Diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI protocol for hepatocellular carcinoma screening.

AIM: To evaluate the diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI (AMRI) in cirrhotic and chronic hepatitis B (CHB) patients for hepatocellular carcinoma (HCC) screening. MATERIALS AND METHODS: Seventy-nine consecutive patients at risk for HCC due to cirrhosis and/or CHB were included in this retrospective study. For each patient, the first gadoxetate disodium-enhanced MRI between 2008 through 2014 was analysed. Two independent readers read an anonymised abbreviated image set comprising axial T1-weighted (W) images with fat saturation in the hepatobiliary phase, 20 minutes or more after gadoxetate injection, and axial T2W single-shot fast spin echo images. Each observation >10 mm was scored as negative or suspicious for HCC. Inter-reader agreement was assessed. A composite reference standard was used to determine the per-lesion diagnostic performance for each reader. RESULTS: Inter-reader agreement was substantial (κ = 0.75). The final reference standard showed 27 HCCs in 13 patients (median 21 mm, range 11-100 mm). The two readers each correctly scored 23 as suspicious for HCC (sensitivity = 85.2%), scored a total of 27 and 32 observations as suspicious for HCC (positive predictive value [PPV] = 85.2% and 71.9%), and scored 83 and 78 observations or complete examinations as negative for HCC (negative predictive value [NPV] = 95.2% and 94.9%). CONCLUSIONS: The AMRI protocol provides higher per-lesion sensitivity and NPV than reported values for ultrasound, the current recommended technique for screening, and similar per-lesion sensitivity and PPV to reported values for complete dynamic contrast-enhanced MRI.

Value of the portal venous phase in evaluation of treated hepatocellular carcinoma following transcatheter arterial chemoembolisation.

AIM: To evaluate the utility of the portal venous phase on multiphasic computed tomography (CT) after treatment of hepatocellular carcinoma (HCC) with trans-arterial chemoembolisation (TACE). MATERIALS AND METHODS: This was a retrospective review of patients who underwent TACE for HCC between 1 April 2012 and 21 December 2014, with appropriate multiphasic, pre- and post-procedural CT examinations. The maximum non-contrast, arterial phase, and portal venous phase attenuation values of the tumour and tumour bed were evaluated within a region of interest (ROI), with values adjusted against background hepatic parenchyma. Linear regression analyses were performed for both the arterial and venous phases, to assess the level of enhancement and to determine if the venous phase had additional value in this setting. RESULTS: A total of 86 cases from 51 patients were reviewed. All pre-procedural CT examinations of lesions demonstrated arterial phase enhancement with portal venous and delayed phase washout compatible with HCC. The post-procedural CT examinations following TACE revealed expected decreased arterial enhancement. Sixty-five cases (76%) showed persistent non-enhancement on the portal venous phase following embolisation therapy. A total of 21 cases (24%), however, demonstrated progressive portal venous hyper enhancement. Linear regression analysis demonstrated a statistical significance between the difference in maximal arterial and portal venous enhancement in these cases. CONCLUSION: Following TACE, the treated lesion may demonstrate portal venous phase hyper-enhancement within the tumour bed. As such, full attention should be given to these images for comprehensive evaluation of tumour response following treatment.

Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease.

AIM: To investigate the relationship between bone marrow fat content and hepatic fat content in children with known or suspected non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This was an institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant, cross-sectional, prospective analysis of data collected between October 2010 to March 2013 in 125 children with known or suspected NAFLD. Written informed consent was obtained for same-day research magnetic resonance imaging (MRI) of the lumbar spine, liver, and abdominal adiposity. Lumbar spine bone marrow proton density fat fraction (PDFF) and hepatic PDFF were estimated using complex-based MRI (C-MRI) techniques and magnitude-based MRI (M-MRI), respectively. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT) were quantified using high-resolution MRI. All images were acquired by two MRI technologists. Hepatic M-MRI images were analysed by an image analyst; all other images were analysed by a single investigator. The relationship between lumbar spine bone marrow PDFF and hepatic PDFF was assessed with and without adjusting for the presence of covariates using correlation and regression analysis. RESULTS: Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD prior to adjusting for covariates (r=0.33, p=0.0002). Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD (r=0.24, p=0.0079) after adjusting for age, sex, body mass index z-score, VAT, and SCAT in a multivariable regression analysis. CONCLUSION: Bone marrow fat content is positively associated with hepatic fat content in children with known or suspected NAFLD. Further research is needed to confirm these results and understand their clinical and biological implications.

