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.

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.

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.

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.

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.

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.

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.

Volumetric Analysis of Carotid Plaque Components and Cerebral Microbleeds: A Correlative Study.

PURPOSE: The purpose of this work was to explore the association between carotid plaque volume (total and the subcomponents) and cerebral microbleeds (CMBs). MATERIALS AND METHODS: Seventy-two consecutive (male 53; median age 64) patients were retrospectively analyzed. Carotid arteries were studied by using a 16-detector-row computed tomography scanner whereas brain was explored with a 1.5 Tesla system. CMBs were studied using a T2*-weighted gradient-recalled echo sequence. CMBs were classified as from absent (grade 1) to severe (grade 4). Component types of the carotid plaque were defined according to the following Hounsfield unit (HU) ranges: lipid less than 60 HU; fibrous tissue from 60 to 130 HU; calcification greater than 130 HU, and plaque volumes of each component were calculated. Each carotid artery was analyzed by 2 observers. RESULTS: The prevalence of CMBs was 35.3%. A statistically significant difference was observed between symptomatic (40%) and asymptomatic (11%) patients (P value = .001; OR = 6.07). Linear regression analysis demonstrated an association between the number of CMBs and the symptoms (P = .0018). Receiver operating characteristics curve analysis found an association between the carotid plaque subcomponents and CMBs (Az = .608, .621, and .615 for calcified, lipid, and mixed components, respectively), and Mann-Whitney test confirmed this association in particular for the lipid components (P value = .0267). CONCLUSIONS: Results of this study confirm the association between CMBs and symptoms and that there is an increased number of CMBs in symptomatic patients. Moreover, we found that an increased volume of the fatty component is associated with the presence and number of CMBs.

No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder worldwide, reaching prevalence up to 90 % in obese patients with type 2 diabetes (T2D), and representing an independent risk factor for cardiovascular mortality. Furthermore, the coexistence of T2D and NAFLD leads to higher incidence of diabetes' complications and additive detrimental liver outcomes. The existence of a close association between NAFLD and hypovitaminosis D, along with the anti-inflammatory and insulin-sensitizing properties of vitamin D, have been largely described, but vitamin D effects on hepatic fat content have never been tested in a randomized controlled trial. We assessed the efficacy and safety of 24-week oral high-dose vitamin D supplementation in T2D patients with NAFLD. METHODS: This randomized, double-blind, placebo-controlled trial was carried out at the Diabetes Centre of Sapienza University, Rome, Italy, to assess oral treatment with cholecalciferol (2000 IU/day) or placebo in T2D patients with NAFLD. The primary endpoint was reduction of hepatic fat fraction (HFF) measured by magnetic resonance; as hepatic outcomes, we also investigated changes in serum transaminases, CK18-M30, N-terminal Procollagen III Propeptide (P3NP) levels, and Fatty Liver Index (FLI). Secondary endpoints were improvement in metabolic (fasting glycaemia, HbA1c, lipids, HOMA-IR, HOMA-ß, ADIPO-IR, body fat distribution) and cardiovascular (ankle-brachial index, intima-media thickness, flow-mediated dilatation) parameters from baseline to end of treatment. RESULTS: Sixty-five patients were randomized, 26 (cholecalciferol) and 29 (placebo) subjects completed the study. 25(OH) vitamin D significantly increased in the active treated group (48.15 ± 23.7 to 89.80 ± 23.6 nmol/L, P < 0.001); however, no group differences were found in HFF, transaminases, CK18-M30, P3NP levels or FLI after 24 weeks. Vitamin D neither changed the metabolic profile nor the cardiovascular parameters. CONCLUSIONS: Oral high-dose vitamin D supplementation over 24 weeks did not improve hepatic steatosis or metabolic/cardiovascular parameters in T2D patients with NAFLD. Studies with a longer intervention period are warranted for exploring the effect of long time exposure to vitamin D. TRIAL REGISTRATION: This trial was approved on July 2011 by the Ethics Committee of Policlinico Umberto I, Sapienza University of Rome, Italy, and registered at www.clinicaltrialsregister.eu number 2011-003010-17.

