Gastrointestinal Imaging Original Research

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1 Gastrointestinal Imaging Original Research Beland et al. Shear-Wave Elastography in Liver Fibrosis Gastrointestinal Imaging Original Research Michael D. Beland 1 Sanford F. Brown 1 Jason T. Machan 2 Ross J. Taliano 3 Kittichai Promrat 4 John J. Cronan 1 Beland MD, Brown SF, Machan JT, Taliano RJ, Promrat K, Cronan JJ Keywords: cirrhosis, elastography, hepatitis C, liver biopsy, ultrasound DOI:1.2214/AJR Received August 13, 213; accepted after revision December 3, 213. The ultrasound unit used in this study was a loan from SuperSonic Imagine. 1 Department of Diagnostic Imaging, Rhode Island Hospital, Warren Alpert Medical School of Brown University, 593 Eddy St, Providence, RI 293. Address correspondence to M. D. Beland (mbeland@lifespan.org). 2 Department of Biostatistics, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI. 3 Department of Pathology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI. 4 Department of Hepatology and Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI. WEB This is a web exclusive article. AJR 214; 23:W267 W X/14/233 W267 American Roentgen Ray Society A Pilot Study Estimating Liver Fibrosis With Ultrasound Shear-Wave Elastography: Does the Cause of Liver Disease or Location of Affect Performance? OBJECTIVE. The purpose of this study was to evaluate the diagnostic accuracy of realtime shear-wave elastography for assessment of liver fibrosis in an unselected patient population, comparing shear-wave elastography measurements obtained at and remote from the site of random liver biopsy. SUBJECTS AND METHODS. In a prospective study of 5 patients (21 with and 29 without hepatitis C) referred for clinically indicated random liver biopsy for diffuse liver disease, shear-wave elastography measurements were taken from four locations before biopsy: one at the left lobe, two at the right lobe, and one at the biopsy location. The mean, minimum, maximum, and of shear-wave elastography were compared with pathologic grading. Steatosis and serum markers were analyzed using multiple logistic regression. Optimized shearwave elastography thresholds were calculated using AUC analysis. RESULTS. The AUC (95% CI) at the biopsy site, ipsilateral lobe, and contralateral lobe were.82 (.63 ),.84 (.67 ), and.59 (.19.99) in hepatitis C patients;.89 (.75 ),.88 (.73 ), and.93 (.8 ) in nonhepatitis C patients; and.85 (.74.96),.89 (.79.99), and.8 (.67.93) in all patients, respectively. Optimized biopsy site shear-wave elastography values for detecting Metavir score F2 or greater were 1.87 m/s (75% sensitivity and specificity), 2. m/s (8% sensitivity and specificity), and 1.89 m/s (76% sensitivity and specificity) in hepatitis C, nonhepatitis C, and all patients, respectively. Steatosis and serum markers were not significant. CONCLUSION. Real-time shear-wave elastography accurately predicted significant fibrosis (stage 2) in an unselected patient population with diffuse disease, including patients with and without hepatitis C. Shear-wave elastography best predicts pathologic grading when taken at the biopsy site or ipsilateral lobe in hepatitis C patients. Percentage steatosis was not predictive of shear-wave elastography results. C irrhosis is a major health problem both in the United States and worldwide, accounting for nearly 3, deaths in the United States alone in 27 [1] and leads to roughly 7, deaths annually worldwide [2]. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis, although nonalcoholic fatty liver disease is emerging as an increasingly important cause [1]. In addition to viral hepatitis, alcohol abuse, and steatohepatitis, there are other causes of elevated liver function tests, including autoimmune and drug-related diseases. These patients often present with clinical and biochemical findings of hepatocellular dysfunction, and the cause may not always be clinically apparent. Given the morbidity and mortality of cirrhosis, accurately diagnosing liver disease is critical to ensure appropriate therapy. Not all patients with abnormal liver function tests have or go on to develop cirrhosis. Emerging treatment options to slow progression or potentially cure the disease are being developed but are costly and may be appropriate only in certain patient populations, depending on disease activity. This requires accurate fibrosis staging, generally by liver biopsy. Although the random liver biopsy is considered the reference standard for evaluating diffuse liver disease, it is not a perfect test. Given that the distribution of fibrosis in the liver may be heterogeneous, histologic staging based on a biopsy specimen that represents at most 1/5, of the total liver mass is suboptimal [3]. A liver biopsy is also expensive and has a risk of bleeding, particularly in patients with advanced liver disease who often have dysfunctional clotting cascade and plate- AJR:23, September 214 W267