Randomised clinical trial: a leucine-metformin-sildenafil combination (NS-0200) vs placebo in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). METHODS: Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). RESULTS: In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. CONCLUSION: These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609).

Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging-derived measures of liver fat and volume are emerging as accurate, non-invasive imaging biomarkers in non-alcoholic steatohepatitis (NASH). Little is known about these measures in relation to histology longitudinally. AIM: To examine any relationship between MRI-derived proton-density fat-fraction (PDFF), total liver volume (TLV), total liver fat index (TLFI), vs. histology in a NASH trial. METHODS: This is a secondary analysis of a 24-week randomised, double-blind, placebo-controlled trial of 50 patients with biopsy-proven NASH randomised to oral ezetimibe 10 mg daily (n = 25) vs. placebo (n = 25). Baseline and post-treatment anthropometrics, biochemical profiling, MRI and biopsies were obtained. RESULTS: Baseline mean PDFF correlated strongly with TLFI (Spearman's ρ = 0.94, n = 45, P < 0.0001) and had good correlation with TLV (ρ = 0.57, n = 45, P < 0.0001). Mean TLV correlated strongly with TLFI (ρ = 0.78, n = 45, P < 0.0001). After 24 weeks, PDFF remained strongly correlated with TLFI (ρ = 0.94, n = 45, P < 0.0001), maintaining good correlation with TLV (ρ = 0.51, n = 45, P = 0.0004). TLV remained strongly correlated with TLFI (ρ = 0.74, n = 45, P < 0.0001). Patients with Grade 1 vs. 3 steatosis had lower PDFF, TLV, and TLFI (P < 0.0001, P = 0.0003, P < 0.0001 respectively). Regression analysis of changes in MRI-PDFF vs. TLV indicates that 10% reduction in MRI-PDFF predicts 257 mL reduction in TLV. CONCLUSIONS: The MRI-PDFF and TLV strongly correlated with TLFI. Decreases in steatosis were associated with an improvement in hepatomegaly. Lower values of these measures reflect lower histologic steatosis grades. MRI-derived measures of liver fat and volume may be used as dynamic and more responsive imaging biomarkers in a NASH trial, than histology.

Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE.

BACKGROUND: Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis. AIM: To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness. METHODS: We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other aetiology of liver disease. All patients underwent a standardised research visit, laboratory tests, MRI-PDFF, and MRE. RESULTS: Mean (±s.d.) age and body mass index (BMI) was 59.7 (±11.2) years and 30.8 (±6.5) kg/m(2) , respectively. The prevalence of NAFLD (defined as MRI-PDFF ≥5%) and advanced fibrosis (defined as MRE ≥3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (P = 0.028) and had higher mean BMI (P = 0.0008), waist circumference (P < 0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, P < 0.0001). Only 26% of those with NAFLD had elevated alanine aminotransferase. CONCLUSIONS: This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-proton density fat fraction and magnetic resonance elastography in T2DM is feasible and may be considered after validation in a larger cohort.

Magnetic resonance elastography identifies fibrosis in adults with alpha-1 antitrypsin deficiency liver disease: a prospective study.

