Nonalcoholic fatty liver disease (NAFLD) is the
|
|
- Madlyn Small
- 5 years ago
- Views:
Transcription
1 Accuracy and Reproducibility of Transient Elastography for the Diagnosis of Fibrosis in Pediatric Nonalcoholic Steatohepatitis Valerio Nobili, 1 Francesco Vizzutti, 2 Umberto Arena, 2 Juan G. Abraldes, 4 Fabio Marra, 2,3 Andrea Pietrobattista, 1 Rodolfo Fruhwirth, 5 Matilde Marcellini, 1 and Massimo Pinzani 2,3 Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in chronic liver disease patients. In this study, we assessed the value of TE for the prediction of fibrosis stage in a cohort of pediatric patients with nonalcoholic steatohepatitis. Furthermore, TE interobserver agreement was evaluated. TE was performed in 52 consecutive biopsy-proven nonalcoholic steatohepatitis patients (32 males, 20 females, age years). The area under the receiver operating characteristic curves for the prediction of any (>1), significant (>2), or advanced fibrosis (>3) were 0.977, 0.992, and 1, respectively. Calculation of multilevel likelihood ratios showed that TE values <5, <7, and <9 kpa, suggest the presence of any fibrosis, significant fibrosis, and advanced fibrosis, respectively. TE values between 5 and 7 kpa predict a fibrosis stage of 1, but with some degree of uncertainty. TE values between 7 and 9 kpa predict fibrosis stages 1 or 2, but cannot discriminate between these two stages. TE values of at least 9 kpa are associated with the presence of advanced fibrosis. The intraclass correlation coefficient for absolute agreement was Conclusion: TE is an accurate and reproducible methodology to identify pediatric subjects without fibrosis or significant fibrosis, or with advanced fibrosis. In patients in which likelihood ratios are not optimal to provide a reliable indication of the disease stage, liver biopsy should be considered when clinically indicated. (HEPATOLOGY 2008;48: ) Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, a cluster of abnormalities related to insulin resistance, which is frequently associated with Abbreviations: BMI, body mass index; CLD, chronic liver diseases; IQR, interquartile range; LR, likelihood ratio; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; TE, transient elastography. From the 1 Liver Unit, Bambino Gesù Children s Hospital and Research Institute, Rome, Italy; 2 Department of Internal Medicine and 3 Center for Research, Higher Education and Transfer DENOThe, University of Florence/Azienda Ospedaliero Universitaria Careggi Firenze (AOUC), Florence, Italy; 4 Hepatic Hemodynamic Laboratory, Liver Unit, IMDiM, Hospital Clínic, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (Ciberehd), University of Barcelona, Barcelona, Spain; 5 Radiology Department Bambino Gesù Children s Hospital and Research Institute, Rome, Italy. Received March 3, 2008; accepted April 10, Supported by the Italian Ministry for Education, Universities, and Research (MIUR), the University of Florence, the Italian Liver Foundation, and Instituto de Salud Carlos III, Spain (FIS 05/0519). Address reprint requests to: Valerio Nobili, M.D., Liver Unit, Research Institute, Bambino Gesù Children s Hospital, Piazza S. Onofrio, 4, Rome, Italy. nobili66@yahoo.it; fax: Copyright 2008 by the American Association for the Study of Liver Diseases. Published online in Wiley InterScience ( DOI /hep Potential conflict of interest: Nothing to report. obesity. Given the strong association of NAFLD with increased body mass index (BMI) and the considerable increase in the prevalence of overweight among children and adolescents, 1 NAFLD represents an emerging clinical problem affecting a substantial proportion of these subjects (2.6%-9.8%), 2-3 especially in the presence of obesity. 4 The high prevalence of NAFLD, and the likelihood of evolution to cirrhosis and its complications warrant increased attention toward this disorder. 5-9 Disease progression depends on the presence of hepatocellular damage, inflammation and fibrogenesis which define a pathological entity called nonalcoholic steatohepatitis (NASH). Currently, histopathological analysis of liver tissue represents the only means to assess fibrosis in NAFLD. 10 In the past decade, major efforts have been directed at identifying noninvasive methods for the assessment of liver fibrosis in different chronic liver diseases (CLD) including NAFLD. 11 These efforts assume a particular relevance in the pediatric setting, where the use of liver biopsy is perceived as bearing higher risks and is less acceptable than in adults. A noninvasive medical device based on transient elastography (TE) (Fibroscan; Echosens, Paris, France) has 442
2 HEPATOLOGY, Vol. 48, No. 2, 2008 NOBILI ET AL. 443 received increasing attention. This system has been proposed for the measurement of liver stiffness, considered to be a direct consequence of the fibrotic evolution of CLD. Accordingly, several studies suggesting a clinical usefulness of TE for the prediction of liver fibrosis in CLD have been published (for a review see Pinzani et al. 11 ). Notably, as recently reported by Yoneda et al., 12 the extent of steatosis does not seem to affect TE even in a cohort of adult patients with NASH. Recently, encouraging results concerning the feasibility and accuracy of TE in the prediction of fibrosis in a cohort of miscellaneous pediatric liver diseases were provided by de Lédinghen et al. 13 The aim of the present study was to assess the accuracy of TE in identifying different degrees of fibrosis in a cohort of consecutive children and adolescents with NASH, by using a multilevel likelihood ratios (LRs) analysis approach. Furthermore, interobserver agreement of TE measurements was evaluated. Patients and Methods Patients. A total of 67 consecutive children and adolescents, 35 males and 32 females, with suspected NASH were referred to Bambino Gesù Children s Hospital and Research Institute between July 15, 2007 and January 15, 2008 for staging and grading of the disease. All the enrolled subjects had serum aminotransferases either persistently or intermittently elevated (at least two abnormal determinations within 6 months prior to enrollment), associated with diffusely hyperechogenic liver tissue at ultrasound examination (so-called bright liver ), and hyperinsulinism. Insulin resistance was assessed by the homeostatic model assessment 14 and insulin sensitivity index composite. 15 After histopathological evaluation, the presence of NASH was confirmed in 52 patients (32 males and 20 females; mean age of years; age range, 4-17 years), which were enrolled in the present study. Subjects with at least one of the following conditions were excluded from the study: cardiopulmonary disease, chronic renal failure, recent-active infections, chronic inflammatory diseases, autoimmune diseases, use of anti-inflammatory drugs, abnormal international normalized ratio, and/or platelet count below /L. 16 Secondary causes of steatosis 17 including alcohol abuse ( 140 g/week), total parenteral nutrition or rapid weigh loss, endocrinological diseases, inborn disorders, inflammatory bowel disease, and the use of drugs known to cause steatosis were excluded in all cases. No patient had been previously subjected to bariatric/abdominal surgery. The concomitant presence of other acute or CLD, particularly viral hepatitis, cytomegalovirus, and Epstein-Barr virus infections; vascular diseases of the liver; biliary tract disorders; and autoimmune, genetic, and other metabolic liver diseases were ruled out using standard clinical and laboratory evaluation as well as through histological examination of the liver biopsy. Laboratory tests, including levels of bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline-phosphate, creatinine, fasting glucose, ferritin, cholesterol and triglycerides, insulin, platelet