ANGPTL3 Deficiency and Risk of Hepatic Steatosis.

BACKGROUND: ANGPTL3 (angiopoietin-like 3) is a therapeutic target for reducing plasma levels of triglycerides and low-density lipoprotein cholesterol. A recent trial with vupanorsen, an antisense oligonucleotide targeting hepatic production of ANGPTL3, reported a dose-dependent increase in hepatic fat. It is unclear whether this adverse effect is due to an on-target effect of inhibiting hepatic ANGPTL3. METHODS: We recruited participants with ANGPTL3 deficiency related to ANGPTL3 loss-of-function (LoF) mutations, along with wild-type (WT) participants from 2 previously characterized cohorts located in Campodimele, Italy, and St. Louis, MO. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction were performed to measure hepatic fat fraction and the distribution of extrahepatic fat. To estimate the causal relationship between ANGPTL3 and hepatic fat, we generated a genetic instrument of plasma ANGPTL3 levels as a surrogate for hepatic protein synthesis and performed Mendelian randomization analyses with hepatic fat in the UK Biobank study. RESULTS: We recruited participants with complete (n=6) or partial (n=32) ANGPTL3 deficiency related to ANGPTL3 LoF mutations, as well as WT participants (n=92) without LoF mutations. Participants with ANGPTL3 deficiency exhibited significantly lower total cholesterol (complete deficiency, 78.5 mg/dL; partial deficiency, 172 mg/dL; WT, 188 mg/dL; P<0.05 for both deficiency groups compared with WT), along with plasma triglycerides (complete deficiency, 26 mg/dL; partial deficiency, 79 mg/dL; WT, 88 mg/dL; P<0.05 for both deficiency groups compared with WT) without any significant difference in hepatic fat (complete deficiency, 9.8%; partial deficiency, 10.1%; WT, 9.9%; P>0.05 for both deficiency groups compared with WT) or severity of hepatic steatosis as assessed by magnetic resonance imaging. In addition, ANGPTL3 deficiency did not alter the distribution of extrahepatic fat. Results from Mendelian randomization analyses in 36 703 participants from the UK Biobank demonstrated that genetically determined ANGPTL3 plasma protein levels were causally associated with low-density lipoprotein cholesterol (P=1.7×10-17) and triglycerides (P=3.2×10-18) but not with hepatic fat (P=0.22). CONCLUSIONS: ANGPTL3 deficiency related to LoF mutations in ANGPTL3, as well as genetically determined reduction of plasma ANGPTL3 levels, is not associated with hepatic steatosis. Therapeutic approaches to inhibit ANGPTL3 production in hepatocytes are not necessarily expected to result in the increased risk for hepatic steatosis that was observed with vupanorsen.

Quantitative ultrasound fatty liver evaluation in a pediatric population: comparison with magnetic resonance imaging of liver proton density fat fraction.

BACKGROUND: Biopsy remains the gold standard for the diagnosis of hepatic steatosis, the leading cause of pediatric chronic liver disease; however, its costs call for less invasive methods. OBJECTIVE: This study examined the diagnostic accuracy and reliability of quantitative ultrasound (QUS) for the assessment of liver fat content in a pediatric population, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. MATERIALS AND METHODS: We enrolled 36 patients. MRI-PDFF involved a 3-dimensional T2*-weighted with Dixon pulse multiple-echo sequence using iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ). QUS imaging relied on the ultrasound system "RS85 A" (Samsung Medison, Seoul, South Korea) and the following software: Hepato-Renal Index with automated region of interest recommendation (EzHRI), Tissue Attenuation Imaging (TAI), and Tissue Scatter Distribution Imaging (TSI). For each QUS index, receiver operating characteristic (ROC) curve analysis against MRI-PDFF was used to identify the associated cut-off value and the area under the ROC curve (AUROC). Concordance between two radiologists was assessed by intraclass correlation coefficients (ICCs) and Bland-Altman analysis. RESULTS: A total of 61.1% of the sample (n=22) displayed a MRI-PDFF ≥ 5.6%; QUS cut-off values were TAI=0.625 (AUROC 0.90, confidence interval [CI] 0.77-1.00), TSI=91.95 (AUROC 0.99, CI 0.98-1.00) and EzHRI=1.215 (AUROC 0.98, CI 0.94-1.00). Inter-rater reliability was good-to-excellent for EzHRI (ICC 0.91, 95% C.I. 0.82-0.95) and TAI (ICC 0.94, 95% C.I. 0.88-0.97) and moderate to good for TSI (ICC 0.73; 95% C.I. 0.53-0.85). CONCLUSION: Our results suggest that QUS can be used to reliably assess the presence and degree of pediatric hepatic steatosis.