Phenotypical heterogeneity linked to adipose tissue dysfunction in patients with Type 2 diabetes.

Adipose tissue (AT) inflammation leads to increased free fatty acid (FFA) efflux and ectopic fat deposition, but whether AT dysfunction drives selective fat accumulation in specific sites remains unknown. The aim of the present study was to investigate the correlation between AT dysfunction, hepatic/pancreatic fat fraction (HFF, PFF) and the associated metabolic phenotype in patients with Type 2 diabetes (T2D). Sixty-five consecutive T2D patients were recruited at the Diabetes Centre of Sapienza University, Rome, Italy. The study population underwent clinical examination and blood sampling for routine biochemistry and calculation of insulin secretion [homoeostasis model assessment of insulin secretion (HOMA-ß%)] and insulin-resistance [homoeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (ADIPO-IR)] indexes. Subcutaneous (SAT) and visceral (VAT) AT area, HFF and PFF were determined by magnetic resonance. Some 55.4% of T2D patients had non-alcoholic fatty liver disease (NAFLD); they were significantly younger and more insulin-resistant than non-NAFLD subjects. ADIPO-IR was the main determinant of HFF independently of age, sex, HOMA-IR, VAT, SAT and predicted severe NAFLD with the area under the receiver operating characteristic curve (AUROC)=0.796 (95% confidence interval: 0.65-0.94, P=0.001). PFF was independently associated with increased total adiposity but did not correlate with AT dysfunction, insulin resistance and secretion or NAFLD. The ADIPO-IR index was capable of predicting NAFLD independently of all confounders, whereas it did not seem to be related to intrapancreatic fat deposition; unlike HFF, higher PFF was not associated with relevant alterations in the metabolic profile. In conclusion, the presence and severity of AT dysfunction may drive ectopic fat accumulation towards specific targets, such as VAT and liver, therefore evaluation of AT dysfunction may contribute to the identification of different risk profiles among T2D patients.

Qualitative analysis of small (≤2 cm) regenerative nodules, dysplastic nodules and well-differentiated HCCs with gadoxetic acid MRI.

BACKGROUND: The characterization of small lesions in cirrhotic patients is extremely difficult due to the overlap of imaging features among different entities in the step-way of the hepatocarcinogenesis. The aim of our study was to evaluate the role of gadoxetic-acid MRI in the differentiation of small (≤2 cm) well-differentiated hepatocellular carcinomas from regenerative and dysplastic nodules. METHODS: Seventy-three cirrhotic patients, with 118 focal liver lesions (≤2 cm) were prospectively recruited. MRI examination was performed with a 3T magnet and the study protocol included T1 - and T2-weighted pre-contrast sequences and T1 -weighted gadoxetic-acid enhanced post-contrast sequences obtained during the arterial, venous, late dynamic and hepatobiliary phases. All lesions were pathologically confirmed. Two radiologists blinded to clinical and pathological information evaluated two imaging datasets; another radiologist analysed the signal intensity characteristics of each lesion. Sensitivity, specificity and diagnostic accuracy were considered for statistical analysis. RESULTS: Good agreement was reported between the two readers (κ 0.70). Both readers reported a significantly improved sensitivity (57.7 and 66.2 vs 74.6 and 83.1) and diagnostic accuracy (0.717 and 0.778 vs 0.843 and 0.901) with the adjunction of the hepatobiliary phase 57.7 vs 74.6 and 66.2 vs 83.1 (p ≤ 0.04). CONCLUSIONS: Gadoxetic-acid MRI is a reliable tool for the characterization of HCC and lesions at high risk to further develop.

Magnetic resonance-guided focused ultrasound for the treatment of painful bone metastases: role of apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) MRI in the assessment of clinical outcome.

