Diffuse Versus Localized Caroli Disease: A Comparative
MRCP Study
Maïté Lewin, MD, PhD1,2, Christophe Desterke, PhD2,3, Catherine Guettier, MD2,4, Pierre-Jean Valette, MD5,
Hélène Agostini, MD6, Stéphanie Franchi-Abella, MD, PhD2,7, Lionel Arrivé, MD8,9, Anita Paisant, MD10, Philippe Petit, MD11,
Olivier Soubrane, MD12,13, Didier Samuel, MD2,14, René Adam2,14, MD, Valérie Vilgrain, MD13,15, Benoît Gallix, MD16,
Marie-Pierre Vullierme, MD13,15
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Gastrointestinal Imaging · Original Research
Keywords
bile ducts, Caroli disease, congenital
­lithiasis, MRI
Submitted: Apr 29, 2020
Revision requested: May 28, 2020
Revision received: Jun 18, 2020
Accepted: Jul 17, 2020
First published online: Apr 21, 2021
The authors declare that they have no
disclosures relevant to the subject matter of
this article.
Lewin et al.
MRCP of Caroli Disease
Gastrointestinal Imaging
Original Research
Lewin M, Desterke C, Guettier C, et al.
doi.org/10.2214/AJR.20.23522
AJR 2021; 216:1530–1538
ISSN-L 0361–803X/21/2166–1530
© American Roentgen Ray Society
1530 | www.ajronline.org AJR:216, June 2021
OBJECTIVE. The purpose of this multicenter retrospective study was to assess the
MRCP features of Caroli disease (CD).
MATERIALS AND METHODS. Sixty-six patients were identified from 2000 to
2019. The inclusion criteria were diagnosis of diffuse or localized CD mentioned in an
imaging report, presence of intrahepatic bile duct (IHBD) dilatation, and having un-
dergone an MRCP examination. The exclusion criteria included presence of obstruc-
tive proximal biliary stricture and having undergone hepatobiliary surgery other
than cholecystectomy. Histopathology records were available for 53 of the 66 (80%)
patients. Diffuse and localized diseases were compared by chi-square and t tests and
Kaplan-Meier model.
RESULTS. Forty-five patients had diffuse bilobar CD ((five pediatric patients [three
girls and two boys] with a mean [± SD] age of 8 ± 5 years [range, 1–15 years] and 40 adult
patients [26 men and 14 women] with a mean age of 35 ± 11 years [range, 20–62 years])
and 21 patients had localized disease (12 men and 9 women; mean age, 54 ± 14 years).
Congenital hepatic fibrosis was found only in patients with diffuse CD (35/45 [78%]), as
was a “central dot” sign (15/35 [43%]). IHBD dilatation with both saccular and fusiform
features was found in 43 (96%) and the peripheral “funnel-shaped” sign in 41 (91%)
of the 45 patients with diffuse CD but in none of the patients with localized disease
(p < .001). Intrahepatic biliary calculi were found in all patients with localized disease
but in only 16 of the 45 (36%) patients with diffuse CD (p < .001). Left liver atrophy was
found in 18 of the 21 (86%) patients with localized disease and in none of the patients
with diffuse CD (p < .001). The overall survival rate among patients with diffuse CD was
significantly lower than that among patients with localized disease (p = .03).
CONCLUSION. Diffuse IHBD dilatation with both saccular and fusiform features
associated with the peripheral funnel-shaped sign can be used for the diagnosis of
CD on MRCP. Localized IHBD dilatation seems to be mainly related to primary intra-
hepatic lithiasis.
Caroli disease (CD) is a fibropolycystic liver disease, which is a clinically and genetically
heterogeneous group of diseases caused by abnormalities in primary cilia, called ciliop-
athies [1]. Impaired ciliary function during embryogenesis leads to hepatic ductal plate
malformation and results in various degrees of duct abnormality [2–4]. Large intrahepat-
ic ducts are involved in CD, whereas abnormal development of small interlobular ducts
results in congenital hepatic fibrosis (CHF) [5, 6]. The coexistence of CD and CHF is called
Caroli syndrome by most medical teams. Liver ciliopathies can include isolated liver in-
1
Service de Radiologie, AP-HP Hôpital Paul Brousse, 12-14 Ave Paul Vaillant Couturier, 94800 Villejuif, France. Address
correspondence to M. Lewin (maite.lewin@aphp.fr).
2
Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
3
Service de Bio-informatique, Hôpital Paul Brousse, Villejuif, France.
4
Service d’Anatomopathologie, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
5
Service de Radiologie, Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France.
6
Service d’Epidémiologie et de Santé Publique, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
7
Service de Radiologie pédiatrique, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
8
Service de Radiologie, AP-HP Hôpital Saint-Antoine, Paris, France.
9
Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France.
10
Service de Radiologue, Centre Hospitalier Universitaire de Rennes, Rennes, France.
11
Service de Radiologie Pédiatrique et Prénatale, AP-HM, Hôpital de la Timone-Enfant, Marseille, France.
12
Service de Chirurgie, AP-HP Hôpital Beaujon, Clichy, France.
13
Université Paris Diderot, Paris, France.
14
Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif, France.
15
Service de Radiologie, AP-HP Hôpital Beaujon, Clichy, France.
16
Université de Strasbourg, Strasbourg, France.
 MRCP of Caroli Disease
volvement but also may be associated with other renal diseases
(kidney ciliopathies), such as autosomal recessive polycystic kid-
ney disease [7–10].
Imaging plays a crucial role in the diagnosis of CD because the
