Baseline values and changes in liver stiffness measured by transient elastography are associated with severity of fibrosis and outcomes of patients with primary sclerosing cholangitis

Gastroenterology. 2014 Apr;146(4):970-9; quiz e15-6. doi: 10.1053/j.gastro.2013.12.030. Epub 2013 Dec 31.

Abstract

Background & aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that leads to extensive liver fibrosis and cirrhosis, which are associated with poor outcome. However, there are no validated noninvasive markers of liver fibrosis in patients with PSC. We assessed the diagnostic performance, reproducibility, longitudinal changes, and prognostic value of liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE).

Methods: In a prospective study, we analyzed percutaneous liver biopsy specimens from 73 consecutive patients with PSC from January 2005 to December 2010. Patients underwent VCTE no more than 6 months after the biopsy specimens were collected. The biopsy specimens were analyzed by a pathologist blinded to the results of VCTE for the stage of fibrosis, and LSM was associated with the stage of fibrosis and other variables using the Kruskal-Wallis and Spearman correlation tests. The cutoff values of LSM were selected based on the accuracy with which they identified the stage of fibrosis on receiver-operating characteristic analysis. The rates of LSM progression were assessed using a linear mixed model, and the association between LSM values and clinical outcomes were evaluated using Cox regression analysis in 168 patients with PSC treated with ursodeoxycholic acid and followed up from November 2004 to July 2013 (mean follow-up period, 4 years).

Results: LSM was independently linked to the stage of fibrosis. Cutoff values for fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 7.4 kPa, 8.6 kPa, 9.6 kPa, and 14.4 kPa, respectively. The adjusted diagnostic accuracy values for severe fibrosis and cirrhosis were 0.83 and 0.88, respectively. The diagnostic performance of LSM was comparable to that of hyaluronic acid measurement but superior to the aspartate aminotransferase/platelet ratio index, FIB-4 score, and Mayo risk score in differentiating patients with significant or severe fibrosis from those without. LSM had a high level of reproducibility between operators for the same measurement site and for the same operator between 2 adjacent sites. LSM increased significantly and exponentially over time. Baseline measurements and rate of LSM progression were strongly and independently linked with patients' outcomes.

Conclusions: VCTE is able to differentiate severe from nonsevere liver fibrosis with high levels of confidence in patients with PSC. Baseline measurements of LSM and longitudinal changes are prognostic factors for PSC.

Keywords: FibroScan; Prognosis; Surrogate Marker; Survival.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Biopsy
  • Cholangitis, Sclerosing / complications*
  • Cholangitis, Sclerosing / diagnosis
  • Cholangitis, Sclerosing / mortality
  • Disease Progression
  • Elasticity
  • Elasticity Imaging Techniques*
  • Female
  • Humans
  • Linear Models
  • Liver / pathology*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / mortality
  • Male
  • Middle Aged
  • Observer Variation
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • ROC Curve
  • Reproducibility of Results
  • Severity of Illness Index
  • Time Factors
  • Young Adult