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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2014, Vol. 8 Issue (1) : 118-126     DOI: 10.1007/s11684-014-0306-6
Sclerosing cholangitis in critically ill patients: an important and easily ignored problem based on a German experience
Ting Lin1,2, Kai Qu1, Xinsen Xu1, Min Tian1,2, Jie Gao1,2, Chun Zhang1,2, Ying Di1,2, Yuelang Zhang3, Chang Liu1,2()
1. Department of Hepatobiliary Surgery; 2. Surgical Intensive Care Unit; 3. Department of Imaging, the First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China
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Intensive care unit (ICU) is important in the rehabilitation of critically ill patients. In the past decades, many patients who received aggressive treatment in ICU developed sclerosing cholangitis in multiple centers. Sclerosing cholangitis in critically ill patients (SC-CIP) is a relatively new issue. To investigate the causes, clinical manifestation, treatment, and prognosis of SC-CIP, we searched for published cases in the databases of PubMed, Highwire, and Elsevier from 2001 to 2012. Data were extracted using a standard form and retrospectively analyzed. Twelve eligible studies covering 88 patients, with 64 men and 24 women, were enrolled in this analysis. The mean age was 49.8 years. All of the patients recovered from critical illnesses, such as trauma, infection, burn, and major surgeries. High pressure positive end-expiratory pressure (PEEP, peak level at 12.8 cm H2O) was utilized for all patients, with the average duration of 36.3 d. In addition, vasopressor agents were administered in approximately 60% of SC-CIP. A rapid increase in cholestasis and irregular strictures in the intrahepatic bile ducts was observed in the following months. With an average follow-up period of 17.9 months, poor outcomes were observed in 54 patients, including 34 deaths. In conclusion, ischemic injury of the biliary tree, which may be affected by PEEP and/or vasopressor administration, affects cholangiopathic procedure. As a newly discovered type of secondary sclerosing cholangitis, SC-CIP is a severe progressive complication of patients in ICU and should be carefully monitored by clinicians.

Keywords intensive care unit      sclerosing cholangitis      ischemic injury      prognosis      systemic review     
Corresponding Authors: Liu Chang,   
Issue Date: 26 April 2014
URL:     OR
YearAuthorCountryNo. of patients(male/female)Age(year)
2001Scheppach et al. [3]Germany3 (1/2)32.0±6.6
2002ter Borg et al. [4]Netherland1 (0/1)48
2003Engler et al. [5]Germany9 (5/4) a56.2±17.0
2005Benninger et al. [6]Germany5 (4/1)48.4±20.0
2006Jaeger et al. [7]Germany10 (5/5)55.0±18.2
2007Gelbmann et al. [1]Germany26 (20/6)46.6±17.6
2008Kulaksiz et al. [2]Germany29 (21/8)52.2 b
2008Esposito et al. [8]Germany10 (9/1)49.7±16.6
2009Schnitzbauer et al. [9]Germany1 (1/0)30
2010Al-Benna et al. [10]Germany1 (1/0)48
2010Tian et al. [11]China1 (1/0)22
2012Kwon et al. [12]Korea1 (1/0)68
Total97 (69/28)a49.8b
Tab.1  Summary of SC-CIP cases reported from 2001 to 2012
Fig.1  Articles and number of cases reported in Germany and other countries.