clinical and pathologic findings are nonspecific. The liver and
small bile ducts are normal at pathologic examination (except af-
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ter long-term disease and in the presence of complications, such
as cholangiocarcinoma, lithiasis, and infection). In the Caroli syn-
drome subtype, additional features of CHF are found in the liver
parenchyma, but the other findings are similar to those of CD [4].
CD is characterized on imaging by nonobstructive marked dila-
tation of the intrahepatic bile ducts (IHBDs) and by the central
dot sign, which corresponds to a portal vein branch protruding
into the lumen of a dilated bile duct [11, 12]. Biliary stones may be
present in the enlarged ducts. Cholangiocarcinoma is also a com-
plication. The localized disease is not fully defined but usually re-
fers to unilobar and not bilobar extension of the disease.
MRCP, which has been found effective for investigating bile
duct obstruction, is the method of choice for diagnosing CD,
because communications between segmental dilatations, the
biliary tree, and the absence of stenosis can be identified [13–
15]. To our knowledge there have been no published studies
evaluating MRCP findings in a large series of patients with CD
to identify imaging features of this disease and obtain a more
confident diagnosis. Furthermore, although a diagnosis of CD
may be suggested in the presence of enlarged bile ducts in dai-
ly practice, another quite different diagnosis, such as polycystic
liver disease, proximal lithiasis, or hilar cholangiocarcinoma, is
often reached with further investigation by a multidisciplinary
team. In addition, accurate diagnosis of CD is especially import-
ant because liver transplant, or combined liver-kidney transplant
in cases of concomitant renal disease, is a curative options for
these patients [16].
The aim of this study was to assess the MRCP characteristics of
CD in a retrospective multicenter study by comparing diffuse and
localized disease to identify imaging criteria for the diagnosis of
this anomaly of embryogenesis.
Materials and Methods
Study Design
This retrospective multicenter study received institutional re-
search ethics board approval (clinicaltrials.gov NCT04007575),
and informed consent was obtained. The inclusion criteria were
identification in the database of a tertiary university center spe-
cialized in hepatobiliary disease between October 2000 and July
2019, diagnosis of CD (including Caroli syndrome) on the basis of
imaging showing marked bile duct dilatation limited to the intra-
hepatic biliary tree, and MRCP examination available in a PACS.
Our reference standard was either a histopathologic result show-
ing nonobstructive bile duct dilatation with CHF or a normal liv-
er or the association of a typical imaging pattern associated with
clinicobiologic follow-up (cholestasis, chronic renal failure). The
exclusion criteria were exploration exclusively by ERCP or biop-
sy, an MRCP finding of obstructive benign or malignant proximal
biliary stricture, and prior surgical intervention other than cho-
lecystectomy for hepatobiliary disease, which can lead to focal
or diffuse secondary IHBD dilatation. A total of 219 patients were
identified, and 153 were excluded (Fig. 1).
AJR:216, June 2021 1531
Patients
The final population included 66 patients: 45 with diffuse bilobar
disease and 21 with localized unilobar disease. The retrospective
clinical data included age, sex, family history of congenital bile duct
or renal disease, prior cholecystectomy or endoscopic intervention,
clinical presentation at diagnosis of MRCP, presence of biochemical
cholestasis, presence of chronic renal failure, operative data, long-
term follow-up findings, and the date of death of CD.
Pathologic Examination
Surgical specimens or liver biopsy records were available for
pathologic examination for 53 of the 66 (80%) patients: 37 of the
45 (82%) with diffuse disease and 16 of the 21 (76%) with localized
disease. Specimens were analyzed by experienced liver patholo-
gists working at tertiary university hospitals where the patients
were treated. The presence of intrahepatic stones was assessed
macroscopically in the surgical specimen. All patients had histo-
logic intrahepatic duct dilatation without bile duct stenosis. His-
topathologic specimens were evaluated for the presence of asso-
ciated CHF, which is our reference standard for the definition of
Caroli syndrome and for the presence of associated malignancy.
MRI Acquisition
All patients underwent MRCP with different MRI systems (Gy-
roscan Intera, Philips Healthcare; Magnetom Avanto, Siemens
Healthcare; and Signa Hdxt, GE Healthcare). A free-breathing
3D high-spatial-resolution fast spin-echo sequence and/or a
breath-hold 2D single-shot sequence in the radiated coronal
plane were performed. MRCP also included a T2-weighted fast
spin-echo sequence with spectral fat suppression, a breath-
hold 3D T1-weighted fat-suppressed gradient-echo pulse se-
Eligible: 219 patients
No MRCP imaging in PACS: 73/219 (33%)
MRCP with prior hepatic surgery: 21/219 (10%)
Reviewed by two observers:
125/219 patients (57%)
Excluded cases: 59/125 patients (47%)
• Noncommunicating cystic liver disease:
26/59 (44%)
• Proximal lithiasis: 13/59 (22%)
• Choledochal cyst: 6/59 (10%)
