Temporal changes in patient-reported outcome measures stratified by liver fibrosis severity in large-duct primary sclerosing cholangitis

ABSTRACT

Background and aims: Patient-reported outcome measures (PROMs) are increasingly used as exploratory end points in clinical trials. The aim of this studywas to evaluate the temporal relationship between health-related quality of life (HrQoL) and liver fibrosis using generic (SF-36) and disease-specific (PSC-PRO) tools. Method: Patients with large-duct PSC were invited to complete HrQoL questionnaires in an outpatient setting at baseline (V1) and follow-up (V2) visits at least 12 months apart. Transient elastography liver stiffness (LS;Echosens, France) measurementswere recorded on the same day. SF-36 and PSC-PRO health domains were scored out of a maximum of 100% and 5, respectively. Mean scores were calculated for each domain with lower SF-36 and higher PSC-PRO scores representing poorer quality of life. Advanced fibrosis (F3-6) was defined based on published cutoff of LS >9.6kPa in PSC. Results: Fifty-five patients (64% male) with median age 45 years (range 20–77) and median PSC duration 11 years (range 2–26) attended both study visits. The median time between visits was 417 days (range 362–582). The mean scores were numerically lower at V2 than V1 in all the SF-36 domains but only three domains showed statistically significant difference bodily pain (74% vs 83%, p < 0.01), energy/fatigue (47% vs 57%, p < 0.0001), and mental summary score (66% vs 71%, p < 0.001). There were no differences in any of the PSCPRO domains between the visits. When stratified by baseline LS >9.6 kPa threshold (Figure 1), SF-36 physical functioning mean score dropped in the F3-6 group but increased slightly in the F0-2 group (−9.0 ± 17% vs 0.4 ± 21%, p = 0.01). In the PSC-PRO, the emotional impact mean score increased in the F3-6 group but decreased in the F0-2 group (0.6 ± 0.7 vs −0.1 ± 0.5, p < 0.01). Therewere no significant differences in mean scores in the other domains between the visits.(Figure Presented)Conclusion: Therewasworsening of bodily pain, levels of energy and mental health even within a year in patients with large-duct PSC. Patients with advanced fibrosis reported lower physical functioning and higher emotional impact of their disease compared to those without advanced fibrosis. Changes in PROMs are related to liver fibrosis and need to be considered in future antifibrotic drug trials. These findings, however, need to be interpreted in the context of imposed restrictions during the Covid-19 pandemic which may have had a significant psycho-social impact on patients.