Liver Stiffness in Primary Sclerosing Cholangitis: Can Annual FibroScan Improve Risk Stratification?

In primary sclerosing cholangitis, two patients may look clinically stable today yet follow very different paths over the next five years. One may remain compensated with slow biochemical change; another may move toward liver transplantation, biliary complications, or death. The challenge for hepatologists is that PSC often progresses unpredictably, and the field still lacks a proven disease-modifying medical therapy that reliably changes the natural history of the disease.

That uncertainty makes risk stratification central to PSC care. Clinicians need tools that are practical, repeatable, and meaningful enough to guide surveillance intensity, referral timing, trial enrollment, and patient counselling. A large prospective international cohort now adds important evidence that liver stiffness measurement by vibration-controlled transient elastography may help identify patients with compensated PSC who are at higher risk of death or liver transplantation.

The study, “Prognostic Performance of Liver Stiffness Measurements in Primary Sclerosing Cholangitis: The Prospective FICUS Cohort,” was published online ahead of print in Gastroenterology on August 4, 2026, with DOI 10.1053/j.gastro.2026.07.019. GI & Hepatology News summarized the findings on August 31, 2026. The official source map for GastroAGI’s audit included GI & Hepatology News and Gastroenterology among the approved sources.

The core finding is clinically straightforward but nuanced: higher baseline liver stiffness and increases in liver stiffness over time were independently associated with death or liver transplantation in adults with compensated PSC. Five-year transplant-free survival ranged from 93.9% in patients with baseline stiffness below 10 kPa to 46.0% in patients with baseline stiffness of at least 15 kPa.

The risk-prediction problem in compensated PSC

PSC is a chronic cholestatic liver disease with heterogeneous progression. Some patients remain clinically stable for many years, while others develop cirrhosis-related complications, biliary cancer, or require liver transplantation. The unmet need is not simply diagnosis; it is prediction. Which patient is quietly moving toward an adverse outcome, and which patient can be monitored without unnecessary escalation?

The FICUS investigators explicitly framed this as an unmet need: predicting PSC outcomes with reliable and simple tools remains difficult. They also noted that no medical therapy of proven efficacy exists for PSC and that liver transplantation remains the only lifesaving option.

Existing PSC risk scores, including the Mayo and Amsterdam-Oxford models, provide useful prognostic information, but routine clinical practice also needs tools that are easy to repeat over time. Liver stiffness measurement is attractive because it is non-invasive, already familiar to hepatologists, and can be performed serially. What had been less certain was how well static and dynamic liver stiffness performed prospectively in PSC.

What the FICUS cohort investigated

The FICUS cohort was conducted under the auspices of the International PSC Study Group. It enrolled adults with PSC across 13 hepatology departments in 11 countries in Europe, North America, and the Middle East between May 2013 and June 2016. Of 617 registered patients, 538 were eligible for analysis after exclusions related to inclusion criteria, changed diagnosis, duplication, lack of valid measurement, or missing follow-up.

Patients were younger than 75 years, had compensated PSC at entry, and had no evidence of malignancy. Median age was 42 years; approximately two-thirds were men; 71% had associated inflammatory bowel disease; and 76% were treated with ursodeoxycholic acid. Median duration since PSC diagnosis was five years, and median baseline liver stiffness was 7.6 kPa. Median follow-up was 60.7 months.

The exposure of interest was liver stiffness measurement, assessed by vibration-controlled transient elastography, commonly known through FibroScan. Measurements were obtained approximately annually, and unreliable measurements were excluded. Liver stiffness was evaluated continuously and using three Baveno VII categories: below 10 kPa, 10 to less than 15 kPa, and 15 kPa or higher. The researchers noted that these Baveno VII classes, developed for compensated advanced chronic liver disease, had not previously been applied in PSC.

The primary outcome was transplant-free survival. The secondary outcome was survival free of liver complications, including ascites, variceal bleeding, hepatic encephalopathy, hepatocellular carcinoma, biliary cancer, sustained marked hyperbilirubinemia, listing for transplantation, and transplantation.