• Intraductual papillary neoplasms of the bile
duct: 5/59 (8%)
• Hilar cholangiocarcinoma: 4/59 (7%)
• Primary sclerosing cholangitis: 3/59 (5%)
• Portal biliopathy: 1/59 (2%)
• Hepatic distomiasis: 1/59 (2%)
Final population:
66/125 patients (53%)
Fig. 1—Flowchart shows steps in collection of study sample.
 Lewin et al.
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A B
quence, and an in-phase and opposed-phase chemical-shift se-
quence in the axial plane. Furthermore, for 45 of the 66 (68%)
patients, a fat-suppressed 3D T1-weighted sequence was per-
formed after IV administration of gadolinium chelate (gadoter-
ate meglumine, Dotarem, Guerbet; gadobutrol, Gadovist 1.0,
Bayer Radiology; 0.1 mmol/kg at 2–3 mL/s) in the late arterial,
portal, and delayed phases.
Image Analysis
To compare diffuse and local disease, images were analyzed
in consensus by two radiologists (M.L. and M.V., who had 20 and
25 years of experience in abdominal MRI). All images were eval-
uated at a PACS workstation (Carestream 13.0, Kodak), includ-
ing those of the 59 excluded patients. The following features
of the lesions were evaluated on both axial and MRCP images:
shape of dilated IHBD classified into three subgroups (saccular
dilatation, also called a communicating cyst; fusiform dilatation;
or both saccular and fusiform dilatation); location of the dilat-
ed IHBD (peripheral or central, i.e., first- or second-order divi-
sion of the biliary tree); size of the largest fusiform or saccular
dilated IHBD; presence of the “funnel-shaped” sign, defined as a
subcapsular lobulated grossly triangular saccular dilated IHDB,
with the tip connected downstream to a mildly enlarged bile
duct without stenosis (Fig. 2); presence of a central dot sign,
defined as tiny dots with strong contrast enhancement within
dilated cystic IHBDs; presence of biliary calculi and their loca-
tion (one or two segments versus diffuse), identified as areas of
high signal intensity on T1-weighted images or markedly low
signal intensity on T2-weighted images within obviously dilated
ducts; and size of the common bile duct.
We also noted the presence of the following liver abnormal-
ities: hepatomegaly or liver atrophy in the right or left liver; liv-
er abscesses; association with biliary hamartomas (other ductal
plate malformation), defined as multiple small diffuse lesions in
the liver measuring up to 15 mm; hepatic nodules with their size
and number; and signs of portal hypertension (splenomegaly,
spontaneous splenorenal shunts or varices). Finally, we evaluat-
ed the presence of renal abnormalities: parenchymal atrophy or
hypertrophy (renal length) and the presence and number (≤ 3 or
multiple) of renal cysts.
1532 AJR:216, June 2021
Fig. 2—45-year-old man with Caroli
disease associated with congenital hepatic
fibrosis (Caroli syndrome).
A and B, Axial thick-slice 2D MRCP image
(A) and drawings (B) show funnel-shaped
sign (arrows, A), which can have two
slightly different configurations of similar
shape, that is, large at periphery and thin
toward liver centrum.
Statistical Analysis
The Pearson chi-square test was used to test qualitative vari-
ables and the two-sided t test to compare the distributions of
continuous variables between the groups of patients with diffuse
disease and those with localized disease. The sensitivity, specific-
ity, NPV, PPV, and accuracy of the presence of the funnel-shaped
sign for the diagnosis of CD were calculated. Survival analysis was
performed with the Kaplan-Meier model for univariate analysis
tested with the log-rank test. Statistical analysis was performed
with open-source R software (version 3.2.3, R Foundation). A val-
ue of p ≤ .05 was considered significant.
Results
Patient Characteristics
Patient characteristics are summarized in Table 1. Forty-five
patients had diffuse bilobar CD (five pediatric patients [three
girls and two boys] with a mean [± SD] age of 8 ± 5 years [range,
1–15 years] and 40 adult patients [26 men and 14 women] with a
mean age of 35 ± 11 years [range, 20–62 years]), and 21 patients
had localized disease (12 men and nine women; mean age, 54 ±
14 years). The group of 21 patients with localized unilobar dis-
ease included only adults. The patients with diffuse disease were
significantly younger than those with localized disease (p < .001),
and there was no predominance of sex in the groups.
Associated CHF was found in 35 of the 45 (78%) patients with
diffuse disease and was not found in patients with localized dis-
ease (p < .001). These 35 patients with CD and CHF presented with
a familial history of liver ciliopathies (6/35 [17%]) or a personal his-
tory of renal ciliopathies (12/35 [34%]). A surgical history of cho-
lecystectomy was significantly more frequent in patients with lo-
calized disease (12/21 [57%]) than in those with diffuse disease
(6/45 [13%]) (p < .001).
Almost all of the patients had symptoms (39/45 [87%]) with
diffuse disease; 18/21 [86%] with localized disease). The most
frequent presenting symptom was severe cholangitis (oth-
er symptoms are reported in Table 1). Abdominal pain was
significantly more frequent in localized than in diffuse disease
(p  = .004). Cholestasis outside of episodes of severe cholangi-
tis was not frequently observed with either diffuse (6/45 [13%])
or localized (3/21 [14%]) disease. Hematemesis due to portal
 MRCP of Caroli Disease