PURPOSE: To assess the correlation between functional MRI, including ADC values obtained from DWI and DCE, and clinical outcome in patients with bone metastases treated with MRgFUS. METHODS AND MATERIALS: Twenty-three patients with symptomatic bone metastases underwent MRgFUS treatment (ExAblate 2100 system InSightec) for pain palliation. All patients underwent clinical and imaging follow-up examinations at 1, 3 and 6 months after treatment. Visual Analog Scale (VAS) score was used to evaluate treatment efficacy in terms of pain palliation while ADC maps obtained by DWI sequences, and DCE data were used for quantitative assessment of treatment response at imaging. Spearman Correlation Coefficient Test was calculated to assess the correlation between VAS, ADC and DCE data. RESULTS: All treatments were performed successfully without adverse events. On the basis of VAS score, 16 (69.6 %) patients were classified as complete clinical responders, 6 (26.1 %) as partial responders and only one (4.3 %) was classified as a non-responder. The mean VAS score decreased from 7.09 ± 1.8 at baseline to 2.65 ± 1.36 at 1 month, 1.04 ± 1.91 at 3 months and 1.09 ± 1.99 at 6 months (p < 0.001). Baseline mean ADC value of treated lesions was 1.05 ± 0.15 mm2/s, increasing along follow-up period (1.57 ± 0.27 mm2/s 1st month; 1.49 ± 0.3 mm2/s 3rd month; 1.45 ± 0.32 mm2/s 6th month, p < 0.001). Non perfused volume (NPV) was 46.4 at 1 month, 45.2 at 3 months and 43.8 at 6 months. Spearman Coefficient demonstrated a statistically significant negative correlation between VAS and ADC values (ρ = -0.684; p = 0.03), but no significant correlation between VAS and NPV (ρ = 0.02216, p = 0.9305). Among other DCE data, Ktrans significantly changed in complete responders (3 months Ktrans = 2.14/min; -ΔKt = 52.65 % p < 0.01) and was not significantly different in partial responders (3 months Ktrans 0.042/min; ΔKt = 11.39 % p > 0.01). CONCLUSION: In patients with painful bone metastases treated with MRgFUS, ADC and Ktrans variation observed in the ablated lesions correlate with VAS values and may play a role as objective imaging marker of treatment response.

The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity.

The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m². Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m² was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16-5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.

Left ventricular dysfunction in obese children and adolescents with nonalcoholic fatty liver disease.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) may increase the risk for cardiac dysfunction. The present study aimed to determine whether, in children, NAFLD is associated with subclinical left ventricular (LV) structural and functional abnormalities independently of metabolic risk factors. We performed a complete echocardiographic study including tissue Doppler imaging, magnetic resonance imaging (MRI) for measurement of hepatic fat fraction (HFF) and abdominal fat mass distribution, along with lipid profile, insulin sensitivity, and high-sensitivity C-reactive protein in 108 obese children, 54 with (HFF ≥5%) and 54 without NAFLD, and 18 lean healthy subjects. The three groups were matched for age, gender, and pubertal status, and obese children with NAFLD were matched for body mass index/standard deviation score with those without NAFLD. Forty-one of the children with NAFLD underwent liver biopsy. Compared to controls and children without liver involvement, those with NAFLD had features of LV diastolic dysfunction, including higher E-to-e' ratio and lower e' tissue velocity. The Tei index (reflecting the combined systolic and diastolic LV function) was also significantly higher in NAFLD children. Among children with biopsy-proven NAFLD, 26 had definite nonalcoholic steatohepatitis (NASH) and 15 were not-NASH. Patients with definite-NASH had significantly lower e' velocity and significantly higher E-to-e' and Tei index (P < 0.001, respectively) than those without NASH. In multiple logistic regression analysis, NAFLD was the only statistically significant variable associated with increased E-to-e' ratio, whereas NAFLD and systolic blood pressure were significantly associated with increased Tei index. CONCLUSION: Asymptomatic obese children with NAFLD exhibit features of early LV diastolic and systolic dysfunction, and these abnormalities are more severe in those with NASH.