2 Beland et al. lets, placing them at higher risk of bleeding. Developing noninvasive methods of estimating liver fibrosis is an area of active research, particularly using elastography. Supersonic shear imaging (SSI) is method of performing real-time shear-wave elastography that uses the acoustic radiation force induced by ultrasound beams combined with the ultrafast echographic imaging approach of transient elastography into a single ultrasonic sequence to provide a quantitative elasticity imaging mode, with a significant reduction of operator dependence compared with static elastography [4]. Several studies performed outside of the United States have shown the safety and efficacy of shear-wave elastography in cirrhosis evaluation in patients with hepatitis C and have shown real-time shear-wave elastography to be more accurate than transient elastography in staging fibrosis [4 7]. Given the potential heterogeneity of liver disease, questions remain regarding the correlation of a focal area of liver assessed by shear-wave elastography with the current reference standard of random liver biopsy. Although most early studies have evaluated patients with hepatitis C, noninvasive estimation of fibrosis in a broader patient population would be advantageous, particularly with the increasing incidence of nonalcoholic fatty liver disease. The effect of steatosis on shearwave elastography values is also uncertain, with studies showing both correlation [8] and noncorrelation [9] between shear-wave elastography and the degree of steatosis. The purpose of this study was to evaluate the diagnostic accuracy of shear-wave elastography in the assessment of liver fibrosis in an unselected patient population, comparing shear-wave elastography measurements obtained both at and remote from the site of random liver biopsy and to assess the impact of steatosis on shear-wave elastography results. Subjects and Methods Patients This prospective research study was approved by the institutional review board and is HIPAA compliant. Over a period of 1 weeks, 5 patients (25 women and 25 men; mean age, 52 years; range, years) referred for a clinically indicated random liver biopsy under ultrasound guidance were prospectively enrolled. Inclusion criteria were consenting adult (18 years old or older) patients referred for nontargeted liver biopsy with no known focal liver lesion, platelet count greater than 5,, and international normalized ratio (INR) lower than 1.9. Twenty-one (42%) patients had known viral hepatitis C, 15 (3%) elevated liver function tests of unknown cause, five (1%) nonalcoholic steatohepatitis, three (6%) cirrhosis not otherwise specified, three (6%) autoimmune hepatitis, two (4%) hepatitis B, and one (2%) methotrexate therapy. Laboratory results recorded included prothrombin time, INR, platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct and indirect bilirubin, and alkaline phosphatase when available within 3 months of the biopsy. Shear-Wave Elastography Before obtaining the core biopsy, shear-wave elastography was performed using the Aixplorer ultrasound system with a convex broadband probe (SC6 1) (SuperSonic Imagine). One elastogram was obtained from the left lobe using a subxyphoid approach. Two elastograms were obtained from the right lobe at two different craniocaudal locations with the patient in a supine or slight right anterior oblique position. s were made during suspended gentle respiration. When performing elastography, we attempted to show a superficial portion of the liver (< 6 cm depth) not superimposed on major blood vessels. For the quantitative measurements, a round ROI of approximately 2 mm in diameter was placed within the shear-wave color box (Fig. 1)., minimum, maximum, and stiffness in kilopascals were recorded. After preparing the patient and selecting the planned approach for liver biopsy on the basis of operator preference, we obtained an additional elastogram of the area planned for biopsy. A measurement was considered successful if the ROI was filled with color. If there was incomplete color fill of the ROI, the measurement was considered potentially invalid and repeated. The stiffness of the liver tissue was measured in kilopascals on the ultrasound machine at the time of the study. In September 212, the United States Food and Drug Administration approved measurement of tissue stiffness in meters per second. Therefore, the manufacturer provided the conversion formula from kpa to m/s as (kpa / 3). For consistency with current reporting standards, data are reported in meters per second. Liver Biopsy Liver biopsies were clinically indicated and performed in accordance with standard departmental protocol using ultrasound guidance. Standard preprocedural nursing assessment and