- Email: [email protected]
1054 TRANSIENT ELASTOGRAPHY (FIBROSCAN®) - THE NORMAL VARIABILITY BETWEEN TWO MEASUREMENTS
POSTERS 1053 ROLE OF ACOUSTIC RADIATION FORCE IMPULSE (ARFI) SONOELASTOGRAPHY FOR NONINVASIVE DIAGNOSIS OF NONALCOHOLIC FATTY LIVER DISEASE C. Fierbinteanu-Braticevici1 , R. Usvat1 , G. Oprea1 , E. Sarbu1 , A. Petrisor1 , E. Panaitescu2 . 1 Gastroenterology, University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 2 Internal Informatics and Biostatistics, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania E-mail: cfi[email protected] Background: Nonalcoholic fatty liver disease (NAFLD) represents a group of conditions ranging from simple liver steatosis, usually asymptomatic, to nonalcoholic steatohepatitis (NASH), which is characterized by a progressive course, evolving to cryptogenic cirrhosis. Acoustic Radiation Force Impulse (ARFI) sonoelastography has recently been proposed as an alternative method to FibroScan to assess liver elasticity. Aim: To evaluate the efficacy of ARFI in differentiating patients with simple steatosis from NASH patients and also, to establish the role of ARFI to predict significant fibrosis in patients with NASH. Methods: We performed ARFI in 64 patients with histologically proven NAFLD (ranging from simple steatosis to severe steatohepatitis). Brunt scoring system for histological evaluation of NAFLD served as reference. The correlation between ARFI and liver biopsy was tested using Spearman’s coefficient. The overall validity was measured using the area under receiver operating characteristic curve (AUROC) with 95% CI. Results: ARFI elastography was a good method for identifying the patients with histologically proven NASH vs. simple steatosis with an AUROC 0.867, 95% CI 0.782–0.953, a sensitivity of 77% and a specificity of 71%. ARFI also correlated with C-reactive protein (r = 0.495,p < 0.001), serum Malonyldialdehide, MDH (r = 0.498, p < 0.001) and serum Glutathione,GTH (r = −0.637, p < 0.001), as index of oxidative stress. In patients with NASH, the diagnosis accuracy of ARFI elastography for significant fibrosis (F≥2) expressed as AUROC had a validity of 94.4% (95%) CI AUROC = 0.891–0.997. ARFI elastography predicted better F4 fibrosis (AUROC – 98.4% (95%)CI AUROC = 0.958–1.000). Conclusion: ARFI elastography is a promising method in differentiating patients with NASH from patients with simple steatosis and could also predict significant fibrosis in these patients. 1054 TRANSIENT ELASTOGRAPHY (FIBROSCAN® ) – THE NORMAL VARIABILITY BETWEEN TWO MEASUREMENTS G.S. Gherlan1 , P.I. Calistru1 , S. Lazar2 , M. Neata1 . 1 Infectious Diseases, Center for Diagnostics and Treatment ‘Dr. Victor Babes’, 2 ‘Dr. Victor Babes’ Hospital of Infectious and Tropical Diseases, Bucharest, Romania E-mail: [email protected] Background and Aims: Transient elastography (Fibroscan® ), a noninvasive method for liver fibrosis assessment is considered a candidate for monitoring the evolution of a chronic liver disease. This study aims to establish the normal variation between two measurements and what values should be considered significant in terms of improvement or aggravation of a liver disease. Methods and Patients: 202 patients underwent two consecutive liver stiffness measurements performed by the same experienced physician (over 500 maneuvers). Only valid measurements (according to manufacturer’s recommendations) were analyzed. We used the average value of the two measurements for stratification, cut-offs of 5.5, 7.1, 9.5, 14.5 KPa for F1-F4 and 7.1 KPa for significant fibrosis. Results: The differences between the two measurements ranged from 0 to 5.3 kPa (0–54% of one of the values). We found a mean variation between two measurements of 13%, with a standard
deviation of 0.122 (12.2%). Discordance between measurements was associated with BMI (p = 0.007, r = 0.474) and not influenced by sex or age. The difference of two measurements increases as median stiffness increases (p < 0.0001, r = 0.575) and is also related to IQR (p < 0.0001, r = 0.556). Based on the mentioned cut-offs, 63 (31.1%) patients were categorized in two different stages by the two different measurements (3 for F3/F4 and 30 for F0/F1). The maximum difference between two measurements would be of one corresponding Metavir stage. For significant/not significant fibrosis (cut-off 7.1 KPa), 24 (11.8%) patients were misclassified. Conclusions: There is a normal variability between two liver stiffness measurements of 13%±12.2%. Therefore only a variation of minimum 25.2% between measurements performed in evolution should be considered significant as a proof of a liver disease improvement or worsening. The larger number of patients who have been misclassified for F0/F1 than for F3/F4 is consistent with the findings of other studies that showed a better concordance of elastography with liver biopsy for higher stages of fibrosis. Using stricter validation criteria (a lower IQR and a larger number of valid measurements) and classifying fibrosis as no significant/ significant/cirrhosis may enhance the use of Fibroscan® as a monitoring tool. Disclosure: Nothing to disclose. 