Severe juvenile dermatomyositis with specific liver involvement onset concomitant with COVID-19 infection: A case report

Juvenile Dermatomyositis (JDM) is an autoimmune disease that involves skin, muscle and internal organ disorders. Its mechanisms still not well established, but the triggering role of viral infections has been described. In this context, the effect of the COVID-19 on the onset of autoimmune disorders such as JDM remains a matter of study and research. We report a severe JDM, following a confirmed COVID-19 infection in a previously healthy 8 year-old boy who presented with various skin lesions and a cholestatic liver involvement. Laboratory findings were consistent with an inflammatory myositis and an autoimmune liver disease. Skin and muscle biopsies confirmed the diagnosis of JDM. The therapy choice was difficult. Finally, he received a second line therapy of the JDM with a favorable outcome. The liver fragment analysis showed a steatosis. This case supports the hypothesis of COVID-19 triggering role in the genesis of JDM and autoimmune diseases.Copyright © 2023 Scientific Publishers of India. All rights reserved.

Multifactorial Effects of Covid-19: A Review of Published Autopsy Reports

Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.

Metabolic-associated fatty liver disease and liver fibrosis scores as COVID-19 outcome predictors: a machine-learning application.

Patients with COVID-19 and metabolic-dysfunction associated fatty liver disease (MAFLD) appear to be at higher risk for severe manifestations, especially in the youngest decades. Our aim was to examine whether patients with MAFLD and/or with increased liver fibrosis scores (FIB-4) are at risk for severe COVID-19 illness, using a machine learning (ML) model. Six hundred and seventy two patients were enrolled for SARS-CoV-2 pneumonia between February 2020 and May 2021. Steatosis was detected by ultrasound or computed tomography (CT). ML model valuated the risks of both in-hospital death and prolonged hospitalizations (> 28 days), considering MAFLD, blood hepatic profile (HP), and FIB-4 score. 49.6% had MAFLD. The accuracy in predicting in-hospital death was 0.709 for the HP alone and 0.721 for HP + FIB-4; in the 55-75 age subgroup, 0.842/0.855; in the MAFLD subgroup, 0.739/ 0.772; in the MAFLD 55-75 years, 0.825/0.833. Similar results were obtained when considering the accuracy in predicting prolonged hospitalization. In our cohort of COVID-19 patients, the presence of a worse HP and a higher FIB-4 correlated with a higher risk of death and prolonged hospitalization, regardless of the presence of MAFLD. These findings could improve the clinical risk stratification of patients diagnosed with SARS-CoV-2 pneumonia.

Nutritional Approaches in Children with Overweight or Obesity and Hepatic Steatosis.

Childhood obesity is a global public health problem. Worldwide, 41 million children under 5 years and 340 million children and adolescents between 5 and 19 years are overweight. In addition, the recent COVID-19 epidemic has further amplified this social phenomenon. Obesity is a condition associated with various comorbidities, such as nonalcoholic fatty liver disease (NAFLD). The pathophysiology of NAFLD in obesity is intricate and involves the interaction and dysregulation of several mechanisms, such as insulin resistance, cytokine signaling, and alteration of the gut microbiota. NAFLD is defined as the presence of hepatic steatosis in more than 5% of hepatocytes, evaluated by histological analysis. It can evolve from hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver failure. Body weight reduction through lifestyle modification remains the first-line intervention for the management of pediatric NAFLD. Indeed, studies suggest that diets low in fat and sugar and conversely rich in dietary fibers promote the improvement of metabolic parameters. This review aims to evaluate the existing relationship between obesity and NAFLD in the pediatric population and to assess the dietary patterns and nutritional supplementations that can be recommended to prevent and manage obesity and its comorbidities.

