Radu Badea

Spleen stiffness measurement using fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients

Background and Aim:  Splenomegaly in a common finding in liver cirrhosis that should determine changes in the spleens density because of portal and splenic congestion and/or because of tissue hyperplasia and fibrosis. These changes might be quantified by elastography, so the aim of the study was to investigate whether spleen stiffness measured by transient elastography varies as liver disease progresses and whether this would be a suitable method for the noninvasive evaluation of the presence of esophageal varices.

Acoustic Radiation Force Impulse Elastography for fibrosis evaluation in patients with chronic hepatitis C: An international multicenter study

AIM The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C. PATIENTS AND METHODS We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5-10 valid measurements, expressed in meters/second - m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6-10 valid measurements, expressed in kiloPascals - kPa). RESULTS Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r=0.654) was found between ARFI measurements and fibrosis (p<0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 - cut-off>1.19 m/s (AUROC=0.779), F ≥ 2 - cut-off>1.33 m/s (AUROC=0.792), F ≥ 3 - cut-off>1.43 m/s (AUROC=0.829), F=4 - cut-off>1.55 m/s (AUROC=0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r=0.728 vs. 0.689, p=0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p=0.01) and fibrosis (F ≥ 1, METAVIR) (p=0.01). CONCLUSION ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients.

Liver Fibrosis: Histopathologic and Biochemical Influences on Diagnostic Efficacy of Hepatobiliary Contrast-enhanced MR Imaging in Staging

PURPOSE To evaluate the diagnostic performance of gadoxetic acid-enhanced magnetic resonance (MR) imaging in the staging of liver fibrosis in patients with diffuse chronic liver diseases (CLDs) and to investigate the factors that may influence the results. MATERIALS AND METHODS With the approval of the Hospital Ethics Committee and waiver of the informed consent requirement, data in 102 patients with histologically proven liver fibrosis (classified according to the METAVIR system) of various underlying causes were retrospectively analyzed. Patients underwent 3.0-T MR imaging with gadoxetic acid. The signal intensity of the liver was defined by using region of interest measurements before contrast material injection and in the hepatobiliary phase (20 minutes after contrast material administration), and relative enhancement was calculated. Univariate and multivariate regression analyses were applied to identify variables associated with relative enhancement measurements, and the performance of relative enhancement measurements in the staging of liver fibrosis was assessed by using area under the receiver operating characteristic curve (AUC) analysis. RESULTS At analysis of the relationship between enhancement measurements and histologic parameters, the relative enhancement values correlated strongly with liver fibrosis stage (r = -0.65, P < .0001) and moderately with necroinflammatory activity grades (r = -0.41, P = .002) and the presence of iron load (r = -0.21, P = .05). In multivariate analysis, only liver fibrosis stage independently influenced relative enhancement values (P < .001). The measurements performed well in the staging of liver fibrosis, with an AUC of 0.81 for stages of F1 or greater, 0.82 for stages of F2 or greater, 0.85 for stages of F3 or greater, and 0.83 for stage F4. Increased aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels were independent predictors of false-negative results. CONCLUSION The presence of hepatic fibrosis can be assessed with good discrimination by using gadoxetic acid-enhanced MR imaging, but assessment can be confounded in the setting of abnormal aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels.

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: A retrospective multicentre study

BACKGROUND Acoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis. AIM To evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography. METHODS A multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients. RESULTS The best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels>5 × the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively. Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively. For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa. CONCLUSION Liver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels.