1055 SIGNATURE OF THREE NOVEL SURROGATE MARKERS PREDICTS LIVER STIFFNESS AND FIBROSIS STAGES IN A COHORT OF PATIENTS WITH CHRONIC LIVER DISEASE 2 M. Krawczyk1 , A. Hoblinger ¨ , G. Hess3 , T. Sauerbruch2 , F. Lammert1 , 1 1 F. Grunhage ¨ . Department of Medicine II, Saarland University Hospital, Homburg, 2 Department of Internal Medicine I, University Hospital Bonn, Bonn, 3 Department of Internal Medicine, University Hospital Mainz, Mainz, Germany E-mail: [email protected] Background and Aims: The latest experimental data suggests that placenta growth factor (PLGF), growth differentiation factor 15 (GDF15) and hepatic growth factor (HGF) are crucial for hepatic fibrogenesis (Hepatology 2011; PLoS One 2011). Our previously reported panel of novel serum fibrosis markers underlines the importance of these markers for the human situation (Grunhage ¨ et al. ASSLD 2010). We now report a novel score of top-predictive markers including PLGF, GDF-15 and HGF for the diagnosis of different degrees of liver stiffness and histological fibrosis stages in a cohort of patients with chronic liver disease. Methods: Overall 834 CLD patients were included (median age 51 years, range 18–84, 61% males). Liver status was phenotyped using transient elastography (TE). Serum levels of PLGF, GDF15 and HGF were measured in 824 patients. The AUC for the prediction of significant fibrosis (>7.5 kPa) and the cut-off values for serum markers were determined. The tested scores included no, one or two markers above the predicted cut-off. Odd ratios were calculated for the presence of significantly increased TE values (>7.5 or >17.5 kPa, respectively) or the presence of histological fibrosis using Chi-square tests. Results: Cut-off levels for the three markers to differentiate between TE < 7.5 and ≥7.5 kPa were PLGF = 19 pg/ml, GDF15 = 730 pg/ml, and HGF = 15 pg/ml. Overall, 28.3% patients displayed no, 23.1% one, 21.2% two and 27.3% three markers above the defined cutoffs. The presence of any marker above the cut-off was associated with an OR of 5.4 (95% CI 3.7–7.8, p < 0.001) to present with TE > 7.5 and with an OR of 18.6 (95% CI 8.1–42.7, p < 0.001) to present with TE > 17.5 kPa. The score was also associated with histological fibrosis stages F > 1 vs. F0/1 (OR = 5.3, 95% CI 2.3–11.0, p < 0.001) and bridging
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deviation of 0.122 (12.2%). Discordance between measurements was associated with BMI (p = 0.007, r = 0.474) and not influenced by sex or age. The difference of two measurements increases as median stiffness increases (p < 0.0001, r = 0.575) and is also related to IQR (p < 0.0001, r = 0.556). Based on the mentioned cut-offs, 63 (31.1%) patients were categorized in two different stages by the two different measurements (3 for F3/F4 and 30 for F0/F1). The maximum difference between two measurements would be of one corresponding Metavir stage. For significant/not significant fibrosis (cut-off 7.1 KPa), 24 (11.8%) patients were misclassified. Conclusions: There is a normal variability between two liver stiffness measurements of 13%±12.2%. Therefore only a variation of minimum 25.2% between measurements performed in evolution should be considered significant as a proof of a liver disease improvement or worsening. The larger number of patients who have been misclassified for F0/F1 than for F3/F4 is consistent with the findings of other studies that showed a better concordance of elastography with liver biopsy for higher stages of fibrosis. Using stricter validation criteria (a lower IQR and a larger number of valid measurements) and classifying fibrosis as no significant/ significant/cirrhosis may enhance the use of Fibroscan® as a monitoring tool. Disclosure: Nothing to disclose. 1055 SIGNATURE OF THREE NOVEL SURROGATE MARKERS PREDICTS LIVER STIFFNESS AND FIBROSIS STAGES IN A COHORT OF PATIENTS WITH CHRONIC LIVER DISEASE 2 M. Krawczyk1 , A. Hoblinger ¨ , G. Hess3 , T. Sauerbruch2 , F. Lammert1 , 1 1 F. Grunhage ¨ . Department of Medicine II, Saarland University Hospital, Homburg, 2 Department of Internal Medicine I, University Hospital Bonn, Bonn, 3 Department of Internal Medicine, University Hospital Mainz, Mainz, Germany E-mail: [email protected] Background and Aims: The latest experimental data suggests that placenta growth factor (PLGF), growth differentiation factor 15 (GDF15) and hepatic growth factor (HGF) are crucial for hepatic fibrogenesis (Hepatology 2011; PLoS One 2011). Our previously reported panel of novel serum fibrosis markers underlines the importance of these markers for the human situation (Grunhage ¨ et al. ASSLD 2010). We now report a novel score of top-predictive markers including PLGF, GDF-15 and HGF for the diagnosis of different degrees of liver stiffness and histological fibrosis stages in a cohort of patients with chronic liver disease. Methods: Overall 834 CLD patients were included (median age 51 years, range 18–84, 61% males). Liver status was phenotyped using transient elastography (TE). Serum levels of PLGF, GDF15 and HGF were measured in 824 patients. The AUC for the prediction of significant fibrosis (>7.5 kPa) and the cut-off values for serum markers were determined. The tested scores included no, one or two markers above the predicted cut-off. Odd ratios were calculated for the presence of significantly increased TE values (>7.5 or >17.5 kPa, respectively) or the presence of histological fibrosis using Chi-square tests. Results: Cut-off levels for the three markers to differentiate between TE < 7.5 and ≥7.5 kPa were PLGF = 19 pg/ml, GDF15 = 730 pg/ml, and HGF = 15 pg/ml. Overall, 28.3% patients displayed no, 23.1% one, 21.2% two and 27.3% three markers above the defined cutoffs. The presence of any marker above the cut-off was associated with an OR of 5.4 (95% CI 3.7–7.8, p < 0.001) to present with TE > 7.5 and with an OR of 18.6 (95% CI 8.1–42.7, p < 0.001) to present with TE > 17.5 kPa. The score was also associated with histological fibrosis stages F > 1 vs. F0/1 (OR = 5.3, 95% CI 2.3–11.0, p < 0.001) and bridging
Journal of Hepatology 2012 vol. 56 | S389–S548
S413