418 GOLD-VALIDATION OF LIVER FIBROSIS ESTIMATES, FIBROTEST (FT) AND LIVER STIFFNESS MEASUREMENT (LSM), USING SURGICAL SAMPLES AND VIRTUAL BIOPSIES

POSTERS and 52%, respectively. Significant correlations were noted between Forn’s score and the LOK index (r = 0.49 p < 0.005) or RE25 (r = −0.31, p < 0.05). Conclusion: The relative enhancement of EOB-MR imaging is reduced in the hepatobiliary phase (RE25) in patients with significant fibrosis. EOB-MRI seems to be an excellent method to determine the staging of fibrosis as a noninvasive method in HCVinfected chronic hepatitis or cirrhosis patients as well as detecting HCC. 416 LONGITUDINAL PROSPECTIVE COMPARISON OF FIBROSURE AND TRANSIENT ELASTOGRAPHY IN RELATION TO VIROLOGIC RESPONSE: A SUBSTUDY OF THE PHASE 3 ALBINTERFERON ALFA-2B TRIALS K. Patel1 , M. Friedrich-Rust2 , M. Torbenson3 , Y. Zhu4 , E. Pulkstenis4 , G. Subramanian4 , J. McHutchison1 , D. Nelson5 , M. Sulkowski3 , Y. Benhamou6 , S. Zeuzem2 , for the ACHIEVE Study Group. 1 Duke Clinical Research Institute, Durham, NC, USA; 2 J.W.Goethe University Hospital, Frankfurt/Main, Germany; 3 Johns Hopkins University School of Medicine, Baltimore, 4 Human Genome Sciences, Inc., Rockville, MD, 5 University of Florida, Gainesville, FL, USA; 6 Hˆ opital Piti´e-Salpˆetri`ere, Paris, France E-mail: [email protected] Background and Aims: Noninvasive alternatives to biopsy that can follow fibrosis changes would be useful to assess histologic therapeutic endpoints. This substudy compared the changes in the validated serum marker panel FibroSURE (FS) and transient elastography (TE) with virologic responses in two phase 3 trials of albinterferon alfa-2b (albIFN) in chronic hepatitis C (CHC) patients. Methods: CHC patients were randomized equally to 3 treatment groups: peginterferon alfa-2a qwk, and albIFN 900 and 1200 mg q2wk, all with ribavirin for 24wk (800 mg/d; genotypes 2/3) or 48wk (1000–1200 mg/d; genotype 1). FS was determined at baseline and wk12 post-treatment follow-up; baseline biopsy evaluation for METAVIR score was done by a single pathologist; and TE was obtained before/after therapy from non-US centers with available TE. Data from both trials were pooled for analysis. Results: At baseline, 2055 CHC patients were classified by biopsy (mean length 17.0 mm) as F0–1 (n = 1678) or F2–4 (n = 377). For F2–4, FS had a sensitivity and specificity of 0.87 and 0.61, respectively, with area under the receiver operating curve of 0.82; the corresponding numbers with TE (n = 214) were 0.77, 0.88, and 0.88. By combining FS and TE, accuracy for F2–4 = 0.86. Agreement between TE-determined F2–4 and FS was 0.71 (k = 0.41). FS and TE scores were available in 2082 and 217 patients, respectively, with virologic response. At wk12 post-therapy follow-up, there was a significant reduction in FS fibrosis scores from baseline for sustained virologic responders (SVR; n = 1197, D=0.06) compared with nonresponders (n = 534; D=0.0; P < 0.001). Changes in FS inflammatory activity scores at follow-up were also lower for SVR vs nonresponders (difference=-0.32; P < 0.001). Although TE scores were lower at baseline in SVR vs nonresponders (6.4vs7.9; P=.003), further small declines in TE score for both groups did not differ appreciably at follow-up (median difference=-0.3). Conclusions: The combination of imaging and serum tests may reliably differentiate mild from moderate-advanced-stage disease. FS fibrosis and TE scores were lower at baseline and follow-up in SVR. Overall TE scores were lower post-therapy, but these declines were not related to virologic response and may reflect differences in inflammatory activity detection between TE and serum biomarkers in relation to response.

