAC. This strategy is particularly beneficial in patients with CKD ≥ stage 3 (eGFR < 60 ml/min). CNI minimization should attempted in patients with CKD in the late postoperative period. Late (> 1 yr) conversion to mTORis is of unclear effect on renal function, particularly in patients with CKD > 3., Albumin dialysis is the best-studied extracorporeal nonbiologic liver support system as a bridge or ultimate therapy for patients with liver failure awaiting liver transplantation or recovery of liver function. Nonbiologic systems use artificial membranes and adsorbents to detoxify the blood in patients with liver failure. Albumin dialysis is based on the removal of albumin-bound and water-soluble substances, such as bilirubin, bile acids, ammonia, nitrotyrosine, and fatty acids. There are three available albumin dialysis systems: the molecular adsorbent reticulating system or MARS (Teraklin, Rostock, Germany), single-pass albumin dialysis (SPAD), and the Prometheus system (Fresenius, Bad Homburg, Germany). Use of albumin dialysis as a supportive treatment for liver failure is successful at removing albumin-bound molecules, such a bilirubin and at improving hepatic encephalopathy. However, survival benefit has not been established yet, after the analysis of 10 randomized control trials (7 of MARS and 3 of Prometheus, no trial of SPAD), and 2 head-to-head trials comparing MARS to Prometheus, with 3688 participants. In our single-center experience SPAD was used in acute-on-chronic patients with acute kidney injury. The results were summarized in the already submitted paper, entitled “Intermittent high-flux albumin dialysis with continuous venovenous hemodialysis for acute-on-chronic liver failure and acute kidney injury” by G. Niewiński, J. Raszeja-Wyszomirska, M. Hrenczuk, A. Rozga, P. Malkowski, J. Rózga. In patients with severe ACLF and acute kidney injury, renal replacement therapy coupled with high-performance albumin dialysis improved estimated 28- and 90-day survival and laboratory parameters. We also published our unique experience with treatment of intractable pruritus and analyzed the efficacy of plasmapheresis in a cohort of patients with primary biliary cholangitis (PBC) in article entitled “Plasmapheresis exerts a long-lasting antipruritic effect in severe cholestatic itch” by M. Krawczyk, R. Liebe, M. Wasilewicz, E. Wunsch, J. Raszeja-Wyszomirska, P. Milkiewicz (Liver Int 2017; 37: 743-747; doi: 10.1111/liv.13281). After the series of plasmapheresis mean pruritus decreased in the entire and antipruritic effect persisted throughout the 90-days follow-up. Thus, there is a need for a large, multicenter, randomized control trials of efficacy and safety of SPAD therapy in acute-on-chronic liver failure, especially with renal complication, with novel filters dedicated to remove proinflammatory cytokines (e.g. the Ci-Ca®CVVHD EMiC®2 kit) and with other indication, i.e. intractable pruritus., Alcohol dependence and abuse is one of the most costly health problems in the world from both a social and an economic point of view. It is a widespread problem, focusing attention not only psychiatrists but also doctors of other specialties. Patterns of drinking appear to be changing throughout the world, with more women and young people drinking heavily. Even risky drinking is a potential health risk, while chronic alcohol abuse contribute to the serious physical and mental complications. Alcohol used disorders associated with alcohol-induced brain damage include: withdrawal state, delirium tremens, alcoholic hallucinosis, alcoholic paranoia, Korsakoffs psychosis, alcoholic dementia, alcoholic depression. On the other hand, mental disorders as panic disorder, social anxiety disorder, agoraphobia, depression, bipolar disorder, schizophrenia, personality disorder most frequently comorbid with alcohol abuse or they trigger alcohol., Of the liver focal lesions, the most common are benign tumors: hemangiomas, cysts, FNH and HCA. Malignant lesions are metastases and primary carcinomas of the liver: HCC and cholangiocarcinomas. After finding the focal lesion in ultrasonography, the basic role in the diagnosis of liver tumors is performed by three-phase CT and magnetic resonance with contrast. Biopsies are less frequently performed only in unclear cases. Cancer markers (AFP, CA19.9, CEA), co-morbidities (HCV, HBV infection) and possibly oncological history of the patient may be helpful in diagnosis. Benign lesions rarely require treatment. The problem is to recognize them clearly. In metastases, depending on the size and number of tumors, we use resection, RFA along with chemotherapy. The possibility of surgical treatment concerns only the metastases of colon cancer and neuroendocrine tumors. In the case of HCC, we base our qualification for treatment on the Barcelona classification. Intrahepatic cholangiocarcinoma is an indication for resection., Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world and the leading cause of death among cirrhotic patients. The radiologic modality most widely used contrast-enhanced CT has sensitivity around 70%, and MRI, around 80%. Positron emission tomography (PET) imaging using fluorodeoxyglucose (18F-FDG) wildly use in oncological disease, but in liver cancer has remained limited The sensitivity of 18F-FDG PET for detecting HCC is not better than conventional imaging (50-70%), mostly because well-differentiated HCC has a high rate of gluconeogenesis comparable with normal liver tissue, resulting in similar uptake of 18F-FDG. PET tracers of lipid metabolism have been proposed as a better method for the detection of HCC. 11C-labeled acetate was reported to be beneficial because of its better sensitivity, as high as 87%, for the detection of low- and intermediate-grade HCC. Choline is one of the components of phosphatidylcholine, an essential element of phospholipids in the cell membrane. 18F-fluorocholine for the detection of intrahepatic HCC is close to published values for 11C-acetate, with a sensitivity ranging from 75% to 87%. The liver is the most frequent site of metastases after the lymph nodes and at the same time the main organ, where the dissemination occurs through blood vessels. 18F-FDG PET/CT is the most sensitive method for the detection of liver metastases especially from multiple gastrointestinal origins, with a mean weighted sensitivity of 90-92%. However 18F-FDG PET/CT has limited utility in cancers with low rate of glucose metabolism as a neuroendocrine tumor, bronchoalveolare carcinoma, mucous cells carcinoma, iodine-avid diff. thyroid cancer, clarocellurare carcinoma and prostate cancer. The eighties brought the discovery of somatostatin receptor(SSTR) overexpression on neuroendocrine tumors. It allows the receptor imaging with radiolabeled somatostatin analogs and somatostatin based radiopeptide therapy as a next step. 111In-(DTPA)–pentetreotide and 99mTc-HYNICTOC are registered for use in Europe, where SPECT/CT equipment is now widely available in many hospitals. 68Ga-DOTATATE PET/CT offers higher spatial resolution and performs better than conventional SSTR imaging, especially in small metastases in liver, bone and lymph nodes. So nowadays, 68Ga-DOTA-labeled radiopeptides is the investigation of choice in managing of neuroendocrine tumors.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously demonstrated decreased energy reserves in the form of phosphocreatine to adenosine-tri-phosphate ratio (PCr/ATP) in the hearts of patients with type 2 diabetes (T2DM). Recent 31P-MRS techniques using 7T systems, e.g. long mixing time stimulated echo acquisition mode (STEAM), allow deeper insight into cardiac metabolism through assessment of inorganic phosphate (Pi) content and myocardial pH, which play pivotal roles in energy production in the heart. Therefore, we aimed to further explore the cardiac metabolic phenotype in T2DM using STEAM at 7T. Seventeen patients with T2DM and twenty-three healthy controls were recruited and their cardiac PCr/ATP, Pi/PCr and pH were assessed at 7T. Diastolic function of all patients with T2DM was assessed using echocardiography to investigate the relationship between diastolic dysfunction and cardiac metabolism. Mirroring the decreased PCr/ATP (1.70±0.31 vs. 2.07±0.39; p2 = 0.33; p = 0.02) in T2DM. No correlation was observed between diastolic function and Pi/PCr and (R2 = 0.16; p = 0.21). In addition, we did not observe any correlation between cardiac PCr/ATP and Pi/PCr (p = 0.19). Using STEAM 31P-MRS at 7T we have for the first time explored Pi/PCr in the diabetic human heart and found it increased when compared to healthy controls. The lack of correlation between measured PCr/ATP and Pi/PCr suggests that independent mechanisms might contribute to these perturbations.

