TY - JOUR
T1 - Predictors of Jaundice Resolution and Survival After Endoscopic Treatment of Primary Sclerosing Cholangitis
AU - Eaton, John E.
AU - Haseeb, Abdul
AU - Rupp, Christian
AU - Eusebi, Leonardo H.
AU - van Munster, Kim
AU - Voitl, Robert
AU - Thorburn, Douglas
AU - Ponsioen, Cyriel Y.
AU - Enders, Felicity T.
AU - Petersen, Bret T.
AU - Abu Dayyeh, Barham K.
AU - Baron, Todd H.
AU - Chandrasekhara, Vinay
AU - Gostout, Christopher J.
AU - Levy, Michael J.
AU - Martin, John
AU - Storm, Andrew C.
AU - Dierkhising, Ross
AU - Kamath, Patrick S.
AU - Gores, Gregory J.
AU - Topazian, Mark
N1 - Funding Information:
Supported by the Division of Gastroenterology and Hepatology, Mayo Clinic (to M.T.).
Funding Information:
This is a retrospective cohort study of consecutive patients with PSC undergoing ERCP for treatment of jaundice. Predictors of jaundice resolution and survival were derived and validated in separate patient sets. The study protocol was approved by the Mayo Clinic Rochester (MCR) institutional review board. Patients who waived review of medical records for research purposes were not enrolled. All patients with PSC undergoing ERCP at MCR between October 23, 1990, and December 5, 2018, were identified from clinical databases, and medical records were reviewed. Patients with jaundice were included in the derivation set if their first ERCP for treatment of jaundice (index ERCP) was performed at MCR; they were excluded if CCA was diagnosed before or during the index episode of care or if they had previously undergone biliary tract surgery (other than cholecystectomy). Jaundice was considered present if total serum bilirubin was ?2.5?mg/dL (?42.75??mol/L). Data abstracted from medical records included age, sex, comorbidities, history of varices, variceal hemorrhage, ascites, encephalopathy, symptoms, physical exam findings, laboratory results, and endoscopic interventions. The Mayo Risk Score (MRS) was calculated from the most recent data available before the index ERCP. Follow-up data were also collected from medical records. Cholangiograms were reviewed with reference to ERCP reports to determine extent of ductal visualization and location of the most advanced biliary stricture. We determined ductal dimensions from cholangiograms by measuring duct and duodenoscope diameter on the radiographs, then calculating the ratio of bile duct diameter to duodenoscope diameter and multiplying by the diameter of the duodenoscope used. The intrahepatic ducts were considered nonvisualized if there was complete obstruction of both the right and left main ducts with no passage of contrast more proximally. The intrahepatic ducts were incompletely visualized if there was a complete obstruction of either the right or the left main intrahepatic duct, but not both, and were completely visualized if sectoral or segmental intrahepatic ducts were visualized on both the right and left sides. Complete drainage was defined as substantial clearance of contrast from right and left hepatic ducts on the final radiograph obtained at the conclusion of ERCP. We defined the most advanced biliary stricture as a potentially flow-limiting stricture that was longer or tighter than the other strictures present elsewhere in the patient?s biliary tree. The most advanced biliary stricture was identified based on the ERCP report and confirmed by review of cholangiograms. Each advanced stricture was characterized by its location, length, minimum luminal diameter, and ductal diameter both proximal and distal to the stricture. We defined the ratio of dilation balloon diameter to duct diameter proximal to the most advanced stricture as (maximum diameter of the dilation balloon)/(bile duct diameter proximal to the treated stricture) (Fig. 1). If this ratio is >1, it implies that a stricture is balloon dilated beyond the upstream caliber of the affected duct. An episode of care was defined as all therapeutic ERCPs performed within a 60-day period. ERCPs performed solely for acquisition of tissue specimens were not considered part of the episode of care. If stents were left in place for >60?days, the duration of the episode of care was extended to include the entire duration of continuous stenting. Treatment success was defined as a decrease of the serum bilirubin to <2.5?mg/dL within the 60-day time period following the episode of care (or, if no serum bilirubin level was documented within 60?days, the next available serum bilirubin), without need for other interventions during that time period. Persistent jaundice was defined as failure of the serum bilirubin to decrease to <2.5?mg/dL. The validation cohort comprised all eligible