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Background: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D). Methods: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of NITs individually or in sequential combination was assessed by area under receiver operating characteristic curve(AUROC) and by decision curve analysis(DCA). Comparison with 2278 NAFLD patients without T2D was also made. Results: In NAFLD with T2D LSM and AGILE 3+ outperformed both NFS and FIB-4 for advanced fibrosis(AUROC:LSM 0.82,AGILE 3+ 0.82,NFS 0.72,FIB-4 0.75,APRI 0.68;p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%.The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40% to 60% in necessary LSM tests. DCA showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH(AUROC LSM 0.79,AGILE 3+ 0.77,NFS 0.71,FIB-4 0.71;p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were sub-optimal for diagnosing NASH. Conclusions: LSM and AGILE 3+ individually or in low availability setting in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

© Asian Pacific Association for the Study of the Liver 2023, Background: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists. Methods and results: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management. Conculsions: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.

Among patients with chronic hepatitis C (CHC) infection, extensive research showed that fibrosis progression is a proper surrogate marker for advanced liver disease, eventually leading to dramatic endpoints such as cirrhosis and hepatocellular carcinoma. Therefore, there is growing interest in the use of noninvasive methods for fibrosis assessment in order to replace liver biopsy (LB) in clinical practice and provide optimal risk stratification. Elastographic techniques, such as Vibration Controlled Transient Elastography (VCTE), point-shear wave elastography (p-SWE), and 2D-SWE have shown promising results in this regard, with excellent performance in diagnosing hepatic cirrhosis, and great accuracy for steatosis detection through the Controlled Attenuation Parameter embedded on the VCTE device. In addition, the recent introduction of highly efficient direct-acting antivirals (DAAs) led to viral eradication and a significant decrease in liver damage, lowering the risk of hepatic decompensation, and HCC. Therefore, CHC patients need proper noninvasive and repeatable methods for adequate surveillance, even after treatment, as there still remains a risk of portal hypertension and HCC. However, the usefulness for monitoring fibrosis after the sustained virological response (SVR) needs further research.

Background: The Baveno VI consensus proposed a dual liver stiffness (LS) by transient elastography threshold of 15 kPa for excluding and diagnosing compensated advanced chronic liver disease (cACLD) in the absence of other clinical signs. Herein, we aimed to validate these criteria in a real-world multicentre study. Methods: We included 5,648 patients (mean age 51 ± 13 years, 53% males) from 10 European liver centres who had a liver biopsy and LS measurement within 6 months. We included patients with chronic hepatitis C (n = 2,913, 52%), non-alcoholic fatty liver disease (NAFLD, n = 1,073, 19%), alcohol-related liver disease (ALD, n = 946, 17%) or chronic hepatitis B (n = 716, 13%). cACLD was defined as fibrosis stage ≥F3. Results: Overall, 3,606 (66%) and 987 (18%) patients had LS 15 kPa, respectively, while cACLD was histologically confirmed in 1,772 (31%) patients. The cut-offs of 15 kPa showed 75% sensitivity and 96% specificity to exclude and diagnose cACLD, respectively. Examining the ROC curve, a more optimal dual cut-off at 12 kPa, with 91% sensitivity and 92% specificity for excluding and diagnosing cACLD (AUC 0.87; 95% CI 0.86–0.88; p 15 kPa dual cut-offs, we found that the 12 kPa dual cut-offs have better diagnostic accuracy in cACLD. Lay summary: The term compensated advanced chronic liver disease (cACLD) was introduced in 2015 to describe the spectrum of advanced fibrosis and cirrhosis in asymptomatic patients. It was also suggested that cACLD could be diagnosed or ruled out based on specific liver stiffness values, which can be non-invasively measured by transient elastography. Herein, we assessed the suggested cut-off values and identified alternative values that offered better overall accuracy for diagnosing or ruling out cACLD.