BackgroundAlthough coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear.MethodsCOVID-HEART is a UK, multicentre, prospective, observational, longitudinal cohort study of patients with confirmed COVID-19 and elevated troponin (sex-specific > 99th centile). Baseline assessment will be whilst recovering in-hospital or recently discharged, and include cardiovascular magnetic resonance (CMR) imaging, quality of life (QoL) assessments, electrocardiogram (ECG), serum biomarkers and genetics. Assessment at 6-months includes repeat CMR, QoL assessments and 6-min walk test (6MWT). The CMR protocol includes cine imaging, T1/T2 mapping, aortic distensibility, late gadolinium enhancement (LGE), and adenosine stress myocardial perfusion imaging in selected patients. The main objectives of the study are to: (1) characterise the extent and nature of myocardial involvement in COVID-19 patients with an elevated troponin, (2) assess how cardiac involvement and clinical outcome associate with recognised risk factors for mortality (age, sex, ethnicity and comorbidities) and genetic factors, (3) evaluate if differences in myocardial recovery at 6 months are dependent on demographics, genetics and comorbidities, (4) understand the impact of recovery status at 6 months on patient-reported QoL and functional capacity.DiscussionCOVID-HEART will provide detailed characterisation of cardiac involvement, and its repair and recovery in relation to comorbidity, genetics, patient-reported QoL measures and functional capacity.Clinical Trial registration:ISRCTN 58667920. Registered 04 August 2020.

