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79 INFLUENCE OF AMINOTRANSFERASES LEVEL ON THE CORRELATION OF LIVER STIFFNESS ASSESSED BY ACOUSTIC RADIATION FORCE IMPULSE (ARFI) ELASTOGRAPHY WITH LIVER FIBROSIS-AN INTERNATIONAL MULTICENTER STUDY
ORAL PRESENTATIONS 79 INFLUENCE OF AMINOTRANSFERASES LEVEL ON THE CORRELATION OF LIVER STIFFNESS ASSESSED BY ACOUSTIC RADIATION FORCE IMPULSE (ARFI) ELASTOGRAPHY WITH LIVER FIBROSIS-AN INTERNATIONAL MULTICENTER STUDY S. Bota1 , I. Sporea1 , R. Sirli1 , H. Tanaka2 , H. Iijima2 , R. Badea3 , M. Lupsor3 , C. Fierbinteanu-Braticevici4 , A. Petrisor4 , H. Saito5 , H. Ebinuma5 , M. Friedrich-Rust6 , C. Sarrazin6 , H. Takahashi7 , N. Ono8 , F. Piscaglia9 , A. Borghi9 , M. D’Onofrio10 , A. Gallotti10 , M. Peck-Radosavljevic11 , A. Ferlitsch11 , A. Popescu1 , M. Danila1 . 1 Gastroenterology and Hepatology, University of Medicine and Pharmacy, Timisoara, Romania; 2 2Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan, 3 IIIrd Medical Clinic, University of Medicine, Cluj-Napoca, 4 IInd Medical Clinic and Gastroenterology, University Hospital, Bucharest, Romania; 5 Department of Internal Medicine, Keio University, Tokyo, Japan; 6 Department of Internal Medicine 1, J.W. Goethe University, Frankfurt/Main, Germany; 7 Department of Internal Medicine, 8 Gastroenterology, Saga Medical School, Saga, Japan; 9 Div. Internal Medicine, Dept. Clinical Medicine, University and General Hospital S. Orsola-Malpighi, Bologna, 10 Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy; 11 Internal Medicine III, Div. of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria E-mail: [email protected] Background and Aim: ARFI elastography is a new method for the evaluation of liver fibrosis. Transient elastography is influenced by elevated aminotransferase-levels. The aim of this study was to establish if, the correlation between the liver stiffness (LS) values measured by ARFI and the severity of histological fibrosis (liver biopsy-LB) is influenced by the eleveted aminotransferases. Methods: Our retrospective study included 1125 patients(p) from 10 centers (5 countries) with chronic hepatitis: 779 with HCV and 172 HBV chronic hepatitis, 12 with HBV+HCV coinfection and 162 with chronic hepatopathies of nonviral etiology. We performed LB (evaluated according to the Metavir score) and ARFI measurements. We performed 10 valid ARFI measurements in each patient and a median value was calculated, expressed in meters/second (m/s). Results: There was a direct, strong correlation (r = 0.597) between the LS values assessed by means of ARFI and fibrosis (p < 0.0001). The mean LS values assessed by ARFI for the same stage of histological fibrosis increased with the alanine aminotransferases (ALT) level (Table 1).
80 BASELINE AND SEQUENTIAL LIVER STIFFNESS MEASUREMENTS (FIBROSCAN® ) ARE INDEPENDENT PREDICTORS OF DEATH, LIVER TRANSPLANTATION OR LIVER DECOMPENSATION IN PRIMARY BILIARY CIRRHOSIS C. Corpechot, A. Poujol-Robert, F. Gaouar, O. Chazouilleres, R. Poupon. Service d’H´epatologie, Centre de R´ef´erence des Maladies Inflammatoires des Voies Biliaires, UMR_S938, Hˆ opital Saint-Antoine, AP-HP, UPMC, Paris, France E-mail: [email protected] Background and Aims: Liver stiffness measurement (LSM) as assessed by transient elastography (Fibroscan® , FS) has been shown as a reliable non-invasive surrogate marker of liver fibrosis in primary biliary cirrhosis (PBC). The present study aimed at assessing the prognostic significance of LSM in PBC. Methods: A total of 150 patients with non-decompensated PBC (mean age, 57 years; 89% women) were followed-up using FS for a period of 2.6±1.2 years (up to 5.3 years), then followed-up for an additional period of 2.3±1.1 years (up to 5.1 years) after last LSM. All were treated with ursodeoxycholic acid (UDCA). Primary endpoint was death, liver transplantation (LT), or liver decompensation (LD) as defined by ascites, variceal bleeding, hepatic encephalopathy, doubling of total bilirubin level above 3 mg/dl, hepatocellular carcinoma, or minimal criteria for LT. Prognostic factors were evaluated using Cox regression analysis. Results: 507 validated LSM were recorded during 395 patient-years of follow-up. The average number of LSM per patient was 3.4±1.4 (range, 2–8). The mean LSM at baseline was 9.4±7.5 kPa (range, 3.1 kPa-48.8 kPa). The mean variation in LSM over time (DLSM/∂t) was 0.5±2.9 kPa/year (range, −6.9 kPa/year – 17.5 kPa/year). Over the extended follow-up, 11 (7.3%) adverse events (2 deaths, including 1 non-liver related, 4 LTs, 5 LDs) occurred. Both baseline LSM and DLSM/∂t were significantly associated with the risk of death, LT or LD (p < 0.0001), independently of baseline total bilirubin level and biochemical response to UDCA. Optimal prognostic thresholds of 9.6 kPa (baseline LSM) and 2.1 kPa/year (DLSM/∂t) were associated with a 5.1 (95% CI, 1.5–15.9) and 8.4 (95% CI, 3.6–36.0) times increased risk of death, LT or LD, respectively (figure). Conclusions: The absolute value of LSM assessed by FS and more significantly its increase over time are major predictors of poor outcome in PBC.