BACKGROUND: Limited data exist on the clinical presentation and non-invasive detection of liver fibrosis in adults with homozygous Z genotype alpha-1 antitrypsin (AAT) deficiency. AIMS: To compare demographic, biochemical, histological and imaging data of AAT deficient patients to normal-control and biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients, and to assess the diagnostic accuracy of magnetic resonance elastography (MRE) in detecting fibrosis in AAT deficiency. METHODS: Study includes 33 participants, 11 per group, who underwent clinical research evaluation, liver biopsy (AAT and NAFLD groups), and MRE. Histological fibrosis was quantified using a modified Ishak 6-point scale and liver stiffness by MRE. Diagnostic performance of MRE in detecting fibrosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Mean (±s.d.) of age and BMI of normal-control, AAT and NAFLD groups was 57 (±19), 57 (±18), and 57 (±13) years, and 22.7 (±2.5), 24.8 (±4.0) and 31.0 (±5.1) kg/m(2) respectively. Serum ALT [mean ± s.d.] was similar within normal-control [16.4 ± 4.0] and AAT groups [23.5 ± 10.8], but was significantly lower in AAT than NAFLD even after adjustment for stage of fibrosis (P < 0.05, P = 0.0172). For fibrosis detection, MRE-estimated stiffness had an area under the ROC curve of 0.90 (P < 0.0001); an MRE threshold of ≥3.0 kPa provided 88.9% accuracy, with 80% sensitivity and 100% specificity to detect presence of any fibrosis (stage ≥1). CONCLUSIONS: This pilot prospective study suggests magnetic resonance elastography may be accurate for identifying fibrosis in patients with alpha-1 antitrypsin deficiency. Larger validation studies are warranted.

Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non-invasive diagnosis of advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease: a prospective study.

BACKGROUND: Two-dimensional magnetic resonance elastography (2D-MRE) is an advanced magnetic resonance method with high diagnostic accuracy for predicting advanced fibrosis in non-alcoholic fatty liver disease (NAFLD) patients. However, no prospective, head-to-head comparisons between 2D-MRE and clinical prediction rules (CPRs) have been performed in patients with biopsy-proven NAFLD. AIM: To compare the diagnostic utility of 2D-MRE against that of eight CPRs (AST:ALT ratio, APRI, BARD, FIB-4, NAFLD Fibrosis Score, Bonacini cirrhosis discriminant score, Lok Index and NASH CRN model) for predicting advanced fibrosis in a prospective cohort with paired liver biopsy as the gold standard. METHODS: This is a cross-sectional analysis of a prospective study of 102 patients (58.8% women) with biopsy-proven NAFLD, 2D-MRE and clinical research assessment within 90 days of biopsy. Receiver operating characteristic (ROC) analysis was performed to assess the performance of 2D-MRE and CPRs for predicting advanced fibrosis. RESULTS: The mean (±s.d.) age and BMI were 51.3 (±14.0) years and 31.7 (±5.5) kg/m(2) respectively. 48, 26, 9, 13 and 6 patients had stage 0, 1, 2, 3 and 4 fibrosis respectively. The area under ROC curve (AUROC) was 0.957 for 2D-MRE and between 0.796 and 0.861 for the CPRs. FIB-4 was the best-performing CPR at predicting advanced fibrosis with AUROC of 0.861. In head-to-head comparisons using the DeLong test, 2D-MRE had significantly better AUROC (P < 0.05) than each CPR for predicting advanced fibrosis. CONCLUSION: Compared to clinical prediction rules, 2D-MRE provides significantly higher accuracy for the diagnosis of advanced fibrosis in NAFLD patients.

Effect of acquisition rate on liver and portal vein enhancement with microbubble contrast.

We showed that tissue enhancement with microbubbles is dependent upon transmit power. Because intermittent imaging decreases bubble exposure to ultrasound, and also decreases the ability of the sonographer to maintain anatomic orientation, we aimed to determine the optimum frame rate that maximizes enhancement and allows for continued anatomic orientation. Seven rabbits with an avascular liver lesion created by percutaneous injection of 1 mL ethyl alcohol 7 days earlier were imaged with an Acuson 128XP/10 using a 7-MHz sector transducer at fixed transmit power. Each rabbit was imaged 5 times in random order, at 1 frame/30 s, 1frame/5 s, 1frame/s, 4 frames/s, and 28 frames/s. The same plane was imaged at all frame rates from before to 15 min after the bolus injection of 0.3-mL (0.1-0.12 mL/kg) of AF0150 (Imagent, Alliance Pharmaceutical Corp., San Diego, CA). Liver and portal vein videointensity relative to the lesion were evaluated over time. In this study, liver enhancement progressively increased as the frame rate was reduced (p<0.001). Peak, duration, and area under the time-intensity curve were all greater at the lower frame rates (1 fr/30 s, 1 fr/5 s, and 1 fr/s) than at 28 fr/s (p<0.05). Anatomic orientation was maintained at 1 frame/s rate at which peak enhancement was 44% greater and duration was 100% longer than at 28 frames/s (p<.05). Portal vein enhancement was not affected by frame rate. In conclusion, with intermittent imaging, enhancement was dependent upon frame rate and the ability of the region being imaged to replenish its bubbles between consecutive acquisitions. The 1 frame/s allowed for anatomic orientation and adequate tissue contrast.