Features of liver injury related to COVID-19

Objective — to study the character of liver function tests' changes in patients with COVID — 19, assess the rate of their onset, their clinical and laboratory manifestations and degree of COVID-19 effects on the liver function with the purpose to implement treatment and preventive measures. Materials and methods. The study included 120 medical records of inpatients with COVID-19, hospitalized in the departments of Clinical Hospital № 8, reprofiled to the infectious wards in the period between November 2020 and April 2021. The most patients were aged 60—69 years (41.7 %) and older than 70 years (25.0 %), the minor portion was younger than 40 years (1.7 %);women prevailed (65.0 %). Results. The increased hepatic transaminases levels were revealed in 52 % of patients, and total bilirubin (especially indirect) was raised in 15 %. Higher transaminases levels, severe course of coronaviral disease and unfavorable prognosis were more common in male patients. Frequency of SARS-CoV-2 — associated liver injury with minimal grade of activity of liver transaminases prevailed in women older than 60 years and men aged 50 to 69 years. COVID¬19-associated hepatitis with moderate activity was observed in women aged 50—69 years and men of working age (40—49 years) and elderly (> 70 years) patients, high degree of transaminases' activity against COVID¬19 background was registered only in men aged 40—59 years with moderate to severe COVID¬19 course. Lethal outcomes due to severe pulmonary injury were registered in 19 patients with severe COVID¬19 course;they also had liver dysfunction. From them, 11 had diagnosed liver steatosis before COVID-19. The most part of deсeased due to COVID-19 were older than 60 years and had a history of comorbidities (type 2 diabetes mellitus, hypertension, coronary heart disease, non-alcoholic fatty liver disease, liver cirrhosis and 2—3 grade obesity). Conclusions. Hepatic impairment occurred in 52 % of inpatients with COVID-19. All patients with moderate course of coronaviral disease demonstrated positive dynamics of transaminases and bilirubin levels and favorable prognosis after hospitalization due to COVID-19. Most of them hadn't had liver injuries before coronaviral disease and six patients had been diagnosed with liver diseases before COVID-19. No cases of fatal liver failure were registered. After in-hospital treatment, the transaminases levels were lower in patients, who hadn't had history of liver diseases before COVID-19 and received hepatoprotective drugs. Treatment with glutathione and ursodeoxycholic acid was confirmed as the most effective therapy in patients with coronaviral disease. © Сучасна гастроентерологія, 2022.

A Novel Combined Model to Predict the Prognosis of COVID-19: Radiological-Metabolic Scoring.

AIM: To investigate the performance of a novel radiological-metabolic scoring (RM-S) system to predict mortality and intensive care unit (ICU) requirements among COVID-19 patients and to compare performance with the chest computed-tomography severity-scoring (C-CT-SS). The RM-S was created from scoring systems such as visual coronary-artery-calcification scoring (V-CAC-S), hepatic-steatosis scoring (HS-S) and pancreatic-steatosis scoring (PS-S). METHODS: Between May 2021 and January 2022, 397 patients with COVID-19 were included in this retrospective cohort study. All demographic, clinical and laboratory data and chest CT images of patients were retrospectively reviewed. RM-S, V-CAC-S, HS-S, PS-S and C-CT-SS scores were calculated, and their performance in predicting mortality and ICU requirement were evaluated by univariate and multivariable analyses. RESULTS: A total of 32 (8.1%) patients died, and 77 (19.4%) patients required ICU admission. Mortality and ICU admission were both associated with older age (p < 0.001). Sex distribution was similar in the deceased vs. survivor and ICU vs. non-ICU comparisons (p = 0.974 and p = 0.626, respectively). Multiple logistic regression revealed that mortality was independently associated with having a C-CT-SS score of ≥14 (p < 0.001) and severe RM-S category (p = 0.010), while ICU requirement was independently associated with having a C-CT-SS score of ≥14 (p < 0.001) and severe V-CAC-S category (p = 0.010). CONCLUSION: RM-S, C-CT-SS, and V-CAC-S are useful tools that can be used to predict patients with poor prognoses for COVID-19. Long-term prospective follow-up of patients with high RM-S scores can be useful for predicting long COVID.

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH.