The subject of "fairness" in artificial intelligence (AI) refers to assessing AI algorithms for potential bias based on demographic characteristics such as race and gender, and the development of algorithms to address this bias. Most applications to date have been in computer vision, although some work in healthcare has started to emerge. The use of deep learning (DL) in cardiac MR segmentation has led to impressive results in recent years, and such techniques are starting to be translated into clinical practice. However, no work has yet investigated the fairness of such models. In this work, we perform such an analysis for racial/gender groups, focusing on the problem of training data imbalance, using a nnU-Net model trained and evaluated on cine short axis cardiac MR data from the UK Biobank dataset, consisting of 5,903 subjects from 6 different racial groups. We find statistically significant differences in Dice performance between different racial groups. To reduce the racial bias, we investigated three strategies: (1) stratified batch sampling, in which batch sampling is stratified to ensure balance between racial groups; (2) fair meta-learning for segmentation, in which a DL classifier is trained to classify race and jointly optimized with the segmentation model; and (3) protected group models, in which a different segmentation model is trained for each racial group. We also compared the results to the scenario where we have a perfectly balanced database. To assess fairness we used the standard deviation (SD) and skewed error ratio (SER) of the average Dice values. Our results demonstrate that the racial bias results from the use of imbalanced training data, and that all proposed bias mitigation strategies improved fairness, with the best SD and SER resulting from the use of protected group models., Comment: MICCAI 2021 conference

Additional file 1. Additional reference ranges. Tables reporting additional normal reference ranges of mitral and tricuspid annular dimensions and tethering indices.

Additional file 1: Table S1. Reproducibility of strain parameters. Table S2. Diagnostic accuracy of predicting new onset AF. Table S3. Differences in age and rate of hypertension between those with and without sarcomeric variants. Figure S1. Flow chart showing inclusion of subjects. Figure S2. Survival curve for HCM patients.

Additional file 1: Supplementary material.

OBJECTIVE Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (

UK Biobank is a population-based cohort of half a million participants aged 40–69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world’s largest multimodal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.