TABLE 1: Characteristics of Patients With Caroli Disease (CD) at MRCP Examination

Patients With Diffuse Patients With Localized
Characteristic ­Bilobar CD (n = 45) ­Unilobar CD (n = 21) p
Age (y), mean ± SD
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Adults 35 ± 11 (n = 40) 54 ± 14 (n = 21) < .001

Children 8 ± 5 (n = 5) (n = 0)
Sex
Male 28 (62) 12 (57) .69
Female 17 (38) 9 (43) .69
Histopathology report available 37 (82) 16 (76) .57
Associated congenital hepatic fibrosis 35 (78) 0 < .001
Familial history of liver ciliopathies 6 (13) 0 .08
Personal history of renal ciliopathies 12 (27) 0 .009
Prior cholecystectomy or endoscopic intervention 12 (27) 13 (62) .006
Cholecystectomy 6 (13) 12 (57) < .001
Sphincterotomy 6 (13) 6 (29) .13
Clinical presentation
Asymptomatic 6 (13) 3 (14) .91
Symptomatic 39 (87) 18 (86) .91
Abdominal pain 4 (9) 8 (38) .004
Severe cholangitis or jaundice 29 (64) 10 (48) .19
Pancreatitis 1 (2) 0 .49
Hematemesis 5 (11) 0 .11
Biology
Cholestasis 6 (13) 3 (14) .91
Chronic renal failure 9 (20) 0 .03
Note—Except where otherwise indicated, data are frequency with percentage in parentheses.

