JHEP reports : innovation in hepatology · 2026
Cholecystectomy before diagnosis of primary sclerosing cholangitis is associated with markedly worsened transplant-free survival.
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Färkkilä Martti A, Arola Johanna T, Tenca Andrea, Jokelainen Kalle, Boyd Sonja, Kautiainen Hannu
Аннотация
BACKGROUND & AIMS: Gallbladder abnormalities are common in primary sclerosing cholangitis (PSC) and commonly lead to cholecystectomy. As the gallbladder plays a role in regulating bile composition and biliary pressure, it has been proposed to exert a protective effect in PSC. We aimed to evaluate the impact of cholecystectomy and its timing on biochemistry, bile composition, and outcomes in PSC.
METHODS: A total of 977 patients with PSC enrolled in the prospective Helsinki PSC registry who underwent endoscopic retrograde cholangiography (ERCP). Of these, 163 patients (16.7%) underwent cholecystectomy, either before (n = 100) or after (n = 63) the diagnosis of PSC. Clinical outcomes were assessed using the composite endpoints of liver-related death, hepatobiliary malignancy, or liver transplantation.
RESULTS: Patients who had undergone cholecystectomy before PSC diagnosis had more advanced disease at baseline, as reflected by higher ERCP scores, (p = 0.012), Mayo risk scores, Fibrosis-4 indices (p <0.001), and more advanced fibrosis on liver histology (p = 0.020). The composite endpoint was reached by 37 patients (37.0%) with prior cholecystectomy, compared with 53 patients (6.5%) with an intact gallbladder and 10 patients (5.9%) who underwent cholecystectomy after PSC diagnosis. In multivariable regression analysis adjusting for timing of cholecystectomy, sex, age, and disease severity, cholecystectomy before PSC diagnosis was associated with a more than fivefold increased risk of reaching the composite endpoint (HR 5.16, 95% CI 3.00-8.88, p <0.001); using patients with PSC with an intact gallbladder as the reference. The restricted mean survival time was 5.0 years shorter in patients with prior cholecystectomy, p <0.001.
CONCLUSIONS: Cholecystectomy performed before the diagnosis of PSC is associated with more advanced disease and markedly impaired prognosis, including significantly reduced liver transplantation-free survival and substantially increased risk of liver transplantation.
IMPACT AND IMPLICATIONS: This large prospective registry study demonstrates that cholecystectomy performed before the diagnosis of PSC is strongly associated with more advanced biliary disease and profoundly worse prognosis. The markedly increased risk of liver transplantation and reduced transplantation-free survival suggest that gallbladder loss may accelerate disease progression or identify a high-risk PSC phenotype. By contrast, cholecystectomy after PSC diagnosis was not clearly associated with adverse outcomes, highlighting the importance of timing. The impact of prior cholecystectomy on prognostic models of PSC should be evaluated. These findings challenge the perceived neutrality of gallbladder removal in PSC and support a more cautious, individualized approach to cholecystectomy, while reinforcing the gallbladder's potential protective role in PSC.
METHODS: A total of 977 patients with PSC enrolled in the prospective Helsinki PSC registry who underwent endoscopic retrograde cholangiography (ERCP). Of these, 163 patients (16.7%) underwent cholecystectomy, either before (n = 100) or after (n = 63) the diagnosis of PSC. Clinical outcomes were assessed using the composite endpoints of liver-related death, hepatobiliary malignancy, or liver transplantation.
RESULTS: Patients who had undergone cholecystectomy before PSC diagnosis had more advanced disease at baseline, as reflected by higher ERCP scores, (p = 0.012), Mayo risk scores, Fibrosis-4 indices (p <0.001), and more advanced fibrosis on liver histology (p = 0.020). The composite endpoint was reached by 37 patients (37.0%) with prior cholecystectomy, compared with 53 patients (6.5%) with an intact gallbladder and 10 patients (5.9%) who underwent cholecystectomy after PSC diagnosis. In multivariable regression analysis adjusting for timing of cholecystectomy, sex, age, and disease severity, cholecystectomy before PSC diagnosis was associated with a more than fivefold increased risk of reaching the composite endpoint (HR 5.16, 95% CI 3.00-8.88, p <0.001); using patients with PSC with an intact gallbladder as the reference. The restricted mean survival time was 5.0 years shorter in patients with prior cholecystectomy, p <0.001.
CONCLUSIONS: Cholecystectomy performed before the diagnosis of PSC is associated with more advanced disease and markedly impaired prognosis, including significantly reduced liver transplantation-free survival and substantially increased risk of liver transplantation.
IMPACT AND IMPLICATIONS: This large prospective registry study demonstrates that cholecystectomy performed before the diagnosis of PSC is strongly associated with more advanced biliary disease and profoundly worse prognosis. The markedly increased risk of liver transplantation and reduced transplantation-free survival suggest that gallbladder loss may accelerate disease progression or identify a high-risk PSC phenotype. By contrast, cholecystectomy after PSC diagnosis was not clearly associated with adverse outcomes, highlighting the importance of timing. The impact of prior cholecystectomy on prognostic models of PSC should be evaluated. These findings challenge the perceived neutrality of gallbladder removal in PSC and support a more cautious, individualized approach to cholecystectomy, while reinforcing the gallbladder's potential protective role in PSC.