In patients with PBC with advanced fibrosis or cirrhosis, progression of liver stiffness can be observed even with standard first-line UDCA treatment.1 Elevated LSM by vibration-controlled transient elastography (VCTE) has been shown to predict poor clinical outcomes in PBC.2 Although seladelpar has demonstrated improvements in markers of cholestasis in patients with PBC, its effect on liver stiffness has not been assessed.
Bowlus and colleagues presented an analysis of longitudinal trends in LSMs in patients receiving seladelpar in the open-label phase 3 ASSURE trial.3 In the trial, LSM was assessed locally at screening and every 12 months using VCTE. At baseline, patients were categorized into LSM groups based on established thresholds for fibrosis in PBC: 73.0% (n=227) were in the low-LSM group (LSM <10.7 kilopascals [kPa], indicating F0-F2 fibrosis); 16.4% (n=51) were in the intermediate-LSM group (LSM ≥10.7 to <16.9 kPa, indicating F3 fibrosis); and 10.6% were in the high-LSM group (LSM ≥16.9 kPa, indicating F4 fibrosis). Confirmed cirrhosis was present at baseline in 4% of the low-LSM group, 27% of the intermediate-LSM group, and 79% of the high-LSM group.
Over the 36-month seladelpar treatment period, LSM remained stable in the overall population, with a median change from baseline of -0.2 kPa (-2.9%). In a subgroup analysis, LSM also remained stable in the lowLSM subset (median change, 0.1 kPa; 2.0%) and in the intermediate-LSM subset (median change, -0.9 kPa; -7.4%); however, there was a trend toward improved LSM over time in the subset of patients with an LSM of 16.9 kPa or more (median change, -5.2 kPa; -29.7%).
Most studies evaluating liver stiffness have demonstrated stability with treatment; however, this study showed some improvement with seladelpar treatment in patients with PBC. Notably, patients with lower levels of fibrosis showed signs of reversibility or decrease in liver stiffness. In particular, in patients with LSM improvement of greater than 30%, the majority had absence of advanced liver fibrosis, or LSM less than 10.7 kPa.
—Robert G. Gish, MD
Investigators also evaluated patterns of change in patients with worsening or improvement (of >30% for each) in liver stiffness with seladelpar treatment. Among 25 patients with an LSM worsening of greater than 30%, 20 patients (80%) were in the lowLSM category at baseline, and half of these patients remained in this category at 36 months. Among 19 patients with an LSM improvement of greater than 30% (including 11 with LSM <10.7 kPa, 3 with LSM ≥10.7 to <16.9 kPa, and 5 with LSM ≥16.9 kPa), 17 (89%) were in the low-LSM group (<10.7 kPa) at 36 months (Figure 5).
Figure 5.
Patients with primary biliary cholangitis with greater than 30% decrease in liver stiffness measurement (kPa) at 36 months of seladelpar treatment. kPa, kilopascal.
Adapted from Bowlus CL, et al. Abstract 5031. Presented at: AASLD 2025; November 7-11, 2025; Washington, DC.3
Overall, 85% of patients (97/114) remained in the same LSM category or improved LSM categories at 36 months. Among patients in the high-LSM baseline cohort (n=11), 3 (27%) shifted to the low group, 4 (36%) shifted to the intermediate group, and 4 (36%) remained in the high group. In the intermediate-LSM baseline cohort of patients (n=14), 5 (36%) shifted to the low group, 5 (36%) remained in the intermediate group, and 4 (29%) shifted to the high group. In the low-LSM baseline cohort of patients (n=89), 76 (85%) remained in the low group, 11 (12%) shifted to the intermediate group, and 2 (2%) shifted to the high group.
In an analysis of baseline characteristics associated with worsening of LSM, younger age at seladelpar initiation and higher baseline ALP category were both significantly associated with developing greater than 30% worsening of liver stiffness at 36 months (P=.0275 and P=.0122, respectively).
Seladelpar treatment was generally associated with stability of LSMs over time in patients with PBC, although there was a trend toward improvement in LSM for patients in the highest LSM group at baseline (≥16.9 kPa).
References
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- Bowlus CL, Hirschfield GM, Villamil AM et al. 36 months of treatment with seladelpar is associated with stable or improved liver stiffness in patients with PBC. Abstract 5031. Presented at: AASLD Liver Meeting; November 7-11, 2025; Washington, DC. [Google Scholar]