Is ARFI elastography reliable for predicting fibrosis severity in chronic HCV hepatitis

AIM To determine whether acoustic radiation force impulse (ARFI) elastography is a reliable method for predicting fibrosis severity in patients with chronic hepatitis C virus (HCV) hepatitis. METHODS We performed a multicenter study including 274 subjects with HCV chronic hepatitis in which we compared ARFI with liver biopsy (LB). In each patient we performed LB (evaluated according to the Metavir score) and ARFI measurements (using a Siemens Acuson S2000™ ultrasound system: 10 valid measurements were performed and median values were calculated and expressed in meters/second (m/s). RESULTS A direct, strong, correlation (Spearman r = 0.707) was found between ARFI measurements and fibrosis (P < 0.0001). For predicting the presence of fibrosis (F ≥ 1 Metavir), significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3) and cirrhosis (F = 4), the cut-off values of 1.19, 1.21, 1.58 and 1.82 m/s were determined, respectively, liver stiffness measurements had 73%, 84%, 84% and 91% Se respectively; 93%, 91%, 94%, 90% Sp, respectively; with AUROCs of 0.880, 0.893, 0.908 and 0.937, respectively. CONCLUSION ARFI measurement is a reliable method for predicting the severity of fibrosis in HCV patients.

Quantitative contrast-enhanced harmonic endoscopic ultrasonography for the discrimination of solid pancreatic masses.

PURPOSE Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for the assessment of microcirculation and the delineation of pancreatic tumors in order to characterize and stage them has only recently become available for commercial use, and few reports have been published. The purpose of the study was the qualitative and quantitative digital image analysis of pancreatic adenocarcinomas using conventional endoscopic ultrasonography (EUS) and CEH-EUS and the evaluation of whether contrast medium injection modified adenocarcinoma staging and patient management. MATERIALS AND METHODS In each of 30 prospectively examined patients with suspected pancreatic solid lesions, CEH-EUS was performed using the same quantity of the contrast agent SonoVue and a low mechanical index (0.3 - 0.4), followed by EUS-FNA. The histology, based on EUS-FNA or surgery and 9 months of follow-up, was: pancreatic adenocarcinoma (n = 15), pseudotumoral chronic pancreatitis (n = 12), neuroendocrine tumor (n = 1), common bile duct tumor (n = 1), lymph node metastases of gastric cancer (n = 1). The quantitative analysis was based on histograms obtained from each CEH-EUS video recording. RESULTS CEH-EUS showed a hypoenhanced pattern in 14 cases of adenocarcinoma and in 10 cases of chronic pancreatitis. The index of the contrast uptake ratio was significantly lower in adenocarcinoma than in mass-forming chronic pancreatitis. A cut-off uptake ratio index value of 0.17 for diagnosing adenocarcinoma corresponded to an AUC (CI 95%) of 0.86 (0.67 - 1.00) with a sensitivity of 80%, a specificity of 91.7%, a positive predictive value of 92.8%, and a negative predictive value of 78%. The size of the pancreatic mass was assessed significantly more effectively by CEH-EUS but adenocarcinoma staging was not modified. CONCLUSION The majority of cases of both pancreatic adenocarcinoma and chronic pancreatitis were hypoenhanced and visual discrimination was not possible. This is the first study about CEH-EUS for the quantitative assessment of uptake after contrast injection which has shown that it can aid differentiation between benign and malignant masses but cannot replace EUS-FNA. Neither tumor stage nor therapeutic management have changed after contrast medium injection during CEH-EUS.

Contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver lesions - a prospective multicenter study of its usefulness in clinical practice.

PURPOSE To assess the value of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign focal liver lesions (FLLs) and for diagnosing different FLL types. MATERIAL AND METHODS CEUS performed in 14 Romanian centers was prospectively collected between February 2011 and June 2012. The inclusion criteria were: age > 18 years; patients diagnosed with 1 - 3 de novo FLLs on B-mode ultrasound; reference method (computed tomography (CT), magnetic resonance imaging (MRI) or biopsy) available; patients informed consent. FLL lesions were characterized during CEUS according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. For statistical analysis, indeterminate FLLs at CEUS were rated as false classifications. RESULTS A total number of 536 cases were included in the final analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The reference method was: CT/MRI - 379 cases (70.7 %), pathological exam - 150 cases (27.9 %) and aspiration of liver abscesses - 7 cases (1.4 %). CEUS was conclusive in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS accuracy for differentiation between malignant and benign liver lesions was similar in tumors with diameter ≤ 2 cm and those with diameter > 2 cm. CONCLUSION CEUS represents a useful method in clinical practice for differentiating between malignant and benign FLLs detected on standard ultrasonography, and the results of this study are in concordance with previous multicenter studies: DEGUM (Germany) and STIC (France).