Is there an association between asymmetry of carotid artery wall thickness (ACAWT) and cerebrovascular symptoms?

PURPOSE: Previous publications demonstrated that multi-detector-row computed tomography Angiography (MDCTA) can evaluate the carotid artery wall thickness (CAWT). The purpose of this work was to compare the asymmetry of CAWT between carotids in symptomatic and asymptomatic patients. MATERIAL AND METHODS: Sixty consecutive symptomatic (males 44; median age 64) and 60 asymptomatic sex- and age-matched patients were analysed by using a 40-detector-row CT system. CAWT was calculated for both carotids in each patient and the ratio between the thicker CAWT and the contra-lateral was calculated to obtain the ACAWT index. Bland-Altman, logistic regression and receiver operating characteristic (ROC) curve analysis were calculated. RESULTS: The Bland-Altman plot demonstrates a very good agreement between measurements with a mean difference value of 3.4% and 95% CI from -8% to 14.8%. The ACAWT was significantly different between symptomatic and asymptomatic patients (with a p value of 0.0001). The ROC area under the curve was 0.742 (p = 0.001). Logistic regression model indicated that ACAWT, CAWT, stenosis degree, and fatty plaques were independent variables associated with cerebrovascular symptoms (p value, respectively, 0.0108, 0.0231, 0.0002, and 0.013). CONCLUSION: Results of our study indicated that the index of asymmetry in the CAWT might be used as a further parameter to stratify the risk of symptoms related to carotid artery.

Is there an association between cerebral microbleeds and leukoaraiosis?

PURPOSE: Cerebral microbleeds (CMBs) are small dot-like lesions appearing as hyposignals on gradient echo (GRE) T2* magnetic resonance (MR) sequences, whereas the leukoaraiosis (LA) indicates the presence of patchy areas of hypersignal on fluid-attenuated inversion recovery (FLAIR) MR sequences in the periventricular white matter. The purpose of this work was to evaluate the association between LA and CMBs. MATERIAL AND METHODS: Eighty-five consecutive (men 55; median age 64 years) patients were retrospectively analyzed using a 1.5 T system; CMBs were studied using a T2*-weighted GRE sequence and classified as absent (grade 1), mild (grade 2; total number of microbleeds, 1-2), moderate (grade 3; total number of microbleeds, 3-10), and severe (grade 4; total number of microbleeds, >10). LA was assessed with FLAIR MR sequences and was graded based on the European Task Force on Age-Related White Matter Changes as follows: 1 (no lesions), 2 (focal lesions > 5 mm), 3 (early confluent lesions), and 4 (diffuse involvement of an entire brain region). RESULTS: We considered 170 cerebral hemispheres. The prevalence of CMBs was 24.7% (42 of 170), whereas the prevalence of LA was 27.1% (46 of 170). A statistically significant correlation was observed between LA and CMBs (correlation rho = .495, P value = .001). Multiple logistic regression analysis showed an association between CMBs and cerebrovascular symptoms (P = .0023). CONCLUSION: Results of this study suggest an association between CMBs and LA. Moreover, we found that LA is associated with the presence of cerebrovascular symptoms.

Ankle-brachial index and its link to automated carotid ultrasound measurement of intima-media thickness variability in 500 Japanese coronary artery disease patients.

The purpose of this study was to evaluate whether the carotid intima-media thickness (cIMT) and intima-media thickness variability (IMTV) along the artery are correlated to the ankle-brachial index (ABI) in Japanese coronary artery disease patients. Five hundred consecutive patients (312 males; median age 69 ± 11 years) who underwent carotid ultrasonography and first coronary angiography were prospectively analyzed. By using automated software (AtheroEdge™, AtheroPoint, Roseville, CA, USA), we obtained the cIMT and IMTV. Pearson correlation analysis was performed to calculate the association between ABI, automatically measured cIMT, automatically measured IMTV, and the SYNTAX score. The mean cIMT was 0.881 ± 0.334 mm and the mean IMTV was 0.141 ± 0.112. IMTV was negatively and significantly correlated to ABI (ρ = -0.147; p = 0.001), whereas cIMT was not (ρ = -0.075; p = 0.097). IMTV and cIMT had the same significant correlation with the SYNTAX score. When we considered patients with a higher risk factor (ABI ≤ 0.9), we found higher values of IMTV and the SYNTAX score, but not higher values of cIMT. Logistic regression analysis showed that IMTV was independently associated with the complexity of the coronary artery disease (as assessed by the SYNTAX score). In conclusion, we show that IMTV automatically measured using AtheroEdge™ was correlated with ABI, whereas cIMT was not. IMTV could be integrated with cIMT measurement to improve the assessment of cardiovascular disease.