count, international normalized ratio, and oral glucose tolerance test, were performed in all patients within 1 week prior the enrollment. Afterward, all patients were prescribed a balanced, low-caloric diet, as detailed elsewhere, 18 to attain a negative caloric balance. All patients underwent TE measurement within 6 months from liver biopsy. The study protocol conformed to the ethical guidelines of the 1975 declaration of Helsinki (revision of Edinburgh, 2000) and was performed according to the recommendations of the Ethics Committee of the Bambino Gesù Children s Hospital and Research Institute. An informed consent was a priori obtained from a responsible guardian. Ultrasound-Assisted Liver Biopsy. Liver biopsy was performed in all subjects, after an overnight fast, using an automatic core biopsy 18-Gauge needle (Biopince, Amedic, Sweden) under general anaesthesia 19 and ultrasound guidance. A Sonoline Omnia Ultrasound machine (Siemens, Germany) provided with a 5-MHz probe (5.0 C 50; Siemens) and with a biopsy adaptor was employed. Two biopsy passes within different liver segments were performed for each subject. The length of liver specimen (in millimeters) was recorded. Only samples with a length 15 mm and including at least complete portal tracts were considered adequate for the purpose of the study. Biopsies were evaluated by a single experienced liver pathologist blinded to TE results. Biopsies were routinely processed (that is, formalin-fixed and paraffin-embedded): sections of liver tissue, 5- m thick, were stained with hematoxylin-eosin, Masson trichrome, Van Gieson, periodic acid Schiff stain after diastase digestion, and Prussian blue stain. Immunohistochemical staining with antibodies to alpha-1-antitrypsin was used to exclude alpha-1-antitrypsin deficiency associated liver disease. Fibrosis was scored using the Brunt classification: 20 0, no fibrosis; 1, zone 3 perisinusoidal fibrosis; 2, as above with portal fibrosis; 3, as above with bridging fibrosis; and 4, cirrhosis. In this study, fibrosis stages were arbitrary stratified on the basis of Brunt s scoring system, unless indicated otherwise, as: any fibrosis ( 1), significant fibrosis ( 2), and advanced fibrosis ( 3). NASH was defined as the presence of steatosis associated with at least two of the following features: lobular inflammation, he-
3 444 NOBILI ET AL. HEPATOLOGY, August 2008 Grade/Stage Table 1. Histological Findings Steatosis, Lobular Inflammation, Ballooning, Fibrosis, 0 2 (4) 24 (48) 11 (22) 1 16 (32) 32 (64) 18 (36) 27 (54) 2 30 (60) 16 (32) 8 (16) 7 (14) 3 4 (8) 2 (4) 4 3 (6) Steatosis in liver specimens was arbitrarily scored by percentage of hepatocytes with fat deposits as: 0, 5%; 1, 5% 33%; 2, 34% 66%; and 3, 66%. Lobular inflammation was graded on a 4-point scale on a 200 field as: 0, no foci; 1, 2 foci; 2, 2-4 foci; and 3, 4 foci. Hepatocyte ballooning was graded from 0 to 2 as: 0, none; 1, few ballooned cells; and 2, many/prominent ballooned cells. Fibrosis was scored according to Brunt et al. 20 n, number of patients. patocyte ballooning with or without Mallory bodies, and fibrosis (Table 1). TE. TE was performed by using the FibroScan apparatus (kindly provided by Axsan, Milan, Italy), which consists of a 3,5-MHz ultrasound transducer probe mounted on the axis of a vibrator. Mild amplitude and low frequency vibrations (50 Hz) are transmitted to the liver tissue, inducing an elastic shear wave that propagates through the underlying liver tissue. The velocity of the wave is directly related to tissue stiffness. With the patient lying in dorsal decubitus with the right arm in the maximal abduction, ultrasound examination previously identified an adequate section of liver tissue free of large vascular structures and gallbladder in the intercostal space on the right lobe, and a skin mark was made to guide the position of the TE transducer. The tip of FibroScan transducer was covered with a drop of gel and placed perpendicularly in the intercostal space. Moreover, under control time motion, the operator checked the correct position of the probe during TE examination. 21,22 Stiffness was measured on a cylinder of hepatic tissue of 1 cm in diameter and 2-4 cm in length. The procedures were performed by two independent investigators (F.V. and U.A.) who were blinded to the clinical and histological data. The interobserver agreement of TE was evaluated in 31 subjects (62%) studied on the same day and using the same Fibroscan apparatus. The operators had previously performed at least 100 TE determinations in patients with CLD. As previously described 22 and as suggested by the provider of the instrumentation, we considered representative measurements the median value of 10 successful acquisitions with a success rate of at least 60%, and with an interquartile range (IQR) lower than 30%. Statistical Analysis. The comparison between clinical and laboratory variables and TE values between fibrosis stages was conducted with analysis of variance. Post hoc comparisons were conducted with the least significant t test. Linear trends were explored with polynomial contrasts. 23 The discriminative ability of TE to predict any fibrosis ( 1), significant fibrosis ( 2), and advanced fibrosis ( 3) was assessed by receiver operating characteristic curve analysis. Multilevel LRs were used to explore the relationship between stiffness and fibrosis stage across the whole spectrum of TE values. The advantage of this approach is that, unlike sensitivity, specificity, and positive and negative predictive values, computation of LRs does not require dichotomization of test results, which may discard useful diagnostic information The LR for each category was calculated by dividing the percentage of patients with the target condition (fibrosis 1, 2, or 3) in that category by the percentage without the condition in that category. Confidence intervals of 90% 26 were calculated using the iterative method suggested by Gart and Nam 27 with the StatsDirect statistical software (StatsDirect Ltd., Cheshire, UK). LRs above 10 and below 0.1 are considered to provide strong evidence to rule in or rule out diagnoses, respectively. 24,25 Multivariable logistic regression analysis was used to evaluate whether any clinical or laboratory variables could add to the diagnostic value of TE. Interobserver reproducibility was estimated with the intraclass correlation coefficient for absolute agreement. 28 Values greater than 0.75 indicate an excellent agreement. All reported P values are twosided. Only P values 0.05 were considered statistically significant. Statistical analysis was performed with the SPSS 15.0 package (SPSS, Chicago, IL). Results Characteristics of Patients. TE was feasible in 50 NASH patients and these were included in the statistical analysis (96%). In two patients, TE determination failed, likely due to high BMI ( 35 kg/m 2 ). The major clinical and biochemical parameters of the subjects included in the analysis are listed in Table 2. All the enrolled patients showed insulin resistance, but none had diabetes. All subjects fulfilled the histopathological requirements, that is, the length of liver specimens was on average mm, and included complete portal tracts. All histological sections were considered adequate for evaluation with the scoring systems employed by the pathologist. In the group of subjects with advanced fibrosis/ cirrhosis, none had a clinical history of clinical decompensation (that is, ascites, portal hypertension related bleeding, or encephalopathy). Considering all investigated subjects, the mean decrease of BMI from biopsy to TE measurement was of 2 2 kg/m 2 (ranging from 4.4 to to 0.2 kg/m 2 ), and the mean decrease in alanine aminotransferase levels did not reach a level of significance (66 75 U/L with extremes of U/L vs.
