Highlight
This large prospective cohort study validates liver stiffness measurement (LSM) via vibration-controlled transient elastography (Fibroscan®) as a robust prognostic tool in primary sclerosing cholangitis (PSC). Both baseline LSM values and longitudinal changes in LSM independently predict transplant-free survival, underscoring their utility for clinical risk stratification and as surrogate endpoints in clinical trials.
Study Background
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts, often progressing to cirrhosis, liver failure, and the need for liver transplantation. Despite advances in research, predicting individual outcomes in PSC remains a significant challenge due to the disease’s heterogeneous clinical course and limited reliable biomarkers. Noninvasive, reproducible, and easily accessible measures capable of forecasting disease progression and adverse outcomes are urgently needed to guide patient management and therapeutic development.
Liver stiffness measurement (LSM) using vibration-controlled transient elastography (Fibroscan®) has emerged as a promising modality for noninvasive assessment of liver fibrosis and portal hypertension across various chronic liver diseases. Prior retrospective studies suggested the capacity of LSM to predict clinical outcomes in PSC, but prospective validation and evaluation of dynamic LSM changes over time remained lacking.
Study Design
The FICUS (Fibroscan in Sclerosing Cholangitis) study is a large, prospective, international cohort study involving 538 adult patients with uncomplicated PSC. Participants underwent standardized assessment annually for up to five years, including clinical examinations, laboratory tests, and liver stiffness measurement by Fibroscan®.
LSM values were analyzed both as continuous variables and stratified into three clinically relevant Baveno VII categories: less than 10 kPa, 10 to less than 15 kPa, and greater than 15 kPa. The primary endpoint was transplant-free survival (survival without liver transplantation). Statistical analyses employed time-dependent multivariable Cox regression models adjusted for confounders to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Joint modeling examined the prognostic influence of LSM dynamics over time, with progression defined by a statistically significant positive slope in individual LSM trajectories.
Key Findings
The median baseline LSM across the cohort was 7.6 kPa (interquartile range, 5.8–11.7). Over a median follow-up of 60.7 months, 19 patients died and 72 underwent liver transplantation. The study demonstrated a strong, independent association between baseline LSM and risk of death or transplantation (RDT).
Five-year transplant-free survival rates varied substantially across LSM strata: 93.9% (90.3%–96.2%) for patients with LSM <10 kPa; 78.1% (66.2%–86.3%) for 10–15 kPa. These gradients confirm the prognostic discrimination provided by LSM categories.
Regarding dynamic assessment, patients with significant progression in LSM (positive slope) exhibited markedly poorer transplant-free survival compared to non-progressors, with an adjusted hazard ratio of 3.12 (95% CI, 1.55–6.24; P=0.001). Moreover, each 1 kPa per year increase in LSM was linked to an 18% elevated risk of death or transplantation, highlighting the incremental prognostic value of monitoring LSM changes over time.
Expert Commentary
The FICUS cohort study provides robust prospective support for the role of transient elastography-derived liver stiffness measurements as pivotal prognostic biomarkers in PSC. Integrating static and dynamic LSM assessments enables clinicians to better stratify patients by risk, potentially improving timing of referral for transplantation evaluation or management intensification.
The simplicity and noninvasive nature of Fibroscan®, combined with its reproducibility, make LSM an attractive tool for routine clinical practice and clinical trial endpoints. However, the study cohort excluded patients with decompensated disease at baseline, limiting generalizability to advanced stages. Additionally, while LSM captures fibrosis and portal hypertension-related changes, it may be influenced by cholestasis, inflammation, or technical factors, necessitating complementary clinical and imaging evaluations.
Future research exploring LSM-guided interventions, mechanistic correlations with histology, and integration with emerging biomarkers may further enhance risk prediction and precision medicine in PSC.
Conclusion
This large, prospective study confirms that liver stiffness measured by Fibroscan® serves as a strong, independent predictor of transplant-free survival in patients with PSC. Both baseline LSM values and their trajectory over time provide clinically relevant prognostic information. These findings support the incorporation of LSM-based risk stratification in clinical management and endorse LSM as a surrogate outcome measure in clinical trials aiming to mitigate disease progression in PSC.
Funding and Trial Registration
The original article did not specify funding sources. The FICUS cohort represents an international collaboration under the International PSC Study Group, reinforcing the study’s rigor and relevance.
References
- Chazouilleres O, Bellet J, Schramm C, et al. Prognostic performance of liver stiffness measurements in primary sclerosing cholangitis: the prospective FICUS cohort. Gastroenterology. 2026 Aug 4. PMID:42551570.
- European Association for the Study of the Liver (EASL) Clinical Practice Guidelines: Management of cholestatic liver diseases. J Hepatol. 2021.
- Angulo P, Gedaly R. Primary sclerosing cholangitis: natural history, prognostic factors, and management. Hepatol Commun. 2018.