CT volume analysis in living donor liver transplantation: accuracy of three different approaches.

OBJECTIVES: The aim of this retrospective study is to compare and evaluate accuracy of three different approaches of liver volume quantification in living donor transplantations. METHODS: This is a single-center, retrospective study of 60 donors. The total and right lobe liver volumes were analyzed in the portal-venous phase by two independent radiologists who estimated the volumes using manual, semi-automated and automated segmentation methods. The measured right lobe liver volume was compared to the real weight of the graft after back-table examinations. RESULTS: The mean estimated overall liver volume was 1164.4 ± 137.0 mL for manual, 1277.4 ± 190.4 mL for semi-automated and 1240.1 ± 108.5 mL for automated segmentation. The mean estimated right lobe volume was 762.0 ± 122.4 mL for manual, 792.9 ± 139.9 mL for semi-automated and 765.4 ± 132.7 mL for automated segmentation. The mean graft weight was 711.2 ± 142.9 g. The manual method better correlated with the graft weight (r = 0.730) in comparison with the semi-automated (r = 0.685) and the automated (r = 0.699) methods (p < 0.001). The mean error ratio in volume estimation by each application was 12.7 ± 16.6% for manual, 17.1 ± 17.3% for semi-automated, 14.7 ± 16.8% for automated methods. There was a statistically significant difference between the mean error ratio of the manual and the semi-automated segmentations (p = 0.017), and no statistically significant difference between the manual and the automated applications (p = 0.199). CONCLUSION: Volume analysis application better correlates with graft weight, but there is no obvious difference between correlation coefficients of all three methods. All three modalities had an error ratio, of which the semi-automated method showed the highest value. CRITICAL RELEVANCE STATEMENT: Volume analysis application was more accurate, but there is no drastic difference between correlation coefficients of all three methods.

Surgical Resection Is Superior to TACE in the Treatment of HCC in a Well Selected Cohort of BCLC-B Elderly Patients-A Retrospective Observational Study.

Hepatocellular carcinoma (HCC) usually develops in cirrhotic liver, with high recurrence rates. However, considering its increasing detection in non-cirrhotic liver, the choice of treatment assumes particular relevance. This study aimed to investigate outcomes of patients among BCLC stages and enrolled for surgical resection (SR) according to a more complex evaluation, to establish its safety and efficacy. A total of 186 selected HCC patients (median age 73.2 yrs), submitted to SR between January 2005 and January 2021, were retrospectively analyzed. Of which, 166 were staged 0, A, B according to the BCLC system, while 20 with a single large tumor (>5 cm) were classified as stage AB. No perioperative mortality was recorded; complications occurred in 48 (25.80%) patients, and all but two were Clavien−Dindo grade I−II. Median follow-up was 9.2 years. Subsequently, 162 recurrent patients (87,1%) were selected for new treatments. Comparable overall survival rates (OS) were observed at 1, 3, 5, and 10 years in 0, A, B and AB stages (p = 0.2). Eventually, the BCLC-B group was matched to 40 BCLC-B patients treated (2015-2021) with TACE. Significant differences in baseline characteristics (p <0.0001) and in OS were observed at 1 and 3 years (p <0.0001); a significant difference was also observed in oncological outcomes, in terms of the absence, residual, or relapse of disease (p <0.05). Surgery might be a valid treatment in HCC for patients affected by chronic liver disease in a condition of compensation, up to BCLC-B stage. Surgical indication for liver resection in case of HCC should be extensively revised.