4 HEPATOLOGY, Vol. 48, No. 2, 2008 NOBILI ET AL. 445 Table 2. Clinical and Laboratory Findings of the Patients Enrolled in the Study Fibrosis (n pts,%) Variable 0 (n 11, 22) 1 (n 27, 54) 2 (n 7, 14) 3 4 (n 5, 10) P (ANOVA) Age (years) Male gender, 4 (36) 18 (67) 6 (86) 3 (60) 0.153* BMI (kg/m 2 ) Obese, 5 (46) 14 (52) 2 (29) 3 (60) 0.664* Overweight, 9 (82) 21 (78) 4 (57) 3 (60) 0.577* ALT (U/L) AST (U/L) INR Bilirubin (mg/dl) Albumin (g/dl) GT (U/L) Fasting glucose (mg/dl) Cholesterol (mg/dl) ISI HOMA Triglycerides (mg/dl) Platelet count ( 10 9 /L) TE (kpa) , ,, Results are expressed as mean standard deviation (SD). Fibrosis was scored according to Brunt classification. Patients were considered overweight or obese if the BMI was greater than the 85th and equal to the 97th or greater than the 97th percentile, respectively. *Chi-square. P for the linear trend. P for the linear trend. P 0.05 versus fibrosis stage 0. P 0.05 versus fibrosis stage 1. P 0.05 versus fibrosis stage 2. Abbreviations: BMI, body mass index; AST, alanine aminotransferase; ALT, aspartate aminotransferase; INR, international normalized ratio; -GT, gamma-glutamyl transpeptidase; HOMA, homeostasis model assessment; ISI, insulin sensitivity index; TE, transient elastography; kpa, kilopascal; n pts, number of patients per class U/L with extremes of U/L at the time of liver biopsy). Mean interval between liver biopsy and TE measurement was months. Mean success rate and the mean IQR of TE measurements were 88.8% and 16%, respectively. Figure 1 shows mean TE values for each stage of fibrosis. Accuracy of TE for Prediction of Any Fibrosis (>1). The accuracy of TE for the diagnosis of any fibrosis is given in Fig. 2A. The data-driven best cutoff for the diagnosis of any fibrosis was 5.1 kpa (Table 3). Multilevel LRs (Table 4) show that only values lower than 5 kpa suggested the absence of any fibrosis. Values between 5 and 7 kpa suggested the presence of fibrosis, but only values higher or equal to 7 kpa were highly indicative of fibrosis. Accuracy of TE for Prediction of Significant Fibrosis (>2). The accuracy of TE for the diagnosis of significant fibrosis is illustrated in Fig. 2B. The datadriven best cutoff for the diagnosis of significant fibrosis was 7.4 kpa (Table 3). Multilevel LRs (Table 4) show that TE values lower than 7 kpa suggested the absence of significant fibrosis, whereas values between 7 and 9 kpa were indeterminate for the diagnosis of significant fibrosis. Accuracy of TE for Prediction of Advanced Fibrosis (>3). The accuracy of TE for the diagnosis of advanced fibrosis is shown in Fig. 2C. The data-driven best cutoff for the diagnosis of advanced fibrosis was 10.2 kpa (Table 3). Multilevel LRs (Table 4) show that values higher or equal to 9 kpa were indicative of advanced fibrosis, whereas values lower than 9 kpa suggested the absence of advanced fibrosis. Fig. 1. Box plots of TE values in relation to the degree of fibrosis. Liver stiffness values are reported on the y axis in kpa, and, on the x axis, the degree of fibrosis according to Brunt scoring system. Top and bottom of boxes are first and second quartiles, respectively. Length of box represents the IQR within which 50% of the values are located. The line through the middle of each box represents the median. Error bars show minimum and maximum values.abbreviations: kpa, kilopascal; TE, transient elastography.
5 446 NOBILI ET AL. HEPATOLOGY, August 2008 Fig. 2. Receiver operating characteristic (ROC) curve showing the prediction of (A) any fibrosis ( 1), (B) significant fibrosis ( 2), and (C) advanced fibrosis ( 3) with TE in the whole patient population. The ideal area under the curve is The straight line represents that based on chance alone (area under the curve, 0.50). The areas under the ROC curves are as follows: (A) 0.97 (90% CI, ); (B) 0.99 (90% CI, ); and (C) 1 (90% CI, ). The best cutoff values for each curve are indicated with black dots (see Table 3). Abbreviation: TE, transient elastography. Multivariable analysis showed that no clinical-analytical variable could add to the discriminative value of TE for any stage of fibrosis investigated. Interobserver Agreement in TE Determination. Reproducibility of TE measurements could be estimated in 31 patients (10, 14, 2, and 5 subjects for Brunt s stages 0, 1, 2, and 3-4, respectively) that were explored by both operators (F.V. and U.A.). Reproducibility was excellent, as indicated by an intraclass correlation coefficient for absolute agreement of 0.96 (90% confidence interval [CI] ). No significant differences in clinical and biochemical variables were observed when compared to subjects investigated by a single operator. In particular, the mean BMI was not statistically different in the two groups (25 6 and 26 4). Complications Related to the Procedures. No major complications were associated with percutaneous liver biopsy. A total of 15 subjects (30%) experienced self-limiting abdominal and/or right shoulder pain, and six subjects (12%) required a single dose of intravenous analgesic drug (Tramadol). There were no complications associated with TE measurements. Discussion Pediatric obesity is an increasingly common problem in Western countries. While the majority of obese children with liver disease will have simple NAFLD, identification of those at risk of progressive liver fibrosis is important to determine prognosis and to offer available interventions. Although histopathological analysis of liver tissue represents the gold standard for NASH and fibrosis stage assessment, its use in a pediatric setting is less tolerable than in adults. Along these lines, it would be ideal to develop a noninvasive methodology to discriminate, among obese/overweight pediatric subjects with NAFLD, those who already have fibrosis. Among other noninvasive methodologies, TE was recently proposed to investigate the degree of fibrotic evolution of CLD in a pediatric setting. De Lédinghen et al. 13 provided evidence on the usefulness of TE for the prediction of fibrosis in a cohort of 116 patients with miscellaneous pediatric CLD. However, in that study, liver biopsy was available only in 33 subjects and it was not stated whether patients with NAFLD were included. Accord- Table 3. Diagnostic Accuracy of TE. Fibrosis Cutoff (kpa) S (%) Sp (%) PPV (%) NPV (%) LR LR (93 100) 91 (77 100) 97 (93 100) 91 (77 100) ( ) 0.02 ( ) (82 100) 92 (82 97) 80 (59 92) 100 (93 100) ( ) 0.00 (0 0.20) (65 100) 100 (94 100) 100 (65 100) 100 (94 100) Inf. (15.95 Inf.) 0.00 (0 0.35) Diagnostic accuracy of TE in predicting any fibrosis ( 1), significant fibrosis ( 2), and advanced fibrosis ( 3). Performance of the selected best TE cutoff values are indicated. Abbreviations: S, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; LR, positive likelihood ratio; LR, negative likelihood ratio; TE, transient elastography; kpa, kilopascal; Inf., infinity.
6 HEPATOLOGY, Vol. 48, No. 2, 2008 NOBILI ET AL. 447 Table 4. Multilevel LRs for the Prediction of Fibrosis Stages LRs for Different Fibrosis Stages TE (kpa) Any Significant Advanced ( ) 0 ( ) 0 ( ) 5 and ( ) 0 ( ) 0 ( ) 7 and 9 Inf. ( Inf.) ( ) 0 ( ) 9 Inf. ( Inf.) Inf. ( Inf.) ( ) LRs above 10 and below 0.1 provide strong evidence to rule in or rule out diagnoses, respectively. Fibrosis stages were classified as: any fibrosis, 1; significant fibrosis, 2; advanced fibrosis, and 3. Abbreviations: LR, likelihood ratio; TE, transient elastography; kpa, kilopascal; Inf., infinity. ingly, the present study was specifically designed to provide information on the clinical utility of this methodology in a pediatric population affected by NASH. It should be noted that the population analyzed in our study is representative of a highly selected cohort typical of a specialized tertiary care referral center, and that the conclusions of the study cannot be applied to pediatric populations seen in primary care settings. In addition, the relatively small number of subjects recruited, reflecting the difficulty of obtaining liver biopsy samples and an accurate clinical framing even in a specialized pediatric referral center, does not allow us to reach definitive conclusions. The results reported herein clearly indicate that while TE mean values are significantly different among closest Brunt s stages of fibrosis, an overlap is observed among patients with lower degrees of liver fibrosis (stages 0 and 1 and stages 1 and 2). However, TE appears to reliably predict the presence of any fibrosis, significant fibrosis, and advanced fibrosis. To explore the whole spectrum of TE measurements, the analysis of multilevel LRs was introduced to estimate the likelihood of having a target degree of fibrosis according to TE measurements. Indeed, the use of multilevel LRs analysis is a more informative and correct approach since it explores the whole spectrum of TE measurements. 24,25 As a result, TE values of 5, 7, and 9 kpa suggest the presence of any fibrosis, significant fibrosis, and advanced fibrosis, respectively. TE values between 5 and 7 kpa predict fibrosis stage 1, but with some degree of uncertainty. TE values between 7 and 9 kpa predict fibrosis stages 1 or 2, but cannot discriminate between these two stages. TE values of at least 9 kpa are associated with the presence of advanced fibrosis. Of note, no clinical or analytical variable considered in the present study contributed to the predictive value of TE. Data obtained in a similar cohort of NAFLD pediatric subjects 29 indicate than in spite of advice on lifestyle modification no effect on fibrosis stage was observed in follow-up biopsies after a period of 24 months. Therefore, the time between biopsy and TE measurements ( 6 months) should not have had any impact on the fibrosis stage. On the contrary, the temporal gap between liver biopsy and TE determination did not allow us to reliably assess the possible interfering role of steatosis, necroinflammatory activity, and hepatocyte ballooning in our cohort of patients. Nevertheless, the degree and/or fluctuations of necroinflammatory activity during the course of NASH are generally moderate. 30 Indeed, aminotransferases were only moderately increased and lower degrees of inflammation at histology were observed in our study population. Therefore, a relevant interfering role of inflammation in this scenario was not expected. Concerning liver steatosis the absence of an interfering role on TE measurements has been already defined in adults affected by NASH 12 or chronic viral hepatitis. 21,31 Our findings on TE reproducibility are consistent with those of Fraquelli et al. 32 in an adult population of CLD patients. In our cohort, the high level of interobserver agreement was maintained in spite of high BMI values, probably because of the use of ultrasound for guidance. From a technical point of view it is of note that de Lédinghen et al. 13 used a specific pediatric probe, while the standard probe, indicated for adults, was successfully employed in our patients cohort as demonstrated by the IQR of TE measurements. In summary, TE is an accurate and reproducible methodology to identify, in children and adolescents affected by NASH, those without any degree of fibrosis or significant fibrosis, or with advanced fibrosis. In subjects in whom LRs are not optimal to provide a reliable indication of the disease stage, liver biopsy should be considered when clinically indicated. However, TE is unlikely to show a similarly good performance for screening purposes in an unselected overweight/obese pediatric population. Therefore, the results of the study offer a promising background for further validating TE for the stratification of NAFLD subjects in childhood, including larger primary care and nonselected obese children and adolescents, before TE can be recommended as a screening test alone or in combination with other noninvasive methodologies.
7 448 NOBILI ET AL. HEPATOLOGY, August 2008 Acknowledgment: We are indebted to all the patients and their legal guardians who participated in this study. References 1. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, JAMA 2004;291: Tominaga K, Kurata JH, Chen YK, Fujimoto E, Miyagawa S, Abe I, et al. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig Dis Sci 1995;40: Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics 2006;118: Chan DF, Li AM, Chu WC, Chan MH, Wong EM, Liu EK, et al. Hepatic steatosis in obese Chinese children. Int J Obes Relat Metab Disord 2004; 28: Adams LA, Lymp JF, St. Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of non-alcoholic fatty liver disease a populationbased cohort study. Gastroenterology 2005;129: Ekstedt M, Franzen LE, Mathiensen UI, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. HEPATOLOGY 2006;44: Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, et al. Expanding the natural history of non-alcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002;123: Kinugasa A, Tsunamoto K, Furukawa N, Sawada T, Kusunoki T, Shimada N. Fatty liver and its fibrous changes found in simple obesity of children. J Pediatr Gatroenterol Nutr 1984;3: Jankowska I, Socha P, Pawlowska J, Teisseyre M, Gliwicz D, Czubkowski P, et al. Recurrence of non-alcoholic steatohepatitis after liver transplantation in a 13-yr-old boy. Pediatr Transplant 2007;11: Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of non-alcoholic fatty liver disease: a longitudinally study of 103 patients with sequential liver biopsies. J Hepatol 2005;42: Pinzani M, Vizzutti F, Arena U, Marra F. Technology Insight: non-invasive assessment of liver fibrosis by biochemical scores and elastography. Nat Clin Pract Gastroenterol Hepatol 2008;5: Yoneda M, Yoneda M, Mawatari H, Fujita K, Endo H, Iida H, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). Dig Liver Dis 2008;40: de Lédinghen V, Le Bail B, Rebouissoux L, Fournier C, Foucher J, Miette V, et al. Liver stiffness measurement in children using fibroscan: feasibility study and comparison with fibrotest, aspartate transaminase to platelets ratio index, and liver biopsy. J Pediatr Gastroenterol Nutr 2007;45: Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostatic model assessment: insulin resistance and beta-cell function from fasting glucose and insulin concentration in man. Diabetologia 1985;28: Matsuda M, De Fronzo R. Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care 1999;22: Sharma P, MacDonald GB, Banaji M. The risk of bleeding after percutaneous liver biopsy: relation to platelet count. J Clin Gastroenterol 1982;4: Cassiman D, Jaeken J. NASH may be trash. Gut 2008;57: Nobili V, Marcellini M, Devito R, Ciampalini P, Piemonte F, Comparcola D, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. HEPATOLOGY 2006;44: Nobili V, Comparcola D, Sartorelli MR, Natali G, Monti L, Falappa P, et al. Blind and ultrasound-guided percutaneous liver biopsy in children. Pediatr Radiol 2003;33: Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999;94: Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, et al. Non-invasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. HEPATOLOGY 2005;41: Castéra L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al. Prospective comparison of transient elastometry, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128: Bewick V, Cheek L, Ball J. Statistics review 9: one-way analysis of variance. Crit Care 2004;8: Guyatt G, Sackett DL, Haynes B. Evaluating diagnostic test. In: Haynes B, Sackett DL, Guyatt G, Tulliez M, eds. Clinical Epidemiology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2006: Deeks JJ, Altman DG. Diagnostic tests 4: likelihood ratios. BMJ 2004; 329: Sterne JA, Davey SG. Sifting the evidence-what s wrong with significance tests? BMJ 2001;322: Gart JJ, Nam J. Approximate interval estimation of the ratio of binomial parameters: a review and correction for skewness. Biometrics 1988;44: Bartko JJ. Measures of agreement: a single procedure. Stat Med 1994;13: Nobili V, Manco M, Devito R, Di Ciommo V, Comparcola D, Sartorelli MR, et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. HEPATOL- OGY 2008; doi: /hep Angulo P. Nonalcoholic fatty liver disease, N Engl J Med 2002;346: Sandrin L, Fourquet B, Haquenoph JM, Yon S, Fournier C, Mal F, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003;29: Fraquelli M, Rigamonti C, Casazza G, Conte D, Donato MF, Ronchi G, et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 2007;56:
CLINICAL LIVER, PANCREAS, AND BILIARY TRACT
GASTROENTEROLOGY 2009;136:160 167 CLINICAL LIVER, BILIARY TRACT Performance of ELF Serum Markers in Predicting Fibrosis Stage in Pediatric Non-Alcoholic Fatty Liver Disease VALERIO NOBILI,* JULIE PARKES,
More informationTransient elastography in chronic viral liver diseases
4 th AISF POST-MEETING COURSE Roma, 26 Febbraio 2011 Transient elastography in chronic viral liver diseases CRISTINA RIGAMONTI, M.D., Ph.D. Transient elastography (TE): a rapid, non-invasive technique
More informationThe role of non-invasivemethods in evaluating liver fibrosis of patients with non-alcoholic steatohepatitis
The role of non-invasivemethods in evaluating liver fibrosis of patients with non-alcoholic steatohepatitis Objectives: Liver biopsy is the gold standard for diagnosing the extent of fibrosis in NAFLD/NASH;
More informationThe role of ARFI and APRI in diagnosis of liver fibrosis on patients with common chronic liver diseases
RESEARCH ARTICLE The role of ARFI and APRI in diagnosis of liver fibrosis on patients with common chronic liver diseases Objective: This study aimed to investigate the value of liver fibrosis assessment
More informationCDHNF & NASPGHAN A Partnership for Research and Education for Children s Digestive and Nutritional Health
CDHNF & NASPGHAN A Partnership for Research and Education for Children s Digestive and Nutritional Health Obesity and NAFLD Definitions: Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver
More informationTransient elastography in chronic liver diseases of other etiologies
4 Post Meeting A.I.S.F. Unmet Clinical Needs in Hepatology: New and upcoming diagnostic tools" Transient elastography in chronic liver diseases of other etiologies Dr. Vincenza Calvaruso Gastroenterologia
More informationJPGN Journal of Pediatric Gastroenterology and Nutrition Publish Ahead of Print
JPGN Journal of Pediatric Gastroenterology and Nutrition Publish Ahead of Print DOI : 10.1097/MPG.0000000000000489 Points to be considered when Applying FibroScan S Probe for Children with Biliary Atresia
More informationTransient elastography (TE) (FibroScan; Echosens, Pitfalls of Liver Stiffness Measurement: A 5-Year Prospective Study of 13,369 Examinations
Pitfalls of Liver Stiffness Measurement: A 5-Year Prospective Study of 13,369 Examinations Laurent Castéra, 1,2 Juliette Foucher, 1,2 Pierre-Henri Bernard, 2 Françoise Carvalho, 1 Daniele Allaix, 1 Wassil
More informationChallenges in the Diagnosis of Steatohepatitis
The Bugaboos of Fatty Liver Disease: Ballooning and Fibrosis Hans Popper Hepatopathology Society Companion Meeting San Antonio, Tx March, 2017 David Kleiner, M.D., Ph.D. NCI/Laboratory of Pathology Challenges
More informationHyaluronic acid predicts hepatic fibrosis in children with nonalcoholic fatty liver disease
ORIGINAL ARTICLES Hyaluronic acid predicts hepatic fibrosis in children with nonalcoholic fatty liver disease VALERIO NOBILI, ANNA ALISI, GIULIANO TORRE, RITA DE VITO, ANDREA PIETROBATTISTA, GIUSEPPE MORINO,
More informationIn Search of New Biomarkers for Nonalcoholic Fatty Liver Disease
REVIEW In Search of New Biomarkers for Nonalcoholic Fatty Liver Disease Ting-Ting Chan, M.R.C.P., and Vincent Wai-Sun Wong, M.D. Nonalcoholic fatty liver disease (NAFLD) affects 15% to 40% of the general
More informationImproved Hepatic Fibrosis Grading Using Point Shear Wave Elastography and Machine Learning
Improved Hepatic Fibrosis Grading Using Point Shear Wave Elastography and Machine Learning Presenter: Hersh Sagreiya 1, M.D. Authors: Alireza Akhbardeh 1, Ph.D., Isabelle Durot 1, M.D., Carlo Filice 2,
More informationUpdate on Non-Alcoholic Fatty Liver Disease. Timothy R. Morgan, MD Chief, Hepatology, VA Long Beach Professor of Medicine, UCI
Update on Non-Alcoholic Fatty Liver Disease Timothy R. Morgan, MD Chief, Hepatology, VA Long Beach Professor of Medicine, UCI February 3, 2018 Disclosure Clinical trials: Genfit Speaker s Bureau: none
More informationNon-Invasive Testing for Liver Fibrosis
NORTHWEST AIDS EDUCATION AND TRAINING CENTER Non-Invasive Testing for Liver Fibrosis John Scott, MD, MSc Associate Professor, University of Washington Associate Clinic Director, Hep/Liver Clinic, Harborview
More informationHEP DART 2017, Kona, Hawaii
HEP DART 2017, Kona, Hawaii Rong Yu 1, Ke Xu 1, Jing Li 1, Tong Sun 1, Shengjiang Zhang 2, Jinhua Shao 2, Jin Sun 2, Qiong He 3, Jianwen Luo 3, Cheng Wang 4, Yudong Wang 4, Jing Chen 4, Vanessa Wu 4, George
More informationEvaluation of liver and spleen stiffness using a ultrasound guided method: Accuracy of ARFI(R) measurements in liver disease patients
Evaluation of liver and spleen stiffness using a ultrasound guided method: Accuracy of ARFI(R) measurements in liver disease patients Poster No.: C-3242 Congress: ECR 2010 Type: Topic: Authors: Keywords:
More informationAssessment of Liver Stiffness by Transient Elastography in Diabetics with Fatty Liver A Single Center Cross Sectional observational Study
IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-issn: 2279-0853, p-issn: 2279-0861.Volume 16, Issue 6 Ver. IV (June. 2017), PP 49-53 www.iosrjournals.org Assessment of Liver Stiffness by Transient
More informationNonalcoholic fatty liver disease (NAFLD) is rapidly
Lifestyle Intervention and Antioxidant Therapy in Children with Nonalcoholic Fatty Liver Disease: A Randomized, Controlled Trial Valerio Nobili, 1 Melania Manco, 1 Rita Devito, 2 Vincenzo Di Ciommo, 3
More informationA Combination of the Pediatric NAFLD Fibrosis Index and Enhanced Liver Fibrosis Test Identifies Children With Fibrosis
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2011;9:150 155 A Combination of the Pediatric NAFLD Fibrosis Index and Enhanced Liver Fibrosis Test Identifies Children With Fibrosis NAIM ALKHOURI,* CHRISTINE
More informationEvaluation of liver and spleen stiffness using a ultrasound guided method: Accuracy of ARFI(R) measurements in liver disease patients
Evaluation of liver and spleen stiffness using a ultrasound guided method: Accuracy of ARFI(R) measurements in liver disease patients Poster No.: C-3242 Congress: ECR 2010 Type: Topic: Authors: Keywords:
More informationAlthough nonalcoholic fatty liver disease (NAFLD) Decreased Survival of Subjects with Elevated Liver Function Tests During a 28-Year Follow-Up
Decreased Survival of Subjects with Elevated Liver Function Tests During a 28-Year Follow-Up Cecilia Söderberg, 1 Per Stål, 2,3 Johan Askling, 1 Hans Glaumann, 3 Greger Lindberg, 3 Joel Marmur, 3 and Rolf
More informationNON-ALCOHOLIC FATTY LIVER DISEASE:
NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER Archita P. Desai, MD Assistant Professor of Medicine University of Arizona 25 th Annual Southwestern Conference on Medicine Outline Pathophysiology
More informationORIGINAL ARTICLE. Both these authors contributed equally to this study. Liver International ISSN
Liver International ISSN 1478-3223 ORIGINAL ARTICLE The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients
More informationPrevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus patients in a tertiary care hospital of Bihar
Original Research Article Prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus patients in a tertiary care hospital of Bihar Naresh Kumar 1, Jyoti Kumar Dinkar 2*, Chandrakishore
More informationNoninvasive Diagnosis and Staging of Liver Disease. Naveen Gara, MD
Noninvasive Diagnosis and Staging of Liver Disease Naveen Gara, MD Outline Brief overview of the anatomy of liver Liver-related lab tests Chronic liver disease progression Estimation of liver fibrosis
More informationReal-time elastography as a noninvasive assessment of liver fibrosis in chronic hepatitis C Egyptian patients: a prospective study
ORIGINAL ARTICLE Annals of Gastroenterology (2016) 29, 1-5 Real-time elastography as a noninvasive assessment of liver fibrosis in chronic hepatitis C Egyptian patients: a prospective study Lamiaa Mobarak
More informationNASH : Diagnosis and investigation. VII Workshop international, Curitiba, Brazil 29/08/2014
NASH : Diagnosis and investigation VII Workshop international, Curitiba, Brazil 29/08/2014 Vlad Ratziu, Université Pierre et Marie Curie, Hôpital Pitié Salpêtrière, Paris, France Usual diagnostic circumstances
More informationArtemisa. Non-invasive assessment of fibrosis in non-alcoholic fatty liver disease (NAFLD) medigraphic.
