Keywords
cholangiopathy - cholangitis - IgG4-related sclerosing cholangitis - PSC
Introduction
Bile is secreted by the hepatocytes into the biliary canaliculi which then coalesce
to form subsegmental and segmental ducts and ultimately drain via the common bile
duct into the duodenum.[1] Both benign and malignant lesions can involve the biliary tree. Patients almost
always present with altered liver functions or jaundice and imaging usually reveals
altered morphology of the biliary drainage system or the hepatic parenchyma.[2]
[3]
Development and Anatomy
The hepatic diverticulum arises from the ventral foregut during the fourth embryonic
week. A thin double layer of cells is seen surrounding the portal vein during development
of the liver, this is termed as the “ductal plate.” Ductal plate malformations give
rise to a variety of diseases including biliary atresia, Caroli disease, Meckel syndrome,
and Alagille syndrome.[4]
[5]
The ducts of the right and left lobe usually follow a predictable pattern of union,
although a number of variations have been described.[4]
[6] The normal common bile duct (CBD) measures 6 to 7 mm in patients aged 18 to 65 years.[7] Extrahepatic ductal diameter increases 1 mm per decade of life. Larger duct diameters
are seen after cholecystectomy.[8]
Imaging Modalities
Ultrasonography (USG): Ultrasound is usually the first method for evaluation of suspected biliary disorders.[9] It is sensitive for biliary radical dilatation (85–95%)[10] and can usually depict the level of block and sometimes the cause of obstruction.
It is, however, operator dependent and limited by body habitus.
Computed tomography (CT): Uses ionizing radiation and requires injection of intravenous contrast for optimal
visualization of liver parenchyma and biliary tree. Exquisite for vascular anatomy
and comparable to percutaneous transhepatic cholangiography (PTC) using minimum intensity
projections (MinIPs) to visualize the biliary tree.[11] CT using biliary contrast agent (meglumine biotrexate) can be used to visualize
the anatomy of the biliary tree.[11]
[12]
Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP): MRI can easily visualize hepatic parenchymal changes and can evaluate the biliary
anatomy. Hepatocyte-specific contrast agents are excreted into the biliary tree and
can be used for evaluation of the biliary anatomy and variations. MRCP images can
be acquired using either two-dimensional (2D) or three-dimensional (3D) heavily T2-weighted
(T2W) images, which preferentially show fluid and suppresses the background. Most
protocols use 2D and 3D MRCP, T2 and T2W fat sat, diffusion-weighted imaging (DWI),
and pre- and postcontrast T1W images for comprehensive evaluation[2]
[3]
[4]
[13]
[14] ([Fig. 1]).
Fig. 1 A 49-year-old male with jaundice. Ultrasonography (USG) images showing linear hypoechoic
tubular structures (arrows) converging toward the hilum in the right (A) and left (B) lobes—dilated intrahepatic biliary radicles (IHBRs). (C) Minimum intensity projection (MinIP) computed tomography (CT) images clearly showing
asymmetrically dilated IHBR.(arrows). Thick (D) and thin (E, F) slab magnetic resonance cholangiopancreatography (MRCP) showing aberrant IHBR drainage
(arrows). Right posterior duct is clearly seen to drain into the cystic duct insertion
on the thin three-dimensional (3D) MRCP sequence.
Hepatobiliary scintigraphy is done using 99mTc hepatobiliary iminodiacetic acid (HIDA) which is cleared through
the hepatobiliary system. It can be used for diagnosis of gallbladder (GB) disease,
biliary atresia, demonstrating biliary leaks, and choledochal cysts (CDCs).[4]
[5]
Endoscopic retrograde cholangiopancreatography (ERCP) and PTC are rarely used as diagnostic tools in the present day. ERCP is usually combined
with a therapeutic procedure such as stenting or with a brush biopsy. Diagnostic choledochoscopy
can be done for strictures of the CBD and for targeting biopsy.[15] MRCP now has diagnostic accuracy comparable to ERCP[2] ([Table 1]).
Table 1
Major causes of benign biliopathy
|
Congenital
|
Caroli disease, choledochal cysts, Alagille syndrome, cystic fibrosis
|
|
Obstructive
|
Choledocholithiasis with/without cholangitis, chronic pancreatitis, portal cavernoma
cholangiopathy, primary sclerosing cholangitis
|
|
Immunologic
|
IgG4-related sclerosing cholangitis, eosinophilic cholangitis
|
|
Infective
|
Recurrent pyogenic cholangitis, AIDS cholangiopathy, parasitic cholangiopathy
|
|
Ischemic
|
Hepatic artery thrombosis, hematologic disorders, vasculitis, post therapy (TACE/TARE),
secondary sclerosing cholangitis in critically ill patients, portal cavernoma cholangiopathy
|
Abbreviations: AIDS, acquired immunodeficiency syndrome; TACE, transarterial chemoembolization;
TARE, transarterial radioembolization.