B-mode enhancement of the liver with microbubble contrast agent: a blinded study in rabbits with VX2 tumors.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy of contrast material-enhanced sonography in the detection of liver lesions by using an animal model. MATERIALS AND METHODS: A total of 36 rabbits, 12 normal and 24 with one, two, or more VX2 tumors implanted percutaneously, were imaged on an Acuson 128XP/10 with a 7-MHz sector transducer by a sonographer blinded to the study assignments. The sonographer assigned rabbits to four groups (no, one, two, more than two tumors) based on the number of lesions detected before and then after the intravenous bolus injection of 0.5 mL of AF0150. S-VHS video segments or pre- and postcontrast images were separated, randomized, and evaluated by a blinded reader. Necropsy served as the gold standard. RESULTS: Classification of rabbits as normal or tumor bearing on the precontrast images produced three false-positive results and three false-negative results for the blinded sonographer and six false-positive results and two false-negative results for the blinded reader. On postcontrast images, all rabbits were correctly classified by both observers. The correlation of the classification of whether rabbits had no, one, two, or more tumors relative to the pathologic classification on precontrast images was poor to fair (K = 0.349 +/- 0.099 for the sonographer and 0.274 +/- 0.111 for the reader), whereas the postcontrast correlation was good to excellent (K = 0.924 +/- 0.099 for the sonographer and 0.809 +/- 0.076 for the reader). CONCLUSION: AF0150 markedly increased the ability of the sonographer and the blinded reader to distinguish normal from tumor-bearing animals and improved the classification of rabbits with more than one liver tumor.

Contrast-enhanced B-mode US angiography in the assessment of experimental in vivo and in vitro atherosclerotic disease.

RATIONALE AND OBJECTIVES: This study was performed to (a) test the hypothesis that filling the arterial lumen with echoes at B-mode ultrasound (US) enables the assessment of wall and luminal abnormalities and (b) compare contrast material-enhanced B-mode US with color and power Doppler US angiography. MATERIALS AND METHODS: Atherosclerotic lesions were created in 14 rabbit aortas and imaged with color Doppler and B-mode US before and after the intravenous administration of 0.3 mL of AF0150, a US contrast agent. In addition, four replicas of diseased human carotid arteries were immersed in a tissue-mimicking phantom and imaged with B-mode and color and power Doppler US before and after the administration of 1 mL of AF0150 per liter of porcine blood. Radiopaque plastic casts of the rabbit aortas and contact radiographs of the plastic replicas served as standards. RESULTS: Although color and power Doppler US allowed immediate localization of the lumen, precise estimation of stenoses and reliable visualization of surface irregularities were not possible. After AF0150 administration, angiogram-like images of the lumen were created with B-mode US, allowing rapid assessment of the entire vessel lumen and wall. Consequently, luminal stenoses were more accurately measured than with unenhanced B-mode US (r2 = 0.94, P < .0001 vs r2 = 0.21, P = .25) or Doppler (r2 = 0.42, P < .03). In addition, plaques and ulcerations were visible only with contrast-enhanced B-mode US. CONCLUSION: Microbubbles fill the arterial lumen with echoes at B-mode US, creating an angiogram-like image. The ability to visualize the inner and outer surfaces of the vascular wall improved the evaluation of luminal and wall abnormalities.