intraprocedural and postprocedural care for patients undergoing liver biopsy was performed in accordance with institutional policy. Biopsies were performed after administration of an anxiolytic (1 mg IV of lorazepam) with no additional sedation. The same probe used for shear-wave elastography was used for biopsy guidance using a needle guide. The operator chose the biopsy site on the basis of the safest approach, irrespective of elastography results. All patients underwent one or two core biopsies with an 18-gauge spring-loaded automated core biopsy needle. The decision of whether to perform a second core biopsy was made on the basis of the perceived adequacy of the first specimen. Six patients (12%) underwent left lobe biopsy, and 44 patients (88%) underwent right lobe biopsy. Specimens were placed in 1% neutral Fig year-old woman with chronic hepatitis C. Ultrasound image obtained at time of shear-wave elastography at planned biopsy location shows shear-wave elastography value of 1.6 kpa, which is equal to 1.88 m/s. This shear-wave elastography value would be predicted to be Metavir F2 or greater using threshold of 1.87 m/s (sensitivity and specificity,.76). Metavir F2 was reported at surgical pathology. W268 AJR:23, September 214

3 Shear-Wave Elastography in Liver Fibrosis buffered formalin immediately after biopsy. Patients were observed after the procedure for approximately 9 minutes before discharge. There were no complications. Pathologic Evaluation Routine tissue processing of the biopsy specimens was performed and serial 5-μm sections were obtained from the paraffin blocks for H and E, iron, reticulin, and Masson trichrome staining. All slides were reviewed by a single gastrointestinal pathologist. For each biopsy, the following information was recorded: aggregate biopsy length, degree of steatosis in 5% increments, number of complete portal tracts present, severity of necroinflammatory component (grade), and degree and distribution of hepatic fibrosis (stage). The commonly used grading and staging criteria of Batts and Ludwig [1] were used for semiquantitative assessment of grade and stage for all cases not showing histologic features characteristic of steatohepatitis (hepatocellular ballooning degeneration and perisinusoidal fibrosis). Because the perivenular-centrilobular perisinusoidal pattern of fibrosis in steatohepatitis is fundamentally different from uncomplicated chronic hepatitis C (at least in precirrhotic stages), those cases showing histologic changes of steatohepatitis were also graded and staged according to the criteria set forth by Brunt et al. [11]. Although exclusion of cases showing histologic characteristics of steatohepatitis would be a consideration, the increasing prevalence of obesity and associated metabolic syndrome certainly suggest that fibrogenic disease in the liver will be multifactorial in a significant proportion of cases. Thus, validation of shear-wave elastography in this setting would be justified. In addition, because the Metavir staging system has been used in some prior studies pertaining to elastography, a Metavir stage was also assigned for these latter cases [12]. At least rare septa are required for inclusion in the Metavir stage 2 group but need not necessarily be present for inclusion into stage 2 of the Batts and Ludwig system [1]. The presence of septa (Metavir score F2) has been previously proposed as an indicator of clinically significant hepatic fibrosis [12, 13]. Statistical Analysis SAS version 9.3 (SAS Institute) software was used for conducting multiple logistic regressions. Subsequent visualizations of models and optimized threshold detection were carried out using in-house routines created using Matlab 64- bit R212b software. Multiple logistic regressions with backward selection were used as a data mining technique. Twenty-four sets of models were tested (2 path measures 2 thresholds 2 hepatitis C classifications 3 shear-wave elastography locations). The two dichotomizations of the Metavir or Batts and Brunt score as the dependent variable were any (> ) versus none and moderate or severe ( 2) vs mild or none (< 2). Patients were stratified by hepatitis C positive or negative and by the location used for shear-wave elastography. The predictors included in the models were the maximum, mean, minimum, and of the shearwave elastography measurements. Only effects remaining statistically significant at the p <.5 level were retained. Final models are presented. This approach was chosen after several rounds of exploratory data analysis revealed rare, minimal, and inconsistent improvement of model predic- TABLE 1: Shear-Wave Elastography Values, Steatosis Quantification, and Pathologic Staging in 21 Hepatitis C Patients Patient No Steatosis (%) F F F F < 5 F F < 5 4 F F < 5 F < 5 3 F F < 5 1 F < 5 3 F < 5 1 F F F < F F F < 5 4 F F1 Note Shear-wave elastography values in m/s. Batts Stage Metavir Score AJR:23, September 214 W269