Table 1 Fibrosis
[ALT] ≤ upper limit of normal (ULN)* (521p)
p 3–5×ULN# (82p)
>5×ULN§ (62p)
F0–1
1.13±0.36 (210p)
1.35±0.39 (17p)
1.45±0.38 (28p)
F2
1.25±0.37 (121p)
1.45±0.25 (21p)
1.55±0.27 (11p)
F3
1.56±0.50 (87p)
1.68±0.38 (24p)
2.13±0.73 (9p)
*# 0.01, *§ <0.0001, #§ 0.40 *# 0.01, *§ :0.002, #§ 0.30 *# 0.27 *§ 0.002, #§ 0.02
F4
2.02±0.68 (103p)
2.52±0.77 (20p)
2.55±0.70 (14p)
*# 0.003, *§ 0.007, #§ 0.90
In this large cohort of patients with chronic hepatopathies, the best ARFI cut-off value to predict liver cirrhosis (F4) was 1.57 m/s (AUROC = 0.845). The percentage of non-cirrhotic patients in whom LS values as assessed by ARFI were >1.57 m/s was significantly higher in patients with ALT levels >5×ULN as compared with those with ALT ≤5×ULN: 21/49p (42.8%) vs. 179/834p (21.4%) (p = 0.0009). Conclusions: The data from this international multicenter study suggest that in patients with high values of aminotransferases (>5×ULN), LS values as assessed by ARFI are significantly higher for the same stage of fibrosis than in patients with normal ALT. Currently in patients with aminotransferases >5×ULN we should not rely on ARFI evaluation until we are able to calculate a correction factor for ARFI measurements.
81 A ROLE FOR ANTICOAGULATION IN FIBROGENESIS: SUPPRESSION OF HUMAN HEPATIC STELLATE CELL CONTRACTILITY AND LIVER FIBROSIS IN VITRO AND VIVO A. Dhar1 , Q.M. Anstee2 , F. Sadiq1 , A. Levene3 , J. Cobbold1 , G. Petts3 , S. Taylor-Robinson1 , R. Goldin3 , M.R. Thursz1 . 1 Department of Hepatology, Imperial College London, London, 2 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, 3 Department of Histopathology, Imperial College London, London, UK E-mail: [email protected] Introduction and Aims: Evidence suggests that thrombin activates hepatic stellate cells (HSC) via PAR-1. The role of Factor Xa (FXa) in hepatic fibrosis however has not been evaluated to date. We therefore aimed to evaluate the impact of FXa, thrombin and their
Journal of Hepatology 2012 vol. 56 | S21–S44
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80 BASELINE AND SEQUENTIAL LIVER STIFFNESS MEASUREMENTS (FIBROSCAN® ) ARE INDEPENDENT PREDICTORS OF DEATH, LIVER TRANSPLANTATION OR LIVER DECOMPENSATION IN PRIMARY BILIARY CIRRHOSIS C. Corpechot, A. Poujol-Robert, F. Gaouar, O. Chazouilleres, R. Poupon. Service d’H´epatologie, Centre de R´ef´erence des Maladies Inflammatoires des Voies Biliaires, UMR_S938, Hˆ opital Saint-Antoine, AP-HP, UPMC, Paris, France E-mail: [email protected] Background and Aims: Liver stiffness measurement (LSM) as assessed by transient elastography (Fibroscan® , FS) has been shown as a reliable non-invasive surrogate marker of liver fibrosis in primary biliary cirrhosis (PBC). The present study aimed at assessing the prognostic significance of LSM in PBC. Methods: A total of 150 patients with non-decompensated PBC (mean age, 57 years; 89% women) were followed-up using FS for a period of 2.6±1.2 years (up to 5.3 years), then followed-up for an additional period of 2.3±1.1 years (up to 5.1 years) after last LSM. All were treated with ursodeoxycholic acid (UDCA). Primary endpoint was death, liver transplantation (LT), or liver decompensation (LD) as defined by