Validation of Transient Elastography and Comparison with Spleen Length Measurement for Staging of Fibrosis and Clinical Prognosis in Primary Sclerosing Cholangitis

Hanno Ehlken, Raluca Wroblewski, Christophe Corpechot, Lionel Arrivé, Tim Rieger, Johannes Hartl, Susanne Lezius, Peter Hübener, Kornelius Schulze, Roman Zenouzi, Marcial Sebode, Moritz Peiseler, Ulrike W Denzer, Alexander Quaas, Christina Weiler-Normann, Ansgar W Lohse, Olivier Chazouilleres, Christoph Schramm, Hanno Ehlken, Raluca Wroblewski, Christophe Corpechot, Lionel Arrivé, Tim Rieger, Johannes Hartl, Susanne Lezius, Peter Hübener, Kornelius Schulze, Roman Zenouzi, Marcial Sebode, Moritz Peiseler, Ulrike W Denzer, Alexander Quaas, Christina Weiler-Normann, Ansgar W Lohse, Olivier Chazouilleres, Christoph Schramm

Abstract

Background: Patients with primary sclerosing cholangitis (PSC) develop progressive liver fibrosis and end-stage liver disease. Non-invasive and widely available parameters are urgently needed to assess disease stage and the risk of clinical progression. Transient elastography (TE) has been reported to predict fibrosis stage and disease progression. However, these results have not been confirmed in an independent cohort and comparison of TE measurement to other non-invasive means is missing.

Methods: In a retrospective study we collected data from consecutive PSC patients receiving TE measurements from 2006 to 2014 (n = 139). Data from 62 patients who also underwent a liver biopsy were used to assess the performance of TE and spleen length (SL) measurement for the staging of liver fibrosis. Follow-up data from this cohort (n = 130, Hamburg) and another independent cohort (n = 80, Paris) was used to compare TE and SL as predictors of clinical outcome applying Harrel's C calculations.

Results: TE measurement had a very good performance for the diagnosis and exclusion of higher fibrosis stages (≥F3: AUROC 0.95) and an excellent performance for the diagnosis and exclusion of cirrhosis (F4 vs. < F4: AUROC 0.98). Single-point TE measurement had very similar predictive power for patient outcome as previously published. In a combined cohort of PSC patients (n = 210), SL measurements had a similar performance as TE for the prediction of patient outcome (5 x cross-validated Harrel's C 0.76 and 0.72 for SL and TE, respectively).

Conclusions: Baseline TE measurement has an excellent performance to diagnose higher fibrosis stages in PSC. Baseline measurements of SL and TE have similar usefulness as predictive markers for disease progression in patients with PSC.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. The Performance of TE Diagnosing…
Fig 1. The Performance of TE Diagnosing Liver Fibrosis in PSC.
Box plot of TE measurement depending on histological fibrosis stage F0-F4 (n = 62). The bottom and top of the boxes represent the 25th and 75th percentile and the horizontal lines the median. The whiskers are the minimum and maximum of the data.
Fig 2. Survival Rates of PSC Patients…
Fig 2. Survival Rates of PSC Patients for Different TE Cut-off Values.
Survival rates according to the different cut-off values (A-C) of TE measurement as previously suggested [15]. (log-rank test, p

Fig 3. Survival rates according to SL…

Fig 3. Survival rates according to SL and TE measurement.

Survival rates according to SL…

Fig 3. Survival rates according to SL and TE measurement.
Survival rates according to SL measurement with 120 mm cut-off and according to TE measurement with different cut-off values (B-D) for the combined cohort of PSC patients (Hamburg + Paris, see text). (log-rank test, p
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    1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. Journal of hepatology. 2009. pp. 237–267. 10.1016/j.jhep.2009.04.009 - DOI - PubMed
    1. Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology. 2011;54: 1842–1852. 10.1002/hep.24570 - DOI - PMC - PubMed
    1. Sandrin L, Fourquet B, Hasquenoph J-M, Yon S, Fournier C, Mal F, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29: 1705–1713. - PubMed
    1. Fraquelli M, Branchi F. The role of transient elastography in patients with hepatitis B viral disease. Dig Liver Dis. 2011;43 Suppl 1: S25–31. 10.1016/S1590-8658(10)60689-5 - DOI - PubMed
    1. Talwalkar JA, Kurtz DM, Schoenleber SJ, West CP, Montori VM. Ultrasound-based transient elastography for the detection of hepatic fibrosis: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2007;5: 1214–1220. 10.1016/j.cgh.2007.07.020 - DOI - PubMed
Show all 27 references
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The study was supported by the DFG (SFB841 and KFO306), the YAEL-Foundation, and the Helmut and Hannelore Greve Foundation, Hamburg, Germany.
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Fig 3. Survival rates according to SL…
Fig 3. Survival rates according to SL and TE measurement.
Survival rates according to SL measurement with 120 mm cut-off and according to TE measurement with different cut-off values (B-D) for the combined cohort of PSC patients (Hamburg + Paris, see text). (log-rank test, p