TABLE 2: MRI Findings at Diagnosis

Finding Patients With Diffuse Bilobar CD (n = 45) Patients With Localized Unilobar CD (n = 21) p
Shape of IHBDs
Only saccular dilatation 1/45 (2) 0 .49
Only fusiform dilatation 1/45 (2) 21/21 (100) < .001
Both saccular and fusiform dilatation 43/45 (96) 0 < .001
Location of dilated IHBDs
Peripheral saccular 42/45 (93) 0 < .001
Central saccular 4/45 (9) 0 .16
Peripheral fusiform 42/45 (93) 21/21 (100) .23
Central fusiform 44/45 (98) 18/21 (86) .06
Size of largest IHBD (mm)
Peripheral saccular 25.24 ± 19.56
Central saccular 37.75 ± 22.69
Peripheral fusiform 10.29 ± 6.80 5.61 ± 2.85 < .001
Central fusiform 8.25 ± 4.20 12.23 ± 4.54 .002
IHBD peripheral funnel-shaped sign 41/45 (91) 0 < .001
(Table 2 continues on next page)

AJR:216, June 2021 1533

 Lewin et al.

TABLE 2: MRI Findings at Diagnosis (continued)

Finding Patients With Diffuse Bilobar CD (n = 45) Patients With Localized Unilobar CD (n = 21) p
Dot sign a
15/35 (43) 0 .02
Biliary lithiasis
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Intrahepatic bile duct stones 16/45 (36) 21/21 (100) < .001
Localized at one or two segments 7/45 (16) 18/21 (86) < .001
Diffuse 9/45 (20) 3/21 (14) < .57
Choledocholithiasis 2/45 (4) 8/21 (38) < .001
Gallbladder lithiasis 4/39 (10)b 5/8 (63)b < .001
Size of main bile duct (mm) 9.2 ± 3.6 8.1 ± 3.4 .23
Liver morphologic changes
Hepatomegaly 18/45 (40) 0 < .001
Right liver atrophy 0 0 NA
Left liver atrophy 0 18/21 (86) < .001
Liver abscess 1/45 (2) 3/21 (14) .06
Note—Except where otherwise indicated, data are frequency with percentage in parentheses or mean ± SD. CD = Caroli disease, IHBDs = intrahepatic bile ducts, NA =
not applicable.
a
MRI with injection of gadolinium.
b
Patients who did not undergo cholecystectomy.

