Background: Risk stratification in Primary Sclerosing Cholangitis (PSC) is challenging due to the interplay of multiple competitive events, including advanced fibrosis and cholangiocarcinoma, which contribute to poor prognosis. Although several prognostic factors, such as serum markers, composite scores, biliary and parenchymal changes, and elastography, have been associated with adverse outcome-free survival, surrogate endpoints for clinical trials remain insufficient. This study aims to identify new prognostic features and approaches to enhance early prediction of adverse outcomes in PSC patients. Materials and Methods: A retrospective analysis of PSC patients from two tertiary centers was conducted. Subgroup analyses were performed on patients with at least one MRI with three-dimensional cholangiography closest to the time of diagnosis. Gallbladder status was evaluated, with gallbladder enlargement defined as >50 mL on MRI. Patients were stratified based on gallbladder size (enlarged vs. normal) or status (removed vs. conserved), and disease features and outcomes were compared between groups. Additionally, sarcopenia was assessed in a single-center cohort using MRI-measured normalized psoas muscle thickness (PMT) and area (PMA). Patients were categorized based on the presence or absence of sarcopenia, and outcomes were compared. In a subgroup of non-cirrhotic PSC patients with at least two MRIs closest to diagnosis, longitudinal analyses of ANALI scores, the Amsterdam Oxford Model (AOM), and the revised Mayo Risk Score (rMRS) were calculated, with progression correlated to adverse outcomes. Results: Among a multicenter cohort of 173 PSC patients, 145 (84%) had a conserved gallbladder, with enlargement observed in 71 (49%). Patients with an enlarged gallbladder showed significantly lower ALP (p = 0.03) and total bilirubin (p = 0.04) levels compared to those with a normal-sized gallbladder. Among patients treated with UDCA, gallbladder enlargement was associated with reduced AST (p = 0.03), ALP (p < 0.01), and bilirubin (p = 0.02) levels, as well as a decreased prevalence of cirrhosis (p = 0.02). Enlarged gallbladder status was linked to longer adverse outcome-free survival in both patient groups (log-rank p = 0.05 and p < 0.01, respectively) and showed a trend toward being an independent protective factor against adverse outcomes (HR: 0.065; 95% CI: 0.152–1.058; p = 0.07). Cholecystectomy (n = 28, 16%) was not associated with significant differences in cholestasis markers or adverse outcome-free survival (log-rank p = 0.76). Sarcopenia was evaluated in 78 patients. Among males, PMT ≤ 14 mm/m and PMA ≤ 561 mm²/m² were significantly associated with shorter adverse outcome-free survival (p < 0.01 for both). PMA-defined sarcopenia correlated with higher ALP (p = 0.03), rMRS (p < 0.01), and AOM (p < 0.01), and was identified as an independent predictor of adverse events (HR: 6.22; 95% CI: 1.19–32.51; p = 0.03). Non-cirrhotic sarcopenic patients showed elevated ALP (p = 0.04), rMRS (p = 0.02), and AOM (p = 0.02). Longitudinal evaluation of 45 patients with a median MRI interval of 24 (16–38) months revealed that early worsening of the ANALI score without gadolinium (n = 7, 16%) was associated with an increased risk of cirrhosis (p = 0.01), cirrhosis decompensation (p = 0.02), and the need for liver transplantation (LT) (p < 0.01). Additionally, rMRS was significantly associated with cirrhosis development (p < 0.01) and showed a trend toward association with LT (p = 0.09). Conclusions: Gallbladder enlargement demonstrated a protective role in PSC patients, while cholecystectomy had no apparent impact on our cohort. Sarcopenia in males emerged as an independent predictor of adverse events and worsened clinical outcomes, regardless presence of cirrhosis. The early dynamic changes in radiological and biochemical scores help identify a more aggressive PSC phenotype.

Analisi sulla stratificazione del rischio nella Colangite Sclerosante Primitiva combinando l'evoluzione precoce di parametri clinici e radiologici.