Purpose: To demonstrate the feasibility and performance of a fully automated deep learning framework to estimate myocardial strain from short-axis cardiac magnetic resonance tagged images. Methods and Materials: In this retrospective cross-sectional study, 4508 cases from the UK Biobank were split randomly into 3244 training and 812 validation cases, and 452 test cases. Ground truth myocardial landmarks were defined and tracked by manual initialization and correction of deformable image registration using previously validated software with five readers. The fully automatic framework consisted of 1) a convolutional neural network (CNN) for localization, and 2) a combination of a recurrent neural network (RNN) and a CNN to detect and track the myocardial landmarks through the image sequence for each slice. Radial and circumferential strain were then calculated from the motion of the landmarks and averaged on a slice basis. Results: Within the test set, myocardial end-systolic circumferential Green strain errors were -0.001 +/- 0.025, -0.001 +/- 0.021, and 0.004 +/- 0.035 in basal, mid, and apical slices respectively (mean +/- std. dev. of differences between predicted and manual strain). The framework reproduced significant reductions in circumferential strain in diabetics, hypertensives, and participants with previous heart attack. Typical processing time was ~260 frames (~13 slices) per second on an NVIDIA Tesla K40 with 12GB RAM, compared with 6-8 minutes per slice for the manual analysis. Conclusions: The fully automated RNNCNN framework for analysis of myocardial strain enabled unbiased strain evaluation in a high-throughput workflow, with similar ability to distinguish impairment due to diabetes, hypertension, and previous heart attack., Comment: accepted in Radiology Cardiothoracic Imaging

Aims: Creatine buffers cellular ATP via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesised that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality.Methods and results: Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day, however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalisation of myocardial creatine. AGAT-/- mice had low plasma homoarginine and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that homoarginine is necessary for normal cardiac function.Conclusions: Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that homoarginine deficiency can impair cardiac function, which may explain why low homoarginine is an independent risk factor for multiple cardiovascular diseases.

Background & Aims The diagnosis of non‐alcoholic steatohepatitis and fibrosis staging are central to non‐alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non‐alcoholic steatohepatitis and fibrosis using histology as standard in non‐alcoholic fatty liver disease. Methods Seventy‐one patients with suspected non‐alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0‐4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non‐alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non‐alcoholic fatty liver disease. Transient elastography was also performed. Results Magnetic resonance success rate was 95% vs 59% for transient elastography (P

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter "stressed saturation transfer" (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (kfCK ) for healthy volunteers and obese patients. TRiST measures kfCK in 40 min at 3 T. StreST extends the previously developed TRiST to also make a further kfCK measurement during

Supplemental Digital Content is available in the text., Background: Exposure to ambient air pollution is strongly associated with increased cardiovascular morbidity and mortality. Little is known about the influence of air pollutants on cardiac structure and function. We aim to investigate the relationship between chronic past exposure to traffic-related pollutants and the cardiac chamber volume, ejection fraction, and left ventricular remodeling patterns after accounting for potential confounders. Methods: Exposure to ambient air pollutants including particulate matter and nitrogen dioxide was estimated from the Land Use Regression models for the years between 2005 and 2010. Cardiac parameters were measured from cardiovascular magnetic resonance imaging studies of 3920 individuals free from pre-existing cardiovascular disease in the UK Biobank population study. The median (interquartile range) duration between the year of exposure estimate and the imaging visit was 5.2 (0.6) years. We fitted multivariable linear regression models to investigate the relationship between cardiac parameters and traffic-related pollutants after adjusting for various confounders. Results: The studied cohort was 62±7 years old, and 46% were men. In fully adjusted models, particulate matter with an aerodynamic diameter

Background: Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity. Methods: 27 HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-magnetic resonance spectroscopy (1H-MRS) to measure MTG (lipid/water, %), 31P-MRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking magnetic resonance imaging for diastolic strain rate. Results: When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45±0.25% vs. 0.64±0.16%, p=0.009) and reduced PCr/ATP (1.60±0.09 vs. 2.00±0.10, p=0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max. Conclusions: Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF., This work was supported by Chest Heart and Stroke Association, Scotland. MM acknowledges support from the National University of Malaysia and Ministry of Higher Education Malaysia. SN and OR acknowledge support from the Oxford NIHR Biomedical Research Centre and the Oxford British Heart Foundation Centre of Research Excellence. JES is a Senior BHF Basic Science Research Fellow (FS/11/50/29038). CTR is funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society [098436/Z/12/Z/B]. OR is a BHF Clinical Intermediate Research Fellow FS/16/70/32157.