BACKGROUND & AIMS: The LIVIFY trial investigated the safety, tolerability, and efficacy, of Vonafexor, a second-generation, non-bile acid farnesoid X receptor agonist in patients with suspected fibrotic non-alcoholic steatohepatitis (NASH). METHODS: This double-blind phase 2a study was conducted in two parts. Patients were randomised (1:1:1:1) to receive placebo, Vonafexor 100 mg twice daily (VONA-100BID), Vonafexor 200 mg once daily (VONA-200QD), or 400 mg Vonafexor QD (VONA-400QD) in Part A (safety run-in, pharmacokinetics/pharmacodynamics) or placebo, Vonafexor 100 mg QD (VONA-100QD), or VONA-200QD (1:1:1) in Part B. Efficacy endpoints were reduction in liver fat content (LFC) from baseline to Week 12 by magnetic resonance imaging proton density fat fraction (MRI-PDFF, primary), imaging biomarker of fibrotic steatohepatitis (corrected T1 signal), and liver enzymes. RESULTS: One hundred and twenty patients were randomised (Part A, n=24; Part B, n=96). In Part B, there was a significant reduction in least-square mean (SE) absolute change in LFC from baseline to Week 12 for VONA-100QD, (-6.3% [0.9]), VONA-200QD (-5.4% [0.9]), versus placebo (-2.3% [0.9], p=0.002 and 0.012, respectively). A >30% relative LFC reduction was achieved by 50.0% and 39.3% of patients in the VONA-100QD and VONA-200QD arms, respectively, but only in 12.5% in the placebo arm. Reductions in body weight, liver enzymes, and corrected T1 were also observed with Vonafexor. Creatinine based glomerular filtration rate (eGFR) improved in the active arms but not the placebo arm. Mild to moderate generalised pruritus was reported in 6.3%, 9.7%, and 18.2% of subjects in the placebo, VONA-100QD, and VONA-200QD arms, respectively. CONCLUSIONS: In patients with suspected fibrotic NASH, Vonafexor was safe and induced potent liver fat reduction, improvement in liver enzymes, weight loss, and a possible renal benefit. CLINICAL TRIAL NUMBER (EUDRACT): 2018-003119-22. GOV IDENTIFIER: NCT03812029. IMPACT AND IMPLICATIONS: NASH has become a leading cause for chronic liver disease and patients are also at higher risk for the development of chronic kidney disease. There are no approved therapies and only few options to treat this population. LIVIFY Phase 2a trial results show that single daily administration of oral Vonafexor, a FXR agonist, leads in the short term to a reduction in liver fat, liver enzymes, fibrosis biomarkers, body weight and abdominal circumference, and a possible improvement in kidney function, while possible mild moderate pruritus (a peripheral FXR class effect) and an LDL-Cholesterol increase are manageable with lower doses and statins. These results support exploration in longer and larger trials to ultimately provide therapies for the unmet medical need in NASH.

A study on the morbid histopathological changes in COVID-19 patients with or without comorbidities using minimally invasive tissue sampling

Introduction: COVID-19 causes morbid pathological changes in different organs including lungs, kidney, liver,etc especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without - not much is known about the differences at histopathological level. Aim(s): It was to compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised(Gr 1), malignancy(Gr 2) or had cardiometabolic conditions (hypertension, diabetes or coronary artery disease)(Gr 3). Method(s): Post-mortem tissue sampling (MITS) was done from the lungs, kidney, heart, and liver using biopsy gun within two hours of death. Routine (H & E stain) and special stains (AFB, SM, PAS) were done besides immunohistochemistry. Result(s): A total of 100 patients underwent MITS and data of 92 were included (immunocompromised: 27, maligancy:18, cardiometabolic conditions:71). Within lung histopathology, capillary congestion was more in those with malignancy while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia etc was equally distributed. Within liver, architecture distortion was significantly different in immunocompromised while steatosis, portal inflammation, Kupffer cell hypertrophy, confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological differences in heart was discerned. Conclusion(s): Certain histopathological features are markedly different in different groups (Gr 1,2 and3)of COVID-19 patients with fatal outcome.

The Comprehensive Effects of Carassius auratus Complex Formula against Lipid Accumulation, Hepatocarcinogenesis, and COVID-19 Pathogenesis via Stabilized G-Quadruplex and Reduced Cell Senescence.