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417 VIRTUAL TOUCH ASSESSMENT OF LIVER STIFFNESS IN CHRONIC LIVER DISEASE: COMPARISON WITH TRANSIENT ELASTOGRAPHY F. Piscaglia1 , V. Salvatore1 , R. Di Donato2 , A. Borghi1 , S. Gualandi1 , E. Peri1 , F. Conti2 , A. Cucchetti3 , P. Andreone2 , L. Bolondi1 . 1 Department of Clinical Medicine, Medicina Interna, 2 Department of Clinical Medicine, Semeiotica Medica, 3 Division of Liver Transplantation, S.Orsola-Malpighi General and University Hospital, Bologna, Italy E-mail: [email protected] Background and Aims: Transient elastography (Fibroscan, Echosense) proved effective in predicting presence of advanced fibrosis. Virtual Touch (Siemens Healthcare), a new ARFI (Acoustic Radiation Force Imaging) technology-based method, incorporated in conventional ultrasound scanners, was recently proposed for the evaluation of liver stiffness. Aim of the present study was to compare Virtual Touch to Fibroscan, considering the latter as reference standard. Methods: A total of 97 patients with chronic liver disease of different stages and etiologies and 25 healthy controls were examined with both Virtual Touch and Fibroscan, in the right hepatic lobe. Since cirrhosis determines an upstream congestion of the spleen, Virtual Touch was assessed also in the spleen. Interobservers’ agreement in liver values was evaluated in 41 random patients. Results: Fibroscan failed valid measurements in 7 (overweight or obese) of 97 subjects, whereas Virtual Touch was successful in all. Fortytwo of the 90 patients making the final study group were considered affected by cirrhosis, since showing Fibroscan >13 Kpa, a threshold in accordance to the literature (Friedrich-Rust, Gastroenterology 2008). A strict correlation was observed between liver stiffness values obtained with FibroScan and Virtual Touch, either considering all subjects (r = 0.879, p < 0.0001) or only patients with chronic liver disease (r = 0.857, p < 0.0001). The product of liver and spleen Virtual Touch values produced the “Spleno-Hepatic Index”, showing an even higher correlation with FibroScan (r = 0.880 for liver patients). Virtual Touch provided sensitivity and specificity for the diagnosis of cirrhosis of respectively 93% and 84.4% at a cut-off of 1.75 m/s for right liver lobe values and of respectively 95.2% and 80.4% at a cut-off of 4.9 m/s for SplenoHepaticIndex. The kappa coefficient of agreement showed no significant difference in VirtualTouch results between the two operators (r = 0.87 and 0.82 for right and left lobe, respectively). Validation of the right liver lobe threshold is going on in a separate case series of patients with bioptic cirrhosis. Conclusions: Virtual Touch modality, appears to be a very promising tool in the evaluation of liver stiffness, with results similar to Fibroscan, but with the advantage of being integrated in ultrasound equipments. 418 GOLD-VALIDATION OF LIVER FIBROSIS ESTIMATES, FIBROTEST (FT) AND LIVER STIFFNESS MEASUREMENT (LSM), USING SURGICAL SAMPLES AND VIRTUAL BIOPSIES T. Poynard1 , G. Lenaour1 , F. Charlotte1 , M. Munteanu2 , J.C. Vaillant1 , Y. Ngo2 , V. Ratziu1 , L. Hannoun1 , F. Capron1 . 1 UPMC APHP Paris Liver Center, 2 Biopredictive, Paris, France E-mail: [email protected] Background: Fibrosis biomarkers FT and LSM (Fibroscan® ) have been validated using biopsy as a reference. In HCV, when compared to large surgical samples (perfect reference), 25% of biopsies (25 mm) were categorized incorrectly (Bedossa 2003). Therefore the true quantitative correlations of FT and LSM with fibrosis area (FA) are unknown.