4 Beland et al. tions when serum measures were included (e.g., ALT, AST, and platelets). For clarity and brevity, these models will not be discussed further in this article. Effect plots with optimized thresholds and inset ROC curves were presented to further illustrate the nature of the relationships and the optimal theoretic performance shear-wave elastography would have achieved under two sets of goals for each path outcome (Metavir and Batts and Brunt dichotomizations) for this patient population. The corresponding ROC curve and area under the ROC curve with its 95% CI are reported (Wilson method for area and Hanley-McNeil method for 95% CI), and 95% CIs extending above were truncated to. Results All 5 patients underwent successful liver biopsy. biopsy core length was 2. cm (range, 3.7 cm). The mean number of portal tracts was 1.2 (range, 3 22). Results of shear-wave elastography (mean and ) for each measurement site are presented in Table 1 (hepatitis C) and Table 2 (nonhepatitis C). On the basis of these results, the sensitivity and specificity were plotted as a function of threshold in mean shear-wave elastography in predicting the same dependent variables and patient stratifications along with the corresponding ROC curves. The point of intersection for the sensitivity and specificity functions was chosen as the optimized threshold, where sensitivity equals specificity, using linear interpolation when that point fell between observed values. The AUC at the biopsy site, ipsilateral lobe, and contralateral lobe were.815 ( ),.843 (.672 ), and.592 ( ) in hepatitis C patients;.894 (.747 1),.883 (.73 ), and.928 (.84 ) in nonhepatitis C patients; and.854 ( ),.891 (.79.99), and.8 ( ) in all patients, respectively. Optimized shear-wave elastography of 1.89 m/s at the biopsy site conferred 75% sensitivity and specificity (AUC,.85; TABLE 2: Shear-Wave Elastography Values, Steatosis Quantification, and Pathologic Staging in 29 Patients Without Hepatitis C Patient No Steatosis (%) Batts-Brunt Stage < 5 1 F < 5 1 F F < 5 4 F F F F F F < 5 F < 5 3 F F < 5 F < 5 F < 5 1 F F < 5 F < 5 3 F < 5 F < 5 F F F < 5 3 F < F F < 5 1 F < 5 1 F < 5 F < 5 4 F4 Note Shear-wave elastography values in m/s. Metavir Score W27 AJR:23, September 214

5 Shear-Wave Elastography in Liver Fibrosis TABLE 3: Values of Serum Markers of Liver Function of Entire 5-Patient Population Values Prothrombin Time INR Platelets AST ALT.75.97) for detecting F2 stage or greater in all patients. In hepatitis C patients, shearwave elastography greater than 1.87 at the site of biopsy conferred 76% sensitivity and specificity (.82,.63 ) (Figs. 2 and 3). In the nonhepatitis C patients, shear-wave elastography greater than 2. m/s at the biopsy site conferred 8% sensitivity and specificity (.89,.75 ) (Fig. 3). Steatosis when present was reported in 5% increments. In our series, there were 35 patients with less than 5%, seven patients with 5 25%, two patients with 25 5%, and six patients with > 5% steatosis. In multivariate analysis the degree of steatosis did not significantly correlate with the degree of fibrosis or shear-wave elastography value (p >.5). The mean, minimum, and maximum recorded laboratory values recorded that are associated with liver function including prothrombin time, INR, platelet count, AST, ALT, total bilirubin, direct and indirect bilirubin, and alkaline phosphatase are presented in Table 3. None of these results showed significant correlation with shear-wave elastography or pathologic scoring (all p >.5). Discussion Our results show real-time shear-wave elastography can accurately predict significant fibrosis (stage 2) in an unselected patient population with diffuse liver disease, including subsets of patients both with and without hepatitis C. To our knowledge, this is the first study aimed at evaluating the site of real-time shear-wave elastography measurements in an unselected patient population undergoing liver biopsy in the same day. We found that in nonhepatitis C patients, the site of shear-wave elastography measurement does not have a significant impact on correlation with pathologic findings. However, in hepatitis C patients, shear-wave elastography measurements taken at the biopsy site or within the same lobe may correlate with pathologic staging better than shear-wave elastography measurements taken in the contralateral lobe from the biopsy site. This finding did not reach statistical significance in our study, Total Bilirubin Direct Bilirubin Indirect Bilirubin Alkaline phosphatase Minimum Maximum Note INR = international normalized ratio, AST = aspartate aminotransferase, ALT = alanine aminotransferase. or Specificity Specificity Threshold as > SWE (m/s 2 ) A possibly related to the small sample size. We did not show a