title: Transient elastography in autoimmune hepatitis: Timing determines the impact of inflammation and fibrosis.
abstract: There is an unmet need for the non-invasive monitoring of fibrosis progression in patients with autoimmune hepatitis (AIH). The aim of this study was to assess the diagnostic performance of transient elastography in patients with AIH and to investigate the impact of disease activity on its diagnostic accuracy.
  
  
  
  Optimal cut-offs were defined in a prospective pilot study (n=34) and the diagnostic performance of transient elastography validated in an independent second cohort (n=60). To explore the impact of disease activity on liver stiffness, patients were stratified according to biochemical response and the time interval between start of immunosuppression and transient elastography.
  
  
  
  Liver stiffness strongly correlated with histological fibrosis stage (pilot study: ρ=0.611, p<0.001; validation cohort: ρ=0.777, p<0.0001). ROC curves defined an area under the receiver operating curve of 0.95 for diagnosing cirrhosis at the optimal cut-off of 16kPa. The performance of transient elastography was impaired when patients were analysed in whom transient elastography was performed within 3months from start of treatment. In this setting, liver stiffness correlated with histological grading (ρ=0.558, p=0.001), but not with staging. In contrast, using the cut-off of 16kPa, the accuracy for diagnosing cirrhosis was excellent in patients treated for 6months or longer (area under the receiver operating curve 1.0).
  
  
  
  Liver inflammation has a major impact on liver stiffness in the first months of AIH treatment. However, transient elastography has an excellent diagnostic accuracy for separating severe from non-severe fibrosis after 6months of immunosuppressive treatment.
  
  
  
  Transient elastography is a special ultrasound scan, which assesses liver stiffness as a surrogate marker for liver fibrosis/scarring. Transient elastography has been shown to be a reliable non-invasive method to assess liver fibrosis in various chronic liver diseases, it takes less than 5min and has a high patient acceptance. The current study validated for the first time this technique in a large cohort of patients with autoimmune hepatitis (AIH) and demonstrates that it is a reliable tool to detect liver fibrosis in treated AIH. For the monitoring of potential disease progression under treatment, the validation of liver stiffness as non-invasive marker of liver fibrosis will greatly improve patient care in autoimmune hepatitis.
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hartl
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany; Interdisciplinary Endoscopy Unit, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Denzer
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany; Interdisciplinary Endoscopy Unit, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Ehlken
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Zenouzi
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Peiseler
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany.
authors.forename: Marcial
authors.initials: M
authors.lastname: Sebode
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany.
authors.forename: Sina
authors.initials: S
authors.lastname: Hübener
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Pannicke
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Weiler-Normann
authors.affiliation: Institute for Pathology, University Hospital of Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany.
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.affiliation: University Medical Centre Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany. Electronic address: cschramm@uke.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schramm
mesh_terms: D001706:Biopsy; D054459:Elasticity Imaging Techniques; D019693:Hepatitis, Autoimmune; D006801:Humans; D007249:Inflammation; D008099:Liver; D008103:Liver Cirrhosis; D010865:Pilot Projects; D011446:Prospective Studies; D012372:ROC Curve
keywords: Autoimmune hepatitis; FibroScan; Fibrosis stage; Liver fibrosis; Non-invasive; Transient elastography