Short summary

Acute cholangitis (AC) is an inflammatory condition in the bile duct caused by a bacterial infection, a condition that requires emergent treatment, as it is associated with a high mortality and morbidity. Although early endoscopic retrograde cholangiopancreatography (ERCP) may be associated with better outcomes, the precise timing for defining early intervention remains to be investigated in sizeable studies. Clinical factors other than early ERCP could have predictive value for the outcome of acute cholangitis as well. These factors include results of blood tests, radiologic findings, the presence of bacteremia and comorbidities. This project will retrospectively review and analyze the clinical variables and clinical outcomes of 835 cases of AC, aiming at:

1. investigating the relationship between time to ERCP intervention and clinical outcomes to establish the optimal timing of ERCP
2. identification of clinical factors with the highest predictive values for outcome of AC patients.

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Rationale

Acute cholangitis (AC) is an inflammatory condition in the bile duct caused by a bacterial infection - secondary to an obstruction in the biliary tract. It is a condition that requires emergent treatment, as it is associated with a high mortality of up to 10%, despite treatment, and morbidities like persistent organ failure. Although early endoscopic retrograde cholangiopancreatography (ERCP) may be associated with better outcomes, the precise timing for defining early intervention remains to be investigated in sizeable studies. Clinical factors other than early ERCP could have predictive value for the outcome of AC as well. These factors include results of blood tests (e.g. hypoalbumenia, plasma-creatinine and blood urea nitrogen), radiologic findings (intrahepatic obstruction and obstruction etiology), the presence of bacteremia or systemic inflammatory response syndrome, and comorbidities in Charlson Comorbidity index. In clinical practice, there are different criteria for diagnosis of acute cholangitis including Charcot's triad criterion and its modified version, the Reynolds' pentad, and recently the Tokyo Guidelines released in 2013, each varies in term of performance (sensitivity and specificity, etc) and predictive value in clinical outcomes.  A proper verification (based on an unique collection of large samples) of the ability to predict clinical outcome by the different clinical factors and diagnostic criteria would be of great clinical value in helping clinicians with identification of patients in high-risk of poor outcome.

This project will retrospectively review and analyze the clinical variables and clinical outcomes of 835 cases of AC treated with ERCP at the Department of Medical Gastroenterology S, OUH, aiming at:

1. investigating the relationship between time to ERCP intervention and clinical outcomes to establish the optimal timing of ERCP in AC patients
2. identification of clinical factors with the highest predictive values for outcome of AC patients
3. verifying  the predictive value for outcome of current severity stratification criteria for AC.

This project will be one of the largest studies on AC to date, and its results are expected to promote more efficient practices within diagnosis, management and treatment of AC - defining an optimal timing for ERCP, as well as an optimal set of factors to diagnose high-risk patients.

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Description of the cohort

All patients with AC that received ERCP treatment in the past 25 years (1990-2015) at department S at OUH will be identified using an internal ERCP database. The database contains records of 14,000 consecutive ERCP interventions performed during the past 25 years. An estimated sample of 835 cases with AC is expected being identified retrospectively. Relevant clinical data from all AC cases will be extracted from their medical records and from Landspatientregistret (LPR).

The inclusion criteria for cases with AC are based on the TG13 - where diagnosis of acute cholangitis defined by the presence of the following criteria [13]: A. Systemic inflammation (fever or laboratory evidence), B. Cholestasis (jaundice or laboratory evidence), C. Imaging (biliary dilatation or evidence of the etiology e.g. stricture, stone, stent etc.). Patients fulfilling either the suspicion criteria (A+ either B or C) or the definite diagnosis criteria (A+B+C) for AC according to TG13 will be enrolled as AC cases in this study. Outcomes are defined as: persistent organ failure, 30-day mortality, in hospital mortality, length of stay at an intensive care unit, length of hospital admission and need of early ERCP intervention (under 48-72 hours from admission).

Data and biological material

Relevant clinical data from all AC cases will be extracted from their medical records and from Landspatientregistret (LPR). Data extracted from the medical records include: Baseline characteristics (e.g. age at ERCP, sex, smoking, alcohol), symptoms and vital parameters at admission (e.g. Charcot's triad, Reynold's pentad, presence of SIRS, body temperature, systolic blood pressure, pulse, RF), relevant blood test results (including P-albumin, P-creatinine, BUN, platelet count, PT, INR, partial thromboplastin time (PTT), B-leucocytes, P-bilirubin and alanine aminotransferase (ALT)). Likewise characteristics of ERCP (e.g. time from admission-to-ERCP, ERCP procedures and post-ERCP complications) and etiology of cholangitis (benign or malign etiologies) will be extracted from the medical records. Diagnosis codes for comorbidities at the time of ERCP, will be extracted from LPR.

Collaborating researchers and departments

Department of Medical Gastroenterology, Odense University Hospital

• Pre-graduate research student Ming Tan
• Postdoc and physician Stig Borbjerg Laursen, PhD
• Professor and Consultant Ove B. Schaffalitzky de Muckadell