Congenital
Biliary Atresia
Biliary atresia is an inflammatory pediatric cholangiopathy causing fibrosis and obliteration
of bile ducts, leading ultimately to biliary cirrhosis. It may be syndromic (associated
with heterotaxy and polysplenia) or nonsyndromic. The primary differential diagnosis
is neonatal hepatitis.
Ultrasound is the most common initial test and biliary dilatation is never seen. The
“triangular cord sign” is increased echogenic soft tissue measuring more than 4 mm
anterior to the anterior wall of the right portal vein (80% sensitive, 98% specific).
GB abnormalities include nonvisualization of the GB lumen, small GB (length < 15–19 mm),
abnormal shape and wall of the GB, and no emptying of the GB after feeding. The “GB
ghost triad” includes small GB, abnormal mucosal lining with indistinct wall, and
knobby or irregular GB outline. Biliary atresia may be associated with macrocysts > 0.5 mm
at the hepatic hilum or microcysts at the confluence, porta, or along the right portal
vein. Increased hepatic subcapsular flow and hepatic artery diameter have been reported.
MRI has almost comparable sensitivity and specificity as ultrasound and findings include
nonvisualized CBD, abnormal GB morphology, and increased periportal soft tissue > 5.1 mm.
MRCP scan be useful to differentiate cysts associated with biliary atresia from CDCs.
Nuclear medicine using HIDA shows lack of excretion of the tracer into the bowel.
In nondiagnostic cases PTC or biopsy may be used for confirmation[5]
[16]
[17] ([Fig. 2]).
Fig. 2 Infant presented with clay colored stools and jaundice. Ultrasonography (USG) showing
increased echogenicity anterior to portal vein division (arrow in A and calipers in B). Abnormal gallbladder shape calipers in (C) and increased diameter of hepatic artery 2.2 mm (calipers) in (D). Findings suggestive of biliary atresia. Ultrasound cases and figures : Courtesy
of Dr. Deeksha Rastogi, Department of Ultrasound, Sir Ganga Ram Hospital, Delhi, India.
Choledochal Cysts
CDCs are cystic dilatation of the intra- or extrahepatic bile ducts or a combination
of both. They are classified using Todani classification[18] I through V with isolated dilatation of the cystic duct proposed by some authors
as type VI CDC. Type I CDC make up the majority of CDC and are further divided into
type IA - cystic, IB - segmental, and IC - diffuse fusiform dilatation of CBD.
Type II CDCs are rare and seen as a diverticulum from the extrahepatic ducts. Type
III CDC is also known as choledochocele and represents dilatation of the intraduodenal
part of CBD.
Type IV CDCs are the second most common type of CDC making up 30 to 40% of CDC. Type
IVA cysts have intra- and extrahepatic biliary dilatation and can be further classified
into cystic-cystic, cystic-fusiform, and fusiform-fusiform types. Type IVB CDCs are
rare and appear as multiple extrahepatic cysts[19] ([Fig. 3]).
Fig. 3 Young child presented with abdominal pain. Ultrasonography (USG) showed dilatation
of common bile duct (CBD). Magnetic resonance cholangiopancreatography (MRCP) was
performed for further evaluation. Coronal MRCP images (A) showing fusiform dilatation of the CBD suggestive of choledochal cyst with narrowing
at lower end (arrowhead) and pancreaticobiliary maljunction with long common channel
(arrow). (B) Excretion of hepatobiliary contrast into the choledochal cyst (arrow).
Pancreaticobiliary Maljunction
Though absolute values of 15 mm have been given for the length of the common channel,
it was defined by the Japanese Biliary Association[20] as a congenital anomaly in which the pancreatic duct and bile duct join anatomically
outside the duodenal wall leading to reflux and mixing of pancreatic and biliary juices.
Patients with CDC type I (except IB) and type IVA almost always are accompanied by
pancreaticobiliary maljunction (PBM). These patients have increased incidence of pancreatitis,
biliary neoplasia, and CBD and GB stones. Morphologically, three types of PBM are
recognized—PBM with right-angled junction, PBM with acute-angled junction, and complex
PBM.
Caroli Disease
Congenital disorder characterized by irregular saccular or fusiform dilatation of
the intrahepatic bile ducts. It may be diffuse, lobar, or segmental in distribution.
It is a ductal plate malformation with autosomal recessive inheritance and more common
in females, and when associated with hepatic fibrosis is known as Caroli syndrome.