Risk factors for hepatic encephalopathy and mortality in cirrhosis: The role of cognitive impairment, muscle alterations and shunts.

INTRODUCTION/AIM: Muscle alterations, portosystemic shunts (SPSS) and minimal hepatic encephalopathy (MHE) are related to hepatic encephalopathy (HE), however no studies have investigated the relative role of all these risk factors detected in the same patients. The aim of the study was to assess the prognostic impact of muscle alterations, MHE and SPSS on hepatic encephalopathy and transplant free survival. PATIENTS/METHODS: 114 cirrhotics were submitted to Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT) to detect MHE. CT scan was used to analyze the skeletal muscle index (SMI), muscle attenuation and SPSS. The incidence of the first episode of HE and survival were estimated. RESULTS: Previous HE was present in 47 patients (41%). The variables independently associated to previous HE were: sarcopenia, MHE and SPSS. 44 patients (39%) developed overt HE during 14±11 months; MHE and SPSS were the only variables significantly asociated to overt HE. During the same follow-up, 42 patients died (37%); MELD and sarcopenia were the only variables significantly asociated to transplant free survival. CONCLUSIONS: MHE, sarcopenia and SPSS are clinically relevant and should be sought for in cirrhotics. In particular, MHE and SPSS are the only risk factors significantly associated to the development of HE while MELD and sarcopenia are independently associated to overall mortality.

HCC in the Era of Direct-Acting Antiviral Agents (DAAs): Surgical and Other Curative or Palliative Strategies in the Elderly.

Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver malignancies, and elderlies have the highest incidence rates. Direct-acting antiviral agents (DAAs) have shown satisfying results in terms of HCV sustained viral response (SVR). However, data regarding HCC risk post-DAA-SVR is still conflicting. This study aims to consider HCC onset in moderate underlying liver disease. We conducted a retrospective study on 227 chronically infected patients (cHCV), treated with DAAs. Patients were divided into three groups: "de novo occurrent HCC", "recurrent HCC", and "without HCC". Fifty-six patients aged <65 years (yDAA) were studied separately. HCC patients aged ≥65 years (DAA-HCC) were compared to a historical group of 100 elderly HCC patients, treated with peginterferon (Peg-IFN) ± ribavirin antiviral agents, non-SVR (hHCC). The HCC prevalence in DAA patients was 32.75%: "de novo occurrent'' 18.13% and "recurrent'' 14.62%, despite 42.85% of them having no fibrosis to mild or moderate fibrosis (F0-F1-F2). yDAA showed 5.36% "de novo occurrent" HCC. Curative procedure rates were compared between DAA-HCC and hHCC at the first and at recurrent presentation (22 (39.29%) vs. 72 (72%); 17 (30.36%) vs. 70 (70%), respectively (p < 0.001)). No significant difference was found in 3-year OS (p = 0.6). However, in cause-specific mortality analysis, HCC-related death was higher in the DAA-treated group, whereas cirrhosis-related death was more common in the historical group (p = 0.0288), considering together the two causes of death. A more accurate patient stratification according to multifactorial and new diagnostic investigations identifying HCC risk might allow an improvement in management and access to curative therapies.

Low serum magnesium concentration is associated with the presence of viable hepatocellular carcinoma tissue in cirrhotic patients.

