1. Non-Invasive Assessment of PSC Progression
Olivier CHAZOUILLERES
Hepatology Department
Saint Antoine Hospital
Paris
Rare Liver Diseases French Network
PSCP and IPSCSG meeting, New Haven, June 2016 1

2. Disclosures Research support: Aptalis
Consulting: Mayoly Spindler, Genfit, Intercept
Sponsored lectures: Mayoly Spindler, Falk Fondation, Aptalis

3. Non-Invasive Tests in PSC (for Evaluation of Liver Disease Severity and Prognosis)
Elastography: liver stiffness quantification
Vibration controlled transient elastography (VCTE)
Magnetic resonance elastography (MRE)
Others
Serum biomarkers of liver fibrosis: ELF score
Abdominal imaging: Magnetic resonance imaging (MRI)
♠ Everyday care
♠ Potential use in clinical trials:
♦ Risk Stratification
♦ Surrogate endpoints ?

4. Liver Stiffness
Validated non-invasive surrogate marker for hepatic fibrosis in chronic liver diseases (performing best at extremes of histological stages)
Prognostic capabilities
PBC
n = 146
VTCE
(Corpechot et al, Hepatology 2012)
Elastography: information from a much larger portion of tissue compared with liver biopsy
PBC
n = 150
VTCE
(Corpechot et al, Hepatology 2012)

5. Vibration Controlled Transient Elastography (VCTE)
FibroScan (Echosens, Paris, France, FDA approved): kilopascals (kPa)
The stiffer the tissue, the faster the shear wave propagates

6. (limited operator experience,
VCTE
Technical issues:
Recommendations:
10 valid measurements
Success rate ≥ 60%
IQR/median value < 30%
Fasting for at least 2 hours (Arena et al, Hepatology 2013)
Limitations: failure or unreliable results ≈ 15%
(limited operator experience,
obesity [XL probe])

7. VCTE and Fibrosis in PSC
(Corpechot et al, Gastroenterology 2014)
Technical failure or unreliable results :10%
reproducibility
between operators
reproducibility
between 2 adjacent sites

8. VCTE and Prognosis in PSC
♠ Transplant and complications free survival: 168 patients, mean F-U: 4 years
(Ehlken et al, personal)
Independent prognostic variables:
LS and bilirubin
(Corpechot et al, Gastroenterology 2014)
♠ Prospective validation mandatory: ongoing FICUS study
♦ strict conditions when performing VCTE
♦ double checking recommended if increased values

9. VCTE and LS Course in PSC
149 patients, mean F-U: 4 years
( VCTE/patient)
(Corpechot et al, Gastroenterology 2014)

10. Magnetic Resonance Elastograpy (MRE)
Advantages:
Very large sampling (almost the entire liver)
Low failure rate ( < 6%) and good applicability in obeses
Better accuracy than VTCE for grading steatosis and fibrosis in NASH ? (Imajo et al, Gastroenterology 2016)
Limitations: reduced availability, high cost (and time consuming), some variability in parameters across series
kPa (comparison: VCTE measurements/3)
(MRE can be performed at the same time as MR cholangiography)

11. MRE and PSC (Eaton et al, J Gastroenterol Hepatol 2016)
Median follow-up: 2 years
n = 20
Optimal cutoff for F4:
4.93 kPa
(Eaton et al, J Gastroenterol Hepatol 2016)

12. Liver Stiffness and PSC
Confounders in terms of fibrosis staging (falsely elevated values)
Dominant stenosis :
- SB = 8.7 mg/dl, LS = 43.8 kPa
Endoscopic stenting
- SB = 1.0 mg/dl, LS = 11.6 kPa
(Ehlken et al, Gastroenterology 2016)
(Tapper et al, Clin Gastroenterol Hepatol 2015)
Liver stiffness: reflects mainly fibrosis but not only !
Cholestasis and inflammation: players in the course of PSC
Advantage in terms of prognostic value ?
Other ultrasound-based techniques [point shear wave elastography (pSWE) (ARFI)
and 2D-SWE (Aixplorer)]: very few data in PSC

13. Elastography and PSC: Summary
Liver stiffness:
More data available with VCTE
Current evidence:
« Non-invasive assessment of liver fibrosis, using VCTE, should be considered in PSC » B (EASL guidelines 2015)
VCTE: « non-validated surrogate endpoint , yet one established to be reasonably likely to predict clinical benefit » (Ponsioen et al, Hepatology 2015)
VCTE:
(?)
(Vuppalanchi et Lindor, Gastroenterology 2014)

14. Enhanced Liver Fibrosis (ELF) Score
ELF: hyaluronic acid, TIMP-1 and PIIIP (circulating markers of hepatic matrix metabolism)
161 PBC
(Mayo et al, Hepatology 2008)

15. ELF Score and PSC (1) (Vesterhus et al, Hepatology 2015)
Derivation panel (n=167)
Validation panel (n=138)
(Vesterhus et al, Hepatology 2015)

16. ELF Score and PSC (2) (Vesterhus et al, Hepatology 2015)
rho=0.706, p=0.001
(Eddowes et al, EASL 2016)

17. Cholangiographic Scores (ERCP)
Invasive
Primary diagnostic modality: MRCP
(Ponsioen et al, Gut 2002 and Endoscopy 2010)

18. MRI Score: Paris Experience (1)
64 patients, 289 3D MRCP, mean F-U: 4 years
(Ruiz et al, Hepatology 2014)
Radiological Course
Stability
Worsening
♦MRI progression risk score (without gadolinium):
1 x dilatation IHBD + 2 x dysmorphy +1 x PHTension
♦ MRI progression risk score (with gadolinium):
1x dysmorphy + 1x parenchymal enhancement heterogeneity
Variables predictive of radiological progression:
mainly parenchymal !

19. MRI Score: Paris Experience (2)
MRI score without gadolinium
(Corpechot et al,
EASL 2016)
External validation required
Standardization of scanning and interpretation protocols mandatory
More data needed before being used as a biomarker

20. The Future: Combination ?
Combination of VCTE and MRI improves the stratification
into low and high-risk groups (Corpechot et al, EASL 2016)
MRI score
Fibroscan
Fibroscan-MRI score

21. Non-Invasive Tests in PSC Conclusions
Emerging tools
Liver stiffness (LS) (especially with VCTE) and ELF score:
Best-documented potential
Full validation still pending
How to go further ?
Combination of available tools
Big data approaches using transcriptomics, proteomics and/or metabolomics…