USG shows anechoic cystic lesions within the liver and associated calculi or sludge
may be present. CT and MRI show multiple cysts with presence of the “central dot sign”
which represents enhancing vascular radicles surrounded by dilated cystic biliary
radicles. The differential diagnosis is polycystic liver disease. MR with hepatobiliary
contrast agent will demonstrate excretion into the cysts in case of Caroli disease.
Complications include cholangitis, abscesses, stones, malignancy, and secondary biliary
cirrhosis[19] ([Fig. 4]).
Fig. 4 A 16-year-old female with recurrent pain abdomen. Coronal thick slab magnetic resonance
cholangiopancreatography (MRCP) (A) and axial T2-weighted (T2W) (B) images showing communicating dilated cysts (black arrowheads) consistent with findings
of Caroli disease with multiple hypointense filling defects suggestive of calculi
within (white arrows).
Obstructive
Choledocholithiasis
Choledocholithiasis is presence of stone in the CBD. Stones may cause biliary obstruction,
cholangitis, and pancreatitis.
Abdominal ultrasound is usually the first modality used and has a reported sensitivity
of approximately 73% and specificity of approximately 91%. Obesity, distal location
of calculus stone, and lack of accompanying CBD dilatation can all reduce sensitivity
of USG for calculus detection.[8]
Cholesterol calculi may not be seen on CT; however, calcified calculi and those with
a nidus of gas within can be seen. CT can be used with biliary contrast agent.[12] The sensitivity of CT in detecting choledocholithiasis is 80%, ranging between 20
and 90% and use of MinIP may increase detection of calculi.[21]
MRCP is now the noninvasive diagnostic modality of choice for diagnosis of choledocholithiasis.
Calculi appear as filling defects on a background of bright fluid. Both 2D and 3D
MRCP sequences can be used, with 3D images being somewhat more sensitive for detection
of stones. Calculi less than 5 mm in size or not surrounded by bile may be missed
on MRCP.[21]
[22]
Pneumobilia may be confused with calculi. Air bubbles are generally ante-dependent
and may show an air/fluid level, and “bloom” on the in-phase images. Hemobilia may
appear dark on T2W images; however, will be hyperintense on T1W sequences. Vascular
impressions may be misinterpreted as Hilar strictures; however, there will be lack
of proximal dilatation.[22]
[23]
Endoscopic ultrasound (EUS) may provide higher diagnostic accuracy than MRI, with
somewhat better sensitivity,[24] however, it is invasive.
Acute Cholangitis
Acute cholangitis (AC) occurs when biliary stenosis elevates pressure within the biliary
system and causes spillover of bile and infection into the systemic circulation.[25]
[26] The Tokyo guidelines are useful for diagnosis (including imaging) and management
of AC.[27]
Ultrasound may show dilated biliary radicles and CBD and may also show the cause of
obstruction. Abscesses may be seen on USG.
CT and MRI demonstrate dilated ducts and are usually able to detect the cause of obstruction.
Enhancement of the walls of the ducts may be seen, more commonly in the delayed images.
Wedge-shaped, peripheral, or geographic areas of increased signal or enhancement may
be seen. These findings have a high specificity in an appropriate clinical setting.
Abscesses may be seen, which may appear clustered in a peribiliary location (cholangiolar
abscesses). Portal vein thrombosis may occur in patients with cholangitis.[25]
[26] Treatment consists of removal of cause of obstruction and/or biliary drainage along
with appropriate antibiotic therapy ([Fig. 5]).
Fig. 5 A 55-year-old male with right hypochondrium pain and fever with chills. Coronal (A) and axial (B) computed tomography (CT) images showing dilated common bile duct (CBD) with tiny
calculus at lower end (arrow in A) with asymmetrically dilated intrahepatic biliary radicle (IHBR) showing periductal
hypodensity at places and ductal thickening (arrowhead in B). Axial CT images in arterial (C) phase showing dilated IHBR (arrowhead) with area of increased enhancement (arrow).
Portal phase images show reduced attenuation around dilated IHBR in left lobe (arrowhead
in D) consistent with findings of cholangitis.