medigraphic Artemisa en línea F Vizzutti Annals et al. of Hepatology Non-invasive 2009; assessment 8(2): April-June: of fibrosis in 89-94 NAFLD 89 Concise Review Annals of Hepatology Non-invasive assessment
More informationNON INVASIVE ASSESSMENT OF LIVER FIBROSIS : FIBROSCAN
NON INVASIVE ASSESSMENT OF LIVER FIBROSIS : FIBROSCAN M. Beaugrand Service d Hépatologied Hopital J. Verdier BONDY 93143 et Université Paris XIII MAINZ 21.09.2008 ASSESSMENT OF FIBROSIS : WHY? Management
More informationTransient elastography the state of the art
Transient elastography the state of the art Laurent CASTERA, MD PhD Department of Hepatology, Hôpital Beaujon, Clichy Université Paris-7, France White Nights of Hepatology, St Petersburg, Russia, june
More informationPreliminary clinical experience with Shear Wave Dispersion Imaging for liver viscosity
Preliminary clinical experience with Shear Wave Dispersion Imaging for liver viscosity Dr. Katsutoshi Sugimoto Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan Introduction
More informationNational Horizon Scanning Centre. Enhanced Liver Fibrosis Test (ELF) for evaluating liver fibrosis. June 2008
Enhanced Liver Fibrosis Test (ELF) for evaluating liver fibrosis June 2008 This technology summary is based on information available at the time of research and a limited literature search. It is not intended
More informationNonalcoholic Fatty Liver Disease: Definitions, Risk Factors, and Workup
REVIEW REVIEW Nonalcoholic Fatty Liver Disease: Definitions, Risk Factors, and Workup Puneet Puri, M.B.B.S., M.D. and Arun J. Sanyal, M.B.B.S., M.D. Nonalcoholic fatty liver disease (NAFLD) is defined
More informationOriginal papers Med Ultrason 2013, Vol. 15, no. 2, Ioan Sporea, Iulia Raţiu, Simona Bota, Roxana Şirli, Ana Jurchiş
Original papers Med Ultrason 2013, Vol. 15, no. 2, 111-115 DOI: 10.11152/mu.2013.2066.152.is1ir2 Are different cut-off values of liver stiffness assessed by Transient Elastography according to the etiology
More informationRelationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease
Gut and Liver, Vol. 10, No. 2, March 2016, pp. 295-302 ORiginal Article Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic
More informationNon-Invasive Assessment of Liver Fibrosis. Patricia Slev, PhD University of Utah Department of Pathology
Non-Invasive Assessment of Liver Fibrosis Patricia Slev, PhD University of Utah Department of Pathology Disclosure Patricia Slev has no relevant financial relationships to disclose. 2 Chronic Liver Disease
More informationLIVER, PANCREAS, AND BILIARY TRACT
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2013;11:295 302 LIVER, PANCREAS, AND BILIARY TRACT Association Between Anthropometric Parameters and Measurements of Liver Stiffness by Transient Elastography GRACE
More informationNAFLD and NASH: The Not-So-New Kids on the Block
NAFLD and NASH: The Not-So-New Kids on the Block Mary E. Rinella, MD Associate Professor of Medicine Feinberg School of Medicine Northwestern University Chicago, Illinois This program is supported by an
More informationPROPOSTA DI UN NUOVO ALGORIMO PER LA DIAGNOSI ECOGRAFICA DELLE MALATTIE CRONICHE DEL FEGATO
PROPOSTA DI UN NUOVO ALGORIMO PER LA DIAGNOSI ECOGRAFICA DELLE MALATTIE CRONICHE DEL FEGATO A. Giorgio Direttore del servizio di Ecografia Interventistica Istituto Clinico S.Rita -IRCCS -Atripalda (Avellino)
More informationNON-ALCOHOLIC STEATOHEPATITIS AND NON-ALCOHOLIC FATTY LIVER DISEASES
NON-ALCOHOLIC STEATOHEPATITIS AND NON-ALCOHOLIC FATTY LIVER DISEASES Preface Zobair M. Younossi xiii Epidemiology and Natural History of NAFLD and NASH 1 Janus P. Ong and Zobair M. Younossi Understanding
More informationNonalcoholic Fatty Liver Disease in Children: Typical and Atypical
Nonalcoholic Fatty Liver Disease in Children: Typical and Atypical Disclosure Naim Alkhouri, MD discloses the following relationships with commercial companies: Membership in the Speakers Bureau for Alexion
More information*APHP: Hôpital Beaujon Professor P Bedossa, Dr F Degos, Professor P Marcellin, Professor
APPENDIX 1 LIST OF COINVESTIGATORS *APHP: Hôpital Beaujon Professor P Bedossa, Dr F Degos, Professor P Marcellin, Professor M Vidaud; Hôpital Cochin-Necker: Professor S Pol, Professor Ph Sogni, Professor
More informationLIVER, PANCREAS, AND BILIARY TRACT
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2012;10:1028 1033 LIVER, PANCREAS, AND BILIARY TRACT Prevalence and Indicators of Portal Hypertension in Patients With Nonalcoholic Fatty Liver Disease FLAVIA D.
More informationALT and aspartate aminotransferase (AST) levels were measured using the α-ketoglutarate reaction (Roche,
Supplemental Methods Analytical determinations ALT and aspartate aminotransferase (AST) levels were measured using the α-ketoglutarate reaction (Roche, Basel, Switzerland). Glucose, triglyceride, total
More informationInvasive. Sampling error. Interobserver variability. Nondynamic evaluation of
How to assess liver fibrosis Serum markers or FibroScan vs. liver biopsy? Laurent CASTERA & Pierre BEDOSSA Hôpital Beaujon, AP-HP, Clichy Université Paris-VII France 4 th Paris Hepatitis Conference, Paris,
More informationThe classical metabolic work-up, approved by the Ethics Committee of the Antwerp
SUPPLEMENTARY MATERIALS METHODS Metabolic work-up The classical metabolic work-up, approved by the Ethics Committee of the Antwerp University Hospital and requiring written informed consent, included a
More informationNonalcoholic fatty liver disease (NAFLD) is the most common
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6:1249 1254 Cytokeratin 18 Fragment Levels as a Noninvasive Biomarker for Nonalcoholic Steatohepatitis in Bariatric Surgery Patients DIMA L. DIAB,* LISA YERIAN,
More informationResearch Elastography: Liver
Research Elastography: Liver Giovanna Ferraioli EFSUMB Ultrasound Learning Center Ultrasound Unit - Infectious Diseases Dept. Fondazione IRCCS Policlinico S. Matteo Medical School University of Pavia,
More informationLiver Pathology in the 0bese
Liver Pathology in the 0bese Rob Goldin Centre for Pathology, Imperial College r.goldin@imperial.ac.uk Ludwig et al. Non-alcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.
More informationNoninvasive Assessment of Liver Fibrosis in Egyptian Children with Chronic Liver Diseases.
Curr Pediatr Res 2016; 20 (1&2): 57-63 ISSN 0971-9032 www.currentpediatrics.com Noninvasive Assessment of Liver Fibrosis in Egyptian Children with Chronic Liver Diseases. Tawhida Abdel Ghaffar 1, Azza
More informationMedical Review Approaches to the Diagnosis of Liver Fibrosis
Medical Review Approaches to the Diagnosis of Liver Fibrosis Hiroko Iijima Department of Hepatobiliary and Pancreatic Disease Ultrasound Imaging Center, Hyogo College of Medicine Hiroko Iijima Department
More informationSimple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease
1 Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK 2 Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne,
More information1264 BOURSIER ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 11 Table 1. Study Design: Assignment of Judges According to Patient and Obser
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6:1263 1269 Reproducibility of Liver Stiffness Measurement by Ultrasonographic Elastometry JÉRÔME BOURSIER,*, ANSELME KONATÉ,*, GABRIELLA GOREA,* STÉPHANE
More informationNovel multiparametric magnetic resonance elastography (MRE) protocol accurately predicts NAS score for NASH diagnosis
Novel multiparametric magnetic resonance elastography (MRE) protocol accurately predicts NAS score for NASH diagnosis Alina M. Allen, Meng Yin, Sudhakar K. Venkatesh, Taofic Mounajjed, Todd A. Kellogg,
More informationSMJ Singapore Medical Journal
SMJ Singapore Medical Journal ONLINE FIRST PUBLICATION Online first papers have undergone full scientific review and copyediting, but have not been typeset or proofread. To cite this article, use the DOIs
More informationtage Percent Total & over Total & over Men Women Men Women
Paul Angulo, MD, FACG, AGAF Professor of Medicine, Section Chief of Hepatology Division i i of Digestive i Diseases and Nutrition i University of Kentucky Medical Center Lexington, KY Paul Angulo, MD University
More informationEarly life determinants of Non-Alcoholic Fatty Liver Disease and NASH DR JULIANA MUIVA-GITOBU KENYA PAEDIATRIC ASSOCIATION CONFERENCE APRIL 2016.