significant association between presence and extent of steatosis with shear-wave elastography nor did we find an association with various serum values typically associated with liver dysfunction to correlate with shear-wave elastography. Conventional elastography was first proposed as a noninvasive technique to assess the degree of liver fibrosis. This initial technique required manual compression and determined liver stiffness at a site in comparison with adjacent parenchyma. This method suffered a high degree of operator dependency and could not provide an objective parameter that could be compared with other cases. In transient elastography, a mechanical pulse is used to produce shear waves at a specified site in the liver. Rapid Doppler analysis provides an objective degree of liver stiffness independent of manual compression. The rapid acquisition eliminates respiratory motion artifact. However, transient elastography offers a blind assessment along a single axis, which could suffer from liver heterogeneity and may include vascular structures that can cause invalid readings. In addition, the mechanical pulses only assess one frequency in the production of shear waves. The next development introduced simultaneous B-mode.2 Wilcoxon AUC =.815 (95% CI, ) Specificity Fig. 2 Graphs show area under curve (AUC) in hepatitis C patients. A and B, Shear-wave elastography (SWE) value of greater than 1.87 taken at site of biopsy conferred 76% sensitivity and specificity (AUC,.82; 95% CI,.63 )..9.8 Specificity.8 * Wilcoxon AUC = (95% CI,.747 ) Threshold as > SWE (m/s 2 ) 1 Specificity A B Fig. 3 Graphs show area under curve (AUC) in non hepatitis C patients. A and B, Shear-wave elastography (SWE) value of greater than 2. m/s taken at biopsy site conferred 8% sensitivity and specificity (AUC,.89; 95% CI,.75 ). or Specificity * B AJR:23, September 214 W271

6 Beland et al. gray-scale visualization of the liver parenchyma, replacing the mechanical pulse with a large bandwidth ultrasound pulse to create shear waves at a user-selectable site. This enables correction for visualized artifacts, is adjustable, provides a larger ROI to better account for heterogeneity, and could enable simultaneous biopsy of the examined site. Two shear-wave elastography methods currently exist, acoustic radiation force impulse imaging (ARFI, Siemens Healthcare) and supersonic shear imaging (SSI Aixplorer, Super- Sonic Imagine). Although these techniques have shown similar accuracy [14], SSI is faster and requires less user input. Ferraioli et al. [9] showed the superiority of SSI in direct comparison with transient elastography in detecting histologically confirmed significant fibrosis ( F2) in a select hepatitis C patient population. In general practice, however, the presenting indication for liver biopsy is not limited to hepatitis C. During the period of our study, for example, less than 5% of the patients presenting for biopsy had hepatitis C, with the remaining patients presenting with a wide array of abnormalities including elevated liver function testing of unknown cause, autoimmune hepatitis, nonalcoholic steatohepatitis, alcohol hepatitis, and long-term methotrexate use. More widespread applicability of shear-wave elastography in an unselected patient population would be of significant value. Studies initially established the reproducibility of shear-wave elastography in normal liver [4] and mapped out expected values at different portions of the liver in healthy subjects [15]. Although one study showed that shear-wave elastography was comparable to transient elastography in hepatitis C patients [14], a study of 142 patients with biopsy-proven liver fibrosis by Bavu et al. [16] showed shear-wave elastography outperformed transient elastography (shear-wave elastography AUC,.95,.96, and.97 vs transient elastography AUC,.9,.93, and.94 in F2, F3, and F4 respectively). A follow-up study by the same group in a selected group of 113 hepatitis C patients with histologically confirmed fibrosis again showed shear-wave elastography (AUC for F2, F3, and F4;.948,.962, and.968, respectively) was superior to transient elastography (AUC for F2, F3, and F4;.846,.857, and.94, respectively) in patients with hepatitis C [5]. Most recently, Ferraioli et al. [9] performed a prospective trial of transient elastography versus shear-wave elastography in 121 hepatitis C patients undergoing biopsy the same day, showing AUC for shearwave elastography of.92,.98, and.98 and transient elastography.84,.96, and.96 for Metavir scores F2, F3, and F4, respectively. In general, the AUC values for shear-wave elastography in our study were lower than the published studies, potentially the result of fewer shear-wave elastography measurements performed as part of our study protocol. As previously indicated, a liver biopsy specimen only represents 1/5, of the