This study aimed to ascertain, for the first time, whether serum magnesium (Mg) concentration is affected by the presence of hepatocellular carcinoma (HCC). We retrospectively enrolled consecutive cirrhotic patients with a diagnosis of HCC (n = 130) or without subsequent evidence of HCC during surveillance (n = 161). Serum levels of Mg were significantly (P < 0.001) lower in patients with HCC than in those without (median [interquartile range]: 1.80 [1.62-1.90] mg/dl vs. 1.90 [1.72-2.08] mg/dl). On multivariate logistic regression, low serum Mg was associated with the presence of HCC (OR 0.047, 95% CI 0.015-0.164; P < 0.0001), independently from factors that can influence magnesaemia and HCC development. In a subset of 94 patients with HCC, a linear mixed effects model adjusted for confounders showed that serum Mg at diagnosis of HCC was lower than before diagnosis of the tumor (ß = 0.117, 95% CI 0.039-0.194, P = 0.0035) and compared to after locoregional treatment of HCC (ß = 0.079, 95% CI 0.010-0.149, P = 0.0259), with two thirds of patients experiencing these changes of serum Mg over time. We hypothesize that most HCCs, like other cancers, may be avid for Mg and behave like a Mg trap, disturbing the body's Mg balance and resulting in lowering of serum Mg levels.

Sarco-Model: A score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation.

BACKGROUND & AIMS: Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an 'urgency' model combining sarcopenia and Model for End-stage Liver Disease Sodium (MELDNa) to predict the risk of dropout and identify an appropriate threshold of post-LT futility. METHODS: A total of 1087 adult cirrhotic patients were listed for a first LT during January 2012 to December 2018. The study population was split into a training (n = 855) and a validation set (n = 232). RESULTS: Using a competing-risk analysis of cause-specific hazards, we created the Sarco-Model2 . According to the model, one extra point of MELDNa was added for each 0.5 cm2 /m2 reduction of total psoas area (TPA) < 6.0 cm2 /m2 . At external validation, the Sarco-Model2 showed the best diagnostic ability for predicting the risk of 3-month dropout in patients with MELDNa < 20 (area under the curve [AUC] = 0.93; P = .003). Using the net reclassification improvement, 14.3% of dropped-out patients were correctly reclassified using the Sarco-Model2 . As for the futility threshold, transplanted patients with TPA < 6.0 cm2 /m2 and MELDNa 35-40 (n = 16/833, 1.9%) had the worse results (6-month graft loss = 25.5%). CONCLUSIONS: In sarcopenic patients with MELDNa < 20, the 'urgency' Sarco-Model2 should be used to prioritize the list, while MELDNa value should be preferred in patients with MELDNa ≥ 20. The Sarco-Model2 played a role in more than 30% of the cases in the investigated allocation scenario. In sarcopenic patients with a MELDNa value of 35-40, 'futile' transplantation should be considered.

Relevance of Spontaneous Portosystemic Shunts Detected with CT in Patients with Cirrhosis.