Mira Florea,1 Cecilia Lazea,2 Remus Gaga,2 Genel Sur,2 Lucia Lotrean,1 Aida Puia,1 Ana Maria Alexandra Stanescu,3 Monica Lupsor-Platon,4 Horatiu Florea,5 Maria Lucia Sur2 1Department of Community Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Department of Pediatrics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3Department of Family Medicine, “carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; 4Medical Imaging Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 5Computer Science Department, Technical University of Cluj-Napoca, Cluj-Napoca, RomaniaCorrespondence: Cecilia Lazea V Babes 8 Street, Cluj-Napoca, 400006, RomaniaTel + 40744353764Email cecilialazea@umfcluj.roIntroduction: Telemedicine has emerged as a critical technology to mitigate SARS-CoV-2 infection. We aim in this work to explore how general practitioners (GPs) perceived the use of telemedicine, recently recognized and reimbursed by the Public Health Insurance House (PHIH) for primary care (PC) provision.Methods: A cross-sectional study was performed in 2020 in one county of Romania using an anonymous questionnaire that assessed physicians’ perceptions regarding teleconsultation, reliability in tele-decision, remote pathology management, pregnant women’s surveillance, patients’ satisfaction with telemedicine, the need for its further reimbursement. Bivariate correlation was used to measure associations between the investigated issues.Results: More than a quarter of GPs (28.6%) found it easier to address patients’ healthcare needs remotely, while 60.7% considered time-consuming teleconsultations compared to face-to-face visits. Tele-diagnostic uncertainty was expressed by 64.3% of physicians, and a quarter were confident in tele-decisions. Almost half of GPs (43%) observed patients’ satisfaction with tele-visits, while half said patients encountered difficulties using technology. A large percentage of doctors (62.5%) perceived that patients felt as well treated by virtual as in-person visit and 91.1% suggested post-pandemic reimbursement. The results of the bivariate correlation showed that physicians who perceived positive patient feedback on telemedicine were more supportive of subsequent reimbursement.Conclusion: This study showed the GPs’ positive perception of the use of telemedicine. Its adoption in PC has shed light on the shadows of the pandemic. The time-consuming nature of teleconsultations, uncertainty in tele-decisions, patients’ difficulties in using technology were seen as shadows of telecare. However, most of the GPs surveyed agreed with the need for further reimbursement. Future work should focus on innovative solutions for integrating telemedicine as complementary form of PC, the need for telemedicine-based training for GPs to improve capacity building, and patients’ perceptions of virtual care, helping to build trust and satisfaction.Keywords: telemedicine, primary care, family doctor, perception, Covid-19 pandemic

BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis.METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284.FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard.FUNDING: The German Federal Ministry of Education and Research and Echosens.

(1) Introduction: Multiparametric magnetic resonance imaging (mpMRI) is the main imagistic tool employed to assess patients suspected of harboring prostate cancer (PCa), setting the indication for targeted prostate biopsy. However, both mpMRI and targeted prostate biopsy are operator dependent. The past decade has been marked by the emerging domain of radiomics and artificial intelligence (AI), with extended application in medical diagnosis and treatment processes. (2) Aim: To present the current state of the art regarding decision support tools based on texture analysis and AI for the prediction of aggressiveness and biopsy assistance. (3) Materials and Methods: We performed literature research using PubMed MeSH, Scopus and WoS (Web of Science) databases and screened the retrieved papers using PRISMA principles. Articles that addressed PCa diagnosis and staging assisted by texture analysis and AI algorithms were included. (4) Results: 359 papers were retrieved using the keywords “prostate cancer”, “MRI”, “radiomics”, “textural analysis”, “artificial intelligence”, “computer assisted diagnosis”, out of which 35 were included in the final review. In total, 24 articles were presenting PCa diagnosis and prediction of aggressiveness, 7 addressed extracapsular extension assessment and 4 tackled computer-assisted targeted prostate biopsies. (5) Conclusions: The fusion of radiomics and AI has the potential of becoming an everyday tool in the process of diagnosis and staging of the prostate malignancies.

