Liver Stiffness Shifts From Diagnostic to Prognostic Tool in PBC and PSC

Liver stiffness measurement (LSM) is evolving from a tool for staging fibrosis into a predictor of long-term outcomes in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), according to Raj Vuppalanchi, MD, of Indiana University School of Medicine.¹ Vuppalanchi discussed the shift during a session at AASLD The Liver Meeting 2026 on LSM as a predictor of outcomes in autoimmune liver diseases.¹

In an interview with HCPLive, Vuppalanchi said early use of vibration-controlled transient elastography (VCTE) focused on how closely stiffness correlated with fibrosis. Clinicians are now asking what a given value means for a patient’s natural history, a change he expects to reshape day-to-day care. He emphasized the role of LSM differs between the 2 diseases, as PBC affects the liver more uniformly while PSC involvement can vary by region and be altered by biliary obstruction or cholangitis.

How Well Does Liver Stiffness Predict Outcomes in PBC?

Vuppalanchi noted the evidence has matured from retrospective studies to prospective cohorts linking LSM to outcomes. In PBC, research has examined baseline LSM, change over time, and the value of combining LSM with established prognostic markers, including bilirubin, alkaline phosphatase, ursodiol response, and the GLOBE and UK-PBC scores.

An international retrospective study of 3985 patients with PBC across 23 centers found LSM independently predicted liver-related complications, transplantation, or death, with an adjusted hazard ratio of 1.040 per additional kPa in the derivation cohort. LSM improved the prognostic ability of biochemical response criteria and prognostic scores, and cutoffs of 8 kPa and 15 kPa separated low-, medium-, and high-risk groups.²

Change over time also carries prognostic weight. In a study of 3078 ursodiol-treated patients, a 20% annual increase in LSM was associated with an adjusted hazard ratio of 2.13 (95% CI, 1.89-2.45) for serious clinical events, while a 20% annual decrease was associated with a hazard ratio of 0.40 (95% CI, 0.33-0.46).³

According to Vuppalanchi, the missing piece for regulatory acceptance as a surrogate endpoint is evidence showing treatment-driven reductions in LSM translate to better outcomes. Once robust data establish this link, he said, a drug could one day be approved based on improvement in liver stiffness.

Why Is Liver Stiffness Harder to Interpret in PSC?

PSC presents a greater challenge given its heterogeneity.

“For PSC, it’s a whole new ball game. It’s a monster because the disease itself is heterogeneous,” Vuppalanchi said.

He pointed to new data from the prospective FICUS cohort, which followed 538 adults with uncomplicated PSC for a median of 60.7 months. Five-year transplant-free survival was 93.9% among patients with baseline LSM below 10 kPa, 78.1% with LSM of 10 to less than 15 kPa, and 46.0% with LSM of 15 kPa or higher. Patients with progressive LSM had worse transplant-free survival than nonprogressors (adjusted hazard ratio, 3.12; 95% CI, 1.55-6.24), and each 1-kPa annual increase raised the risk of death or transplant by 18%.⁴

As in PBC, Vuppalanchi said evidence linking treatment-related LSM improvement to better PSC outcomes is still lacking. He described cutoffs around 10 kPa and 15 kPa as thresholds where prognosis may diverge, complementing treatment response and biochemical markers.

Vuppalanchi urged clinicians to interpret LSM in context, since stiffness reflects inflammation, cholestasis, and biliary obstruction in addition to fibrosis. In PSC, he recommended checking bilirubin and asking about recent cholangitis or biliary intervention before drawing conclusions.

“It’s just not a number. It’s the biomarker of what’s happening in the liver, and taken into the context of the clinical events,” he said.

References:

1. Vuppalanchi R. Liver stiffness measurement as a predictor of outcomes in autoimmune liver diseases (primary biliary cholangitis and primary sclerosing cholangitis). Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Corpechot C, Carrat F, Gaouar F, et al. Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis. J Hepatol. 2022;77(6):1545-1553. doi:10.1016/j.jhep.2022.06.017

3. Lam L, Soret PA, Lemoinne S, et al. Dynamics of liver stiffness measurement and clinical course of primary biliary cholangitis. Clin Gastroenterol Hepatol. 2024;22(12):2432-2441.e2. doi:10.1016/j.cgh.2024.06.035

4. Chazouillères O, Bellet J, Schramm C, et al. 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