Early life determinants of Non-Alcoholic Fatty Liver Disease and NASH DR JULIANA MUIVA-GITOBU KENYA PAEDIATRIC ASSOCIATION CONFERENCE APRIL 2016. Outline Definition NAFLD and NASH Magnitude of the problem
More informationPEDIATRIC FOIE GRAS: NON-ALCOHOLIC FATTY LIVER DISEASE
PEDIATRIC FOIE GRAS: NON-ALCOHOLIC FATTY LIVER DISEASE Updates on New insights into NAFLD and NASH pathophysiology New AASLD/AGA/ACG guidelines for NAFLD and NASH, as pertains to pediatrics Evidence-based
More informationNAFLD: evidence-based management. Curso de residentes AEEH Salvador Augustin, MD Liver Unit Vall d Hebron Hospital Barcelona, Spain
NAFLD: evidence-based management Curso de residentes AEEH 2017 Salvador Augustin, MD Liver Unit Vall d Hebron Hospital Barcelona, Spain Clinical case - 55 yo female - Sent for incidental steatosis at abdominal
More informationLaboratory analysis of the obese child recommendations and discussion. MacKenzi Hillard May 4, 2011
Laboratory analysis of the obese child recommendations and discussion MacKenzi Hillard May 4, 2011 aka: What to do with Fasting Labs The Obesity Epidemic The prevalence of obesity in adolescents has tripled
More informationAspartate aminotransferase-to-platelet ratio index in children with cholestatic liver diseases to assess liver fibrosis
The Turkish Journal of Pediatrics 2015; 57: 492-497 Original Aspartate aminotransferase-to-platelet ratio index in children with cholestatic liver diseases to assess liver fibrosis Aysel Ünlüsoy-Aksu 1,
More informationLiver stiffness predicts liver related events and mortality in HIV/HCV coinfected patients
Liver stiffness predicts liver related events and mortality in HIV/HCV coinfected patients José Vicente Fernández-Montero, Pablo Barreiro, Eugenia Vispo, Pablo Labarga, Francisco Blanco, Fernanda Rick,
More informationAAIM: GI Workshop Follow Up to Case Studies. Non-alcoholic Fatty Liver Disease Ulcerative Colitis Crohn s Disease
AAIM: GI Workshop Follow Up to Case Studies Non-alcoholic Fatty Liver Disease Ulcerative Colitis Crohn s Disease Daniel Zimmerman, MD VP and Medical Director, RGA Global October 2015 Non-alcoholic Fatty
More informationNoninvasive Techniques for the Evaluation and Monitoring of Patients With Chronic Liver Disease
Noninvasive Techniques for the Evaluation and Monitoring of Patients With Chronic Liver Disease Policy Number: 2.04.41 Last Review: 2/2019 Origination: 2/2017 Next Review: 2/2020 Policy Blue Cross and
More informationCIRROSI E IPERTENSIONE PORTALE NELLA DONNA
Cagliari, 16 settembre 2017 CIRROSI E IPERTENSIONE PORTALE NELLA DONNA Vincenza Calvaruso, MD, PhD Ricercatore di Gastroenterologia Gastroenterologia & Epatologia, Di.Bi.M.I.S. Università degli Studi di
More informationNON INVASIVE EVALUATION OF DISEASE PROGRESSION IN CHRONIC LIVER DISEASES
Best of EASL -, Ethiopia 29 Sep to 01 Oct, 2016 Inaugural meeting of the Sub Saharan GI-Hepatology Working Group Incorporating Best of AGA and Best of EASL NON INVASIVE EVALUATION OF DISEASE PROGRESSION
More informationTitle: The Baveno VI criteria for predicting esophageal varices: validation in real life practice
Title: The Baveno VI criteria for predicting esophageal varices: validation in real life practice Authors: Mafalda Sousa, Sónia Fernandes, Luísa Proença, Ana Paula Silva, Sónia Leite, Joana Silva, Ana
More informationBackground of the FIB-4 Index in Japanese Non-Alcoholic Fatty Liver Disease
ORIGINAL ARTICLE Background of the FIB-4 Index in Japanese Non-Alcoholic Fatty Liver Disease Takashi Wada and Mikio Zeniya Abstract Objective We investigated the distribution and characteristics of the
More informationMP Noninvasive Techniques for the Evaluation and Monitoring of Patients With Chronic Liver Disease
Medical Policy BCBSA Ref. Policy: 2.04.41 Last Review: 11/15/2018 Effective Date: 11/15/2018 Section: Medicine Related Policies 9.01.502 Experimental / Investigational Services DISCLAIMER Our medical policies
More informationDIAGNOSIS OF CIRRHOSIS BY TRANSIENT ELASTOGRAPHY (FIBROSCAN ): A PROSPECTIVE STUDY.