Simple Summary Non-alcoholic fatty liver disease (NAFLD) attracts a lot of attention, due to the increasing prevalence and progression to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Consequently, new non-invasive, cost-effective diagnostic methods are needed. This review aims to explore the diagnostic performance of ultrasound (US) elastography in NAFLD and NAFLD-related HCC, adding a new dimension to the conventional US examination—the liver stiffness quantification. The vibration controlled transient elastography (VCTE), and 2D-Shear wave elastography (2D-SWE) are effective in staging liver fibrosis in NAFLD. VCTE presents the upside of assessing steatosis through the controlled attenuation parameter. Hereby, we critically reviewed the elastography techniques for the quantitative characterization of focal liver lesions (FLLs), focusing on HCC: Point shear wave elastography and 2D-SWE. 2D-SWE presents a great potential to differentiate malignant from benign FLLs, guiding the clinician towards the next diagnostic steps. As a disease-specific surveillance tool, US elastography presents prognostic capability, improving the NAFLD-related HCC monitoring. Abstract The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population prompts for a quick response from physicians. As NAFLD can progress to liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC), new non-invasive, rapid, cost-effective diagnostic methods are needed. In this review, we explore the diagnostic performance of ultrasound elastography for non-invasive assessment of NAFLD and NAFLD-related HCC. Elastography provides a new dimension to the conventional ultrasound examination, by adding the liver stiffness quantification in the diagnostic algorithm. Whilst the most efficient elastographic techniques in staging liver fibrosis in NAFLD are vibration controlled transient elastography (VCTE) and 2D-Shear wave elastography (2D-SWE), VCTE presents the upside of assessing steatosis through the controlled attenuation parameter (CAP). Hereby, we have also critically reviewed the most important elastographic techniques for the quantitative characterization of focal liver lesions (FLLs), focusing on HCC: Point shear wave elastography (pSWE) and 2D-SWE. As our paper shows, elastography should not be considered as a substitute for FLL biopsy because of the stiffness values overlap. Furthermore, by using non-invasive, disease-specific surveillance tools, such as US elastography, a subset of the non-cirrhotic NAFLD patients at risk for developing HCC can be detected early, leading to a better outcome. A recent ultrasomics study exemplified the wide potential of 2D-SWE to differentiate benign FLLs from malignant ones, guiding the clinician towards the next steps of diagnosis and contributing to better long-term disease surveillance.

Background Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. Aim To determine how to use CAP in interpreting liver stiffness measurements. Methods This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. Results Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. Conclusions Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Clinically significant portal hypertension (CSPH) is responsible for most of the complications in patients with cirrhosis. Liver stiffness (LS) measurement by vibration-controlled transient elastography (VCTE) is currently used to evaluate CSPH. Bi-dimensional shear wave elastography from General Electric (2D-SWE.GE) has not yet been validated for the diagnosis of PHT. Our aims were to test whether 2D-SWE.GE-LS is able to evaluate CSPH, to determine the reliability criteria of the method and to compare its accuracy with that of VCTE-LS in this clinical setting. Patients with chronic liver disease referred to hepatic catheterization (HVPG) were consecutively enrolled. HVPG and LS by both VCTE and 2D-SWE.GE were performed on the same day. The diagnostic performance of each LS method was compared against HVPG and between each other. 2D-SWE.GE-LS was possible in 123/127 (96.90 %) patients. The ability to record at least 5 LS measurements by 2D-SWE.GE and IQR 30 % were the only features associated with reliable results. 2D-SWE.GE-LS was highly correlated with HVPG (r = 0.704; p 0.0001), especially if HVPG 10 mmHg and was significantly higher in patients with CSPH (15.52 vs. 8.14 kPa; p 0.0001). For a cut-off value of 11.3 kPa, the AUROC of 2D-SWE.GE-LS to detect CSPH was 0.91, which was not inferior to VCTE-LS (0.92; p = 0.79). The diagnostic accuracy of LS by 2D-SWE.GE-LS to detect CSPH was similar with the one of VCTE-LS (83.74 % vs. 85.37 %; p = 0.238). The diagnostic accuracy was not enhanced by using different cut-off values which enhanced the sensitivity or the specificity. However, in the subgroup of compensated patients with alcoholic liver disease, 2D-SWE.GE-LS classified CSPH better than VCTE-LS (93.33 % vs. 85.71 %, p = 0.039). 2D-SWE.GE-LS has good accuracy, not inferior to VCTE-LS, for the diagnosis of CSPH.ZIEL: Klinisch signifikante portale Hypertonie (CSPH) ist für die meisten Komplikationen bei Patienten mit Zirrhose verantwortlich. Die Messung der Lebersteifigkeit (LS) mittels vibrationsgesteuerter transienter Elastografie (VCTE) wird derzeit zur Abschätzung einer CSPH verwendet. Die 2-dimensionale Scherwellenelastografie von General Electric (2D-SWE.GE) wurde für die Diagnose der PHT noch nicht validiert. Unser Ziel war es zu untersuchen, ob die LS mittels 2D-SWE.GE in der Lage ist, eine CSPH abzuschätzen, die Zuverlässigkeitskriterien der Methode zu bestimmen und ihre Treffsicherheit in diesem klinischen Anwendungsbereich mit der VCTE-LS zu vergleichen. Patienten mit chronischer Lebererkrankung, die für einen Lebervenendruckgradienten (HVPG) mittels Lebervenenkatheter vorgesehen wurden, wurden nacheinander eingeschlossen. HVPG und LS wurden sowohl mittels VCTE als auch 2D-SWE.GE am selben Tag durchgeführt. Die diagnostische Leistung jeder LS-Methode wurde mit dem HVPG sowie untereinander verglichen. 2D-SWE.GE-LS war bei 123/127 (96,90 %) Patienten durchführbar. Die Fähigkeit, mindestens 5 LS-Messungen mit 2D-SWE.GE und einer IQR 30 % aufzuzeichnen, waren die einzigen Parameter, die zu zuverlässigen Ergebnissen führten. Die 2D-SWE.GE-LS korrelierte stark mit dem HVPG (r = 0,704; p 0,0001), insbesondere bei HVPG 1 mmHg, und war bei Patienten mit CSPH signifikant höher (15,52 vs. 8,14 kPa; p 0,0001). Bei einen Cut-off von 11,3 kPa betrug die AUROC der 2D-SWE.GE-LS zum Nachweis einer CSPH 0,91, was der VCTE-LS nicht unterlegen war (0,92; p = 0,79). Die diagnostische Genauigkeit der LS mittels 2D-SWE.GE-LS zur Erkennung von einer CSPH war ähnlich wie bei VCTE-LS (83,74 % gegenüber 85,37 %; p = 0,238). Die diagnostische Genauigkeit wurde durch den Einsatz unterschiedlicher Cut-offs, die die Sensitivität oder Spezifität erhöhten, nicht verbessert. In der Untergruppe der kompensierten Patienten mit alkoholbedingter Lebererkrankung klassifizierte die 2D-SWE.GE-LS eine CSPH jedoch besser als die VCTE-LS (93,33 % gegenüber 85,71 %, p = 0,039). Für die Diagnose der CSPH zeigt die 2D-SWE.GE-LS eine gute Treffsicherheit – diese ist nicht schlechter als die der VCTE-LS.