PURPOSE: Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3T, with measurement in the supine position. A shorter “stressed saturation transfer” (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (k(f)(CK)) for healthy volunteers and obese patients. THEORY AND METHODS: TRiST measures k(f)(CK) in 40 minutes at 3T. StreST extends the previously developed TRiST to also make a further k(f)(CK) measurement during

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter "stressed saturation transfer" (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (kfCK ) for healthy volunteers and obese patients. TRiST measures kfCK in 40 min at 3 T. StreST extends the previously developed TRiST to also make a further kfCK measurement during

Background: The trend towards large-scale studies including population imaging poses new challenges in terms of quality control (QC). This is a particular issue when automatic processing tools, e.g. image segmentation methods, are employed to derive quantitative measures or biomarkers for later analyses. Manual inspection and visual QC of each segmentation isn't feasible at large scale. However, it's important to be able to automatically detect when a segmentation method fails so as to avoid inclusion of wrong measurements into subsequent analyses which could lead to incorrect conclusions. Methods: To overcome this challenge, we explore an approach for predicting segmentation quality based on Reverse Classification Accuracy, which enables us to discriminate between successful and failed segmentations on a per-cases basis. We validate this approach on a new, large-scale manually-annotated set of 4,800 cardiac magnetic resonance scans. We then apply our method to a large cohort of 7,250 cardiac MRI on which we have performed manual QC. Results: We report results used for predicting segmentation quality metrics including Dice Similarity Coefficient (DSC) and surface-distance measures. As initial validation, we present data for 400 scans demonstrating 99% accuracy for classifying low and high quality segmentations using predicted DSC scores. As further validation we show high correlation between real and predicted scores and 95% classification accuracy on 4,800 scans for which manual segmentations were available. We mimic real-world application of the method on 7,250 cardiac MRI where we show good agreement between predicted quality metrics and manual visual QC scores. Conclusions: We show that RCA has the potential for accurate and fully automatic segmentation QC on a per-case basis in the context of large-scale population imaging as in the UK Biobank Imaging Study., Comment: 14 pages, 7 figures, Journal of Cardiovascular Magnetic Resonance

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p

Accelerating the acquisition of magnetic resonance imaging (MRI) is a challenging problem, and many works have been proposed to reconstruct images from undersampled k-space data. However, if the main purpose is to extract certain quantitative measures from the images, perfect reconstructions may not always be necessary as long as the images enable the means of extracting the clinically relevant measures. In this paper, we work on jointly predicting cardiac motion estimation and segmentation directly from undersampled data, which are two important steps in quantitatively assessing cardiac function and diagnosing cardiovascular diseases. In particular, a unified model consisting of both motion estimation branch and segmentation branch is learned by optimising the two tasks simultaneously. Additional corresponding fully-sampled images are incorporated into the network as a parallel sub-network to enhance and guide the learning during the training process. Experimental results using cardiac MR images from 220 subjects show that the proposed model is robust to undersampled data and is capable of predicting results that are close to that from fully-sampled ones, while bypassing the usual image reconstruction stage., Comment: This work is published at MLMIR 2018: Machine Learning for Medical Image Reconstruction

Figure S2. Animations of the first four PCA components. (PPTX 2780 kb)

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p −8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.

Large prospective epidemiological studies acquire cardiovascular magnetic resonance (CMR) images for pre-symptomatic populations and follow these over time. To support this approach, fully automatic large-scale 3D analysis is essential. In this work, we propose a novel deep neural network using both CMR images and patient metadata to directly predict cardiac shape parameters. The proposed method uses the promising ability of statistical shape models to simplify shape complexity and variability together with the advantages of convolutional neural networks for the extraction of solid visual features. To the best of our knowledge, this is the first work that uses such an approach for 3D cardiac shape prediction. We validated our proposed CMR analytics method against a reference cohort containing 500 3D shapes of the cardiac ventricles. Our results show broadly significant agreement with the reference shapes in terms of the estimated volume of the cardiac ventricles, myocardial mass, 3D Dice, and mean and Hausdorff distance., Comment: Accepted for publication in MICCAI 2019

Figure S1 â Detailed effect of CMR scan on occupational disposal. (PPTX 68 kb)