Portal Cavernoma Cholangiopathy
Portal cavernoma cholangiopathy (PCC) is defined as abnormalities in the extrahepatic
biliary system including the cystic duct and GB with or without abnormalities in the
1st and 2nd generation biliary ducts in a patient with portal cavernoma. Presence
of a cavernoma, typical cholangiographic findings, and absence of any other cause
of cholangiopathy are required to arrive at this diagnosis. The mechanisms for findings
of PCC include extrinsic compression of the bile ducts by the periportal vessels and
biliary fibrosis secondary to ischemia related to thrombosis of tiny venules in the
walls of the bile ducts.[28]
[29]
Radiologic features of PCC include extrinsic indentation of the bile ducts, bile duct
strictures, bile duct wall thickening, angulation and displacement of the extrahepatic
bile duct, cholelithiasis, choledocholithiasis, and hepatolithiasis. In long-standing
extrahepatic portal vein obstruction (EHPVO) peripheral atrophy of the liver may be
seen due to reduced peripheral perfusion. Ultrasound with color Doppler can be used
for evaluation of portal cavernoma formation, superior mesenteric and splenic veins,
as well as evaluation of the intrahepatic ducts. CT also easily demonstrates EHPVO
with associated findings and collaterals. Liver morphology alterations and transient
hepatic attenuation differences may be seen after administration of intravenous contrast.
Contrast-enhanced (CE) MRI with MRCP can easily demonstrate all the above findings
as well, along with mural thickening of bile duct walls ([Fig. 6]). Delayed duct wall enhancement may suggest fibrosis.
Fig. 6 Coronal magnetic resonance cholangiopancreatography (MRCP) images in a 45-year-old
patient with extrahepatic portal vein obstruction (EHPVO) showing multiple extrinsic
indentations on the right and left hepatic duct and the common bile duct (CBD), consistent
with portal cavernoma cholangiopathy.
Classifications of PCC include morphological classification—classification by level
of biliary obstruction and classification by severity of biliary abnormalities. Treatment
includes biliary stenting, different forms of biliary drainage, and surgical shunts.
PCC cholangiography may resemble a variety of entities including sclerosing cholangitis
(SC) due to other causes and cholangiocarcinoma (CCA).[30]
Immunological
Sclerosing Cholangitis
SC are diseases which are associated with recurrent inflammation with progressive
fibrosis and injury to the biliary system and imaging manifestations of bile duct
stricturing. They may have a known cause (e.g., immunoglobulin G4 [IgG4] disease)
or be idiopathic—primary SC (PSC).[2]
[31]
Primary Sclerosing Cholangitis
PSC is a disease of unknown etiology characterized by chronic progressive biliary
inflammation and fibrosis leading to luminal narrowing and biliary strictures. It
is associated with inflammatory bowel disease and is more common in males. The disease
causes progressive hepatic fibrosis and cirrhosis and is associated with increased
risk of malignancy including CCA, hepatocellular carcinoma, GB carcinoma, and colonic
carcinoma. It has three subtypes—classic, (most common) small duct PSC, and PSC overlap
with autoimmune hepatitis.[2]
[32]
[33]
[34] Diagnosis of PSC is made by typical cholangiographic findings and exclusion of secondary
causes. The European Association for the Study of the Liver (EASL) guidelines recommend
MRCP as the first option for imaging of suspected cases of PSC. Small duct PSC is
diagnosed in patients with idiopathic cholestasis, normal imaging, and compatible
histology. MRI is approximately 86% sensitive and 94% specific for diagnosis of PSC.
The imaging hallmark of PSC is biliary strictures involving both intra- and extrahepatic
ducts. The strictures are usually bilobar and multisegmental. Strictures are usually
short, with variable upstream dilatation, which sometimes produce “beaded” appearance.
Progressive fibrosis causes worsening of strictures with obliteration of peripheral
ducts showing a “pruned tree” appearance. Diverticular outpouching of bile ducts is
a characteristic finding that occurs in a minority of patients. Widening of the angles
at the site of duct branching may be seen. Up to half the patients will show biliary
mural thickening (> 2 mm) and enhancement. Isolated involvement of CBD is almost never
seen. Intrahepatic stones may be seen. Strictures with more than 75% luminal narrowing
are known as high-grade stricture. A dominant stricture is defined as a stricture
with a luminal diameter of < 1.5 mm in CHD or < 1 mm in right or left duct, whereas
a relevant stricture is any stricture associated with cholestasis or cholangitis.[35]
Signal intensity changes may be seen on T2W and DWI and these may or may not show
associated enhancement. Morphological changes may be seen in the liver with segmental
atrophy and caudate hypertrophy. Ultrasound may show dilated ducts; however, due to
thickening, the duct may be obliterated and periductal fibrosis may prevent proximal
ductal dilatation with normal appearing ultrasound. CT imaging may show irregular,
discontinuous ductal dilatation, beading, irregularity, and thickening and enhancement
around the ducts, as well as liver parenchymal changes ([Figs. 7] and [8]).
Fig. 7 A 45-year-old male, a known case of ulcerative colitis, presenting with fatigue and
pruritus. Coronal magnetic resonance cholangiopancreatography (MRCP) images (A, B) showing cholangiographic findings of primary sclerosing cholangitis (PSC) with short
segment strictures and irregularities shown by small white arrows. White arrowhead
in (A) showing tiny diverticulae. Yellow arrowhead in (B) showing loss of acute angle at biliary branching. Note irregular outline of the
biliary radicles and visualization of biliary radicles up to the periphery of liver.
(C) Computed tomography (CT) with minimum intensity projection (MinIP) showing irregular
dilatation of the bile ducts with small focal band-like strictures.
Fig. 8 A 55-year-old male with case of primary sclerosing cholangitis (PSC) on follow-up.
Axial T2-weighted (T2W) images (A) showing increased signal (black arrowhead) in the hepatic parenchyma with a prominent
caudate lobe. Note dilated biliary radicles (white arrowhead). Postcontrast images
(B) in a different patient who presented with altered liver function tests (LFTs) reveal
increased periductal enhancement (arrows) around the dilated biliary radicles.
Smaller duct involvement and calculi may be missed on CT.
Imaging is used to follow-up not only the primary disease in patients but also for
development of malignancy. MRI-based risk scores[36] may predict risk of progression of patients. ERCP is used only as a problem-solving
modality or for evaluation of suspicious strictures.
Approximately a third of patients with PSC who develop CCA will develop it within
1 year of diagnosis of PSC. The patients at risk for CCA are males with large duct
disease and concomitant ulcerative colitis. Radiologically, most CCA develop from
dominant strictures, and mass forming CCAs are less common in PSC. CE cross-sectional
imaging should be performed when CCA is suspected followed by ERCP with sampling.[33] Presence of perihilar mass or periductal soft tissue that enhances maximally on
delayed phase, with vascular encasement or hepatic invasion, with or without intraductal
soft tissue is considered definitive for CCA in patients with PSC.[36] The definitive treatment for PSC is liver transplantation. The EASL reccomendation[32] for large duct PSC is to image yearly with USG and/or MRI for large duct PSC and
image every 6 month for patients who have chronic liver disease. Liver elastography
is suggested every 2 to 3 years ([Table 2]).
Table 2
Findings of PSC
|
Demographics
|
Males > Females
|
|
Associated diseases
|
Inflammatory bowel disease
|
|
Cholangiographic abnormalities
|
Pruning, beading, skip dilatation, webs, diverticulae, calculi, strictures, lack of
proximal dilatation
|
|
Signal and enhancement changes
|
Increased T2 and DWI signal, periductal enhancement, dysmorphia, cirrhosis
|
|
Complications
|
Cholangiocarcinoma
|
Abbreviations: DWI, diffusion-weighted imaging; PSC, primary sclerosing cholangitis.
IgG4-Related Sclerosing Cholangitis
IgG4-related sclerosing cholangitis (IgG4SC) is a disease of unknown etiology causing
strictures in the biliary tree and is part of the spectrum of IgG4-related disease.[37] These patients have increased igG4 levels with dense infiltrates of IgG4 plasma
cells and duct wall fibrosis.[38] Unfortunately, serum IgG4 levels may be raised in a number of pathologies including
PSC and malignancy as well.
The HISORT criteria by Ghazale et al[39] and the Japanese Clinical Diagnostic Criteria 2012 and reviewed in 2020 are used
for diagnosis of IgG4SC.[40]
[41]
Note that 87 to 92% of the cases of IgG4SC are related with autoimmune pancreatitis
(AIP), in which the pancreas shows typical findings of type 1 AIP—fusiform “sausage”
shape, peripancreatic halo, lack of main pancreatic duct (MPD) dilatation, reduced
T1 signal, tapering of MPD, and usually diffusion restriction[42] ([Fig. 9]).
Fig. 9 A 45-year-old male with pain abdomen and altered liver function test (LFT). Axial
T2-weighted (T2W) (A) and T1W (B) images show typical fusiform enlargement of the pancreas (arrows) which shows increased
T2 and decreased T1 signal. Coronal magnetic resonance cholangiopancreatography (MRCP)
(C) images show narrowing at lower end of common bile duct (CBD) (arrowhead), with mildly
dilated irregular main pancreatic duct (MPD). Findings are suggestive of autoimmune
pancreatitis, confirmed on biopsy.
Nakazawa et al[43] proposed a cholangiographic classification for IgG4SC based on the pattern of biliary
involvement—type 1 - lower CBD stenosis, type 2a - intrahepatic stricture with dilation,
2b - intrahepatic stricture without dilatation, type 3 - Hilar and lower CBD stricture,
and type 4 - Hilar stricture. Type 3 and 4 patterns of involvement may need additional
investigations including ERCP for ruling out other pathology including CCA ([Fig. 10]). Involvement of other organs including salivary glands, kidneys, and retroperitoneum
may be seen. MR findings include thickening of the walls of the bile ducts with relatively
preserved/visible lumen, long segment involvement, funnel-like narrowing, preferential
involvement of lower end of CBD, and occasionally prestenotic dilatation. Bile duct
thickening is relatively hypointense on T2 and diffusion restriction is usually seen.
Homogenous enhancement of the thickened segments of bile ducts is seen ([Fig. 11]). Associated GB wall thickening may be seen in 50% of patients.[2]
[31]
[41]
Fig. 10 Classification of immunoglobulin G4-related sclerosing cholangitis (IgG4SC) based
on pattern of biliary tree involvement: (A) type 1 - lower common bile duct (CBD); (B) type 2A - intrahepatic with prestenotic dilatation; (C) type 2B - intrahepatic without prestenotic dilatation; (D) type 3 - Hilar and lower CBD involvement; (E) type 4 - Hilar involvement. Illustrations modified from Nakazawa et al. Digital
Artwork by Dr. Varun Holla, Department of Radio Diagnosis, Sir Ganga Ram Hospital,
Delhi, India.
Fig. 11 A 37-year-old female patient with immunoglobulin G4-related sclerosing cholangitis
(IgG4SC). Axial (A) contrast-enhanced computed tomography (CECT) showing dilated intrahepatic biliary
radicle (IHBR) (arrows) with thickened, enhancing walls. Coronal (B) CECT images showing thickened enhancing common bile duct (CBD) walls (arrows) with
lumen seen despite the thickened walls.
CECT may show similar findings as MR in the ductal system and may also show the findings
of AIP, renal, and GB involvement. USG may pick up bile duct strictures and wall thickening,
EUS and intraductal ultrasound show preserved mucosa with thickened walls showing
vessels within.
In contradistinction to PSC, the disease responds well to steroid therapy. Response
to steroid therapy is assessed by imaging and this should be done within 2 weeks of
initiation of therapy[41] ([Table 3]).
Table 3
IgG4SC vs. PSC cholangiographic findings
|
PSC
|
IgG4SC
|
|
Diverticulae
|
Classical, when present
|
Not seen
|
|
Strictures
|
Shorter, band like
|
Longer, lumen seen through thickened walls
|
|
Mural thickening > 2.5 mm
|
Rare
|
More likely
|
|
Prestenotic dilatation
|
Usually absent
|
May be seen
|
|
Distal CBD involvement
|
Less likely
|
More likely
|
|
Hepatic parenchymal changes
|
Signal changes and morphological changes may be seen
|
Usually absent
|
Abbreviations: CBD, common bile duct; IgG4SC, immunoglobulin G4-related sclerosing
cholangitis; PSC, primary sclerosing cholangitis.
Eosinophilic Cholangitis
Eosinophilic cholangitis is a benign disease defined by eosinophilic infiltration
in the walls of the bile ducts. It is associated with hypereosinophilic syndrome,
allergic and parasitic conditions, and may be associated with eosinophilic gastroenteritis.
Cholangiographic findings include segmental or diffuse thickening of the bile ducts
with multifocal stricturing, which may be difficult to differentiate from PSC.[44] Involvement of the GB and cystic duct may be seen.[45] The disease responds well to steroid therapy.
Infective
Recurrent Pyogenic Cholangitis
Recurrent pyogenic cholangitis (RPC) is endemic in Southeast Asia including India.
The proposed etiology for the disease is infestation by parasites such as Ascaris lumbricoides and Clonorchis sinensis. Chronic inflammation results in fibrosis and infiltration of bile duct walls and
portal tracts leading to biliary strictures. The hallmark is marked central and extrahepatic
biliary dilatation with associated large pigment calculi in the intrahepatic and extrahepatic
ducts. Impacted calculi in the ducts can lead to complete nonvisualization of the
ducts—“the missing duct sign”[45] ([Fig. 12]).
Fig. 12 Coronal magnetic resonance cholangiopancreatography (MRCP) images (A, B) and T2-weighted (T2W) axial images (C, D) in a 38-year-old patient with jaundice showing markedly dilated biliary radicles
showing hypointense filling defects suggestive of calculi in the dilated biliary radicles
(white arrows) and in the dilated common bile duct (CBD) (white arrowheads). Findings
are suggestive of recurrent pyogenic cholangitis.
Decreased arborization and caliber of peripheral ducts are seen leading to arrowhead-shaped
ducts. Segmental parenchymal atrophy, abscesses, bilomas, and portal vein thrombosis
may be seen.[46] Ductal involvement and parenchymal atrophy occur most frequently in the left lateral
segment and the right posterior segment. Significant caudate lobe hypertrophy may
be seen. Postcontrast images may reveal heterogeneous enhancement. CCA may be seen
as a complication of RPC.