Chronic infection with hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC). Surveillance of these patients is an essential strategy in the prevention chain, including in the pre/post-antiviral treatment states. Ultrasound elastography techniques are emerging as key methods in the assessment of liver diseases, with a number of advantages such as their rapid, noninvasive, and cost-effective characters. The present paper critically reviews the performance of vibration-controlled transient elastography (VCTE) in the assessment of HCV patients. VCTE measures liver stiffness (LS) and the ultrasonic attenuation through the embedded controlled attenuation parameter (CAP), providing the clinician with a tool for assessing fibrosis, cirrhosis, and steatosis in a noninvasive manner. Moreover, standardized LS values enable proper staging of the underlying fibrosis, leading to an accurate identification of a subset of HCV patients that present a high risk for complications. In addition, VCTE is a valuable technique in evaluating liver fibrosis prior to HCV therapy. However, its applicability in monitoring fibrosis regression after HCV eradication is currently limited and further studies should focus on extending the boundaries of VCTE in this context. From a different perspective, VCTE may be effective in identifying clinically significant portal hypertension (CSPH). An emerging prospect of clinical significance that warrants further study is the identification of esophageal varices. Our opinion is that the advantages of VCTE currently outweigh those of other surveillance methods.

Hepatocellular carcinoma (HCC) represents the most frequent form of liver cancer. It evolves from cirrhosis, as the result of a restructuring phase at the end of which dysplastic nodules appear. HCC is the main cause of death in people affected by cirrhosis. The most reliable method for HCC diagnosis, the golden standard, is the needle biopsy, but this is an invasive technique, dangerous for the human body. We develop computerized methods, based on ultrasound images, in order to perform automatic diagnosis of HCC in a noninvasive manner. In our previous research, we elaborated the textural model of HCC, based on classical and advanced texture analysis methods, in combination with traditional classification techniques, which led to a satisfying accuracy. We aim to improve this performance in our current and further research. In this article, we analyzed the role of specific deep learning techniques concerning the automatic recognition of HCC from ultrasound images. We chose the Convolutional Neural Networks (CNN), this method being well known for its performance in the field of image recognition. Thus, CNN are based on artificial neural networks, they also performing image processing operations, such as inner convolutions. In order to evaluate the newly adopted technique, we assessed the classification accuracy achieved in the cases of distinguishing HCC from the cirrhotic parenchyma on which it had evolved, respectively when differentiating HCC from the hemangioma benign liver tumor. We compared the accuracy of CNN with our previous results, based on texture analysis methods and it resulted that CNN yielded better recognition rates than the classical texture analysis techniques, respectively comparable with those provided by the advanced texture analysis methods. However, further improvements will be necessary, which we mention within the last section of this article.