Background Handgrip strength, a measure of muscular fitness, is associated with cardiovascular (CV) events and CV mortality but its association with cardiac structure and function is unknown. The goal of this study was to determine if handgrip strength is associated with changes in cardiac structure and function in UK adults. Methods and results Left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), mass (M), and mass-to-volume ratio (MVR) were measured in a sample of 4,654 participants of the UK Biobank Study 6.3 ± 1 years after baseline using cardiovascular magnetic resonance (CMR). Handgrip strength was measured at baseline and at the imaging follow-up examination. We determined the association between handgrip strength at baseline as well as its change over time and each of the cardiac outcome parameters. After adjustment, higher level of handgrip strength at baseline was associated with higher LVEDV (difference per SD increase in handgrip strength: 1.3ml, 95% CI 0.1±2.4; p = 0.034), higher LVSV (1.0ml, 0.3±1.8; p = 0.006), lower LVM (-1.0g, -1.8 ±-0.3; p = 0.007), and lower LVMVR (-0.013g/ml, -0.018 ±-0.007; p Conclusions Better handgrip strength was associated with cardiac structure and function in a pattern indicative of less cardiac hypertrophy and remodeling. These characteristics are known to be associated with a lower risk of cardiovascular events.

Aims Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97–13.48 g] to 6.30 g (IQR 1.38–17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (≺MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate ≺1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85–13.79; P = 0.002). Conclusion Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.

Purpose We present a new Bloch‐Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first‐order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four‐angle saturation transfer (FAST) method using amplitude‐modulated radiofrequency pulses, phosphorus Bloch‐Siegert B1+‐mapping to determine the per‐voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Methods Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1H localization). Results BOAST kfCK values were 0.281 ± 0.002 s−1 in the calf and 0.35 ± 0.05 s−1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg−1 s−1. The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. Conclusion BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10‐cm loop coil. Magn Reson Med 78:20–32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Objectives The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. Background In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial bloodflow. T1 mapping using cardiac magnetic resonance (CMR) is highly sensitive to changes in myocardial water content, including MBV. We propose that T1 mapping at rest and during adenosine vasodilatory stress can detect MBV changes in normal and diseased myocardium in CAD. Methods Twenty normal controls (10 at 1.5-T; 10 at 3.0-T) and 10 CAD patients (1.5-T) underwent conventional CMR to assess for left ventricular function (cine), infarction (late gadolinium enhancement [LGE]) and ischemia (myocardial perfusion reserve index [MPRI] onfirst-pass perfusion imaging during adenosine stress). These were compared to novel pre-contrast stress/rest T1 mapping using the Shortened Modified Look-Locker Inversion recovery technique, which is heart rate independent. T1 values were derived for normal myocardium in controls and for infarcted, ischemic, and remote myocardium in CAD patients. Results Normal myocardium in controls (normal wall motion, MPRI, no LGE) showed normal resting T1 (954±19 ms at 1.5-T; 1,189±34 ms at 3.0-T) and significant positive T1 reactivity during adenosine stress compared to baseline (6.2±0.5% at 1.5-T; 6.3±1.1% at 3.0-T; all p Conclusions T1 mapping at rest and during adenosine stress can differentiate between normal, infarcted, ischemic, and remote myocardium with distinctive T1 profiles. Stress/rest T1 mapping holds promisefor ischemia detection without the need for gadolinium contrast.

Synopsis: Determination of human cardiac Pi using 31P-MRS is challenging as the resonance frequency of Pi is concealed by a close resonating 2,3-DPG signal originating from blood. Long TR acquisition using adiabatic excitation at 7T can compensate for the rapid blood signal replacement in partially-saturated short TR scans. In order to quantify Pi concentration in vivo, knowledge about longitudinal relaxation of Pi is still required. We have measured the T1 of Pi in 4 healthy volunteers at 7T using dual-TR method and used this value to quantify cardiac Pi concentration in 8 healthy volunteers., We acknowledge financial support from a Sir Henry Dale Fellowship awarded by the Wellcome Trust and the Royal Society (098436/Z/12/Z), and from Slovak Grant Agencies VEGA (2/0001/17) and APVV (15-0029).