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POSTERS Aim: To better estimate FT and LSM performances, we assessed the strength of concordance between FT and LSM with FA of surgical samples, according to biopsy length. Methods: Surgical samples, FT and LSM, from 12 consecutive patients with chronic liver diseases and 4 controls, were prospectively studied. From the digitized image (Aperio Scanner, TRIBVN, France), 22,119 virtual biopsies of increasing length (5/10/15/20/25/30 mm) were produced: 5,106 HCV, 4,572 ALD, 3,240 NAFLD, 3,988 HBV, 1,458 PBC and 4,665 controls. The concordance of FT and LSM with FA was assessed using the Spearman correlation coefficient (S), and R2 of best curve fitting. Results: FA reference values were 3.8% (4 subjects METAVIR stage F0), 5.0% (1 F1), 7.1% (3 F2), 9.0% (1 F3) and 18.2% (7 F4) similar to those previously described in HCV. In all liver diseases the coefficient of variation decreased with biopsy length from 0.87 (5 mm) to 0.69 (30 mm) biopsy. FT ranged from 0.13 to 0.98 and LSM from 3.7 to 23.8 kPa. For FT and LSM there was a steady increase in concordance with FA according to biopsy length: FT from 5 mm S = 0.68 (95% CI 0.66–0.70) to 30 mm S = 0.78 (0.76–0.79); FS from 5 mm S = 0.60 (0.57–0.62) to 30 mm S = 0.65 (0.62–0.67). Differences between S were significant between biopsy lengths (p < 0.05) for FT and not for LSM. For FT the best curves fitting was obtained using linear association after logarithmic transformation of FA; R2 steadily increased from 0.51 to 0.69. For LSM the best fitting was obtained using linear association after logarithmic transformation of both FA and LSM; R2 increased from 0.35 to 0.49. S and R2 were all significantly higher for FT vs. LSM (P < 0.01). Conclusion: Both FT and LSM strength of concordance with area of fibrosis increased with length of biopsy, with a significantly higher association for FT than LSM. 419 THE CORRELATION OF LIVER STIFFNESS WITH PORTAL PRESSURE AND FIBROSIS STAGE IS INFLUENCED BY VASOACTIVE TREATMENT AND ETIOLOGY OF LIVER DISEASE T. Reiberger1 , A. Ferltisch1 , M. Pinter1 , M. Homoncik1 , G. Ulbrich2 , M. Peck-Radosavljevic1 . 1 Internal Medicine III, Div. of Gastroenterology & Hepatology, Medical University Vienna, 2 Internal Medicine, Div. of Gastroenterology & Hepatology, Hospital Hietzing, Vienna, Austria E-mail: [email protected] Introduction: Recently published studies support the use of transient elastography (TE) for evaluating patients with portal hypertension since liver stiffness (LS) is significantly correlated with the hepatovenous pressure gradient (HVPG). However, negative (NPV) and positive predictive values (PPV) for diagnosis of clinically significant portal hypertension (CSPH) by TE should be used to evaluate clinical applicability. In addition, certain limitations of TE, e.g. the influence of sex, age, etiology and levels of aminotransferases levels have to be considered. Methods: Retrospective analysis of the 717 measurements of LS performed in 559 patients evaluated at the hepatic hemodynamic laboratory. 88 sequential HVPG measurements with and without vasactive treatment with betablockers were performed. 175 transjugular liver biopsies were obtained. Demographic patient data were documented. Results: A significant correlation of LS and HVPG was noted (R = 0.795; p < 0.0001), which was stronger in patients with viral disease (R = 0.836; p < 0.0001) than in patients with alcoholic disease (R = 0.740; p < 0.0001). The correlation of LS in patients with CSPH was stronger under vasoactive treatment than without (R = 0.451 vs. R = 0.662; p < 0.0001). Analysis of the area under the receiver operating curve (AUROC) indicated that a cutoff at 18 kPa can identify CSPH with a sensivity and specifity of 80% and 77%, respectively. The PPV and NPV for diagnosis of CSPH were 81% and 76% using a TE threshold at 18 kPa. AUROC for diagnosis of F2 was 0.669 (>7.2 kPa; p = 0.03), 0.0694 for F3 (>9.6 kPa; p = 0.004) and