Gut Online First, published on July 14, 2005 as 10.1136/gut.2005.069153 DIAGNOSIS OF CIRRHOSIS BY TRANSIENT ELASTOGRAPHY (FIBROSCAN ): A PROSPECTIVE STUDY. Juliette Foucher (1), Elise Chanteloup (1), Julien
More informationThe effect of aerobic exercise on serum level of liver enzymes and liver echogenicity in patients with non-alcoholic fatty liver disease
Gastroenterology and Hepatology From Bed to Bench. 2013 RIGLD, Research Institute for Gastroenterology and Liver Diseases ORIGINAL ARTICLE The effect of aerobic exercise on serum level of liver enzymes
More informationNONINVASIVE TECHNIQUES FOR EVALUATION AND MONITORING OF CHRONIC LIVER DISEASE
LIVER DISEASE Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs are
More informationWhat to do about the high ALT picked up at the annual review. Dr Michael Yee Consultant in Diabetes and Endocrinology
What to do about the high ALT picked up at the annual review Dr Michael Yee Consultant in Diabetes and Endocrinology Mrs DC HPC PMH Type 2 Diabetes (decades) Regular retinal screening No foot complications/neuropathy
More informationOriginal Article. Significance of Hepatic Steatosis in Chronic Hepatitis B Infection INTRODUCTION
Original Article Bhanthumkomol P, et al. THAI J GASTROENTEROL 2013 Vol. 14 No. 1 Jan. - Apr. 2013 29 Bhanthumkomol P 1 Charatcharoenwitthaya P 1 Pongpaiboon A 2 ABSTRACT Background: Significance of liver
More informationABNORMAL LIVER FUNCTION TESTS. Dr Uthayanan Chelvaratnam Hepatology Consultant North Bristol NHS Trust
ABNORMAL LIVER FUNCTION TESTS Dr Uthayanan Chelvaratnam Hepatology Consultant North Bristol NHS Trust INTRODUCTION Liver function tests Cases Non invasive fibrosis measurement Questions UK MORTALITY RATE
More informationScreening for Portal Hypertension in Cirrhosis
Screening for Portal Hypertension in Cirrhosis MASSIMO PINZANI, MD, PhD, FRCP Sheila Sherlock Chair of Hepatology UCL Institute for Liver and Digestive Health Royal Free Hospital, London, UK m.pinzani@ucl.ac.uk
More informationHepatology for the Nonhepatologist
Hepatology for the Nonhepatologist Kenneth E. Sherman, MD, PhD Gould Professor of Medicine Director, Division of Digestive Diseases University of Cincinnati College of Medicine Cincinnati, Ohio Learning
More informationFat, ballooning, plasma cells and a +ANA. Yikes! USCAP 2016 Evening Specialty Conference Cynthia Guy
Fat, ballooning, plasma cells and a +ANA. Yikes! USCAP 2016 Evening Specialty Conference Cynthia Guy Goals Share an interesting case Important because it highlights a common problem that we re likely to
More informationNormal ALT for men 30 IU/L 36% US males abnormal. Abnl ALT. Assess alcohol use/meds. Recheck in 6-8 weeks. still pos
Fatty liver disease Its not just for big boys anymore Ken Flora, MD, FAASLD, FACG, AGAF No disclosures Common situation Normal ALT for men 30 IU/L 36% US males abnormal Normal ALT for women 20 IU/L 28%
More informationCONFOUNDING FACTORS affecting the performance of US elastography
Clinical Ultrasound in Hepatology: Training for Hepatologists UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK June 2018 CONFOUNDING FACTORS affecting the performance of US
More informationNoninvasive Techniques for the Evaluation and Monitoring of Patients With Chronic Liver Disease
Noninvasive Techniques for the Evaluation and Monitoring of Patients With Chronic Liver Disease Policy Number: 2.04.41 Last Review: 2/2018 Origination: 2/2017 Next Review: 2/2019 Policy Blue Cross and
More informationMaking the best use of liver biopsy: clinical perspective. Steve Ryder Wolfson Digestive Diseases Centre University of Nottingham
Making the best use of liver biopsy: clinical perspective Steve Ryder Wolfson Digestive Diseases Centre University of Nottingham Trepanning most efficacious for the relief of maladies so diverse and troublesome
More informationEvaluation on liver fibrosis stages using the k-means clustering algorithm
Annals of University of Craiova, Math. Comp. Sci. Ser. Volume 36(2), 2009, Pages 19 24 ISSN: 1223-6934 Evaluation on liver fibrosis stages using the k-means clustering algorithm Marina Gorunescu, Florin
More informationPOWERED BY. Innovation in liver disease management
POWERED BY VCTE Innovation in liver disease management An intelligent solution to aid clinical diagnosis, FibroScan uses state of the art fibrosis and steatosis quantification with the most advanced non-invasive
More informationHepatocytes produce. Proteins Clotting factors Hormones. Bile Flow
R.J.Bailey MD Hepatocytes produce Proteins Clotting factors Hormones Bile Flow Trouble.. for the liver! Trouble for the Liver Liver Gall Bladder Common Alcohol Hep C Fatty Liver Cancer Drugs Viruses Uncommon
More informationClinical Policy Title: Liver elastography
Clinical Policy Title: Liver elastography Clinical Policy Number: CCP.1118 Effective Date: October 1, 2014 Initial Review Date: June 18, 2014 Most Recent Review Date: August 7, 2018 Next Review Date: August
More informationRepeating measurements by transient elastography in nonalcoholic fatty liver disease patients with high liver stiffness
bs_bs_banner doi:10.1111/jgh.14311 HEPATOLOGY Repeating measurements by transient elastography in nonalcoholic fatty liver disease patients with high liver stiffness Jeremy Chak-Lun Chow,* Grace Lai-Hung
More information/ FIB4 Index , simple steatosis. FIB4 Index. FIB4 Index. FIB4 Index FIB4 Index. Sterling FIB4 Index. FIB4 Index AST AST ALT
原 著 29 34-41, 2014 FIB4 Index 1 1 1 1 2 1 1 FIB4 Index FIB4 Index cut off 2.67 2.67 12,059 FIB4 IndexFIB4 Index 2.67 / FIB4 Index AST ALT FIB4 Index 2.67 161 1.3% FIB4 Index 5 FIB4 Index 1.1 5 1.6 FIB4
More information1. Introduction. Correspondence should be addressed to Daniela Cabibi;
Analytical Cellular Pathology Volume 2015, Article ID 431750, 7 pages http://dx.doi.org/10.1155/2015/431750 Research Article Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation
More informationFirst European NAFLD-NASH Summit European Parliament, Brussels, May 31 st NAFLD/NASH : an expanding burden on liver health
First European NAFLD-NASH Summit European Parliament, Brussels, May 31 st 2017 NAFLD/NASH : an expanding burden on liver health Vlad Ratziu, Université Pierre et Marie Curie, Hôpital Pitié Salpêtrière,
More informationFatty Liver Disease. Mark Thursz. Imperial College
Fatty Liver Disease Mark Thursz Imperial College Non-Alcoholic Fatty Liver Disease UK adult obesity (BMI>30) 1980: 6% [M], 8% [F]. 1997: 17% [M], 20% [F]. By 2004, 23.6% of men and 23.8% of women were
More informationMR Elastography of Liver
MR Elastography of Liver Sudhakar K. Venkatesh, MD, FRCR Professor of Radiology Mayo Clinic College of Medicine Consultant, Abdominal Division Radiology, Mayo Clinic Rochester, MN, USA 19 th May 2018 2018
More informationNon-Alcoholic Fatty Liver Disease
Non-Alcoholic Fatty Liver Disease None Disclosures Arslan Kahloon M.D Chief, Division of Gastroenterology and Hepatology University of Tennessee College of Medicine Chattanooga Objectives Understand the
More informationUpdate on Nonalcoholic Fatty Liver Disease. Kathleen E Corey, MD, MPH, MMSc Director, Mass General Fatty Liver Clinic
Update on Nonalcoholic Fatty Liver Disease Kathleen E Corey, MD, MPH, MMSc Director, Mass General Fatty Liver Clinic Outline Defining the phenotypes of nonalcoholic fatty liver disease NAFLD Diagnostics
More informationPrognosis of NASH VII Workshop Intenracional de Actualizaçao em Hepatologia, Aug 29th 2014
Prognosis of NASH VII Workshop Intenracional de Actualizaçao em Hepatologia, Aug 29th 2014 Vlad Ratziu, Université Pierre et Marie Curie, Hôpital Pitié Salpêtrière, Paris, France NASH : a severe hepatic
More informationMedical technologies guidance Published: 23 September 2015 nice.org.uk/guidance/mtg27
Virtual Touch Quantification to diagnose and monitor liver fibrosis in chronic hepatitis B and C Medical technologies guidance Published: 23 September 2015 nice.org.uk/guidance/mtg27 NICE 2017. All rights
More informationTransient Elastography and Sonography for Prediction of Liver Fibrosis in Infants With Biliary Atresia
ORIGINAL RESEARCH Transient Elastography and Sonography for Prediction of Liver Fibrosis in Infants With Biliary Atresia Na-Young Shin, MD, Myung-Joon Kim, MD, Mi-Jung Lee, MD, Seok Joo Han, MD, Hong Koh,
More informationOriginal article On-treatment monitoring of liver fibrosis with transient elastography in chronic hepatitis B patients
Antiviral Therapy 2011; 16:165 172 (doi: 10.3851/IMP1726) Original article On-treatment monitoring of liver fibrosis with transient elastography in chronic hepatitis B patients Grace Lai-Hung Wong 1,2,
More informationAmerican Journal of Oral Medicine and Radiology
American Journal of Oral Medicine and Radiology e - ISSN - XXXX-XXXX ISSN - 2394-7721 Journal homepage: www.mcmed.us/journal/ajomr PREVALENCE OF NONALCOHOLIC FATTY LIVER DISEASE AMONG TYPE 2 DIABETIC POPULATION
More information