Abdominal Tumor Characterization and Recognition Using Superior-Order Cooccurrence Matrices, Based on Ultrasound Images

The noninvasive diagnosis of the malignant tumors is an important issue in research nowadays. Our purpose is to elaborate computerized, texture-based methods for performing computer-aided characterization and automatic diagnosis of these tumors, using only the information from ultrasound images. In this paper, we considered some of the most frequent abdominal malignant tumors: the hepatocellular carcinoma and the colonic tumors. We compared these structures with the benign tumors and with other visually similar diseases. Besides the textural features that proved in our previous research to be useful in the characterization and recognition of the malignant tumors, we improved our method by using the grey level cooccurrence matrix and the edge orientation cooccurrence matrix of superior order. As resulted from our experiments, the new textural features increased the malignant tumor classification performance, also revealing visual and physical properties of these structures that emphasized the complex, chaotic structure of the corresponding tissue.

Inflammation-adapted liver stiffness values for improved fibrosis staging in patients with hepatitis C virus and alcoholic liver disease

It is well known that inflammation increases liver stiffness (LS) in patients with chronic hepatitis C (HCV) and alcoholic liver disease (ALD) independent of fibrosis stage, but no inflammation‐adapted cut‐off values have been settled so far. An early identification of rapid fibrosers, however, is essential to decide whom to treat first with the novel but expensive antiviral drugs.

Evolutionary-driven support vector machines for determining the degree of liver fibrosis in chronic hepatitis C

OBJECTIVE Hepatic fibrosis, the principal pointer to the development of a liver disease within chronic hepatitis C, can be measured through several stages. The correct evaluation of its degree, based on recent different non-invasive procedures, is of current major concern. The latest methodology for assessing it is the Fibroscan and the effect of its employment is impressive. However, the complex interaction between its stiffness indicator and the other biochemical and clinical examinations towards a respective degree of liver fibrosis is hard to be manually discovered. In this respect, the novel, well-performing evolutionary-powered support vector machines are proposed towards an automated learning of the relationship between medical attributes and fibrosis levels. The traditional support vector machines have been an often choice for addressing hepatic fibrosis, while the evolutionary option has been validated on many real-world tasks and proven flexibility and good performance. METHODS AND MATERIALS The evolutionary approach is simple and direct, resulting from the hybridization of the learning component within support vector machines and the optimization engine of evolutionary algorithms. It discovers the optimal coefficients of surfaces that separate instances of distinct classes. Apart from a detached manner of establishing the fibrosis degree for new cases, a resulting formula also offers insight upon the correspondence between the medical factors and the respective outcome. What is more, a feature selection genetic algorithm can be further embedded into the method structure, in order to dynamically concentrate search only on the most relevant attributes. The data set refers 722 patients with chronic hepatitis C infection and 24 indicators. The five possible degrees of fibrosis range from F0 (no fibrosis) to F4 (cirrhosis). RESULTS Since the standard support vector machines are among the most frequently used methods in recent artificial intelligence studies for hepatic fibrosis staging, the evolutionary method is viewed in comparison to the traditional one. The multifaceted discrimination into all five degrees of fibrosis and the slightly less difficult common separation into solely three related stages are both investigated. The resulting performance proves the superiority over the standard support vector classification and the attained formula is helpful in providing an immediate calculation of the liver stage for new cases, while establishing the presence/absence and comprehending the weight of each medical factor with respect to a certain fibrosis level. CONCLUSION The use of the evolutionary technique for fibrosis degree prediction triggers simplicity and offers a direct expression of the influence of dynamically selected indicators on the corresponding stage. Perhaps most importantly, it significantly surpasses the classical support vector machines, which are both widely used and technically sound. All these therefore confirm the promise of the new methodology towards a dependable support within the medical decision-making.