Baseline stiffness separated clinically different risk groups

Among 468 patients with a reliable baseline measurement, liver stiffness categories strongly stratified five-year transplant-free survival. Patients below 10 kPa had a five-year transplant-free survival of 93.9%. Those between 10 and less than 15 kPa had survival of 78.1%. Patients at 15 kPa or higher had survival of 46.0%. During follow-up, 19 patients died and 72 underwent liver transplantation.

This gradient is clinically meaningful. It suggests that a single baseline liver stiffness value may help distinguish patients with compensated PSC who carry substantially different medium-term risks. Importantly, this is not a claim that stiffness causes the outcome. Liver stiffness is more plausibly a marker of disease severity, fibrosis burden, cholestatic injury, inflammation, or a combination of pathophysiologic processes that correlate with future adverse outcomes.

In multivariable analysis excluding the Mayo and Amsterdam-Oxford risk scores, the adjusted hazard ratio for transplantation or death was 3.35 in the 10 to less than 15 kPa group and 5.82 in the 15 kPa or higher group compared with the lowest category. Ursodeoxycholic acid treatment was not a significant prognostic factor in either univariable or multivariable analysis in this cohort.

For clinicians, the practical interpretation is not that liver stiffness should replace clinical judgment. Rather, baseline stiffness may provide a simple, non-invasive risk signal that complements routine assessment in compensated PSC.

Added value beyond established PSC scores

A clinically useful biomarker should add information beyond what is already available. In FICUS, liver stiffness retained prognostic value when assessed alongside established PSC risk scores. Adding stiffness class to either the Mayo score or the Amsterdam-Oxford score significantly improved prognostic performance by likelihood ratio testing.

After adjustment for the Mayo score, patients with stiffness of at least 15 kPa had a hazard ratio of 4.18 for transplantation or death, while the intermediate group did not reach statistical significance. After adjustment for the Amsterdam-Oxford score, hazard ratios were 2.71 for the intermediate group and 6.30 for the highest stiffness group.

This is one of the most practice-relevant aspects of the study. It suggests that liver stiffness is not merely duplicating traditional risk scores. It may capture an aspect of disease severity or trajectory that improves risk classification. However, the study does not establish a management algorithm based on liver stiffness thresholds. It supports prognostic value; it does not prove that changing care based on these values improves outcomes.

Dynamic stiffness may matter as much as baseline stiffness

PSC is not static, and neither is liver stiffness. Among 416 patients with at least two reliable measurements, patients moved across Baveno VII categories in both directions. Of 354 patients starting below 15 kPa, 19% progressed to a higher category. Among 130 patients starting at 10 kPa or higher, 25% regressed to a lower category.

The investigators used joint modeling to evaluate stiffness trajectory. In an adjusted joint model including 400 patients with complete data, each 1-kPa-per-year increase in liver stiffness was associated with an 18% higher hazard of transplantation or death. Forty-one patients were classified as progressors based on a significantly positive individual slope. Their estimated five-year transplant-free survival was 54.3%, compared with 91.2% among nonprogressors, whose slopes were stable or decreasing. In multivariable analysis restricted to 318 patients with complete data, progressors had an adjusted hazard ratio of 3.12 for transplantation or death.

This finding supports the value of serial measurement. A patient’s stiffness trajectory may be more informative than an isolated value, particularly when baseline stiffness is borderline or when clinical and biochemical features do not clearly indicate progression.

The source also provides an important caution. The association between a 1-kPa-per-year increase and outcome was not uniform across all starting categories. The researchers emphasized that the overall 18% figure represented an average across patients with complete data, not a universal effect for every individual patient.

Liver complications were predicted, but biliary cancer was not

The secondary outcome also showed clinically relevant associations. Five-year survival free of liver complications was 78.5%, with events occurring in 117 patients over a median of 5.0 years. Baveno VII liver stiffness classes stratified this outcome, with adjusted hazard ratios of 2.69 for the intermediate group and 6.48 for the highest group.

This supports liver stiffness as a broader marker of liver-related progression in compensated PSC. But a key negative finding is equally important: liver stiffness did not identify patients who later developed biliary cancer. Among 17 patients diagnosed with cholangiocarcinoma, median baseline liver stiffness was 10.5 kPa, and eight had baseline measurements below 10 kPa.

Clinicians should not use liver stiffness as a substitute for cholangiocarcinoma vigilance. PSC cancer risk has a distinct clinical logic, and this cohort does not support liver stiffness as a reliable tool for identifying who will develop biliary cancer. This distinction matters because overextending a biomarker beyond its demonstrated use can lead to false reassurance in a high-risk disease.

Why FibroScan is appealing—but imperfect—in PSC

Vibration-controlled transient elastography is appealing because it is non-invasive, quick, repeatable, and already embedded in many hepatology services. In a rare, heterogeneous disease such as PSC, a practical tool that can be used annually across centers has obvious value for both clinical care and trials.

But liver stiffness is not a pure fibrosis meter. In PSC, stiffness may be affected by cholestasis, inflammation, uneven distribution of liver lesions, cholangitis, and technical conditions of measurement. The FICUS investigators noted variability related to factors such as absence of fasting, supine positioning, heterogeneous liver involvement, and inflammatory or cholestatic flares. Of 2,262 measurements obtained, 234, or 10.3%, were unreliable or failed.

These limitations are not minor details. They affect how clinicians should implement liver stiffness monitoring. A sudden increase should prompt contextual interpretation rather than automatic prognostic labeling. Was the patient fasting? Was there a cholestatic flare? Was there intercurrent inflammation? Was the measurement technically reliable? Serial trends should be interpreted alongside bilirubin, alkaline phosphatase, platelets, imaging, symptoms, dominant strictures, IBD status, and overall clinical course.

Strengths of the FICUS evidence

FICUS has several important strengths. It was prospective, international, multicenter, and conducted under the International PSC Study Group. It included adults with compensated PSC and recorded clinical, biological, and liver stiffness data annually over five years. The sample size was substantial for PSC, a rare disease, and the study assessed both baseline stiffness and changes over time.

The use of transplant-free survival as the primary endpoint is clinically meaningful. Death and liver transplantation are hard outcomes that matter to patients, clinicians, and trialists. The study also examined liver complication-free survival, providing a broader view of clinically relevant progression.

Another strength is comparison with established PSC risk scores. Showing that liver stiffness adds value beyond these scores strengthens the argument that it may have a role in risk stratification rather than merely serving as a redundant marker.

Limitations that should temper clinical adoption

Despite its strengths, this remains an observational cohort study. Associations between stiffness and outcomes do not prove that stiffness itself causes progression, nor do they prove that interventions triggered by liver stiffness improve survival. The study supports prognostic use, not treatment efficacy.

The participating sites were specialized centers, which may limit generalizability to community settings or regions with different PSC populations and transplant pathways. The researchers also noted that because most patients had baseline stiffness below 10 kPa, a group unlikely to be considered for transplantation, prognostic accuracy may have been overestimated. There was no independent validation cohort.

Transplantation indications may vary between countries. Although competing-risk analysis adjusted for country did not change results, international differences in transplant listing practice remain relevant when the endpoint includes transplantation.

Comparison with other non-invasive fibrosis markers was limited to platelet count and FIB-4. The investigators stated that liver stiffness should be compared with a broader panel of serum markers, including the Enhanced Liver Fibrosis test, in future studies.

What clinicians should conclude—and what they should not

Clinicians can reasonably conclude that, in this prospective compensated PSC cohort, baseline and dynamic liver stiffness measurements were independently associated with transplant-free survival. Liver stiffness also added prognostic information beyond established risk scores and may help stratify risk in both clinical care and trial design.

Clinicians should not conclude that FibroScan replaces PSC surveillance, imaging, biochemical assessment, endoscopic decision-making, or specialist judgment. They should not conclude that liver stiffness identifies future cholangiocarcinoma risk, because the study did not show that. They should also not treat the Baveno VII thresholds as PSC-specific treatment thresholds. In this study, those categories were applied to PSC and appeared prognostically useful, but the source does not establish a management algorithm based on them.

The most appropriate clinical application is careful integration. Annual liver stiffness measurement may be a practical addition to longitudinal PSC assessment, particularly when interpreted as a trend and combined with existing risk models and clinical context.

Implications for trials and future research

The investigators concluded that their findings support liver stiffness as a risk stratification tool and potential surrogate endpoint in future PSC clinical trials. They also pointed to growing regulatory recognition of liver stiffness as a reasonably likely surrogate endpoint in metabolic dysfunction-associated steatohepatitis and expressed hope that similar recognition may extend to rare liver diseases.

For PSC trials, this could be important. Hard outcomes such as transplantation and death may require long follow-up and large sample sizes. A validated surrogate or enrichment biomarker could make trials more feasible. But the word “potential” is essential. Surrogate endpoint acceptance requires evidence that changes in the marker reliably predict meaningful clinical outcomes and, ideally, that treatment-induced changes translate into patient benefit.

Future studies should validate the FICUS findings independently, compare liver stiffness with broader biomarker panels, clarify how cholestatic flares affect interpretation, test risk algorithms that combine stiffness with clinical scores, and determine whether stiffness-guided monitoring or intervention improves outcomes.

Clinical Takeaway

The FICUS cohort provides strong prospective evidence that liver stiffness measurement by vibration-controlled transient elastography is associated with transplant-free survival in adults with compensated primary sclerosing cholangitis. Baseline stiffness separated patients into markedly different five-year risk groups, and increasing stiffness over time was also associated with worse outcomes.

For clinicians, the value is practical: FibroScan may help make PSC risk assessment more objective and longitudinal. But the evidence should be used with discipline. This is an observational prognostic study, not proof that stiffness-guided management changes outcomes. Liver stiffness should not be used to predict cholangiocarcinoma risk, and it should not replace established PSC surveillance or specialist assessment.

For researchers, FICUS strengthens the case for liver stiffness as a risk-stratification tool and possible surrogate endpoint in PSC trials. The next step is independent validation and careful implementation into risk models that are clinically useful, reproducible, and tied to outcomes that matter to patients.

Source reference: Chazouillères O, Bellet J, Schramm C, Trivedi P, Thorburn D, Färkkilä M, Floreani A, Parés A, Levy C, Beuers U, Ytting H, Zigmond E, Mason A, Invernizzi P, Lohse AW, Hirschfield G, Cazzagon N, Llovet LP, Ponsioen CY, Carbone M, Fuessel K, Pezzato F, Patel I, Helder J, Khan S, Belkacem KB, Gaouar F, Monegier du Sorbier AM, Housset C, Lemoinne S, Soret PA, Carrat F, Corpechot C; International PSC Study Group. “Prognostic Performance of Liver Stiffness Measurements in Primary Sclerosing Cholangitis: The Prospective FICUS Cohort.” Gastroenterology. Published online August 4, 2026. DOI: 10.1053/j.gastro.2026.07.019. GI & Hepatology News summary published August 31, 2026.

Five key clinical takeaways

1. FICUS was a prospective international cohort evaluating liver stiffness measurement by FibroScan in adults with compensated PSC.

2. Baseline liver stiffness strongly stratified transplant-free survival, with five-year survival ranging from 93.9% below 10 kPa to 46.0% at ≥15 kPa.

3. Dynamic change also mattered: each 1-kPa/year increase in stiffness was associated with higher risk of death or transplantation, but this was an average effect, not a uniform individual prediction.

4. Liver stiffness added prognostic value beyond Mayo and Amsterdam-Oxford risk scores, supporting its role as a complementary risk-stratification tool.

5. The study does not support liver stiffness as a biliary cancer prediction tool and does not prove that stiffness-guided care improves outcomes.