PROSPECTIVE STUDY OF THE PROGNOSTIC VALUE OF TRANSIENT ELASTOMETRY (FIBROSCAN) IN PRIMARY SCLEROSING CHOLANGITIS (PSC) PATIENTS (FICUS STUDY)

PSC is a rare (prevalence rate around 10/100.000 in northern European
descendants) and chronic cholestatic liver disease of unknown cause commonly
associated with inflammatory bowel disease (IBD) and characterized by
progressive obliterative fibrosis of the biliary tree. Although the natural
course may be variable from one patient to another, PSC is often progressive,
leading to biliary cirrhosis and its complications. In addition, one specific
complication is the occurrence of cholangiocarcinoma whose early diagnosis is
highly challenging. Overall, median survival ranges from 11 to 18 years.
Several therapeutic modalities (medical, endoscopic and surgical) have been
investigated. Unfortunately none except liver transplantation (LT) has been
proven to alter the course of the disease significantly. Several prognostic
models including clinical and biochemical parameters have been developed.
However, it appears that these models are useful in predicting outcomes in
patient cohorts but cannot reliably be used to predict outcome in an individual
patient.

Advanced fibrosis is a major prognostic factor in all liver diseases, including
PSC. Liver biopsy (LB) has traditionally been the standard for evaluation of
fibrosis. However, LB is an invasive procedure that is prone to sampling errors
and to intra- and interobserver variation. These limitations have fueled the
development of noninvasive methods to assess liver fibrosis over the past
decade. Fibrosis can be measured non invasively, based on a *biological*
approach (quantifying biomarkers in serum samples) or based on a *physical*
approach (measuring liver stiffness). In cholestatic diseases (primary biliary
cirrhosis (PBC) and PSC), the diagnostic performance of current serum markers
of fibrosis is lower than that of liver stiffness for detecting significant
fibrosis.

Liver fibrosis can be staged using 1-dimensional ultrasound transient
elastography (TE) which measures the velocity of a low-frequency (50 Hz)
elastic shear wave propagating through the liver (Echosens, Paris, France). The
stiffer the tissue, the faster the shear wave propagates. The results are
expressed in kilopascals (kPa) and range from 2.5 to 75 kPa (normal value
around 5 kPa). TE is a short time (< 10 minutes) and totally non-invasive
procedure. TE has been implemented in many countries (more than 1300 devices
worldwide) and no side effects have been ever reported. Numerous studies have
shown a good correlation between liver stiffness and histologic stage of
fibrosis in various chronic liver diseases, especially in chronic hepatitis C
(CHC). The development of TE (and serum markers of fibrosis) has markedly
reduced the need for liver biopsy analysis in CHC. Furthermore, it has been
demonstrated that liver stiffness can predict 5-year survival of patients with
CHC. Fibroscan is also used in other chronic liver diseases, including
cholestatic diseases. In PBC or PSC, several studies have shown that TE has
high accuracy in diagnosing significant fibrosis. Lastly, our group has
recently demonstrated that liver stiffness is predictive of poor outcome
(survival without liver complications) in PBC patients.

In most referral centers, Fibroscan is routinely performed in PSC patients.
Thus, there is a strong rationale for studying the prognostic value of liver
stiffness in PSC, a severe liver disease without any prognostic models
currently recommended in clinical practice. At the same time, search for
accurate biomarkers of fibrosis and, more widely, of prognosis in PSC has to be
done and compared to Fibroscan.

The International PSC Study Group (worldwide network of referral centers for
PSC, www.ipscsg.org) provides a frame perfectly adapted to such a study.

To determine the prognostic value of transient elastography (Fibroscan) in PSC
patients.

International, prospective multicohort study

Negligible burden or risk.