Hugo Perazzo1, Raluca Pais2, Mona Munteanu3, Yen Ngo3, Denis Monneret4, Françoise Imbert-Bismut4, Joseph Moussalli1, Pascal Lebray1, Yves Benhamou1, Dominique Thabut1, Vlad Ratziu1, Victor de Ledhingen5, Thierry Poynard6. 1. Hepatology Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France. 2. Hepatology Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; UMR_S 938, INSERM, Université Pierre et Marie Curie, Université Paris 06, Institute of Cardiometabolism and Nutrition (ICAN), Centre de Recherche Saint-Antoine & Paris, France. 3. BioPredictive, Paris, France. 4. Biochemistry Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 5. Hepatology, Hôpital Haut Leveque, Bordeaux, France. 6. Hepatology Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; UMR_S 938, INSERM, Université Pierre et Marie Curie, Université Paris 06, Institute of Cardiometabolism and Nutrition (ICAN), Centre de Recherche Saint-Antoine & Paris, France. Electronic address: tpoynard@teaser.fr.
Abstract
BACKGROUND: The aspartate aminotransferase platelet ratio index (APRI) is a validated, non-patented blood test for diagnosing fibrosis or cirrhosis in patients with chronic hepatitis C. We assess the impact of two limitations, the variability of the upper limit of normal for aspartate aminotransferase (AST-ULN) and the risk of overestimating fibrosis stage due to necroinflammatory activity. METHODS: The variability of AST-ULN was assessed by an overview of the literature and an assessment of AST-ULN in 2 control populations 7521 healthy volunteers and 393 blood donors. We assessed the impact of AST-ULN variability on APRI performance for estimating fibrosis prevalence and on the Obuchowski measure using individual data of 1651 patients with APRI, FibroTest and biopsy. RESULTS: The overview, and the analysis of the control populations found that ULN-AST ranged from 26 to 49 IU/L according to gender, body mass index and serum cholesterol. When this AST-ULN variability was applied to the chronic hepatitis group, the prevalence of advanced fibrosis and cirrhosis as presumed by APRI varied (P<0.001) from 34.7% to 68.5%, and from 11.4% to 32.3%, respectively. This spectrum effect induced variability in APRI performance, which could be similar 0.862 (if AST-ULN=26 IU/L) or lower 0.820 (AST-ULN≥30IU/L) than the stable FibroTest performance (0.867; P=0.35 and P<0.0001 respectively). When applied to 18 acute hepatitis C patients, the rate of false positives of APRI varied from 0% to 61% due to AST-ULN. CONCLUSION: The AST-ULN variability is high highly associated with the variability of metabolic risk factors between the different control groups. This variability induces a spectrum effect, which could cause misleading interpretations of APRI performance for the staging of fibrosis, comparisons of APRI with other non-invasive tests, and estimates of false positive rate.
BACKGROUND: The aspartate aminotransferase platelet ratio index (APRI) is a validated, non-patented blood test for diagnosing fibrosis or cirrhosis in patients with chronic hepatitis C. We assess the impact of two limitations, the variability of the upper limit of normal for aspartate aminotransferase (AST-ULN) and the risk of overestimating fibrosis stage due to necroinflammatory activity. METHODS: The variability of AST-ULN was assessed by an overview of the literature and an assessment of AST-ULN in 2 control populations 7521 healthy volunteers and 393 blood donors. We assessed the impact of AST-ULN variability on APRI performance for estimating fibrosis prevalence and on the Obuchowski measure using individual data of 1651 patients with APRI, FibroTest and biopsy. RESULTS: The overview, and the analysis of the control populations found that ULN-AST ranged from 26 to 49 IU/L according to gender, body mass index and serum cholesterol. When this AST-ULN variability was applied to the chronic hepatitis group, the prevalence of advanced fibrosis and cirrhosis as presumed by APRI varied (P<0.001) from 34.7% to 68.5%, and from 11.4% to 32.3%, respectively. This spectrum effect induced variability in APRI performance, which could be similar 0.862 (if AST-ULN=26 IU/L) or lower 0.820 (AST-ULN≥30IU/L) than the stable FibroTest performance (0.867; P=0.35 and P<0.0001 respectively). When applied to 18 acute hepatitis C patients, the rate of false positives of APRI varied from 0% to 61% due to AST-ULN. CONCLUSION: The AST-ULN variability is high highly associated with the variability of metabolic risk factors between the different control groups. This variability induces a spectrum effect, which could cause misleading interpretations of APRI performance for the staging of fibrosis, comparisons of APRI with other non-invasive tests, and estimates of false positive rate.
Authors: Flavia F Fernandes; Hugo Perazzo; Luiz E Andrade; Alessandra Dellavance; Carlos Terra; Gustavo Pereira; João L Pereira; Frederico Campos; Maria L Ferraz; Renata M Perez Journal: Biomed Res Int Date: 2017-09-13 Impact factor: 3.411