ReferencePrimary critical diseasesTotal
Emergency diseasesPost major surgeryOthersa
TraumaInfectionBurnCardiothoracic surgeryAbdominal surgery
Scheppach et al. [3] 0300003
Engler et al. [5]0100001
Benninger et al. [6] 4010005
Jaeger et al. [7]50000510
Gelbmann et al. [1] 713020426
Kulaksiz et al. [2]555122029
Esposito et al. [8]11170010
Schnitzbauer et al. [9] 1000001
Al-Benna et al. [10] 0010001
Tian et al. [11] 1000001
Kwon et al. [12] 0001001
Total (%)24 (27.3)23 (26.1)8 (9.1)22 (25.0)2 (2.3)9 (10.2)88 (100)
Tab.2  Primary diseases of SC-CIP
ReferenceMechanical ventilationVasopressor administrationc[n/total (%)]
n/TotalTime (d)aPressure(cm H2O)
Scheppach et al. [3]3/344.3±16.210.8±3.82/3 (66.7)
Engler et al. [5] 9/941.1±17.110.1±4.27/9 (77.8)
Benninger et al. [6] 5/530.4±19.815.3±7.43/5 (60.0)
Jaeger et al. [7] 10/1028.0a11.6±6.64/10 (40.0)
Gelbmann et al. [1] 26/2640.7±32.9-b17/26 (65.4)
Esposito et al. [8] 10/1034.3±12.714.9±5.54/10 (40.0)
Schnitzbauer et al. [9]1/128231/1 (100.0)
Al-Benna et al. [10] 1/113121/1 (100.0)
Kwon et al. [12]1/1210/1 (0)
Summary66/6636.312.839/66 (59.1)
Tab.3  Mechanical ventilation and vasopressor treatment performed before SC occurrence
Fig.2  Liver function parameters of different SC-CIP cohorts. (A) The TB levels of patients in the three SC-CIP cohorts were higher than normal ranges. No significant difference was determined among the three cohorts. (B) The ALP levels of patients in the three SC-CIP cohorts were higher than normal ranges. Compared with cohort B, cohorts A and C revealed a significant increase in ALP levels. (One patient was excluded in cohort A.) (C) The GGT levels of patients in three SC-CIP cohorts were higher than normal ranges. The mean level of cohort A was higher than that of cohort B. (Two patients were excluded in cohort A. The detailed data of cohort C was not reported in the original article.) (D and E) Analysis results of 20 patients showed that the ALT and AST levels of SC-CIP were higher than the normal range. The detailed data of cohorts B and C were not reported in the original article.
Fig.3  Pathological progression of ICU-related sclerosing cholangitis. SC-CIP pathogenesis can be divided into four categories, including ischemic causes, toxic causes, infectious causes, and others. The significant pathological changes include stricture and dilation of bile ducts, mixed inflammatory infiltrate, perivenular hepatocellular bilirubinostasis, and hepatocellular damage.
Scheppach et al. [3] 3/30/30/33/32/3
ter Borg et al. [4] 1/10/10/11/10/1
Engler et al. [5] 9/97/95/98/99/9
Benninger et al. [6] 5/55/50/53/55/5
Jaeger et al. [7] 10/1010/1010/103/10
Esposito et al. [8] 10/1010/105/10
Schnitzbauer et al. [9] 1/10/11/11/11/1
Al-Benna et al. [10] 1/11/10/11/11/1
Tian et al. [11] 1/10/11/11/10/1
Kwon et al. [12] 1/10/11/11/11/1
Summary (%)42/42 (100.0)33/42 (78.6)18/32 (56.2)27/42 (64.3)19/22 (86.4)
Tab.4  Diagnosis and treatment options for SC-CIP
ReferenceNumber of patientsFollow-up(months)SurviveDeath
Biliary cirrhosisNeed for liver transplantationHepatic failureOthers
Scheppach et al. [3] 311.7 (11–12)2100
ter Borg et al. [4] 114.00100
Benninger et al. [6] 537.8 (12–55)3110
Jaeger et al. [7] 1021.0 (3–54)8101
Gelbmann et al. [1] 25a(4-49)11770
Kulaksiz et al. [2] 2921.0 (1–123)37181
Esposito et al. [8] 1014.4 (2–92)4051
Schnitzbauer et al. [9] 1500100
Al-Benna et al. [10]10100
Tian et al. [11] 1121000
Kwon et al. [12] 16.01000
Summary (%)8717.9 b33 (37.9)20 (23.0)31 (35.6)3 (3.4)
Tab.5  Clinical outcomes of SC-CIP
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