Background Cirrhosis leads to portal hypertension and to the consequent formation of spontaneous portosystemic shunts (SPSSs), leading to complications related to the diversion of portal blood into the systemic circulation, which is called portosystemic shunt syndrome. Purpose To investigate the characteristics of patients with cirrhosis and an SPSS and secondarily to assess the prognostic impact of SPSSs on portal hypertension-related complications and transplant-free survival. Materials and Methods A retrospective database review of patients with cirrhosis (observed from March 2015 to July 2019) was performed to identify patients with CT imaging and outcomes data. For each patient, clinical and biochemical data were collected, and the presence, types, and sizes of SPSSs were investigated with CT. Patients were followed for a mean of 27.5 months ± 22.8. Multivariable logistic analysis was used to identify the clinical characteristics associated with the presence of SPSSs (any size) and presence of SPSSs 1 cm or larger. Competitive risk analysis (Fine and Gray model) was used to identify the association between SPSSs and complications and mortality. Results Two hundred twenty-two patients with cirrhosis (157 male, 65 female; mean age, 62 years ± 12 [standard deviation]) were evaluated. An SPSS was found in 141 of 222 patients (63.5%), and 40 of 222 (18%) had a shunt diameter of at least 1 cm. At presentation, variables independently associated with the presence of SPSSs (any size) were portal vein thrombosis (odds ratio, 5.5; P = .008) and Child-Pugh class C (odds ratio, 3.0; P = .03). Previous hepatic encephalopathy (odds ratio, 4.4; P = .001) and portal vein thrombosis (odds ratio, 5.3; P = .001) were the only variables associated with SPSSs larger than 1 cm. Patients with SPSSs of any size had higher mortality (subdistribution hazard ratio, 1.9; P < .001) and higher frequency of hepatic encephalopathy (subdistribution hazard ratio, 2.3; P = .023), gastrointestinal bleeding (subdistribution hazard ratio, 2.9; P = .039), and portal vein thrombosis (subdistribution hazard ratio, 7.6; P = .005). Conclusion The presence of spontaneous portosystemic shunts on CT images in patients with cirrhosis was associated with higher mortality and complications, including portal vein thrombosis, hepatic encephalopathy, and gastrointestinal bleeding. © RSNA, 2021 See also the editorial by Reeder in this issue.

HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD).

Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (-18.6%; p < 0.001) as well as that mediated by cholesterol transporters (-25.3% ABCA1; -16.3% ABCG1; -14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.

Intra-procedural dual phase cone beam computed tomography has a better diagnostic accuracy over pre-procedural MRI and MDCT in detection and characterization of HCC in cirrhotic patients undergoing TACE procedure.

PURPOSE: This study was directed to compare diagnostic accuracy of dual-phase cone beam computed tomography (DP-CBCT) vs pre-procedural second line imaging modality (SLIM [multidetector computed tomography and magnetic resonance imaging]) to detect and characterize hepatocellular carcinoma (HCC) in cirrhotic patients with indication for trans-arterial chemoembolization (TACE). METHODS: This is a single centre, retrospective, and observational study. Exclusion criteria were not-assisted DP-CBCT TACE, and unavailable follow-up SLIM. We evaluated 280 consecutive patients (January/2015-Febraury/2019). Seventy-two patients were eligible. Three radiologists in consensus reviewed: pre-procedural SLIM, DP-CBCT, and SLIM at follow-up, with 4 months of interval between each reading. Hyper-vascular foci (HVF) were detected and characterized. Diameter was recorded. Radiological behaviour, according to LI-RADS criteria, of HFV throughout follow-up time was the reference standard. Diagnostic accuracy was calculated for pre-procedural SLIM and DP-CBCT and evaluated through receiver operating characteristic curve. HVF only visible on DP-CBCT (defined as occult) were analysed. Tumour diameters were compared. RESULTS: Median time between pre-procedural SLIM and DP-CBCT and between DP-CBCT and definitive radiological diagnosis of HVF were 46.0 days (95%CI 36.5-55.0) and 30.5 days (95%CI 29.0-33.0), respectively. DP-CBCT had a better diagnostic performance than pre-examination SLIM (sensitivity 99%vs78%; specificity 89%vs85%; PPV 99%vs99%; NPV 92%vs30%; and accuracy 94%vs79%). DP-CBCT diagnosed 63 occult HVF. Occult HCC were 54/243 (22.2%). Six were occult angiomas. Three were false positive. Mean diameter was significantly higher in DP-CBCT vs pre-procedural SLIM (+7.5% [95%CI 3.7-11.3], p < 0.05). CONCLUSIONS: DP-CBCT has a better diagnostic accuracy and NPV than pre-procedural SLIM in cirrhotic patients with indication for TACE.

The decline in muscle strength and muscle quality in relation to metabolic derangements in adult women with obesity.