0.904 for F4 (12.1 kPa; p = 0.0001), respectively. Using a cut-off at 12.1 kPa the PPV and NPV for diagnosis of F4 were 77% and 91%. Conclusions: Poor PPV and NPV limit the diagnostic use of TE for discriminating patients with and without CSPH. The better correlation of LS and HVPG under vasoactive medication may reflect the fact that TE is not assessing the dynamic component of portal hypertension. TE is able to exclude the diagnosis of histological cirrhosis with a NPV of 91%. 420 TRANSIENT ELASTOGRAPHY EARLY PREDICTS PROGRESSIVE RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION C. Rigamonti1 , M.F. Donato1 , M. Fraquelli2 , F. Agnelli3 , G. Rossi3 , M. Colombo1 . 1 First Division of Gastroenterology, 2 Second Division of Gastroenterology, 3 Liver Transplant Unit, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy E-mail: [email protected] Background and Aims: Early graft damage following liver transplantation (OLT) predicts rapid evolution of recurrent hepatitis C to cirrhosis. We evaluated whether transient elastography (TE) performed early after OLT may help in identifying patients at risk of progressive disease. Methods: 37 consecutive HCV-infected liver recipients transplanted from June 2005 to December 2007 were prospectively submitted to repeated TE examinations at 3, 6, 9 and 12 months after OLT, and to a liver biopsy at month 12. Staging (S) was assessed according to Ishak score. Patients with 12 month S <3 were defined slow fibrosers, compared to rapid fibrosers with S≥3. The linear slope of TE progression for the two groups was assessed using a longitudinal mixed model for repeated measurements. Results: 33 patients completed the follow-up (4 died within 6 months after OLT). 21 (64%) patients were slow fibrosers and 12 (36%) rapid fibrosers including 3 who developed cirrhosis at month 12. Median TE at 3, 6, 9, 12 months were 7.5, 7.0, 6.9, 6.4 kPa in slow fibrosers and 8.9, 10.9, 11.8, 13.0 kPa in rapid fibrosers. TE values were significantly correlated with 12 month-staging at 6 (rho = 0.48, p = 0.006), 9 (rho = 0.78, p < 0.0001) and 12 months (rho = 0.83, p < 0.0001). Rapid fibrosers had significantly higher AST serum levels at 3, 6, 9, 12 months, gamma-GT serum levels at 6, 12 months and TE values at 6, 9, 12 months with respect to slow fibrosers. The slope of TE variations was significantly greater in rapid fibrosers (0.40 kPa/month) than in slow fibrosers (−0.05 kPa/month) (p < 0.0001). Proportion of patients with >7.9 kPa (previous published TE cut-off for S≥3) at 3, 6, 9 and 12 months were 29%, 26%, 31% and 28% in slow fibrosers and 60%, 67%, 100%, 95% in rapid fibrosers (p = 0.22, p = 0.06, p = 0.001 and p = 0.001). The areas under receiver operating characteristic in identifying rapid fibrosers were 0.74 (95% CI 0.53–0.94) at 6 months, 0.92 (95% CI 0.74–0.99) at 9 months and 0.94 (95% CI 0.79–0.99) at 12 months. Conclusions: Repeated TE examinations early after OLT may help identifying HCV-infected recipients at risk of progressive graft disease. 421 COMPARISON OF LIVER STIFFNESS ASSESSMENT BY FIBROSCAN® AND ACOUSTIC RADIATION FORCE IMPULSE IMAGING® FOR THE EVALUATION OF LIVER FIBROSIS AND CIRRHOSIS P. Salzl, T. Reiberger, M. Homoncik, B. Payer, B. Schwengerer, M. Peck-Radosavljevic, A. Ferlitsch, Hepatic Hemodynamic Lab. Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria E-mail: [email protected] Background: Staging of liver fibrosis is an essential part in the management of chronic liver disease. Invasive screening tests like liver biopsy, hepatic venous pressure gradient (HVPG) measurement and Upper-GI-Endoscopy have a significant burden on patients. We compared two different noninvasive methods of liver stiffness

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