Hepatocellular carcinoma (HCC) in non-cirrhotic liver: clinical, radiological and pathological findings.

OBJECTIVES: Our aim was to evaluate the clinical and pathological findings, mutidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) appearances, treatment and 1-year survival of patients with HCC in non-cirrhotic liver. METHODS: Histopathological and laboratory findings of 30 non-cirrhotic patients with 32 HCCs were reviewed retrospectively. MDCT and gadobenate dimeglumine-enhanced MR images were evaluated in consensus by two radiologists in terms of HCC size, presence of tumour capsule, necrosis, haemorrhage, fat and calcification, and vascular involvement. Imaging patterns were compared directly with HCC findings in a matched group of cirrhotic patients. RESULTS: No differences between non-cirrhotic and cirrhotic patients were noted in terms of serum α-fetoprotein levels (elevated in 11 [36.7%] and 21 [35%] patients, respectively). The imaging appearance at CT and contrast-enhanced MRI was typical in 27 (84.3%) and 28 (87.5%) cases respectively. Most lesions presented as a well-differentiated large solitary mass, with well-defined margins, areas of necrosis and peripheral capsule. No significant differences in HCC pattern were observed between cirrhotic and non-cirrhotic liver. CONCLUSIONS: In non-cirrhotic patients, HCC is more likely to manifest as an asymptomatic mass with elevation of serum tumour markers similar to that seen in cirrhotic patients. HCC in cirrhotic and non-cirrhotic livers show similar enhancement patterns. KEY POINTS: HCC shows similar CT/MRI pattern in cirrhotic and non-cirrhotic livers. Non-invasive diagnostic criteria for HCC should also be extended to non-cirrhotic livers. No differences were found between α-fetoprotein levels in non-cirrhotic and cirrhotic patients.

Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging.

OBJECTIVES: To prospectively compare the diagnostic performance of ultrasound (US), multidetector computed tomography (MDCT) and contrast-enhanced magnetic resonance imaging (MRI) in cirrhotic patients who were candidates for liver transplantation. METHODS: One hundred and forty consecutive patients with 163 hepatocellular carcinoma (HCC) nodules underwent US, MRI and MDCT. Diagnosis of HCC was based on pathological findings or substantial growth at 12-month follow-up. Four different image datasets were evaluated: US, MDCT, MRI unenhanced and dynamic phases, MRI unenhanced dynamic and hepatobiliary phase. Diagnostic accuracy, sensitivity, specificity, PPV and NPV, with corresponding 95 % confidence intervals, were determined. Statistical analysis was performed for all lesions and for three lesion subgroups (<1 cm, 1-2 cm, >2 cm). RESULTS: Significantly higher diagnostic accuracy, sensitivity and NPV was achieved on dynamic + hepatobiliary phase MRI compared with US, MDCT and dynamic phase MRI alone. The specificity and PPV of US was significantly lower than that of MDCT, dynamic phase MRI and dynamic + hepatobiliary phase MRI. Similar results were obtained for all sub-group analyses, with particular benefit for the diagnosis of smaller lesions between 1 and 2 cm. CONCLUSIONS: Dynamic + hepatobiliary phase MRI improved detection and characterisation of HCC in cirrhotic patients. The greatest benefit is for diagnosing lesions between 1 and 2 cm.