total liver mass, which is suboptimal given that the distribution of fibrosis in the liver may be heterogeneous. For this reason, we obtained shear-wave elastography values for the ipsilateral and contralateral lobes and at the site of biopsy to assess for differences in correlation between biopsy findings and shear-wave elastography values. The AUC for hepatitis C and all patients was lower in the contralateral lobe versus biopsy site (.592 vs.815 and.8 vs.854, respectively). However, there was significant overlap of the 95% CIs, showing no significant difference in association. This overlap may be related to the small sample size in our study, and future larger studies evaluating correlation between biopsy site versus shear-wave elastography, particularly in hepatitis C patients, are needed. This knowledge is important for two primary reasons. First, if liver biopsy is considered the reference standard, the validity of studies assessing the accuracy of noninvasive methods of staging fibrosis may be affected by the location of measurement versus biopsy. Second, if the goals of staging of liver disease are based on measuring the most severe areas of fibrosis, a method of evaluation that can assess large areas of the liver, such as shear-wave elastography, may be of significant benefit over the much smaller sample given by liver biopsy. On the other hand, our study suggests that in other causes of liver disease, the disease may be more evenly distributed and the site of biopsy of noninvasive assessment may not be as critical. In the 29 patients in our study without hepatitis C, the AUC for the contralateral lobe was.93 versus.88 and.89 in the ipsilateral lobe and biopsy site. Again, the small sample size, particularly of given subsets of nonhepatitis C causes, warrants further investigation with larger patient cohorts. The influence of steatosis on shear-wave elastography has been unclear. An ex vivo mouse model study suggested that liver steatosis can be separated from fibrosis by assessing the dispersion or frequency dependence of shear wave propagations, possibly enabling estimation of hepatic steatosis [17]. Zoumpoulis et al. [8] evaluated 12 patients with fatty liver and found the mean of shearwave elastography significantly different from a healthy population of 18 patients. More recently, Ferraioli et al. [9] showed no relationship between degree of steatosis and the shear-wave elastography or fibrosis stage in hepatitis C patients. In our series, the degree of steatosis did not significantly correlate with shear-wave elastography or fibrosis. Given the increasing prevalence of hepatitis steatosis and conflicting results, future studies with larger patient populations evaluating the effect of increasing degrees of steatosis on the shear-wave elastography value are needed. The primary limitation in this study was the small sample size, as evidenced by a wider range of 95% CIs when analyzing population subsets. Our results improved to an AUC of.891 (.71.99) when including all 5 patients, and we would expect the results to be even more comparable with a larger sample size. This same limitation decreases our ability to determine differences in shear-wave elastography values at various sites in the liver and the effect of steatosis on the shear-wave elastography parameter or degree of fibrosis. Our study focused on obtaining shear-wave elastography values at various sites throughout the liver, with fewer samples at the biopsy site itself; we obtained two measurements in the right lobe, one in the left lobe, and one at the site of biopsy. This differed from prior studies investigating shearwave elastography in relation to fibrosis, which focused on taking multiple measurements at one site, up to 12 in one study [9]. Although increasing the number of samples may have improved the accuracy in our study, the amount of time to do the assessment would have also increased. One of the goals of our study design was to perform shear-wave elastography in a way that would best fit into a busy clinical practice as an adjunctive measurement tool for performing liver ultrasound. To further improve accuracy, performing more than one measurement in multiple lobes may be considered. Finally, the accuracy of liver fibrosis assessment can be affected by many factors, including sampling errors and intra- or interobserver variability. Because a single pathologist reviewed all of the liver biopsy specimens in our study, intraobserver variability may be a limitation. In conclusion, the results of this study show real-time shear-wave elastography is accurate in assessing significant liver fibrosis in a nonselected patient population and that it can be used in daily practice. The site selected for shear-wave elastography may be more impor- W272 AJR:23, September 214

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