Background & Aims: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP. Methods: This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres. Consecutive alcohol-overusing patients underwent concomitant CAP, regular ultrasound, and liver biopsy. In addition, we measured CAP before and after admission for detoxification in a separate single-centre cohort. Results: A total of 562 patients were included in the study: 269 patients in the diagnostic cohort with steatosis scores S0, S1, S2, and S3 = 77 (28%), 94 (35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and moderate steatosis with fair accuracy (area under the receiver operating characteristic curve [AUC] ≥S1 = 0.77; 0.71–0.83 and AUC ≥S2 = 0.78; 0.72–0.83), and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75–0.88). CAP was superior to bright liver echo pattern by regular ultrasound. CAP above 290 dB/m ruled in any steatosis with 88% specificity and 92% positive predictive value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62% negative predictive value. In the 293 patients who were admitted 6.3 days (interquartile range 4–6) for detoxification, CAP decreased by 32 ± 47 dB/m (p 2 had a significantly higher CAP, which did not decrease significantly during detoxification. Conclusions: CAP has a good diagnostic accuracy for diagnosing severe alcoholic liver steatosis and can be used to rule in any steatosis. In non-obese but not in obese, patients, CAP rapidly declines after alcohol withdrawal. Lay summary: CAP is a new ultrasound-based technique for measuring fat content in the liver, but has never been tested for fatty liver caused by alcohol. Herein, we examined 562 patients in a multicentre setting. We show that CAP highly correlates with liver fat, and patients with a CAP value above 290 dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound for determining the severity of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese) patients rapidly decrease in CAP after short-term alcohol withdrawal. In contrast, obese alcohol-overusing patients were more likely to have higher CAP values than lean patients, irrespective of drinking.

Objectives: Evaluation of Acoustic Radiation Force Impulse Imaging (ARFI) elastography performance in predicting the elasticity of the submandibular glands in normal situations and after radiation therapy. Material and method: A number of 54 normal submandibular glands from 27 voluntary subjects and 33 pathological submandibular glands (radiation submaxillities) from 18 patients who had undergone radiation therapy for various cervical and facial oncological conditions were included in study. All the patients had undergone a B mode ultrasonography (Tissue Harmonic Imaging, 8-14 MHz) while the submandibular volume was determined and subsequently an ARFI examination while the shear wave velocity (SWV) was measured (in the central, peripheral and subcapsular areas, with the results expressed in m/s). Results: In the volunteers’ group the mean value of the SWV of the left submandibular gland was 1.68 ± 0.46 m/s, determined in the centre of the gland, 1.88 ± 0.4 m/s in the periphery (corresponding to the subcapsular parenchyma) and the SWV of the right submandibular gland was 1.74 ± 0.35 m/s (centrally) and 1.84 ± 0.43 m/s in the periphery. The mean value of all measurements was 1.82 ± 0.41 m/s. The mean volume of the glands was 7.97 ± 2.63 cm3. In the group of patients who had underwent radiation therapy (at least 35Gy), the mean value of the SWV was 2.24 ± 0.49 m/s centrally and 2.1 ± 0.58 m/s in the periphery on the left and 1.99 ± 0.5 m/s centrally and 2.21 ± 0.52 m/s in the periphery on the right. The mean value of all the measurements was 2.13 ± 0.52 m/s and the mean volume of the gland was 5.95 ± 4.16 cm3. Conclusions: Elastography using ARFI technique is a valid examination in the evaluation of the normal and pathological submandibular gland stiffness. The values of the shear wave velocities that correspond to a normal stiffness, determined through the ARFI technique, are similar in the two glands. After cervical and facial radiation therapy the values of the SWV are increased, indicating a change in the consistency of the gland thus implying a structural transformation. The ARFI technique can be used in the evaluation of the salivary glands pathology.

Aim: The purpose of this study is to evaluate pancreatic stiffness by ARFI abdominal elastography. In the current literature, there are relatively few studies that have assessed the clinical utility of this technique. Material and method: A number of 37 healthy subjects were included. The data were collected in a prospective manner and afterwards included in an observational, analytical and longitudinal study. Subsequently viewing the pancreatic parenchyma in bidimensional mode (2D-US) mode, 10 shear wave velocity (SWV) measurements for each segment: head, body and tail were performed. Statistical analysis by regression models targeted also the possible influence of other factors in assessing SWV. A comparative analysis was performed regarding the statistical significance of 5 versus 10 SWV measurements for each segment. Results: The pancreas was entirely evaluated in all subjects. The mean SWV from the entire parenchyma was 1.216 m/s±0.36 and between the three segments SWV were similar (head: 1.224 m/s, body: 1.227 m/s and tail: 1.191 m/s). A ratio of the IQR/Median >0.4 was interpreted as statistically invalid, relevant data being highlighted in the percentage of 83.78% for the head of the pancreas, 78.37% for the body, and 67.56% at the caudal level. Significant correlations were observed between the data (mean and median SWV) provided by the group with 5 measurements of the SWV versus the standard group: 93.9% for the head, 96.6% for the body, and 98.7% accordingly to the tail. Conclusions: SWV determination by percutaneous approach represents a useful imaging method for evaluating pancreatic stiffness, of course within these limitations. Because we did not observe statistically significant differences between the results obtained by 5 or 10 measurements, we suggest that it would be sufficient to perform only five measurements of the SWV per pancreatic segment. The data obtained in the normal pancreas could be used in future comparative assessments regarding the inflammatory or tumoral pathology of the pancreas.

