title: Noninvasive elastography-based assessment of liver fibrosis progression and prognosis in primary biliary cirrhosis.
abstract: The development of liver fibrosis markers in primary biliary cirrhosis (PBC) is needed to facilitate the assessment of its progression and the effectiveness of new therapies. Here, we investigated the potential usefulness of transient elastography (TE) in the noninvasive evaluation of liver fibrosis stage and disease progression in PBC. We performed, first, a prospective performance analysis of TE for the diagnosis of METAVIR fibrosis stages in a diagnostic cohort of 103 patients and, second, a retrospective longitudinal analysis of repeated examinations in a monitoring cohort of 150 patients followed-up for up to 5 years. All patients were treated with ursodeoxycholic acid. Diagnostic thresholds of liver stiffness in discriminating fibrosis stages ≥ F1, ≥ F2, ≥ F3, and =F4 were 7.1, 8.8, 10.7, and 16.9 kPa, respectively. TE showed high performance and was significantly superior to biochemical markers (e.g., aspartate aminotransferase [AST]/platelet ratio, FIB-4, hyaluronic acid, AST/alanine aminotransferase ratio, and Mayo score) in diagnosing significant fibrosis, severe fibrosis, or cirrhosis. Analysis of the monitoring cohort data set using generalized linear models showed the following: (1) an overall progression rate of 0.48 ± 0.21 kPa/year (P = 0.02) and (2) no significant progression in patients with F0-F1, F2, or F3 stages, but a significant increase (4.06 ± 0.72 kPa/year; P < 0.0001) in cirrhotic patients. A cut-off value of 2.1 kPa/year was associated with an 8.4-fold increased risk of liver decompensations, liver transplantations, or deaths (P < 0.0001, Cox regression analysis).
  
  
  CONCLUSIONS
  TE is one of the best current surrogate markers of liver fibrosis in PBC. Over a 5-year period, on-treatment liver stiffness appears stable in most noncirrhotic PBC patients, whereas it significantly increases in patients with cirrhosis. Progression of liver stiffness in PBC is predictive of poor outcome.
authors.affiliation: Service d'Hépatologie, Centre de référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France. christophe.corpechot@sat.aphp.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Corpechot
authors.forename: Fabrice
authors.initials: F
authors.lastname: Carrat
authors.forename: Armelle
authors.initials: A
authors.lastname: Poujol-Robert
authors.forename: Farid
authors.initials: F
authors.lastname: Gaouar
authors.forename: Dominique
authors.initials: D
authors.lastname: Wendum
authors.forename: Olivier
authors.initials: O
authors.lastname: Chazouillères
authors.forename: Raoul
authors.initials: R
authors.lastname: Poupon
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001707:Biopsy, Needle; D016001:Confidence Intervals; D018450:Disease Progression; D054459:Elasticity Imaging Techniques / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000000981:diagnostic imaging / Q000473:pathology; D008111:Liver Function Tests; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors