CHOLANGITIS JOURNAL

Review Article

Cholangitis: Diagnosis, Treatment and Prognosis
Amir Houshang Mohammad Alizadeh*

Abstract
Cholangitis is a serious life-threatening situation affecting the hepatobiliary system. This review provides an update regard- ing the clinical and pathological features of various forms of cholangitis. A comprehensive search was performed in the PubMed, Scopus, and Web of Knowledge databases. It was found that the etiology and pathogenesis of cholangitis are heterogeneous. Cholangitis can be categorized as primary sclerosing (PSC), secondary (acute) cholangitis, and a re- cently characterized form, known as IgG4-associated chol- angitis (IAC). Roles of genetic and acquired factors have been noted in development of various forms of cholangitis. PSC commonly follows a chronic and progressive course that may terminate in hepatobiliary neoplasms. In particular, PSC commonly has been associated with inflammatory bowel disease. Bacterial infections are known as the most common cause for AC. On the other hand, IAC has been commonly encountered along with pancreatitis. Imaging evaluation of the hepatobiliary system has emerged as a crucial tool in the management of cholangitis. Endoscopic retrograde cholan- giography, magnetic resonance cholangiopancreatography and endoscopic ultrasonography comprise three of the mo- dalities that are frequently exploited as both diagnostic and therapeutic tools. Biliary drainage procedures using these methods is necessary for controlling the progression of cholangitis. Promising results have been reported for the role of antibiotic treatment in management of AC and PSC; however, immunosuppressive drugs have also rendered clin- ical responses in IAC. With respect to the high rate of complications, surgical interventions in patients with cholan- gitis are generally restricted to those patients in whom other therapeutic approaches have failed.
Citation of this article: Mohammad Alizadeh AH. Cholangitis: diagnosis, treatment and prognosis. J Clin Transl Hepatol 2017;5(4):1–10. doi: 10.14218/JCTH.2017.00028.
Keywords: Primary sclerosing cholangitis; Acute cholangitis; IgG4-associated cholangitis; Endoscopic retrograde cholangiography; Magnetic resonance cholangiopancreatography; Endoscopic ultrasonography.Abbreviations: AC, acute cholangitis; ALP, alkaline phosphatase; ALT, alanine aminotransferase; CBD, common bile duct; CIP, chronically ill patients; ERCP, endo- scopic retrograde cholangiography; EUS, endoscopic ultrasonography; EUS-BD, EUS-guided biliary drainage; EUS-CDS, EUS-guided choledo-choduodenostomy; EUS-GBD, EUS-guided gallbladder drainage; EUS-HGS, EUS-guided hepaticogas- trostomy; IAC, IgG4-associated cholangitis; IBD, inflammatory bowel disease; IDUS, intraductal ultrasonography; MDR, multidrug resistance; MRCP, magnetic resonance cholangiopancreatography; PSC, primary sclerosing cholangitis; PTBD, percutaneous transhepatic biliary drainage; SC-AIP, cholangitis-associated autoim- mune pancreatitis; UC, ulcerative colitis.
Received: 28 April 2017; Revised: 23 June 2017; Accepted: 12 July 2017
*Correspondence to: Amir Houshang Mohammad Alizadeh, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Parvaneh Ave, Tabnak Str, Evin, Tehran 19857, Iran. Tel: +98-21-22432521, Fax: +98-21-22432517, E-mail: ahmaliver@yahoo.com

Definition of cholangitis
Cholangitis syndromes are complex end-stage hepatobiliary
1
tual narrowing and obstruction of the bile ducts. interventions for obviating the obstructive lesions in biliary- hepatic ducts is the primary approach for management of cholangitis. Nevertheless, the only established curative therapy for cholangitis is liver transplantation, especially in
3
The etiology and pathogenesis of various forms of cholangitis
are heterogeneous. Cholangitis may be triggered by both
4genetic and acquired mediators. Cholangitis may also
5
(PSC), secondary cholangitis, and immune cholangitis.
PSC is a serious disorder with yet unknown etiology; however, a role has been proposed for immune dysregulation
4

Journal of Clinical and Translational Hepatology 2017 vol. 5 | 1–10
Copyright: © 2017 Authors. This article has been published under the terms of Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0), which permits noncommercial unrestricted use, distribution, and reproduction in any medium, provided that the following statement is provided. “This article has been published in Journal of Clinical and Translational Hepatology at DOI: 10.14218/JCTH.2017.00028 and can also be viewed on the Journal’s website at http://www.jcthnet.com”.

disorders.
malities fall into the diagnostic criteria for cholangitis. These are generally associated with severe inflammation and fibro- sis of the hepatobiliary system that is characterized by even-
2
patients with progressed disease.
however, as improvements have been reported with therapies involving antibiotics and antifibrotic drugs.
Various type of cholangitis

Given this broad concept, a wide range of abnor-

present as a primary immune condition.
cation system, cholangitis cases can be divided into three main categories, including primary sclerosing cholangitis
6
Bacterial infections secondary to

in the progression of PSC.

bile fluid stasis may also complicate PSC.

7

On the other hand,

the most common form of secondary cholangitis is acute chol-
angitis (AC; also known as recurrent pyogenic cholangitis,
supportive cholangitis and ascending cholangitis). AC is char-
acterized by infections involving the biliary system and
leading to inflammation and obstruction of the biliary
8,9
biliary epithelial cell have been recently identified in IAC. Nevertheless, the immune system may not be the sole con- tributor in IAC, as bile stones or bile duct abnormalities also

ducts.
system has been highlighted in IgG4-associated cholangitis (IAC). Autoantibodies of IgA class that are reactive against
10
PSC is a heterogeneous disease regarding histopathological features, clinical presentation and treatment response, as

New hopes are emerging,

Furthermore, the insidious role of the immune

Therapeutic

In a broad classifi-

have been related to occurrence of this condition.
PSC

11

12follows a chronic and progressive course that may terminate

well as malignant transformation rate.

PSC commonly

in hepatobiliary neoplasms.

13

PSC has shown higher rates of

incidence in recent years, with reports of 1/10000 in the pop-
14,15ulation of Northern Europe. The majority of PSC-affected

patients are men of European origin.

15,16

However, PSC

In cases of isolated IAC without autoimmune pancreatitis, some features of IAC, including stenosis on cholangiography, stromal inflammation and response to immunosuppressive

affects all age groups worldwide, with higher prevalence in
rdth 17the 3 and 7 decades of life. Despite the suspected auto-
immune nature of PSC, this condition is not responsive to

27other hand, PSC patients show hepatic fibrous change, and

18It has been noted that 90% of PSC cases are related to

immunosuppressive therapies.

acquired environmental factors.

13

PSC is commonly associ-

ated with inflammatory bowel disease (IBD).

In fact,

clinical differentiation of these two entities.

In addition to

IBD-PSC has been proposed as a distinct clinical entity from
isolated PSC, suggesting a strong association between the

generally younger that those with IAC.
AC

33

20PSC suffer from IBD, with the majority presenting with ulcer-

two disorders.

A range of 34–75% of the patients with

2,21,22association highlights the role of gut microorganisms in

ative colitis (UC).

There has been reported that this

PSC-IBS syndrome.

23

Reduced number of T-regulatory cells

AC (as well as suppurative cholangitis or ascending cholangi-
tis) was first identified as a disorder associated with recurrent
fever, abdominal pain and jaundice. This clinical combination
has been traditionally known as Charcot’s triad. AC is primarily
an infectious disease characterized by the proliferation of
bacteria within bile and with the secondary blockage of biliary

in inflamed hepato-biliary tissues of patients with PSC sug-
gests a role for immune hyperactivity in pathogenesis of this

condition.

24

In line with this, PSC may also develop in the

context of other immune-mediated conditions, such as

immune hepatitis, type 1 diabetes, sarcoidosis and immune tracts.

8

The Reynolds’ pentad is defined as the occurrence of

25The role of demographic features in PSC remains contro-

36
The initial version of the Tokyo Guidelines for the Manage-
ment of AC and Cholecystitis (TG07) was introduced for the
first time as a standard for diagnosis and management of AC;
however, the TG07 suffered from lack of specificity and
sensitivity, as well as having limited application in clinical
37,38
tory and imaging findings, with 2, 4 and 1 items (Table 1).
A severity score was also incorporated into the TG13. Based on this, AC can be classified into the following three grades: Grade III, severe form associated with organ failure; Grade II, moderate form requiring biliary drainage therapy; and

thyroiditis.

confusion and shock along with Charcot’s triad.

versial. In a cohort study by Fraga et al.

26

demographic

parameters including male sex, pancolitis, non-smoking and
previous appendectomy were significant risk factors for PSC.
Smoking seems to be a protective factor against cholangi-

20noted. To date, 23 identified genetic loci have been related

tis.

The role of genetic predisposition in PSC has been

practice.
by the revised guidelines that were published in 2013 (version TG13). The TG13 statements achieved both high sensitivity and specificity (87.6% and 77.7% respectively). This approach uses three domains, including clinical, labora-
38

13leukocyte antigen loci is one of the loci with strong relation

to PSC susceptibility.

The DRB01*03 haplotype of human

to PSC development.
IAC

16

Cholangitis presentation may be observed in the context of a
broader autoimmune disorder characterized with high levels
of IgG4 in serum along with proliferation of lymphocytic
populations positive for IgG4 (known as IgG4-related chol-

37,39Bile stone and obstruction of the bile duct are considered

angitis).

Accordingly, IAC is characterized with infiltration 28

the main causes for acute bacterial cholangitis.

In addition,

11,27

36bile duct obstruction in AC may also be triggered by other

of the biliary system with IgG4-positive lymphocytes.

Involvement of the bile ducts and pancreatitis are common
features described in AIC. IAC is predominantly encountered
in older individuals, and is mainly a feature of male sub-
27,29,30
IAC or PSC, a diagnostic dilemma
With respect to the similar clinical features of IAC and PSC,
22

Table 1. Diagnostic criteria for acute cholangitis, Tokyo Guidelines

19

35these, one can bring into mind that patients with PSC are

Mohammad Alizadeh A.H.: Cholangitis updates

drugs, may be helpful in differential diagnosis.

On the

33obstructive jaundice, which is rarely seen in PSC, can assist in

segmental stricture as pathological findings.

Presentation of

These flaws were obviated to a large extent

Grade I, mild form including otherwise.

jects.
and adolescents;31 the pathogenesis of this form of cholangi- tis is under investigation.

However, IAC has also been reported in children

Parameter
Clinical features
Laboratory features
Imaging findings
Definite diagnosis

Items
1. Previous biliary disorder
2. Fever and/or chills
3. Jaundice
4. Abdominal pain
5. Presence of inflammation indicators (elevated leukocyte count, positivity for C-reactive protein)
6. Elevated liver enzymes
7. Biliary dilatation, other abnormalities suggesting hepatobiliary disorder
Either Charcot’s triad (2+3+4) or two items in the clinical features along with both items in the laboratory and imaging findings

However, these two entities can be differentiated based on the domi- nance of IgM and albumin serum level in PSC, while elevated

the two may be misdiagnosed for one another.

22has also been suggested as useful for differentiating IAC from
32

levels of IgG4 are a feature of IAC.

The ratio of IgG4/IgG1

PSC.
the context of its specific histological features, such as more pronounced infiltration by immune cells (plasma cells,
30
Eosinophilic Association of IAC with pancreatitis is a useful parameter
27,30

IAC may also be distinguished from PSC according to

Suspected diagnosis

Two or more items of clinical features

lymphocytes, and eosinophils).
cells have been shown to express IgG4 in IAC.
infiltration of hepatic tissue in IAC may also be useful for

differentiation of the two conditions.
that could be exploited for discriminating IAC from PSC.

The infiltrating plasma

34

33

  

2 Journal of Clinical and Translational Hepatology 2017 vol. 5 | 1–10

Mohammad Alizadeh A.H.: Cholangitis updates

etiologies. Choledocholithiasis has been described among the most common etiologies for AC; nevertheless, this phenom- enon is often accompanied by secondary bacterial infections
40

the rate of recurrent cholangitis by 37%.
ERCP is recommended to be performed within 24 hours of admission for patients with AC, as delaying this procedure

within the biliary system.
stones, malignancies (source being pancreas, gallbladder, cholangiocarcinoma, or metastatic tumors) or benign

can prolong hospital stay for these patients.
no significant differences were reported in mortality rate or hospital stay among patients with cholangitis who had under-

cholangitis.

A diagnostic imaging procedure for various

Other etiologies include gall-

Nevertheless,

obstructions (surgical, pancreatitis, or chronic cholangitis),8 56

and some parasitic disorders. In a survey of 31 patients,
41

reported cholecystectomy, stones in bile ducts, chronic pancreatitis, and abdominal trauma as the

factors, such as resuscitation period and hemostatic disease. ERCP is associated with higher rates of complications respective to other endoscopic procedures. These complica- tions include pancreatitis, bleeding, trauma, and cardiopul-

Gossard et al.causes for AC.Diagnostic modalities for cholangitis

57as pancreatitis in 1.2–4% and cholangitis in 2–2.5% of

Imaging evaluation of the hepatobiliary system has the
primary role in diagnostic modalities for cholangitis. Imaging
evaluation also has applications in staging and management of
42

Pancreatitis, perforation and bleeding, as well as

forms of cholangitis should be able to reveal multiple charac-
teristics of the biliary hepatic system, including stenosis and
dilatation of bile ducts, as well as thickness of bile ducts walls,
intrahepatic calculus, abnormalities of hepatic parenchymal
tissue, evidences of hepatic dysplasia, and portal hyperten-

tion, and cholangiocarcinoma.
MRCP

sion.

6,43

The most frequently used imaging studies are endo-

scopic retrograde cholangiography (ERCP), magnetic resonance
cholangiopancreatography (MRCP), and endoscopic ultrasonog-

MRCP, along with ERCP, is known to be one the most reliable procedures for diagnosing PSC. One major advantage of MRCP, however, is its noninvasive nature. In MRCP imaging, degree of intra- and extrahepatic bile duct, as well as gall- stones and cholesterol stones, can be evaluated. In addition,

44
Role of ERCP in cholangitis

raphy (EUS).

45,46 ERCP may also be applied as a reference method for evaluat-

ERCP is the gold standard for diagnosis of cholangitis.

ing other imaging procedures, such as MRCP.

47

ERCP can be

and its related complications, MRCP is gaining more and more
pros as the first line assessment procedure in suspected
63
use of MRCP resulted in a 3-fold increase in identification of
64
63,65
In addition; MRCP may miss bile duct dilatations in PSC.
Role of EUS in cholangitis

effectively exploited for diagnosis of cholangiocarcinoma in
PSC, with specificity and sensitivity of 97% and 65%, respec-
48
lution, thereby allowing for small ducts to be visualized.

63patients, and for screening to provide timely diagnosis of

tively.
rate. Asymmetrical dilatation of bile ducts, as well as pres- ence of calculi, is seen in ERCP. Decreased divisions of the biliary tree may be seen in ERCP with a more detailed reso-
49

Furthermore, ERCP delivers a high (98.8%) success

the use of ERCP, complete assessment of a ductal tree may be
accomplished, showing the presence of obstructive lesions
50
formed as a therapeutic procedure for biliary drainage in
51

MRCP analysis.
detect stones of large size in the CBD.
tivity of MRCP in identifying small stones is not satisfactory.
66

and stenosis.
Instead of a diagnostic method, ERCP may also be per-

MRCP has the ability to accurately

cholangitis.
ical importance in the management of cholangitis. This approach provides a therapeutic alternative for patients who

The role of biliary drainage procedures is of crit-

51guided implantation of a biliary endoprosthesis or stent repre-

may not tolerate surgical drainage interventions.

ERCP-

52 method is an effective therapeutic modality that can be toler-

Sonography is a relatively inexpensive and widely available method of imaging. EUS eventually may replace ERCP as a
67
68
of MRCP to detect cholangitis lesions in early stages of the disease, EUS has been proposed as a useful first-line diag-
69

sents the gold standard therapeutic for biliary stricture.

This

51cated when patients are in shock, show signs of nervous
51

ated even by elderly patients.

Therapeutic ERCP may be indi-

system involvement, or show coagulation defects.
other drainage procedures may be considered in cases in which ERCP is not possible, or under conditions for which ERCP is not available. Performing ERCP may not be feasible when there is pyloric or duodenal stenosis. ERCP may also fail if the catheter cannot be inserted properly or in patients

52It is suggested that the biliary drainage procedure be

with prior operations on the gastrointestinal tract.

53 Delay in performance of ERCP has been shown to increase

performed with 24 hours of the cholangitis diagnosis.

Overall,

By

PSC can be characterized by randomly distrib-

gone ERCP during 24, 48 or 72 hours after admission for the procedure. Timing of ERCP can be influenced by some
55
58,59
ing hospital stay in PSC patients has been reported as 10%. Other ERCP-related complications include increased common bile duct (CBD) diameter, biliary dilatation, biliary stent inser-
61

monary problems.

ERCP may lead to complications such
cases.
cholangitis comprise the most common complications of ERCP in PSC patients. The overall rate of ERCP complications requir-
60

62vides 80% and 90% sensitivity and specificity for diagnosis of
42

low-diameter strictures are detectable by MRCP.

MCRP pro-

PSC, respectively.

Considering the invasive nature of ERCP

PSC.

MRCP is also an effective method to follow up the

complications.
In comparison to clinical based-diagnostic approaches,

PSC patients.
uted annular strictures alternating with slightly dilated bile ducts, usually on both intra- and extrahepatic bile ducts in

primary procedure for biliary drainage.
dures are important in many aspects for managing patients with cholangitis, encompassing diagnostic, therapeutic and monitoring of the disease. Biliary duct dilatation, and small

44malignant transformations, EUS is a useful method and supe-

stones can be well diagnosed by EUS.

For detection of

rior to ERCP.
Regarding the invasiveness of ERCP and the low sensitivity

nostic tool for cases with suspected cholangitis.
respect to ERCP, EUS has the benefit of lower complication rates; and with respect to MRCP, it has significantly lower

Journal of Clinical and Translational Hepatology 2017 vol. 5 | 1–10 3

44

Nevertheless, sensi- 44

54
55

In accordance,

Endoscopic proce-

With

70
The therapeutic approach of EUS in biliary hepatic diseases, designated as EUS-guided biliary drainage (EUS-BD), has been introduced as an alternative option for other drainage methods, such as percutaneous transhepatic biliary drainage (PTBD) and ERCP (Table 2). The endoscopic drainage encompasses balloon- dilatation and/or stenting of strictures, and improves the clin-
72
(EUS-CDS), EUS-guided hepaticogastrostomy (EUS-HGS) and EUS-guided gallbladder drainage (EUS-GBD) that can be used in various obstructive biliary hepatic disorders, each with a
73

costs.
nostic method for biliary hepatic disorders in the near future.

Transabdominal US has been successfully applied for diagnosis of IAC, by observing thickness of the bile duct
80
mucosal lesions continuous to the hilar.
IDUS findings could also be used for estimating severity of
cholangitis, namely by irregular inner surface, heterogeneous internal echo, and irregular outer contour, which correlate

EUS may become the first-line therapeutic and diag-
EUS is also considered as an alternative drainage method walls.

for cases in which ERCP has failed.

67,71

In this regard, results of IDUS can be used for char- acterization and identification of cholangitis-associated auto- immune pancreatitis (SC-AIP) from PSC or biliary caner, which is characterized with symmetrical wall thickness, pres- ence of homogeneous internal foci and presence of lateral
81

ical picture and biliary-liver enzyme profile.
EUS-BD is divided into EUS-guided choledo-choduodenostomy

with severity of cholangitis.

82

high rate of success (93%, 97% and 100%, respectively). Nevertheless, regarding the low rate of complications of EUS, there has been suggestion to consider the EUS-BD as the first

Antibiotics for cholangitis
New light has been shedding on the role of microbial compo- nents in development of various forms of cholangitis. Due to the high rate of positive microbial cultures from the bile ducts of cholangitis patients, it has been suggested to obtain a microbial profile before performing drainage methods. The most common bacterial infections in cholangitis include the Escherichia coli, Klebsiella spp., pesudomonal species, Enter- obacter spp., Acinetobacter spp. of Gram-negative bacteria, and enterococcus, streptococcus, and staphylococcus Gram-
84,85
84of the disease. For the best practice, administrated
antibiotics for cholangitis should be those with broad range antimicrobial activities and which are capable of passing into the bile duct, such as third-generation cephalosporins,

67,74 advantage of the EUS-BD approach is preserving bile flow, as

line therapy, even in cases without failed ERCP.

Another

compared to PTBD or surgical drainage methods.

75

However,

stent occlusion, migration and shortening are among the diffi-
culties faced by EUS-BD, all of which may necessitate stent
76
Concentric wall thickness of bile ducts has been noted as the most reliable finding to predict correct diagnosis of AC by this
77
IDUS analysis in IAC patients shows circular-symmetric wall thick- ness, smooth outer margin, smooth inner margin and homo- geneous internal echo in the stricture. A bile duct wall thickness greater than 0.8 mm in regions of non-stricture
79

replacement.
Radial EUS has been applied for diagnostic goals in AC.

Intraductal ultrasonography (IDUS) diagnostic modalities have been noted to be useful in differentiation of PSC and IAC. Irregular inner margin, diverticulum-like out- pouching and obliteration of three layers are the IDUS fea-
78

method.

tures specific for PSC, in comparison with IAC.

on the cholangiogram is a feature specific to IAC.

levofloxacin.

87,88

Table 2. Applications of endoscopic ultrasonography in cholangitis

Mohammad Alizadeh A.H.: Cholangitis updates

Selection of antibiotics may be influ- enced by multiple factors, such as prior exposure of patients with hospital-acquired infections, as well as the severity

positive bacteria.

ureidopenicillins, carbapenems and fluoroquinolones.

86

The

most effective antibiotics for cholangitis patients have been
noted as imipenem-cilastatin, meropenem, amikacin, cefe-
pime, ceftriaxone, gentamicin, piperacillin-tazobactam and

Type of cholangitis
IAC
AC
AIDS- related sclerosing cholangitis

EUS approach
Transabdominal ultrasonography
Radial EUS
Simple

Number
of patients
2
28
50

Specific diagnostic findings Bile duct thickening
Diffuse and/or concentric wall thickening (more than 1.5 mm), and intraductal heterogeneous echogenicity without acoustic shadowing are suggestive for AC
EUS findings are highly correlated with ERCP findings

Reference, year
Kobori et al.,80 2016
Alper et al.,77 2011
Daly et al.,83 1996

PSC and IAC IDUS 15 patients with PSC and 35 patients
with IAC

Irregular inner margin, diverticulum-like Naitoh et al.,78 outpouching, disappearance of three 2015
layers are specific for PSC

IAC Transpapillary 23 Bile duct wall thickness more than 0.8 mm Naitoh et al.,79 IDUS in regions of non-stricture is highly 2009
suggestive of IAC

   

Abbreviations: AC; acute cholangitis; AIDS, autoimmune deficiency syndrome; EUS, endoscopic ultrasonography; ERCP, endoscopic retrograde cholangiography; IAC, IgG4- associated cholangitis; IDUS, intraductal ultrasonography; PSC, primary sclerosing cholangitis.

4 Journal of Clinical and Translational Hepatology 2017 vol. 5 | 1–10

Mohammad Alizadeh A.H.: Cholangitis updates

Antibiotics in AC
40

resulted in an elevation in T-regulatory CD4+, CD25+ lym- phocytes, which can modulate immune system activity. This was further reported to be associated with normalization of
43

The rates of polymicrobial-positive cultures in AC vary from 86,89,90

ALT and leukocyte counts in PSC.
Role of surgery in cholangitis

30–78%, and the response rate to antibiotics in AC is

40effective antibiotic therapy for AC decreased the death rate of

satisfactory in the majority of patients.
this condition dramatically during the 1970s through 1980. An appropriate profile of antibiotic administration is vital in the early stages of acute infectious cholangitis. The majority of patients with acute bacterial cholangitis benefit from

Surgical intervention in cholangitis provides either a selective
or emergency option. Although invasive, surgical intervention
generally results in more persistent regression of the chol-
102
tures of the hepatobiliary lesions and obstructions (Table 3). Surgical therapy has been indicated for PSC patients with major obstructive lesions which failed removal by endoscopic
104

36administrate antibiotic therapy along with procedures per-
90
no adverse outcomes on the clinical course of the disease. In parallel, short-duration antibiotic therapy (of 3 days) appears sufficient when adequate drainage is achieved and
91

board-spectrum antibiotics.

It is an immediate need to

angitis.
upon multiple factors, including patient characteristics (fulfill- ing requirement for general anesthesia, tolerability of surgical procedure, history of treatment failure) and pathological fea-
103
drainage methods.
been described as an effective treatment in AC that can be associated with significant improvement of clinical symptoms
105

There are no recommendations for discontinuing of antibiotic therapy, however, and it seems that cessation after relief from clinical symptoms, such as fever, and following drainage therapy has
53
Regardless, it is highly recommended to

formed for correcting the biliary obstruction.

fever is abating.

preserve antibiotic therapy in the early phases of AC.

44

Fur-

It’s

thermore, as septic shock is a potential threat in AC, it is a
necessity to administrate broad-spectrum antibiotic therapies
as early as possible (within 1–4 hours) following signs of
92septic shock development. Either oral or intravenous
administration of antibiotics seemed to be of equal efficiency
93
carbapenems, vancomycin and ampicillin, has been observed
90

with the least post-surgical complications (3–6%). noteworthy that caution must be taken to avoid unnecessary surgical intervention for IAC cases who may be misdiagnosed

in eradiation of bacteria in AC patients.
Resistance to various antibiotics, including quinolone,

103

In such cases, surgery is the method of

in cultures isolated form AC patients.
population, 29% multidrug resistant (MDR) isolates were recovered from bile cultures of patients with AC. Risk factors for MDR in that study included male sex, previous anti- biotic therapy and biliary stenting, with the recent factor

90reported as a significant risk factor for acquiring MDR infec-
94

111performed as partial hepatectomy in patients with cholangi-

being an independent risk factor.

Also, stent therapy was

treated with endoscopic drainage.

Surgery may also be

tions in AC patients.
Antibiotics in PSC

112cases with tissue hypertrophy or in cases with suspected

95 A high rate of positive cultures has been reported for PSC

Interestingly, curative success of partial liver 112

The beneficial role of antibiotics in PSC is controversial.

patients.

86,89

The idea that antibiotic therapy may be useful

in slowing down the progression of PSC originates from
studies that described a role for bacterial species residing in
the human gastrointestinal tract in the pathogenesis of
97
ursodeoxycholic acid therapy resulted in decreased liver enzyme levels in PSC patients, and in a relief of some clinical
98
with ursodeoxycholic acid and placebo.
istration also improved alanine aminotransferase (ALT), gamma-glutamyl transpeptidase, and erythrocyte sedimen-
100
effective during a 3-month treatment period resulting in
reduced ALT and bilirubin levels, and in the Mayo PSC risk

Regardless of etiology, cholangitis is a serious life-threatening biliary-hepatic condition. A scoring system based on four parameters, including fever, hyper bilirubinemia, bile duct dilatation and presence of bile duct stones, has been pro-
113
In a comparison between PSC and secondary SC patients, those with secondary diseases showed poorer prognosis and
41
early mortality in AC patients.
Severe obstructions of bile ducts can cause extreme
infected bile reflux and appearance of bacteria in blood, rendering a dire situation. In addition, low level of serum albumin along with prothrombin time (international normal- ized ratio) of >1.5 were associated with poorer prognosis and

96min resulted in no significant effects on the clinical course of

PSC.

However, antibiotic therapy for 12 weeks with rifaxi-
PSC.
In contrast, using vancomycin in conjunction with routine

posed to predict severity of cholangitis.
Prognostic features of AC

symptoms such as fatigue, pruritus, diarrhea and anorexia. Significant reduction of alkaline phosphatase (ALP) enzyme was also observed in PSC patients treated with a combination of ursodeoxycholic acid and metronidazole, in comparison
99
tation rate in children with PSC.
Both vancomycin and metronidazol therapy were found

shorter life expectancy.
reflects the number of circulating immature granulocytes in blood has been noted as a significant prognostic factor in AC. In this regard, higher index corresponded with higher rate of
114

score.

101

Vancomycin administration in patients with PSC-IBD

The achievement of

In a study of a German

along with surgery is indicated in cases with duct strictures,
dilation or obstructive stones. Most commonly, hepaticojeju-
nostomy is the method of choice for surgical biliary drain-

Vancomycin admin-

Choosing a surgical intervention is dependent

Accordingly, the surgical approach has

106,107Liver transplantation is the definitive surgical treatment for
108
EUS-BD are not possible.

as bile duct carcinoma.

PSC.
age procedure.
choice when other drainage methods such as ERCP and
108

Surgical treatment may also be indicated as a drain-

103higher mortality rate and longer hospital stay than those

age.

Patients who underwent surgical drainage showed a

tis.

Generally, liver resection approaches are considered in

103resection has been noted in three patents with PSC, but

cancer.
large cohort studies are needed for confirmation. Outcome and prognosis of cholangitis

Journal of Clinical and Translational Hepatology 2017 vol. 5 | 1–10 5

The drainage interventions

Using a delta neutrophil index which

Table 3. Surgical interventions in cholangitis

Cholangitis type
Recurrent pyogenic cholangitis

Number of patients, period and country of origin, sex, median age
94, 2007–2016 India, 66 women and 28 men, median age 40 years

Surgical procedures
Drainage procedure (HJ) (53%), left hepatectomy (19%), left lateral segmentectomy (14%), right hepatectomy (4%), right posterior sectorectomy (1%), left hepatectomy + HJ 5%, left lateral segmentectomy + HJ (2%), Right hepatectomy +
HJ (1%)
Hepatectomy (65.9%), left hepatectomy (15.3%), left lateral sectionectomy (47.1%), right hepatectomy (2.4%), right posterior sectionectomy (1.2%), hepatectomy + drainage procedure (9.4%), left hepatectomy + HJ (2.4%), left lateral sectionectomy + HJ (4.7%), left lateral sectionectomy + sphincteroplasty (1.2%), right hepatectomy + HJ (1.2%), drainage procedure (14.1%), hepaticojejunostomy (7.1), transduodenal sphincteroplasty (1.2%), T-tube drainage (5.9%), percutaneous choledochoscopy (10.6%)

Complications Ref
Surgery-related complications in 102 32/94 patents, mild wound infection
(9), severe wound infection (10), postoperative bile leak (6),
postoperative hemorrhage requiring blood transfusion (1), chest infection (2), acute cholangitis (2), acute renal failure (1), sepsis (1)
Wound infection (50%), intra- 103 abdominal collection (21.7%),
pleural effusion (6.5%), bile leak
(4.3%), atrial fibrillation (4.3%),
wound dehiscence (2.2%), incisional hernia (2.2%), others (8.7%)

Mohammad Alizadeh A.H.: Cholangitis updates

Recurrent pyogenic cholangitis

80, 2001–2010 Hong Kong, 45 women and 35 men, median age 60 years

Hepaticocutaneousjejunostomy (100%), left lateral sectionectomy (19/80), left hepatectomy (11/80), right hepatectomy (5/80), right posterior hepatectomy (2/80), segment VIII resection (1/80)

23/80 (28.8%) residual stones, 109 31.3% recurrent stones, wound
infection (9), postoperative ileus (1), intra-abdominal collection requiring drainage (1), bile leak (1), incisional
hernia (2)

Recurrent pyogenic cholangitis

85, 1995–2008 China, 50 women and 35 men, median age 61 years

Recurrent pyogenic cholangitis 27, 1986–2005 USA, 15 women and 12 men, median age 54.3 years Liver resection+ choledochojejunostomy with Hutson access loop (11/27), liver resection only (6/27), common bile duct exploration (10/27) Wound infection (3), deep venous thrombosis (1), perihepatic hematoma (1), perihepatic abscess (3), hepatic insufficiency (1)

110

Abbreviation: HJ, hepaticojejunostomy.

115predictive factors of AC included hyperbilirubinemia, high

refractory disease in AC.

In another study, the five adverse

drugs involves slowing down the progression of the disease, but the mechanism is not clear. Liver transplantation is currently the only established treatment. Antibiotic and anti- fibrotic agents have shown beneficial effects in PSC,2 but the overall results are controversial.
Hepatic involvement in PSC is characterized by a progres- sive fibrotic condition. Eventual deterioration of the bile duct in PSC may ultimately result in liver cirrhosis. Furthermore, development of extra- and intrahepatic ducts may accelerate

fever, leukocytosis, advance age and hypoalbuminemia.

36

Likewise, parameters such as higher age, low blood pressure,
leukocytosis, high C-reactive protein, and long period of
antibiotic therapy were associated with poor prognosis in

116bilirubin >10 mg/dL have been associated with adverse

Likewise, severe leukocytosis (>20.000/mL) and total

AC.
outcome in AC.

117

Prognostic features in PSC
Generally, PSC is a progressive disorder associated with the least response to routine therapeutics. There is still no established drug with true known positive effect on PSC. Despite the proposed role for the immune system in the development of PSC, effectiveness of immunosuppressive

The patients are at risk of chol- The estimated rate of cholangiocarcinoma is

6 Journal of Clinical and Translational Hepatology 2017 vol. 5 | 1–10

16angiocarcinoma, hepatic cancer, biliary cancer, and colon

neoplastic transformation.

2,4,118as high as 10–12% in PSC patients.
118

cancer.
should incorporate a 2–4% risk of hepatocellular carcinoma

in end-stage liver disease.
diseases in PSC is estimated to be 13–14%.
crude estimate, PSC patients are considered likely to die

118,119

To this rate, one The overall risk of neoplastic

42

In another

Mohammad Alizadeh A.H.: Cholangitis updates

from cancer in 40–58% of cases.
of >10 years has reached 80% for PSC patients who

Overall, life expectancy undergo liver transplantation. Patients with PSC may

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42survive 12–15 years following diagnosis of PSC if not

2,23
are timely diagnosis, appropriate timing of liver transplanta-
42

treated with liver transplantation.
The main determinants of prognosis of PSC patients

tion, and well management of the complications. reported prognostic factors with poor outcome include higher ages,120,121 higher levels of serum bilirubin,120–122 albumin, alkaline phosphatase, presence of hepatomegaly,

121,122terial infection is a further adverse feature of PSC that can

and/or splenomegaly.

Complications of PSC with bac-

7ment of liver transplant, and malignancy were significantly
123
124
Generally, IAC patients seem to have more favorable prog-
22
The author has no conflict of interest related to this publication.
Author contributions
Conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript (AHMA).
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Mohammad Alizadeh A.H.: Cholangitis updates