Aims: Non-invasive methods are required to diagnose presence and grading of esophageal varices in patients with he- patic cirrhosis and in this respect we have evaluated the role of transient elastography and abdominal ultrasound parameters. Material and methods: Cirrhotic patients were prospectively evaluated by transient elastography and Doppler ultrasound for diagnosis of presence and grading of esophageal varices, the results being compared with the findings of the esophagogas- troduodenoscopy. Results: Sixty patients with hepatic cirrhosis were analysed. The parameters that reached statistical signifi- cance for diagnosis of esophageal varices were: liver stiffness (LSM) > 15 kPa, hemodynamic liver index (PVr1) ≥ 0.66, portal vascular resistance (PVR) > 17.66 and splenoportal index (SPI) > 4.77. The only parameter that reached statistical power for the diagnosis of large esophageal varices was LSM at a cut-off value of 28.8 kPa. Conclusions: Assessment of LSM in patients with liver cirrhosis can predict both the presence of esophageal varices and of large esophageal varices. The PVr1, PVR and SPI Doppler indexes can be used to diagnose the presence of esophageal varices but have no role in the prediction of large esophageal varices. Further studies are required to confirm these results and offer a stronger clinical significance.

Background & Aims Liver stiffness (LS), spleen stiffness (SS) and serum markers have been proposed to non-invasively assess portal hypertension or oesophageal varices (EV) in cirrhotic patients. We aimed to evaluate the performance of a stepwise algorithm that combines Lok score with LS and SS for diagnosing high-risk EV (HREV) and to compare it with other already-validated non-invasive methods. Methods We performed a cross-sectional study including 136 consecutive compensated cirrhotic patients with various aetiologies, divided into training (90) and validation (46) set. Endoscopy was performed within 6 months from inclusion for EV screening. Spleen diameter was assessed by ultrasonography. LS and SS were measured using Fibroscan. Lok score, platelet count/spleen diameter ratio, LSM-spleen diameter to platelet ratio score and oesophageal varices risk score (EVRS) were calculated and their diagnostic accuracy for HREV was assessed. The algorithm classified patients as having/not-having HREV. Its performance was tested and compared in both groups. Results In the training set, all variables could select patients with HREV with moderate accuracy, the best being LSPS (AUROC = 0.818; 0.93 sensitivity; 0.63 specificity). EVRS, however, was the only independent predictor of HREV (OR = 1.521; P = 0.032). The algorithm correctly classified 69 (76.66%) patients in the training set (P