Aims: Ventricular arrhythmia triggers sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM), yet electrophysiological biomarkers are not used for risk stratification. Our aim was to identify distinct HCM phenotypes based on ECG computational analysis, and characterize differences in clinical risk factors and anatomical differences using cardiac magnetic resonance (CMR) imaging. Methods: High-fidelity 12-lead Holter ECGs from 85 HCM patients and 38 healthy volunteers were analyzed using mathematical modeling and computational clustering to identify phenotypic subgroups. Clinical features and the extent and distribution of hypertrophy assessed by CMR were evaluated in the subgroups. Results: QRS morphology alone was crucial to identify three HCM phenotypes with very distinct QRS patterns. Group 1 (n = 44) showed normal QRS morphology, Group 2 (n = 19) showed short R and deep S waves in V4, and Group 3 (n = 22) exhibited short R and long S waves in V4-6, and left QRS axis deviation. However, no differences in arrhythmic risk or distribution of hypertrophy were observed between these groups. Including T wave biomarkers in the clustering, four HCM phenotypes were identified: Group 1A (n = 20), with primary repolarization abnormalities showing normal QRS yet inverted T waves, Group 1B (n = 24), with normal QRS morphology and upright T waves, and Group 2 and Group 3 remaining as before, with upright T waves. Group 1A patients, with normal QRS and inverted T wave, showed increased HCM Risk-SCD scores (1A: 4.0%, 1B: 1.8%, 2: 2.1%, 3: 2.5%, p = 0.0001), and a predominance of coexisting septal and apical hypertrophy (p < 0.0001). HCM patients in Groups 2 and 3 exhibited predominantly septal hypertrophy (85 and 90%, respectively). Conclusion: HCM patients were classified in four subgroups with distinct ECG features. Patients with primary T wave inversion not secondary to QRS abnormalities had increased HCM Risk-SCD scores and coexisting septal and apical hypertrophy, suggesting that primary T wave inversion may increase SCD risk in HCM, rather than T wave inversion secondary to depolarization abnormalities. Computational ECG phenotyping provides insight into the underlying processes captured by the ECG and has the potential to be a novel and independent factor for risk stratification.

Image demonstrating visual assessment and comparison between automated segmentation and manual segmentation. (PDF 210 kb)

Rationale: Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell-driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) is an emerging imaging technology that generates contrast agents with 10- to 20 000-fold improvements in MR signal, enabling cardiac metabolite mapping. Objective: To determine whether hyperpolarized MR using [1-13C]pyruvate can assess the local cardiac inflammatory response after MI. Methods and Results: We performed hyperpolarized [1-13C]pyruvate MR studies in small and large animal models of MI and in macrophage-like cell lines and measured the resulting [1-13C]lactate signals. MI caused intense [1-13C]lactate signal in healing myocardial segments at both day 3 and 7 after rodent MI, which was normalized at both time points after monocyte/macrophage depletion. A near-identical [1-13C]lactate signature was also seen at day 7 after experimental MI in pigs. Hyperpolarized [1-13C]pyruvate MR spectroscopy in macrophage-like cell suspensions demonstrated that macrophage activation and polarization with lipopolysaccharide almost doubled hyperpolarized lactate label flux rates in vitro; blockade of glycolysis with 2-deoxyglucose in activated cells normalized lactate label flux rates and markedly inhibited the production of key proinflammatory cytokines. Systemic administration of 2-deoxyglucose after rodent MI normalized the hyperpolarized [1-13C]lactate signal in healing myocardial segments at day 3 and also caused dose-dependent improvement in IL (interleukin)-1β expression in infarct tissue without impairing the production of key reparative cytokines. Cine MRI demonstrated improvements in systolic function in 2-DG (2-deoxyglucose)-treated rats at 3 months. Conclusions: Hyperpolarized MR using [1-13C]pyruvate provides a novel method for the assessment of innate immune cell-driven inflammation in the heart after MI, with broad potential applicability across other cardiovascular disease states and suitability for early clinical translation.