Carassius auratus complex formula (CACF) is a traditional Chinese medicine known for its antidiabetic effects. Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide, and there are currently no effective therapies for advanced HCC. This study explores the comprehensive effects and possible mechanisms of CACF on HCC. The results show that CACF reduces the viability of hepatoma cells in vitro, while benefiting normal hepatocytes. In addition, CACF inhibits hepatoma cell growth in a zebrafish xenotransplantation model and decreases lipid accumulation, represses inflammation and cell proliferation markers in fatty acid translocase (CD36) transgenic zebrafish, and inhibits the expression of cell proliferation and ß-catenin downstream targets in telomerase (tert) transgenic zebrafish models. Ingenuity Pathway Analysis reveals that CACF exerts multiple functions, including reduction of inflammation and inhibition of lipid transporter and PPAR signaling pathway. Surprisingly, CACF also regulates the expression of genes and reduces coronavirus infection and pathogenesis in a zebrafish model. CACF treatment is validated to regulate the expression of genes for anti-coronavirus activity. Mechanistically, CACF stabilizes G-quadruplex and reduces cell senescence associated ß-galactosidase activity. In summary, CACF may be a promising therapeutic agent with multiple functions including anticancer, anti-inflammation, and anti-microorganisms in a zebrafish model.

Relationship between hepatic and pancreatic steatosis and the COVID-19 pneumonia total severity score and prognosis with an emphasis on prognostic strength.

PURPOSE: To investigate the relationship between hepatic steatosis (HS), pancreatic steatosis (PS), and coexisting HS and PS and the Coronavirus disease-2019 (COVID-19) pneumonia total severity score (TSS) and prognosis, assessed through computed tomography (CT), and to evaluate the degree of effectiveness of the three steatosis conditions on TSS and prognosis. METHODS: This retrospective study involved 461 patients (255 male and 206 female, median age of 53 years) with COVID-19 who underwent unenhanced chest CT. HS, PS, and coexisting HS and PS, assessed through CT, were compared with patient demographics, comorbidities, TSS, hospitalization and intubation requirements, and mortality rates. The parameters were compared using Mann-Whitney U and chi-square tests. The parameters of three groups of patients with only HS, only PS, and both HS and PS were compared using the Kruskal-Wallis test. RESULTS: Results revealed that TSS (P < 0.001 for all) and hospitalization rates (P < 0.001 for all except for HS [P = 0.004]) were higher in patients with HS, PS, and both than in those without. Intubation (P = 0.003) and mortality rates (P = 0.018) were significant solely in patients with PS. However, TSS, hospitalization, and diabetes mellitus were significant in age-standardized analyses for PS. In a comparison between only HS, only PS, and coexisting HS and PS in 210 patients, the highest TSS was in the coexistence group (P < 0.001). CONCLUSION: The TSS and hospitalization rates correlate with HS, PS, and coexisting HS and PS, whereas intubation and mortality rates only correlate with PS. However, TSS correlates with coexisting HS and PS at the highest rate.

Non-alcoholic fatty liver disease in diabetes mellitus patients on chronic hemodialysis - A case series addressing cardiovascular and mortality risks.

Non-alcoholic fatty liver disease (NAFLD) has an important role in the pathogenesis of cardiovascular diseases in the population with diabetes and it is highly prevalent in end-stage renal disease (ESRD) patients. This case series describes NAFLD associated factors and survival in type 2 diabetes patients (T2DM) who have ESRD treated with hemodialysis. NAFLD prevalence in patients with T2DM and ESRD is 69.2%. A high number of patients (15 out of 18) have obesity evaluated by calculating body mass index (BMI) and bioimpedance measurements. Patients with NAFLD have higher cardiovascular mortality risk, 13 of 18 patients were already diagnosed with coronary heart disease, 6 of 18 had cerebrovascular disease, and 6 of 18 had peripheral artery disease. Fourteen patients were treated with insulin, two patients with sitagliptin (renal adjusted dose of 25mg/day) and two patients with medical nutrition therapy, with an HbA1c ranging from 4.4 to 9.0%. After one-year follow-up 7 of 18 patients died, the causes having roughly equal proportions: myocardial infarction, SARS-CoV2 infection, and pulmonary edema. In conclusion, our population of type 2 diabetic patients with ESRD in hemodialysis had a prevalence of ultrasound-diagnosed NAFLD of 69.2%. Also, this population had a high death rate at one-year follow-up, cardiovascular causes being among the most common.

Pathogenesis of Alcohol-Associated Fatty Liver: Lessons From Transgenic Mice.