BACKGROUND & AIMS: The metabolic and functional characteristics related to sarcopenic obesity have not been thoroughly explored in the earlier stages of the aging process. The aim of the present study was to examine the phenotype of sarcopenic obesity, in terms of lean body mass, muscle strength and quality, in adult women with and without the Metabolic Syndrome (MetS), and its relationship with the features of myosteatosis. METHODS: Study participants were enrolled at the Sapienza University, Rome, Italy. Body composition was assessed by DXA. The Handgrip strength test (HGST) was performed. HGST was normalized to arm lean mass to indicate muscle quality; intermuscular adipose tissue (IMAT) and intramyocellular lipid content (IMCL) were measured by magnetic resonance imaging and spectroscopy, as indicators of myosteatosis. Different indices of sarcopenia were calculated, based on appendicular lean mass (ALM, kg) divided by height squared, or weight. The NCEP-ATPIII criteria were used to diagnose the MetS. HOMA-IR was calculated. The physical activity level (PAL) was assessed through the IPAQ questionnaire. RESULTS: 54 women (age: 48 ± 14 years, BMI: 37.9 ± 5.4 kg/m2) were included. 54% had the MetS (metabolically unhealthy, MUO). HGST/arm lean mass was lower in MUO women than women without the MetS (6.3 ± 1.8 vs. 7.8 ± 1.6, p = 0.03). No differences emerged in terms of absolute ALM (kg) or other indices of sarcopenia (ALM/h2 or ALM/weight) between metabolically healthy (MHO) vs. MUO women (p > 0.05). Muscle quality was negatively associated with HOMA-IR (p = 0.02), after adjustment for age, body fat, hs-CRP levels, and PAL. IMAT, but not IMCL, was significantly higher in obese women with the MetS compared to women without the MetS (p > 0.05). No association emerged between HGST/arm lean mass and IMAT or IMCL when HOMA-IR was included in the models. CONCLUSION: Insulin resistance, and not sarcopenia or myosteatosis per se, was associated with muscle weakness, resulting in the phenotype of "dynapenic obesity" in middle-aged women with the metabolic syndrome.

Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity.

OBJECTIVES: To comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children. METHODS: Two hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for PNPLA3, TM6SF2, GCKR, and MBOAT7 gene variants. Percentage hepatic fat content (HFF%) was measured by nuclear magnetic resonance. RESULTS: HFF% was positively related with BMI, HOMAIR, metabolic syndrome, ALT, AST, γGT, and albumin. Carriers of [G] allele in PNPLA3, [T] allele in GCKR and [T] allele in TM6SF2 genes had significantly higher hepatic fat content than wild-type carriers. HFF% was explained for 8.7% by metabolic and for 16.1% by genetic factors and, a model including age, gender, BMI, HOMAIR, PNPLA3, GCKR, and TM6SF2 variants was the best predictor of HFF%, explaining 24.8% of its variation (P < 0.001). A weighted-genetic risk score combining PNPLA3, GCKR, and TM6SF2 risk alleles was associated with almost eightfold higher risk of NAFLD. CONCLUSIONS: Our data highlighted the predominant role of genetic factors in determining the amount of liver fat content in children with obesity.

Locoregional therapy response in patients with hepatocellular cancer waiting for liver transplantation: Only selection or biological effect?

Locoregional treatments (LRT) represent a broad strategy used for reducing the risk of drop-off and contextually improving the survivals in patients with hepatocellular cancer receiving a liver transplantation (LT). However, it is not sufficiently clear if LRT are only a surrogate of tumor aggressiveness or if they consent a real benefit in terms of tumor stabilization. A recent study by Pommergaard et al reported the results from the European Liver Transplant Registry. Patients receiving LRT before LT had better 5-year survival rates respect to no-LRT cases (69.7% vs 65.8%; P < 0.001). When the number of LRT was tested, one-to-two treatments were connected with improved survivals respect to no treatment [hazard ratio (HR) = 0.85 and 0.71, respectively]. The efficacy of LRT was also reported in the presence of larger tumors (HR = 0.78) and micro-macrovascular invasion (HR = 0.71). The results observed in the present study are partially in discordance with other analyses showing a detrimental effect of LRT. The main problem in the interpretation of these results is connected with the possible initial selection biases present in the studies. The most recent guidelines suggest to perform LRT before the transplant, but the level of evidence is typically low due to the absence of prospectively designed studies.