USG usually shows increased periportal echogenicity with marked ductal dilatation
with intraductal calculi. Visualization of calculi is variable on CT; however, brown
pigment stones of RPC are usually seen on CT. MRI is the imaging modality of choice
and shows the imaging findings described above. Treatment consists of biliary drainage,
surgical stone removal, or biliary bypass. Liver failure may occur, prompting transplantation.[47]
Biliary Parasites
Manifestations of parasitic infestation vary with the specific infestation and presence
of eosinophilia, serology and stool examination may help clinch the diagnosis. The
most common parasitic infestations include Echinococcus granulosus, which is seen initially as a unilocular cyst surrounded by a pericyst, or the typical
spoke wheel appearance. Rupture or fistulization may occur with the biliary tree causing
cholangitis and jaundice depending on the site of rupture. The imaging finding in
that case is that of a focal defect in the wall of the cyst communicating with dilated
biliary radicles which may also show cysts within on MRCP.
Ascariasis may be seen in the biliary tree, in the CBD, biliary radicles, or even
GB. Ascaris worms on ultrasound are seen as parallel echogenic lines, on CT they are
seen as somewhat hyperattenuating compared to bile, and on MRI they are seen as linear
filling defects, hypointense on a background of bright bile. Biliary radicle dilatation
may be seen and accompanying changes of AC may be seen as well.
Fasciola hepatica metacercariae perforate the duodenal wall and migrate into the peritoneal
cavity, thereafter they penetrate the liver capsule and enter the hepatic parenchyma
leading to clusters of sterile necrotic cavities and abscesses. They may be misdiagnosed
as pyogenic abscesses. The flukes mate and start releasing eggs, which can cause biliary
inflammation, wall thickening, and biliary radicle dilatation. CT may show the entire
path of migration from the entry site to central liver with the “tunnels and caves”
sign. Ultrasound may show the parasites and the serpentine echogenic tracks. MRI shows
similar findings as CT[25]
[48] ([Fig. 13]).
Fig. 13 A young female with fever and eosinophilia. Outside computed tomography (CT) report
of liver abscesses. Follow-up CT was done followed by ultrasonography (USG). Transverse
USG (A) image showing irregular heteroechoic track with echogenic central and marginal areas.
Axial CT (B) showing irregular branching tracks in the right lobe of liver extending up to the
hepatic margins (tunnels and caves sign). Findings are suggestive of hepatic Fascioliasis.
Partial resolution was seen on anti-helminthic treatment.
Acquired Immunodeficiency Syndrome-Related Cholangitis
Acquired immunodeficiency syndrome-related cholangitis, also known as human immunodeficiency
virus cholangiopathy, is seen in patients with a CD4 count of less than 100 cells/mm3. The prevalence has reduced due to highly active antiretroviral therapy. The underlying
mechanisms is possibly related to opportunistic biliary infections.[49] Four types of appearances have been described—type I - papillary stenosis, type
II - intrahepatic SC-like pattern, type III - intrahepatic involvement with papillary
stenosis, most common type, and type IV - long extrahepatic bile duct strictures with
or without intrahepatic involvement.[49]
[50] MRI is the imaging modality of choice and can show the above findings. USG can show
ductal dilatation ([Fig. 14]).
Fig. 14 Young male with jaundice, known human immunodeficiency virus (HIV) positive. Coronal
three-dimensional (3D) magnetic resonance cholangiopancreatography (MRCP) thin slab
image (A) showing narrowing at the lower end of the common bile duct (CBD) (arrow) with dilatation
of the intrahepatic biliary radicle dilatation consistent with HIV cholangiopathy.
Axial T2-weighted (T2W) images (B) showing circumferential thickening of lower end of the CBD.
Ischemic Cholangitis
Ischemic cholangitis arises due to compromise of the hepatic artery supply. These
are most commonly seen in posttransplant patients with hepatic artery thrombosis (HAT).
Polyarteritis nodosa and giant cell arteritis are some of the primary arterial pathologies
which may cause ischemic cholangitis. Disorders such as paroxysmal nocturnal hemoglobinuria,
sickle cell anemia, and hereditary hemorrhagic telangiectasia may cause ischemic cholangitis.