Association between novel MRI-estimated pancreatic fat and liver histology-determined steatosis and fibrosis in non-alcoholic fatty liver disease.

BACKGROUND: Ectopic fat deposition in the pancreas and its association with hepatic steatosis have not previously been examined in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). AIM: To quantify pancreatic fat using a novel magnetic resonance imaging (MRI) technique and determine whether it is associated with hepatic steatosis and/or fibrosis in patients with NAFLD. METHODS: This is a cross-sectional study including 43 adult patients with biopsy-proven NAFLD who underwent clinical evaluation, biochemical testing and MRI. The liver biopsy assessment was performed using the NASH-CRN histological scoring system, and liver and pancreas fat quantification was performed using a novel, validated MRI biomarker; the proton density fat fraction. RESULTS: The average MRI-determined pancreatic fat in patients with NAFLD was 8.5% and did not vary significantly between head, body, and tail of the pancreas. MRI-determined pancreatic fat content increased significantly with increasing histology-determined hepatic steatosis grade; 4.6% in grade 1; 7.7% in grade 2; 13.0% in grade 3 (P = 0.004) respectively. Pancreatic fat content was lower in patients with histology-determined liver fibrosis than in those without fibrosis (11.2% in stage 0 fibrosis vs. 5.8% in stage 1-2 fibrosis, and 6.9% in stage 3-4 fibrosis, P = 0.013). Pancreatic fat did not correlate with age, body mass index or diabetes status. CONCLUSIONS: In patients with NAFLD, increased pancreatic fat is associated with hepatic steatosis. However, liver fibrosis is inversely associated with pancreatic fat content. Further studies are needed to determine underlying mechanisms to understand if pancreatic steatosis affects progression of NAFLD.

Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD.

BACKGROUND: Conventional magnetic resonance imaging (MRI) techniques that measure hepatic steatosis are limited by T1 bias, T(2)* decay and multi-frequency signal-interference effects of protons in fat. Newer MR techniques such as the proton density-fat fraction (PDFF) that correct for these factors have not been specifically compared to liver biopsy in adult patients with non-alcoholic fatty liver disease (NAFLD). AIM: To examine the association between MRI-determined PDFF and histology-determined steatosis grade, and their association with fibrosis. METHODS: A total of 51 adult patients with biopsy-confirmed NAFLD underwent metabolic-biochemical profiling, MRI-determined PDFF measurement of hepatic steatosis and liver biopsy assessment according to NASH-CRN histological scoring system. RESULTS: The average MRI-determined PDFF increased significantly with increasing histology-determined steatosis grade: 8.9% at grade-1, 16.3% at grade-2, and 25.0% at grade-3 with P ≤ 0.0001 (correlation: r(2) = 0.56, P < 0.0001). Patients with stage-4 fibrosis, when compared with patients with stage 0-3 fibrosis, had significantly lower hepatic steatosis by both MRI-determined PDFF (7.6% vs. 17.8%, P < 0.005) and histology-determined steatosis grade (1.4 vs. 2.2, P < 0.05). NAFLD patients with grade 1 steatosis were more likely to have characteristics of advanced liver disease including higher average AST:ALT (0.87 vs. 0.60, P < 0.02), GGT (140 vs. 67, P < 0.01), and INR (1.06 vs. 0.99, P < 0.01), higher stage of fibrosis and hepatocellular ballooning. CONCLUSIONS: MRI-determined proton density-fat fraction correlates with histology-determined steatosis grade in adults with NAFLD. Steatosis is non-linearly related to fibrosis progression. In patients with NAFLD, a low amount of hepatic steatosis on imaging does not necessarily indicate mild disease.

Body MRI artefacts: from image degradation to diagnostic utility.