Volumetric Distribution of the White Matter Hyper-Intensities in Subject with Mild to Severe Carotid Artery Stenosis: Does the Side Play a Role?

PURPOSE: The purpose of this paper was to assess the difference in the distribution of white matter hyperintensities (WMHs) on left and right sides of the brain hemispheres of subjects with mild to severe carotid artery stenosis. MATERIAL AND METHODS: Eighty consecutive patients (mean age 71 ± 6 years, males 66) with carotid artery stenosis were prospectively recruited. FLAIR-WMH lesion volume was performed using a semiautomated segmentation technique (Jim, Xinapse System, Leicester, UK). The Wilcoxon test was applied to verify the differences in the volume of WMHs between the right and left hemispheres. RESULTS: A statistically significant difference was found in the middle cerebral artery (MCA) territory for the volume of the lesions (median volume of WMHs of the left side = 889.5 mm3; median volume of WMHs on the right side = 580.5 mm3; P = .0416); no statistically significant difference was found on the other territories by taking into considerations the lesions. By analyzing the degree of stenosis, we found a higher degree of stenosis of the left side (67.9%; 95% confidence interval [CI], 64.8%-70.9%) compared with the right side (65.7%; 95% CI, 62.4%-68.9%), but the Mann-Whitney test did not show a statistically significant difference (P = .3235). CONCLUSIONS: Results of our study suggest that there is a difference in the distribution of WMHs in the brain hemispheres according to the left/right side on the MCA territories and for the periventricular white matter in subjects with mild to severe carotid artery stenosis.

Peritoneal and pleural fluids may appear hyperintense on hepatobiliary phase using hepatobiliary MR contrast agents.

AIM: To describe the effect of hepatobiliary-specific MR imaging contrast agent (HBCA) administration on the signal intensity of peritoneal and pleural fluid effusions on T1-weighted MR images. MATERIALS AND METHODS: From October 2015 to May 2016 139 patients (mean 60±10 years old, 69 % males) with peritoneal or pleural effusions without biliary leakage who underwent HBCA-MRI (Gd-BOPTA or Gd-EOB-DTPA) at 1.5T and 3T were included from two centres. The fluid signal intensity was classified as hypo/iso/hyperintense before/after HBCA administration. The relative signal enhancement (RE) was calculated. RESULTS: On hepatobiliary phase (HBP), peritoneal fluids appeared hyper/isointense in 88-100 % and pleural effusions in 100 % of the patients following Gd-BOPTA administration. All fluids remained hypointense following Gd-EOB-DTPA. The signal intensity of fluids increased with both HBCA but RE was significantly higher following Gd-BOPTA (p=0.002 to <0.001). RE was correlated with HBP acquisition time-point (r=0.42, p<0.001 and r=0.50, p=0.033 for peritoneal and pleural fluids). CONCLUSION: The signal intensity of pleural and peritoneal fluids progressively increases following HBCA administration in the absence of biliary leakage. Due to its later hepatobiliary phase, this is more pronounced after Gd-BOPTA injection, leading to fluid hyperintensity that is not observed after Gd-EOB-DTPA injection. KEY POINTS: • Fluids appear hyper/isointense on HBP in most patients after Gd-BOPTA injection. • Fluids remain hypointense on HBP after Gd-EOB-DTPA injection. • RE of fluids increases with time after liver-specific Gd injection. • RE of fluids is higher in patients with chronic liver disease.

Radiation dose and image quality of computed tomography of the supra-aortic arteries: A comparison between single-source and dual-source CT Scanners.