Ischemia is believed to be the cause for chemotherapy-associated cholangitis caused
by drugs which include floxuridine and arterial chemotherapeutic agents, regardless
of the agents used, including 5-fluorouracil, cisplatin, paclitaxel, mitomycin C,
and Yttrium-90.[51]
In the acute stages, desquamation of the biliary epithelium occurs which leads to
the formation of biliary casts, followed by obstruction and dilatation of the bile
ducts. Casts appear hyperintense on T1W images and tend to be linear and branching
which may help differentiate them from calculi. Severe insults can cause transmural
biliary necrosis and breakdown followed by formation of bilomas and abscesses. If
the patient survives the acute event, then multiple irregular strictures may form
accompanied by variable biliary dilatation which may give a PSC-like picture; however,
the strictures tend to be Hilar or mid-CBD in location. Biliary dilatation and abscesses
along with areas of breakdown are readily seen on USG, MR, and CT. CT angiography
is most commonly used to confirm HAT. Hepatic artery patency may also be evaluated
by color Doppler or MR angiography. Drainage procedures including percutaneous biliary
drainages and cast removals may be done for symptom mitigation of these patients;
however, posttransplant HAT patients will require retransplant[2]
[31]
[51] ([Fig. 15]).
Fig. 15 Coronal magnetic resonance cholangiopancreatography (MRCP) images in a 4-year-old
male child with hepatic artery thrombosis showing multiple irregular nonanastomotic
strictures on follow-up (arrows). Findings consistent with ischemic cholangiopathy.
Secondary Sclerosing Cholangitis in Critically Ill Patients
Secondary sclerosing cholangitis is a relatively recently recognized entity in patients
receiving intensive care unit (ICU) treatment. It presents as a cholestatic liver
disease in patients without history of hepatobiliary disease in critically ill patients
due to a variety of conditions including polytrauma, burns, major surgery, and acute
respiratory distress syndrome including coronavirus disease pneumonia. The diagnosis
is one of exclusion in the correct clinical context. The course is usually severe
and progressive with a high mortality. The most accepted causative theory proposes
a combination of ischemia along with changes in bile composition leading to necrosis
with cast formation.[52]
[53]
Ultrasound is not a sensitive test.[52] Early MRI may show presence of biliary casts later on progressing to strictures,
biliary wall thickening, and progressive destruction of the peripheral bile ducts.
Imaging findings of biliary casts in an ICU patient are suggestive of this entity.
Delayed scans reveal pruned tree appearance with persistence of only the central biliary
tree typical up to the second order ducts. ERCP is the gold standard. Associated findings
include acalculous cholecystitis, GB rupture, and liver abscess formations.[2]
Treatment includes biliary drainage and antibiotic therapy. In patients with biliary
cirrhosis, liver transplant is the only curative procedure.[53]
Biliary Strictures
Biliary strictures often present a diagnostic challenge during preoperative evaluation
to determine their benign or malignant nature. Benign biliary strictures are secondary
to a wide spectrum of etiologies; however, the key is to be able to differentiate
benign from malignant etiologies ([Table 4]).[54]
[55]
[56]
[57]
Table 4
Malignant vs. benign biliary stricture
|
Malignant
|
Benign
|
|
Length of involvement
|
Long stenosis > 12 mm
|
Short segment
|
|
Duct wall thickness
|
Wall thickness > 3 mm
|
Wall thickness < 3 mm
|
|
Duct wall enhancement
|
Hyperenhancement of ductal wall on portal venous phase images
|
Absence of hyperenhancement
|
|
Stricture morphology
|
Asymmetrical wall thickening with luminal irregularity and shouldering
|
Smooth concentric narrowing
|
|
Outer margins
|
Indistinct outer margins of involved bile duct wall
|
Smooth outer margin
|
|
Presence of diffusion restriction
|
Presence of diffusion restriction
|
Absence of diffusion restriction
|
In the absence of a mass on imaging, ERCP is the next modality that permits stricture
assessment, tissue sample acquisition, and biliary drainage. Strictures with negative
or inconclusive brush cytology and transpapillary biopsies are defined as “indeterminate
biliary strictures” and an additional cholangioscopy for visual impression and targeted
biopsies is recommended at a subsequent ERCP.[58]
Distal CBD strictures can be targeted by alternate approaches including EUS and percutaneous
cholangioscopies with subsequent fine-needle aspiration/biopsy. In patients with negative
visual assessment as well as tissue diagnosis, serial follow-up with cross-sectional
imaging for at least 6 months is recommended before considering benign etiology.[59]
Conclusion
A wide variety of benign diseases can involve the biliary system, some of which may
have only subtle differences in the imaging findings. Though ultrasound is the first
imaging modality to be used in a suspected case of obstructive jaundice or suspected
cholangiopathy, CT may help to visualize cholangiopathies and may show many similar
findings as MRI; however, CE MRI along with MRCP should be used for comprehensive
evaluation of biliary diseases. The radiologist, however, should also be aware of
the pitfalls and differential diagnoses of the various MRI and cholangiographic findings,
many of which may overlap.