Magnetic resonance (MR) imaging, as with any other imaging modality, has its share of artefacts, and MR studies of the abdomen and pelvis are particularly affected. These artefacts cause image degradation, can have an adverse effect on imaging quality and are usually considered detrimental. It is thus important to recognise common abdominopelvic MR imaging artefacts and know how to choose protocols and modify scan parameters to eliminate or at least minimise them. Many MR artefacts, on the other hand, provide diagnostically useful information about the underlying tissue, and many powerful MR sequences, such as in-phase or out-of-phase gradient-recalled-echo (GRE) sequences, may be thought of as imaging artefacts applied creatively. To distinguish friend from foe MR artefacts or to convert foes into friends, MR radiologists must recognise and understand the physical basis of such artefacts to take advantage of them for diagnostic purposes.

Capsular retraction: an uncommon imaging finding in hepatic inflammatory pseudotumour.

Capsular retraction is an infrequent but characteristic feature of malignant liver lesions such as hepatic metastases and intrahepatic cholangiocarcinoma. Rarely, this finding may be observed in association with benign lesions, such as atypical haemangiomas. Capsular retraction has not previously been reported in association with hepatic inflammatory pseudotumour (IPT). Hepatic IPT is an uncommon benign hepatic lesion with a good clinical prognosis. In this report, we discuss the case of a 48-year-old woman with capsular retraction secondary to multifocal hepatic inflammatory IPTs.

Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of paediatric liver disease. Similar to NAFLD in adults, NAFLD in children is associated with obesity and insulin resistance and requires liver histology for diagnosis and staging. However, significant histological differences exist between adult and paediatric NAFLD to warrant caution in extrapolation of adult data. AIM: To review the available data on the epidemiology, pathogenesis, diagnosis and treatment of paediatric NAFLD. METHODS: Relevant articles were identified by Medline searches using the keywords: nonalcoholic fatty liver disease, steatohepatitis, obesity and children. RESULTS: The rise in childhood obesity has been accompanied by an increase in paediatric NAFLD. Age, gender and race/ethnicity are significant determinants of risk, and sex hormones, insulin sensitivity and adipocytokines are implicated in the pathogenesis of paediatric NAFLD. There is no consensus for treatment of NAFLD; however, data suggest that diet, exercise and some pharmacological therapies may be of benefit. CONCLUSIONS: To evaluate and effectively treat paediatric NAFLD, the pathophysiology and natural history of the disease should be clarified and non-invasive methods for screening, diagnosis, and longitudinal assessment developed. Randomized, controlled, double-blind trials of pharmacological therapies in children with biopsy-proven disease are necessary.

Unusual cause of ureteral obstruction in transplant kidney.

Ultrasound and computed tomographic images are described in a patient who underwent renal transplantation and presented with hydronephrosis and partial ureteral obstruction secondary to herniation of the transplant ureter into a left inguinal hernia. To our knowledge, this is the first report of herniation of a transplanted ureter in the inguinal canal resulting in or exacerbating ureteral obstruction.

Ruthenium (II)-derived organometallic compounds induce cytostatic and cytotoxic effects on mammalian cancer cell lines through p53-dependent and p53-independent mechanisms.

The metallic compound cisplatin has been used for many years to treat various human cancers. Here, we describe the cytostatic and cytotoxic properties of a new class of organometallic compounds that contain a ruthenium (II) atom covalently linked to carbon and nitrogen atoms. We found that several ruthenium-derived compounds (RDCs) led to G1 arrest and induced apoptosis in tumor cell lines derived from glioblastomas, neuroblastomas, and lymphoid tumors at least as efficiently as cisplatin. We further analyzed the signaling pathways underlying these effects, and we showed that both RDCs and cisplatin induced p53 and p73 protein levels but with different intensities and kinetics. This accumulation of p53 and p73 proteins correlated with an increase in p21 and Bax expression, two p53 target genes linked to cell growth arrest and apoptosis. However, in contrast to cisplatin-induced apoptosis, overexpression of DeltaNp73, a p53 and p73 dominant-negative isoform, only partly reduced RDC-induced apoptosis, suggesting p53-dependent and p53-independent modes of action. This observation was further confirmed by the ability of RDC to induce apoptosis in p53-/- cells. Altogether, this study highlights key cellular and molecular features of RDCs and suggests that further development of this new class of compounds may contribute to improve future chemotherapeutic protocols.