CATANZARO, ELISA
2022/2023

Abstract

Background: Risk stratification in Primary Sclerosing Cholangitis (PSC) is challenging due to the interplay of multiple competitive events, including advanced fibrosis and cholangiocarcinoma, which contribute to poor prognosis. Although several prognostic factors, such as serum markers, composite scores, biliary and parenchymal changes, and elastography, have been associated with adverse outcome-free survival, surrogate endpoints for clinical trials remain insufficient. This study aims to identify new prognostic features and approaches to enhance early prediction of adverse outcomes in PSC patients. Materials and Methods: A retrospective analysis of PSC patients from two tertiary centers was conducted. Subgroup analyses were performed on patients with at least one MRI with three-dimensional cholangiography closest to the time of diagnosis. Gallbladder status was evaluated, with gallbladder enlargement defined as >50 mL on MRI. Patients were stratified based on gallbladder size (enlarged vs. normal) or status (removed vs. conserved), and disease features and outcomes were compared between groups. Additionally, sarcopenia was assessed in a single-center cohort using MRI-measured normalized psoas muscle thickness (PMT) and area (PMA). Patients were categorized based on the presence or absence of sarcopenia, and outcomes were compared. In a subgroup of non-cirrhotic PSC patients with at least two MRIs closest to diagnosis, longitudinal analyses of ANALI scores, the Amsterdam Oxford Model (AOM), and the revised Mayo Risk Score (rMRS) were calculated, with progression correlated to adverse outcomes. Results: Among a multicenter cohort of 173 PSC patients, 145 (84%) had a conserved gallbladder, with enlargement observed in 71 (49%). Patients with an enlarged gallbladder showed significantly lower ALP (p = 0.03) and total bilirubin (p = 0.04) levels compared to those with a normal-sized gallbladder. Among patients treated with UDCA, gallbladder enlargement was associated with reduced AST (p = 0.03), ALP (p < 0.01), and bilirubin (p = 0.02) levels, as well as a decreased prevalence of cirrhosis (p = 0.02). Enlarged gallbladder status was linked to longer adverse outcome-free survival in both patient groups (log-rank p = 0.05 and p < 0.01, respectively) and showed a trend toward being an independent protective factor against adverse outcomes (HR: 0.065; 95% CI: 0.152–1.058; p = 0.07). Cholecystectomy (n = 28, 16%) was not associated with significant differences in cholestasis markers or adverse outcome-free survival (log-rank p = 0.76). Sarcopenia was evaluated in 78 patients. Among males, PMT ≤ 14 mm/m and PMA ≤ 561 mm²/m² were significantly associated with shorter adverse outcome-free survival (p < 0.01 for both). PMA-defined sarcopenia correlated with higher ALP (p = 0.03), rMRS (p < 0.01), and AOM (p < 0.01), and was identified as an independent predictor of adverse events (HR: 6.22; 95% CI: 1.19–32.51; p = 0.03). Non-cirrhotic sarcopenic patients showed elevated ALP (p = 0.04), rMRS (p = 0.02), and AOM (p = 0.02). Longitudinal evaluation of 45 patients with a median MRI interval of 24 (16–38) months revealed that early worsening of the ANALI score without gadolinium (n = 7, 16%) was associated with an increased risk of cirrhosis (p = 0.01), cirrhosis decompensation (p = 0.02), and the need for liver transplantation (LT) (p < 0.01). Additionally, rMRS was significantly associated with cirrhosis development (p < 0.01) and showed a trend toward association with LT (p = 0.09). Conclusions: Gallbladder enlargement demonstrated a protective role in PSC patients, while cholecystectomy had no apparent impact on our cohort. Sarcopenia in males emerged as an independent predictor of adverse events and worsened clinical outcomes, regardless presence of cirrhosis. The early dynamic changes in radiological and biochemical scores help identify a more aggressive PSC phenotype.
2022
Analyzing risk stratification of Primary Sclerosing Cholangitis by combining early clinical and radiological changes
PSC
risk stratification
magnetic resonance
clinical outcomes
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12608/81464