patients with PSC undergoing endoscopic treatment of jaundice at Sheila Sherlock Liver Centre, Royal Free Hospital, University College London Institute of Liver and Digestive Health, London, United Kingdom; University Hospital of Heidelberg, Heidelberg, Germany; and Amsterdam Universitair Medische Centra, from December 5, 2018, moving backward in time as far as local databases allowed. The same inclusion and exclusion criteria were applied to both the derivation (MCR) and validation sets. For the derivation cohort, univariate and multivariable logistic regression models were used to measure associations with the outcome of jaundice resolution in the 60?days after the episode of care. Best subsets variable selection using the score statistic was used to identify an initial multivariable model up to a maximum size based on a 10:1 event to variable ratio. Variables were removed from this model using backward elimination with a 0.10 type I error level. Variance inflation factors were used to assess multicollinearity among predictors, and all values were less than 10. In the subset of patients with jaundice resolution, the cumulative incidence of a subsequent jaundice recurrence was estimated using the competing risk extension of the Kaplan-Meier method, where the occurrence of death or transplant constituted the competing event. The cumulative incidence of all-cause death or liver transplant was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to assess associations with jaundice recurrence and death/transplant. Multivariable Cox models were obtained using best subsets variable selection followed by a backward elimination, as described previously. Subjects who developed CCA during follow-up were not excluded. The models developed during the derivation phase were then applied to the validation cohort. A concordance statistic was computed for each model as a discrimination measure (area under the receiver operating characteristic curve (AUROC] in the jaundice resolution model and Harrell?s concordance statistic in the death/transplant model). Calibration was assessed by comparing the expected outcome risk to the observed outcome risk for five equally sized groups, as defined by quintiles of the model linear predictor.
Publisher Copyright:
© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
PY - 2022/4
Y1 - 2022/4
N2 - The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow-up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1-year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1-year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1-point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5-0.79) in the validation set. Independent predictors of death or transplant during follow-up included higher MRS at the time of ERCP (P < 0.0001; hazard ratio [HR], 2.33 for every 1-point increase), lower total serum bilirubin before ERCP (P = 0.031; HR, 0.91 for every 1 mg/dL increase), and persistence of jaundice after endoscopic therapy (P = 0.003; HR, 2.30). Conclusion: Resolution of jaundice after endoscopic treatment of biliary strictures is associated with longer transplant-free survival of patients with PSC. The likelihood of resolution is affected by demographic, hepatic, and biliary variables and can be predicted using noninvasive data. These findings may refine the use of ERCP in patients with jaundice with PSC.
AB - The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow-up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1-year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1-year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1-point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5-0.79) in the validation set. Independent predictors of death or transplant during follow-up included higher MRS at the time of ERCP (P < 0.0001; hazard ratio [HR], 2.33 for every 1-point increase), lower total serum bilirubin before ERCP (P = 0.031; HR, 0.91 for every 1 mg/dL increase), and persistence of jaundice after endoscopic therapy (P = 0.003; HR, 2.30). Conclusion: Resolution of jaundice after endoscopic treatment of biliary strictures is associated with longer transplant-free survival of patients with PSC. The likelihood of resolution is affected by demographic, hepatic, and biliary variables and can be predicted using noninvasive data. These findings may refine the use of ERCP in patients with jaundice with PSC.
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U2 - 10.1002/hep4.1813
DO - 10.1002/hep4.1813
M3 - Article
C2 - 34558848
AN - SCOPUS:85114049282
SN - 2471-254X
VL - 6
SP - 809
EP - 820
JO - Hepatology Communications
JF - Hepatology Communications
IS - 4
ER -