hypertension or chronic renal failure was observed only in CHF-­
associated disease.
Imaging Findings
The shape of the IHBD dilatation depended on the diffuse or lo-
calized involvement of the liver. IHBD dilatation with both saccular
and fusiform features was found in 43 of the 45 (96%) patients with
diffuse CD and was not found in patients with localized disease (p <
.001) (Table 2 and Figs. 3–5). Patients with localized disease had only
fusiform enlargement of the IHBDs. The location of dilated IHBDs
affected both the peripheral and central bile ducts regardless of the
type of disease, but peripheral saccular enlargement of IHBDs was
found only in diffuse CD (p < .001). The diameter of the fusiform dil-
atation of IHBD in localized disease was always larger downstream
near the hilum (mean, 12.23 ± 4.54 mm vs 5.61 ± 2.85 mm in periph-
eral bile ducts), whereas in diffuse CD, the diameter of the IHBDs
was larger at the periphery of the liver (p < .001).
The IHBD peripheral funnel-shaped sign was present in 41 of 45
patients (91%) with diffuse CD and in none of the patients with lo-
calized disease (p < .001). This sign was a feature of only diffuse dis-
ease, with sensitivity of 91% (41/45), specificity of 100% (21/21), NPV
of 84% (21/25), PPV of 100% (41/41), and accuracy of 94% (62/66).

Fig. 4—41-year-old man with Caroli disease.

MRCP image shows mainly peripheral and
central fusiform dilatation of intrahepatic
bile duct (arrows) associated with peripheral
saccular dilatation of intrahepatic bile duct.

Fig. 3—9-year-old girl with Caroli disease associated

with congenital hepatic fibrosis (Caroli syndrome).
MRCP image shows multiple areas of mainly saccular Fig. 5—22-year-old man with Caroli disease
dilatation of intrahepatic peripheral bile ducts associated with congenital hepatic fibrosis
(arrows) that communicate with major biliary tree (Caroli syndrome). MRCP image shows mainly
associated with peripheral and central fusiform peripheral saccular dilatation of intrahepatic
dilatation of intrahepatic bile duct (arrowheads). bile duct (arrows) communicating with biliary
Cystic dilatations are mainly peripheral, subcapsular, tree associated with peripheral and central
and larger in periphery than in center. fusiform dilatation of intrahepatic bile duct.