Alcohol-associated liver disease (ALD) is a major public health issue that significantly contributes to human morbidity and mortality, with no FDA-approved therapeutic intervention available. The health burden of ALD has worsened during the COVID-19 pandemic, which has been associated with a spike in alcohol abuse, and a subsequent increase in hospitalization rates for ALD. A key knowledge gap that underlies the lack of novel therapies for ALD is a need to better understand the pathogenic mechanisms that contribute to ALD initiation, particularly with respect to hepatic lipid accumulation and the development of fatty liver, which is the first step in the ALD spectrum. The goal of this review is to evaluate the existing literature to gain insight into the pathogenesis of alcohol-associated fatty liver, and to synthesize alcohol's known effects on hepatic lipid metabolism. To achieve this goal, we specifically focus on studies from transgenic mouse models of ALD, allowing for a genetic dissection of alcohol's effects, and integrate these findings with our current understanding of ALD pathogenesis. Existing studies using transgenic mouse models of ALD have revealed roles for specific genes involved in hepatic lipid metabolic pathways including fatty acid uptake, mitochondrial ß-oxidation, de novo lipogenesis, triglyceride metabolism, and lipid droplet formation. In addition to reviewing this literature, we conclude by identifying current gaps in our understanding of how alcohol abuse impairs hepatic lipid metabolism and identify future directions to address these gaps. In summary, transgenic mice provide a powerful tool to understand alcohol's effect on hepatic lipid metabolism and highlight that alcohol abuse has diverse effects that contribute to the development of alcohol-associated fatty liver disease.

Nonalcoholic fatty liver disease and diabetes.

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

Epidemiology and Disease Burden of Alcohol Associated Liver Disease.

Consumption of alcohol in excess leads to substantial medical, economic, and societal burdens. Approximately 5.3% of all global deaths may be attributed to alcohol consumption. Moreover, the burden of alcohol associated liver disease (ALD) accounts for 5.1% of all disease and injury worldwide. Alcohol use disorder (AUD) affects men more than women globally with significant years of life loss to disability in low, middle and well-developed countries. Precise data on global estimates of alcohol related steatosis, alcohol related hepatitis, and alcohol related cirrhosis have been challenging to obtain. In the United States (US), alcohol related steatosis has been estimated at 4.3% based on NHANES data which has remained stable over 14 years. However, alcohol-related fibrotic liver disease has increased over the same period. In those with AUD, the prevalence of alcohol related hepatitis has been estimated at 10-35%. Globally, the prevalence of alcohol-associated cirrhosis has been estimated at 23.6 million individuals for compensated cirrhosis and 2.46 million for those with decompensated cirrhosis. The contribution of ALD to global mortality and disease burden of liver related deaths is substantial. In 2016 liver disease related to AUD contributed to 50% of the estimated liver disease deaths for age groups 15 years and above. Data from the US report high cost burdens associated with those admitted with alcohol-related liver complications. Finally, the recent COVID-19 pandemic has been associated with marked increase in alcohol consumption worldwide and will likely increase the burden of ALD.

Predicting model of mild and severe types of COVID-19 patients using Thymus CT radiomics model: A preliminary study.