PURPOSE: The purpose of this work was to compare the image quality and radiation dose delivered to patients during computed tomography (CT) angiography (CTA) of the supra-aortic arteries using two single-source (SS) and two dual-energy (DE) CT scanners. MATERIAL AND METHODS: In this retrospective study, 120 patients who underwent CTA of supra-aortic arteries were studied using four different types of CT scanners: a sixteen and forty-detector-row SS and two DE CT scanners. Seventy milliters of contrast medium were injected at a flow rate of 4mL/s using a power injector. For each patient the dose-length product (DLP), the volume computed tomography dose index (CDTIvol), the length of the scan and the effective dose (ED) were calculated. Qualitative and quantitative [image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)] image quality assessment was performed. RESULTS: A statistically significant lower value of the DE compared to the SS technology (P<0.0001) for the CDTI, DLP and ED was found, whereas we did not find any statistically significant difference between the four scanners for the measurements of the image noise, SNR and CNR. CONCLUSION: DS CT scanners allow performing CTAs with a reduced dose compared to SS CT scanner with comparable image quality.

WISP1 Is a Marker of Systemic and Adipose Tissue Inflammation in Dysmetabolic Subjects With or Without Type 2 Diabetes.

CONTEXT: Wnt1-inducible signaling pathway protein 1 (WISP1) is a novel adipokine participating in adipose tissue (AT) dysfunction; so far, no data on WISP1 in diabetes are available. OBJECTIVES: To evaluate plasma WISP1 in subjects with type 2 diabetes (T2D) and its correlates linked to AT inflammation. DESIGN AND PARTICIPANTS: For this cross-sectional study, 97 consecutive dysmetabolic patients were recruited at the diabetes outpatient clinics of Sapienza University in Rome; 71 of them had T2D, with (n = 35) or without (n = 36) obesity, and 26 were obese patients without diabetes. Twenty-one normal-weight nondiabetic individuals were enrolled as a control group. Study participants underwent clinical workup and blood sampling for metabolic/inflammatory characterization; magnetic resonance imaging (MRI) data on subcutaneous AT and visceral AT (VAT) area, hepatic fat content, and VAT homogeneity were available for most diabetic patients. RESULTS: Plasma WISP1 significantly increased throughout classes of obesity and correlated with greater VAT area, interleukin-8 (IL-8), and lower adiponectin levels, without differing between diabetic and nondiabetic participants. Higher IL-8 was the main determinant of increased WISP1. MRI-assessed VAT inhomogeneity was associated with higher WISP1, IL-8 and C-reactive protein levels, independent of obesity; high WISP1 strongly predicted VAT inhomogeneity (P < 0.001). CONCLUSIONS: WISP1 levels are increased in obese persons and are directly related to adiposity, independent of glycemic status or insulin resistance; moreover, they are strongly associated with increased plasma IL-8 and signal abnormalities of VAT. The overall data add insights to the mechanisms underlying metabolic alterations and may open a scenario for innovative therapeutic approaches for diabetes prevention and care.

Imaging Features of Non-Alcoholic Fatty Liver Disease in Children and Adolescents.

Non-invasive diagnosis and quantification of liver steatosis is important to overcome limits of liver biopsy, in order to follow up patients during their therapy and to establish a reference standard that can be used in clinical trials and longitudinal studies. Imaging offers several methods in this setting: ultrasound, which is the cheapest technique and easy to perform; magnetic resonance spectroscopy (MRS), which reflects the real content of triglycerides in a specific volume; and proton density fat fraction (PDFF) magnetic resonance, which is a simple method that reflects the distribution of the fat in the whole liver. Other techniques include ultrasound elastography (EUS) and magnetic resonance elastrography (MRE), which can evaluate the progression of non-alcoholic fatty liver disease (NAFLD) into non-alcoholic steato-hepatitis (NASH) and cirrhosis, by quantifying liver fibrosis.