1534 AJR:216, June 2021

 MRCP of Caroli Disease
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A B
The central dot sign was not seen in patients with localized disease
and was present in 15 of 35 (43%) patients with diffuse CD who un-
derwent gadolinium-enhanced MRI (p < .02) (Fig. 6).
Intrahepatic biliary stones complicating the IHBD dilatations
were found in all patients with localized disease (p < .001) (Fig.
7). Intrahepatic lithiasis was found in the left liver in all but two
patients. The right liver was normal in all of these patients (19/21
[90%]), without bile duct enlargement or stones (except in three
patients who had one contralateral stone). Intrahepatic abscess-
es were found in four of 37 (11%) patients with intrahepatic lithi-
asis (one with diffuse and three with localized disease). Hepato-
megaly was found in 18 of 45 (40%) patients with diffuse CD and
in none of the patients with localized disease (p < .001). To the
contrary, marked left liver atrophy was found in 18 of 21 (86%) pa-
tients with localized disease and in none of the patients with dif-
fuse CD (p < .001) (Fig. 7B).
There were no major differences in IHBD imaging between
CHF-associated and non–CHF-associated diffuse CD except for
certain atypical presentations. Patterns in patients with non–CHF-­
associated disease compared with CHF patterns were saccular
only (1/10 [10%] vs 0/35) or fusiform (1/10 [10%] vs 0/35) IHBD dil-
atation (p =.06); more frequent central IHBD saccular enlargement
(3/10 [30% vs 1/35 [3%]) (p = .008); significantly less frequent IHBD
peripheral funnel-shaped sign (7/10 [70%] vs 34/35 [97%]) (p  =
.008) and significantly fewer dot signs (1/10 [10%] vs 14/25 [56%])
(p = .01) (Table 3). In addition, there was no difference in the pres-
A B
AJR:216, June 2021 1535
Fig. 6—53-year-old woman with Caroli disease
associated with congenital hepatic fibrosis (Caroli
syndrome).
A, Axial T2-weighted MR image shows intrahepatic
bile duct peripheral funnel-shaped sign (arrow)
associated with dot sign (arrowheads) in peripheral
fusiform dilatation of intrahepatic bile duct.
B, Axial portal venous phase T1-weighted MR image
shows presence of intrahepatic bile duct peripheral
funnel-shaped sign (arrow) associated with dot sign
(arrowheads) in peripheral saccular dilatation of
intrahepatic bile duct. Absence of liver dysmorphy
is evident.
ence of stones, changes in liver morphology, or renal abnormali-
ties. However, some distinct CHF findings were found in patients
with CHF-associated CD, in particular, associated signs of portal hy-
pertension; associated ductal plate malformations, such as biliary
hamartomas; and large regenerative nodules (Table 3).
Follow-Up
Patient follow-up is summarized in Table 4. Surgical manage-
ment included only liver transplant in patients with diffuse CD
(14/45 [31%]). Anatomic liver resection was mainly performed in
patients with localized disease (15/21 [71%]). Intrahepatic lithia-
sis was found at histopathologic analysis in all of these cases. The
causes of death among patients with diffuse CD were intrahepat-
ic cholangiocarcinoma (1/45 [2%]), severe cholangitis (1/45 [ 2%]),
gastrointestinal hemorrhage (2/45 [4%]), and postoperative com-
plications after liver transplant (1/14 [7%]). The cause of the death
of the patient with localized disease (1/21 [5%]) was severe chol-
angitis. The overall survival rate among patients with diffuse CD
was significantly lower than that among patients with localized
disease (log-rank test, p = .03).
Discussion
CD is a rare biliary disease that can be diagnosed with MRCP in-
cluding axial and coronal T2-weighted sequences. The typical im-
aging features of diffuse CD were peripheral IHBD dilatation with
both saccular and fusiform enlargement communicating with a
Fig. 7—40-year-old man with
left intrahepatic lithiasis initially
considered as localized Caroli
disease.
A, MRCP image shows dilatation of
left intrahepatic bile duct (arrow).
B, Axial T2-weighted MRCP
image shows hepatic atrophy of
segment II with intrahepatic calculi
(arrowheads).
 Lewin et al.