ascites, variceal bleeding, hepatic encephalopathy, doubling of total bilirubin level above 3 mg/dl, hepatocellular carcinoma, or minimal criteria for LT. Prognostic factors were evaluated using Cox regression analysis. Results: 507 validated LSM were recorded during 395 patient-years of follow-up. The average number of LSM per patient was 3.4±1.4 (range, 2–8). The mean LSM at baseline was 9.4±7.5 kPa (range, 3.1 kPa-48.8 kPa). The mean variation in LSM over time (DLSM/∂t) was 0.5±2.9 kPa/year (range, −6.9 kPa/year – 17.5 kPa/year). Over the extended follow-up, 11 (7.3%) adverse events (2 deaths, including 1 non-liver related, 4 LTs, 5 LDs) occurred. Both baseline LSM and DLSM/∂t were significantly associated with the risk of death, LT or LD (p < 0.0001), independently of baseline total bilirubin level and biochemical response to UDCA. Optimal prognostic thresholds of 9.6 kPa (baseline LSM) and 2.1 kPa/year (DLSM/∂t) were associated with a 5.1 (95% CI, 1.5–15.9) and 8.4 (95% CI, 3.6–36.0) times increased risk of death, LT or LD, respectively (figure). Conclusions: The absolute value of LSM assessed by FS and more significantly its increase over time are major predictors of poor outcome in PBC.
Table 1 Fibrosis
[ALT] ≤ upper limit of normal (ULN)* (521p)
p 3–5×ULN# (82p)
>5×ULN§ (62p)
F0–1
1.13±0.36 (210p)
1.35±0.39 (17p)
1.45±0.38 (28p)
F2
1.25±0.37 (121p)
1.45±0.25 (21p)
1.55±0.27 (11p)
F3
1.56±0.50 (87p)
1.68±0.38 (24p)
2.13±0.73 (9p)
*# 0.01, *§ <0.0001, #§ 0.40 *# 0.01, *§ :0.002, #§ 0.30 *# 0.27 *§ 0.002, #§ 0.02
F4
2.02±0.68 (103p)
2.52±0.77 (20p)
2.55±0.70 (14p)
*# 0.003, *§ 0.007, #§ 0.90
In this large cohort of patients with chronic hepatopathies, the best ARFI cut-off value to predict liver cirrhosis (F4) was 1.57 m/s (AUROC = 0.845). The percentage of non-cirrhotic patients in whom LS values as assessed by ARFI were >1.57 m/s was significantly higher in patients with ALT levels >5×ULN as compared with those with ALT ≤5×ULN: 21/49p (42.8%) vs. 179/834p (21.4%) (p = 0.0009). Conclusions: The data from this international multicenter study suggest that in patients with high values of aminotransferases (>5×ULN), LS values as assessed by ARFI are significantly higher for the same stage of fibrosis than in patients with normal ALT. Currently in patients with aminotransferases >5×ULN we should not rely on ARFI evaluation until we are able to calculate a correction factor for ARFI measurements.
81 A ROLE FOR ANTICOAGULATION IN FIBROGENESIS: SUPPRESSION OF HUMAN HEPATIC STELLATE CELL CONTRACTILITY AND LIVER FIBROSIS IN VITRO AND VIVO A. Dhar1 , Q.M. Anstee2 , F. Sadiq1 , A. Levene3 , J. Cobbold1 , G. Petts3 , S. Taylor-Robinson1 , R. Goldin3 , M.R. Thursz1 . 1 Department of Hepatology, Imperial College London, London, 2 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, 3 Department of Histopathology, Imperial College London, London, UK E-mail: [email protected] Introduction and Aims: Evidence suggests that thrombin activates hepatic stellate cells (HSC) via PAR-1. The role of Factor Xa (FXa) in hepatic fibrosis however has not been evaluated to date. We therefore aimed to evaluate the impact of FXa, thrombin and their
Journal of Hepatology 2012 vol. 56 | S21–S44
S35