Imaging becomes more and more important for all clinical specialities, including gastroenterology. This issue is focusing on some very interesting and new applications of imaging procedures in liver, biliary tract, and digestive tube pathology. The content is representative for this “new era” of visual diagnosis that we live. In the article entitled “Preliminary study on hepatocyte-targeted phosphorus-31 MRS using ATP-loaded galactosylated chitosan oligosaccharide nanoparticles” R.-S. Yu et al. are describing their preliminary work on MR spectroscopy for evaluating the hepatocyte uptake of ATP-loaded Gal-CSO (Gal-CSO/ATP) nanoparticles. They show significant targeting efficiency in hepatic cells in vitro and enhancement efficiency of ATP peaks in HepG-2 cells. Furthermore, they demonstrate that phosphorus-31 MR spectroscopy could be applied in the research of hepatic molecular imaging. V. Granata et al. in the article “Surveillance of HCC patients after liver RFA: role of MRI with hepatospecific contrast versus three-phase CT scan—experience of high volume oncologic institute” compare the diagnostic accuracy of hepatospecific contrast-enhanced MRI versus triple-phase CT scan after radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients. This is an excellent paper with a very good design. The authors examine a cohort of thirty-four consecutive HCC patients (42 hepatic nodules), treated with percutaneous RFA, who underwent MR and CT scan. All patients were enrolled in a research protocol that included CT with iodized contrast medium injection and MR with hepatospecific contrast medium injection and restaged within four weeks and at 3 months after ablation. Following this work, hepatospecific contrast-enhanced MRI seems to be more effective than multiphase CT in assessment of HCC treated with RFA. T. Gorycki et al. in the article entitled “Bile duct strictures caused by solid masses: MR in differential diagnosis and as a prognostic tool to plan the endoscopic treatment” assess the meaning of qualitative parameters counted from magnetic resonance (MR) plane images as well as from cholangiopancreatography (MRCP) including cases of bile duct obstructions caused by solid masses in differential diagnosis between benign and malignant conditions and as the prognostic factors for endoscopic treatment. They conclude that the probability of malignancy of solid lesions obstructing biliary duct is increasing with higher SIR in T2W images and with longer strictures. Passing the stricture during ERCP treatment was easier and more probable in cases of shorter strictures caused by lesions with higher SIR in STIR T2W images. B. Malkowski et al. make a study entitled “18F-FLT PET/CT in patients with gastric carcinoma” focused on gastric carcinoma. Gastric cancer is a neoplasm presenting different types, frequently containing mucus. Cellularity of this tumor type can be limited and 18F-glucose uptake is not high enough to be seen in PET. The aim of the study was to evaluate the usefulness of 18F-FLT PET/CT in the detection and differentiation of gastric cancers. The work suggests that there is a good accumulation of fluorothymidine in such a tumor which enabled the visualization and evaluation. Simultaneously to neoplastic cells fluorothymidine was accumulated in normal mucosa, so the authors analyzed optimal cut-off value for SUVmax in normal and neoplastic tissue. Ultrasonography (especially EUS) plays the important role in gastric cancer staging but it should be used together with other imaging modalities (e.g., PET) indicating possible invasion of any anatomical and pathological structures. The enterovesical fistulas (the paper entitled “Enterovesical fistulae: aetiology, imaging, and management”) are discussed in the report made by T. Golabek et al. The study provides a state-of-the-art overview of the clinical and radiological diagnosis of enterovesical fistulae. The treatment of fistulae is also briefly discussed. The diagnosis of EVF can be challenging and is often delayed for several months after the symptoms begin. Computed tomography and magnetic resonance imaging remain ideal modality options in establishing the site, course, and complexity of fistulae and in identifying an aetiological factor. Management of fistulae is mainly dependent on the underlying pathology, site of the bowel lesion, and patient's preoperative performance status and may involve conservative or invasive treatment. However, surgical one-stage strategy is a preferred option in most of the cases. Dr. W. Memon et al. in the paper entitled “MDCT of small bowel obstruction: how reliable are oblique reformatted images in localizing point of transition?” evaluate prospectively the additional value of oblique reformations from isotropic voxels obtained using a 64-slice MDCT (multidetector row CT) to localize POT (point of transition), having surgery as a reference standard. Early diagnosis of SBO (small bowel obstruction) is essential to prevent bowel ischemia. Although plain X-ray abdominal evaluation still remains the investigation of first choice in cases of suspected SBO due to its low cost and wide availability, it cannot reliably diagnose the exact level of obstruction and thus can only serve as a basis for triage for further imaging workup. With the ongoing developments in imaging techniques overtime, computed tomography (CT) has emerged as an excellent modality in the diagnosis of SBO. CT scan is not only reliably diagnose SBO but also can be of great help in determining the cause, severity, and the precise point of obstruction. Localizing the point of transition (POT) is empirical as it increases confidence in diagnosis, guides patient care, and thus helps in further management. The authors found that although the oblique MPR increases the image load and is time consuming it surely represents a development and new perspective of utilizing the available information whereby it can significantly prove as a powerful adjunct in diagnosis and management of SBO. Dr. T. S. Kirtane and M. S. Wagh in the work entitled “Endoscopic optical coherence tomography (OCT): advances in gastrointestinal imaging” present the current status of OCT and its practical applications in imaging normal and abnormal mucosa in the esophagus, stomach, small and large intestines, and biliary and pancreatic ducts. They also highlight technical aspects and principles of imaging, assess published data, and suggest future directions for OCT-guided evaluation and therapy. Finally, the group of Dr. A. Gebesce et al. (in the work entitled “Importance of the ultrasonography in diagnosis of ileal duplication cyst”) are presenting an interesting case of intestinal duplication cyst and are discussing the role of ultrasonography for the diagnosis of this rare condition, both ante- and postpartum. In conclusion, the present issue represents a holistic approach of the visual diagnosis in modern gastroenterology. Radu Badea Iwona Sudol-Szopinsk Sebastian Mueller Horia Stefanescu Monica Lupsor Platon