References

    1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. Journal of hepatology. 2009. pp. 237–267. 10.1016/j.jhep.2009.04.009
    1. Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology. 2011;54: 1842–1852. 10.1002/hep.24570
    1. Sandrin L, Fourquet B, Hasquenoph J-M, Yon S, Fournier C, Mal F, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29: 1705–1713.
    1. Fraquelli M, Branchi F. The role of transient elastography in patients with hepatitis B viral disease. Dig Liver Dis. 2011;43 Suppl 1: S25–31. 10.1016/S1590-8658(10)60689-5
    1. Talwalkar JA, Kurtz DM, Schoenleber SJ, West CP, Montori VM. Ultrasound-based transient elastography for the detection of hepatic fibrosis: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2007;5: 1214–1220. 10.1016/j.cgh.2007.07.020
    1. Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142: 1293–1302.e4. 10.1053/j.gastro.2012.02.017
    1. Gaia S, Carenzi S, Barilli AL, Bugianesi E, Smedile A, Brunello F, et al. Reliability of transient elastography for the detection of fibrosis in Non-Alcoholic Fatty Liver Disease and chronic viral hepatitis. J Hepatol. European Association for the Study of the Liver; 2011;54: 64–71. 10.1016/j.jhep.2010.06.022
    1. Corpechot C, Naggar El A, Poujol-Robert A, Ziol M, Wendum D, Chazouillères O, et al. Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC. Hepatology. 2006;43: 1118–1124. 10.1002/hep.21151
    1. Floreani A, Cazzagon N, Martines D, Cavalletto L, Baldo V, Chemello L. Performance and utility of transient elastography and noninvasive markers of liver fibrosis in primary biliary cirrhosis. Dig Liver Dis. 2011;43: 887–892. 10.1016/j.dld.2011.06.011
    1. Gómez-Dominguez E, Mendoza J, García-Buey L, Trapero M, Gisbert JP, Jones EA, et al. Transient elastography to assess hepatic fibrosis in primary biliary cirrhosis. Aliment Pharmacol Ther. 2008;27: 441–447. 10.1111/j.1365-2036.2007.03585.x
    1. Wang J-H, Changchien C-S, Hung C-H, Tung W-C, Kee K-M, Chen C-H, et al. Liver stiffness decrease after effective antiviral therapy in patients with chronic hepatitis C: Longitudinal study using FibroScan. J Gastroenterol Hepatol. 2010;25: 964–969. 10.1111/j.1440-1746.2009.06194.x
    1. Merchante N, Rivero-Juárez A, Téllez F, Merino D, José Ríos-Villegas M, Márquez-Solero M, et al. Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis. Hepatology. 2012;56: 228–238. 10.1002/hep.25616
    1. Wong VW-S, Vergniol J, Wong GL-H, Foucher J, Chan HL-Y, Le Bail B, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010;51: 454–462. 10.1002/hep.23312
    1. Corpechot C, Carrat F, Poujol-Robert A, Gaouar F, Wendum D, Chazouillères O, et al. Noninvasive elastography-based assessment of liver fibrosis progression and prognosis in primary biliary cirrhosis. Hepatology. 2012;56: 198–208. 10.1002/hep.25599
    1. Corpechot C, Gaouar F, Naggar El A, Kemgang A, Wendum D, Poupon R, et al. 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;146: 970–9– quiz e15–6. 10.1053/j.gastro.2013.12.030
    1. Ehlken H, Wroblewski R, Corpechot C, Arrivé L, Lezius S, Hartl J, et al. Spleen size for the prediction of clinical outcome in patients with primary sclerosing cholangitis. Gut. BMJ Publishing Group Ltd and British Society of Gastroenterology; 2016;: gutjnl–2016–311452. 10.1136/gutjnl-2016-311452
    1. Frenzel C, Koch J, Lorenzen V, Werner T, Lohse AW, Denzer UW. Complications and risk factors in 2731 diagnostic mini-laparoscopies in patients with liver disease. Liver Int. 2012;32: 970–976. 10.1111/j.1478-3231.2012.02767.x
    1. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19: 1513–1520.
    1. Harrell FE, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247: 2543–2546.
    1. Ponsioen CY, Chapman RW, Chazouillères O, Hirschfield GM, Karlsen TH, Lohse AW, et al. Surrogate endpoints for clinical trials in primary sclerosing cholangitis; review and results from an International PSC Study Group consensus process. Hepatology. 2015;: n/a–n/a. 10.1002/hep.28256
    1. Claessen MMH, Vleggaar FP, Tytgat KMAJ, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol. 2009;50: 158–164. 10.1016/j.jhep.2008.08.013
    1. Fevery J, Henckaerts L, Van Oirbeek R, Vermeire S, Rutgeerts P, Nevens F, et al. Malignancies and mortality in 200 patients with primary sclerosering cholangitis: a long-term single-centre study. Liver Int. 2012;32: 214–222. 10.1111/j.1478-3231.2011.02575.x
    1. Millonig G, Reimann FM, Friedrich S, Fonouni H, Mehrabi A, Büchler MW, et al. Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis. Hepatology. 2008;48: 1718–1723. 10.1002/hep.22577
    1. Fung J, Lai C-L, Cheng C, Wu R, Wong DK-H, Yuen M-F. Mild-to-moderate elevation of alanine aminotransferase increases liver stiffness measurement by transient elastography in patients with chronic hepatitis B. Am J Gastroenterol. 2011;106: 492–496. 10.1038/ajg.2010.463
    1. Ehlken H, Lohse AW, Schramm C. Transient elastography in primary sclerosing cholangitis-the value as a prognostic factor and limitations. Gastroenterology. 2014;147: 542–543. 10.1053/j.gastro.2014.04.058
    1. Vesterhus M, Hov JR, Holm A, Schrumpf E, Nygård S, Godang K, et al. Enhanced liver fibrosis score predicts transplant-free survival in primary sclerosing cholangitis. Hepatology. 2015;62: 188–197. 10.1002/hep.27825
    1. Eaton JE, Dzyubak B, Venkatesh SK, Smyrk TC, Gores GJ, Ehman RL, et al. Performance of magnetic resonance elastography in primary sclerosing cholangitis. J Gastroenterol Hepatol. 2016;31: 1184–1190. 10.1111/jgh.13263

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