OBJECTIVE: To predict COVID-19 severity by building a prediction model based on the clinical manifestations and radiomic features of the thymus in COVID-19 patients. METHOD: We retrospectively analyzed the clinical and radiological data from 217 confirmed cases of COVID-19 admitted to Xiangyang NO.1 People's Hospital and Jiangsu Hospital of Chinese Medicine from December 2019 to April 2022 (including 118 mild cases and 99 severe cases). The data were split into the training and test sets at a 7:3 ratio. The cases in the training set were compared in terms of clinical data and radiomic parameters of the lasso regression model. Several models for severity prediction were established based on the clinical and radiomic features of the COVID-19 patients. The DeLong test and decision curve analysis (DCA) were used to compare the performances of several models. Finally, the prediction results were verified on the test set. RESULT: For the training set, the univariate analysis showed that BMI, diarrhea, thymic steatosis, anorexia, headache, findings on the chest CT scan, platelets, LDH, AST and radiomic features of the thymus were significantly different between the two groups of patients (P < 0.05). The combination model based on the clinical and radiomic features of COVID-19 patients had the highest predictive value for COVID-19 severity [AUC: 0.967 (OR 0.0115, 95%CI: 0.925-0.989)] vs. the clinical feature-based model [AUC: 0.772 (OR 0.0387, 95%CI: 0.697-0.836), P < 0.05], laboratory-based model [AUC: 0.687 (OR 0.0423, 95%CI: 0.608-0.760), P < 0.05] and model based on CT radiomics [AUC: 0.895 (OR 0.0261, 95%CI: 0.835-0.938), P < 0.05]. DCA also confirmed the high clinical net benefits of the combination model. The nomogram drawn based on the combination model could help differentiate between the mild and severe cases of COVID-19 at an early stage. The predictions from different models were verified on the test set. CONCLUSION: Severe cases of COVID-19 had a higher level of thymic involution. The thymic differentiation in radiomic features was related to disease progression. The combination model based on the radiomic features of the thymus could better promote early clinical intervention of COVID-19 and increase the cure rate.

Obesity-Associated Hepatic Steatosis, Somatotropic Axis Impairment, and Ferritin Levels Are Strong Predictors of COVID-19 Severity.

The full spectrum of SARS-CoV-2-infected patients has not yet been defined. This study aimed to evaluate which parameters derived from CT, inflammatory, and hormonal markers could explain the clinical variability of COVID-19. We performed a retrospective study including SARS-CoV-2-infected patients hospitalized from March 2020 to May 2021 at the Umberto I Polyclinic of Rome. Patients were divided into four groups according to the degree of respiratory failure. Routine laboratory examinations, BMI, liver steatosis indices, liver CT attenuation, ferritin, and IGF-1 serum levels were assessed and correlated with severity. Analysis of variance between groups showed that patients with worse prognoses had higher BMI and ferritin levels, but lower liver density, albumin, GH, and IGF-1. ROC analysis confirmed the prognostic accuracy of IGF-1 in discriminating between patients who experienced death/severe respiratory failure and those who did not (AUC 0.688, CI: 0.587 to 0.789, p < 0.001). A multivariate analysis considering the degrees of severity of the disease as the dependent variable and ferritin, liver density, and the standard deviation score of IGF-1 as regressors showed that all three parameters were significant predictors. Ferritin, IGF-1, and liver steatosis account for the increased risk of poor prognosis in COVID-19 patients with obesity.

Metabolic associated fatty liver disease is highly prevalent in the post-acute COVID syndrome

Background and Aims : Recently a proposal has been advanced to change the traditional definition of Non-Alcoholic Fatty Liver Disease to Metabolic Associated Fatty Liver Disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long COVID is a smoldering inflammatory condition, characterized by a number of symptom clusters. This study aims to determine the prevalence of MAFLD in patients with post-acute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Method(s): We included 235 patients followed at a single university outpatient clinic. The diagnosis of PACS was based on >=1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first post-discharge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Result(s): Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P<0.001). Insulin resistance (OR=1.5, 95%CI: 1.14-1.96), body mass index (OR=1.14, 95%CI: 1.04-1.24), and the metabolic syndrome (OR=2.54, 95%CI: 1.13-5.68), were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR=0.86, 95%CI: 0.76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusion(s): MAFLD was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications. Copyright © 2022

May an incidental finding on chest CT be a predictor of access in intensive care unit? Role of hepatic steatosis in patients affected by SARS-CoV-2.

Background: Due to the high prevalence of hepatic steatosis (HS), the aim of the study is to verify the frequency of HS incidentally detected in chest computed tomography (CT) imaging in our population affected by SARS-CoV-2 and to investigate its association with the severity of the infection and outcome in terms of hospitalization. Design and methods: We retrospectively analyzed 500 patients with flu syndrome and clinically suspected of having Sars-CoV-2 infection who underwent unenhanced chest CT and have positive RT-PCR tests for Sars-CoV-2 RNA. Two radiologists both with >5 years of thoracic imaging experience, evaluated the images in consensus, without knowing the RT-PCR results. Liver density was measured by a region of interest (ROI), using a liver attenuation value ≤40 Hounsfield units (HU). Results: On 480 patients, 23.1% (111/480) had an incidental findings of HS on chest CT. The steatosis group, included 83 (74.7%) males and 28 (25.3%) females. Patients with HS were more likely to be hospitalized in the intensive care unit (ICU). On univariate analysis, there is a correlation between probability to be intubate (access in the ICU) and HS: patients with HS are twice as likely to be intubated (OR 2.04, CI 95% 1.11-3.73). Conclusion: Chest CT is an important diagnostic tool for COVID-19 and can provide information about the prognosis of the disease. HS can easily be detected on chest CT taken for the diagnosis of the COVID-19 disease, is an important sign for a poor prognosis and possible predictor of admission in ICU.

Pancreatic Steatosis Evaluated by Automated Volumetric CT Fat Fraction of the Pancreas: Association with Severity in COVID-19 Pneumonia.

This study investigated the relationship between the severity of pneumonia based on chest CT findings and that of pancreatic steatosis assessed using an automated volumetric measurement of the CT fat volume fraction (CT-FVF) of the pancreas, using unenhanced three-dimensional CT in polymerase chain reaction (PCR)-confirmed COVID-19 patients. The study population consisted of 128 patients with PCR-confirmed COVID-19 infection who underwent CT examinations. The CT-FVF of the pancreas was calculated using a histogram analysis for the isolation of fat-containing voxels in the pancreas. The CT-FVF (%) of the pancreas had a significantly positive correlation with the lung severity score on CT (ρ = 0.549, p < 0.01). CT-FVF (%) of the pancreas in the severe pneumonia group was significantly higher than that of the non-severe pneumonia group (21.7% vs. 7.8%, p < 0.01). The area under the curve of CT-FVF (%) of the pancreas in predicting the severity of pneumonia on CT was calculated to be 0.82, with a sensitivity of 88% and a specificity of 68% at a threshold for the severity score of 12.3. The automated volumetric measurement of the CT-FVF of the pancreas using unenhanced CT can help estimate disease severity in patients with COVID-19 pneumonia based on chest CT findings.

Deep-learning-based hepatic fat assessment (DeHFt) on non-contrast chest CT and its association with disease severity in COVID-19 infections: A multi-site retrospective study.

BACKGROUND: Hepatic steatosis (HS) identified on CT may provide an integrated cardiometabolic and COVID-19 risk assessment. This study presents a deep-learning-based hepatic fat assessment (DeHFt) pipeline for (a) more standardised measurements and (b) investigating the association between HS (liver-to-spleen attenuation ratio <1 in CT) and COVID-19 infections severity, wherein severity is defined as requiring invasive mechanical ventilation, extracorporeal membrane oxygenation, death. METHODS: DeHFt comprises two steps. First, a deep-learning-based segmentation model (3D residual-UNet) is trained (N.ß=.ß80) to segment the liver and spleen. Second, CT attenuation is estimated using slice-based and volumetric-based methods. DeHFt-based mean liver and liver-to-spleen attenuation are compared with an expert's ROI-based measurements. We further obtained the liver-to-spleen attenuation ratio in a large multi-site cohort of patients with COVID-19 infections (D1, N.ß=.ß805; D2, N.ß=.ß1917; D3, N.ß=.ß169) using the DeHFt pipeline and investigated the association between HS and COVID-19 infections severity. FINDINGS: The DeHFt pipeline achieved a dice coefficient of 0.95, 95% CI [0.93...0.96] on the independent validation cohort (N.ß=.ß49). The automated slice-based and volumetric-based liver and liver-to-spleen attenuation estimations strongly correlated with expert's measurement. In the COVID-19 cohorts, severe infections had a higher proportion of patients with HS than non-severe infections (pooled OR.ß=.ß1.50, 95% CI [1.20...1.88], P.ß<.ß.001). INTERPRETATION: The DeHFt pipeline enabled accurate segmentation of liver and spleen on non-contrast CTs and automated estimation of liver and liver-to-spleen attenuation ratio. In three cohorts of patients with COVID-19 infections (N.ß=.ß2891), HS was associated with disease severity. Pending validation, DeHFt provides an automated CT-based metabolic risk assessment. FUNDING: For a full list of funding bodies, please see the Acknowledgements.