The current study aimed to establish the liver stiffness (LS) cut-off values and their performance in the prediction of the fibrosis stage in chronic hepatitis C (CHC) patients, to find the anthropometric and biochemical factors leading to overestimation of the fibrosis stage and to analyze the factors leading to the technique failure.1,202 consecutive CHC patients were prospectively included in the study. All of them underwent percutaneous liver biopsy for grading and staging the disease (METAVIR) and were referred to LS measurement 1 day prior to biopsy.LS values varied between 2.8-75 kPa. Transient elastography success rate (SR) ranged between 0-100% (84.82 +/- 24.46%). In 27 patients (2.2%), no valid measurement was obtained; high BMI influenced independently the measurement failure. In 11.2% of cases, the SR was60%, but 10 valid measurements were nevertheless recorded; the female sex and high BMI were the only factors independently leading to a SR60%. AUROCs for the diagnosis of fibrosis F≥1, F≥2, F≥3, and F=4 were 0.879, 0.889, 0.941 and 0.970, for the cut-off values of 5.3 kPa, 7.4 kPa, 9.1 kPa and 13.2 kPa respectively, and they did not significantly differ from the adjusted AUROC values. The patients with false positive results were younger and had significantly higher serum aminotransferase (ALT, AST) and gamma glutamyl-transpeptidase levels than the patients with concordant results. The multivariate analysis showed that only high ALT levels influenced independently the occurrence of false positive results.Transient elastography is a useful non-invasive method for the assessment of fibrosis in CHC patients. However, it must be interpreted in the clinical and biochemical context, in order to insure high-quality results.

The geometry of some medical images of tissues, obtained by elastography and ultrasonography, is characterized in terms of complexity parameters such as the fractal dimension (FD). It is well known that in any image there are very subtle details that are not easily detectable by the human eye. However, in many cases like medical imaging diagnosis, these details are very important since they might contain some hidden information about the possible existence of certain pathological lesions like tissue degeneration, inflammation, or tumors. Therefore, an automatic method of analysis could be an expedient tool for physicians to give a faultless diagnosis. The fractal analysis is of great importance in relation to a quantitative evaluation of “real-time” elastography, a procedure considered to be operator dependent in the current clinical practice. Mathematical analysis reveals significant discrepancies among normal and pathological image patterns. The main objective of our work is to demonstrate the clinical utility of this procedure on an ultrasound image corresponding to a submandibular diffuse pathology.

Transient elastography (TE) is increasingly employed in clinical practice for the noninvasive detection of tissue fibrosis in patients with chronic liver disease (CLD), and particularly chronic hepatitis C virus (HCV)-related hepatitis. The present study was designed to provide a definitive characterization of the “confounding” increase in liver stiffness (LS) following a standardized meal in a consecutive population of 125 patients with chronic HCV infection at different stages of fibrotic evolution. LS values were obtained after overnight fasting and 15, 30, 45, 60, and 120 minutes following the onset of a standardized liquid meal (400 mL, 600 Kcal, 16.7% protein, 53.8% carbohydrates, 29.5% fat). An evident increase in LS values was observed 15 to 45 minutes after the onset of the meal with return to baseline premeal levels within 120 minutes in all patients. The peak postmeal delta increase in LS was progressively more marked with increasing stages of fibrosis (P < 0.001), becoming maximal in patients with cirrhosis. However, the probability of identifying the Metavir stage of fibrosis, the Child-Pugh class, or the presence/absence of esophageal varices with the postmeal delta increase in LS was inferior to that obtained with baseline LS values. Conclusion: The results of the present study provide definitive evidence of the confounding effect of a meal on the accuracy of LS measurements for the prediction of fibrosis stage in patients with chronic HCV hepatitis and suggest that a fasting period of 120 minutes should be observed before the performance of TE. (HEPATOLOGY 2013;)

Background & Aims The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. Methods A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0–S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. Results Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5–17) for NAFLD/NASH patients, 10 (3.5–16) for diabetics and 4.4 (3.8–5.0) per BMI unit. Areas under the curves were 0.823 (0.809–0.837) and 0.865 (0.850–0.880) respectively. Optimal cut-offs were 248 (237–261) and 268 (257–284) for those above S0 and S1 respectively. Conclusions CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. Lay summary There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.