TABLE 3: Imaging Findings of Diffuse Caroli Disease With or Without Associated Congenital Hepatic
Fibrosis (Caroli Syndrome)
Finding Patients With CD With CHF (n = 35) Patients With CD Without CHF (n = 10) p
Shape of IHBD
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Both saccular and fusiform dilatation 35/35 (100) 8/10 (80) .007
Only saccular dilatation 0 1/10 (10) .06
Only fusiform dilatation 0 1/10 (10) .06
Location of dilated IHBD
Peripheral saccular 34/35 (97) 8/10 (80) .06
Central saccular 1/35 (3) 3/10 (30) .008
Peripheral fusiform 33/35 (94) 9/10 (90) .63
Central fusiform 35/35 (100) 9/10 (90) .63
Size of largest IHBD (mm)
Peripheral saccular 26.23 ± 21.25 21.0 ± 9.43 .30
Central saccular 24 42.33 ± 25.42 .30
Peripheral fusiform 10.15 ± 7.04 10.80 ± 6.23 .78
Central fusiform 8.04 ± 4.39 9.0 ± 3.56 .49
IHBD peripheral funnel-shaped sign 34/35 (97) 7/10 (70) .008
Dot signa 14/25 (56) 1/10 (10) .01
Biliary lithiasis
Intrahepatic bile duct stones 11/35 (31) 5/10 (50) .28
Choledocholithiasis 1/35 (3) 1/10 (10) .33
Gallbladder lithiasis 3/32 (9)b 1/7 (14)b .70
Liver morphologic changes
Hepatomegaly 15/35 (43) 3/10 (30) .46
Right liver atrophy 0 0 NA
Left liver atrophy 0 0 NA
Biliary hamartoma 15/35 (43) 0 .01
Large regenerative nodules 5/35 (14) 0 .20
Signs of portal hypertension
Splenomegaly 28/35 (80) 2/10 (20) < .001
Portosystemic shunt 27/35 (77) 1/10 (10) < .001
Renal abnormalities
Three or fewer cortical cysts 7/35 (20) 4/10 (40) .19
Multiple cysts 14/35 (40) 4/10 (40) > .99
Renal hypertrophy 12/35 (34) 2/10 (20) .39
Renal atrophy 1/35 (3) 1/10 (10) .33
Note—Except where otherwise indicated, data are frequency with percentage in parentheses or mean ± SD. CD = Caroli disease, CHF = congenital hepatic fibrosis,
IHBD = intrahepatic bile duct, NA = not applicable.
a
MRI with injection of gadolinium.
b
Patient who did not undergo cholecystectomy.

nonobstructed biliary tree associated with a peripheral IHBD fun-
nel-shaped sign. Localized enlarged IHBD can be difficult to char-
acterize because the lack of stenosis can be difficult to evaluate.
Our results suggest that acquired IHBD dilatation due to primary
intrahepatic lithiasis is the main cause of localized (left liver) en-
larged bile ducts and is not a localized type of CD.
Our results show that CD can be diagnosed on the basis of a
combination of imaging features on MRCP. Visualization of a com-
munication between the dilated IHBD and the biliary system is a
well-known key diagnostic imaging feature of CD [13–15]. Howev-
er, our study clearly shows that it is not necessary to classify cases
according to the saccular or fusiform pattern of bile duct enlarge-

1536 AJR:216, June 2021

 TABLE
M R C P o 4:
f C Patient
a r o l i D i s Follow-Up
ease
Patients With CD Patients With CD All Patients With
Follow-Up With CHF (n = 35) Without CHF (n = 10)
Treatment
Conservative management 22 (63) 8 (80)
Surgery 13 (37) 2 (20)
Downloaded from www.ajronline.org by 103.148.194.50 on 12/18/22 from IP address 103.148.194.50. Copyright ARRS. For personal use only; all rights reserved
Hepatectomy 1 (3) 0 1 (2)
Biliodigestive anastomosis 0 0
Liver transplant 12 (34) 2 (20)
Kidney transplant 8 (23) 0 8 (18)
Follow-up finding
Duration of follow-up after MRI (y) 6.17 ± 3.11 4.75 ± 3.62
Intrahepatic cholangiocarcinoma 1 (3) 0 1 (2)
Death 4 (11) 1 (10)
Note—Except where otherwise indicated, data are frequency with percentage in parentheses or mean ± SD. CD = Caroli disease, CHF = congenital hepatic fibrosis.
a
Between all patients with CD and those with localized disease.
ment because these patterns coexisted in almost all patients with
diffuse CD (43/45 [96%] in this study) [17]. In addition, the pres-
ence of the subcapsular IHBD funnel-shaped sign, which is easily
detectable on axial T2-weighted imaging, strengthens the diag-
nosis with high sensitivity and specificity. This sign was found in
97% (34/35) of patients with CHF-associated CD, in 70% (7/10) of
patients with non–CHF-associated diffuse CD, and in none of the
patients with localized disease. The central dot sign, which is high-
ly specific for CD, was seen in only 43% (15/35) of patients with dif-
fuse CD who underwent gadolinium-enhanced MRI, suggesting
low sensitivity. This result is similar to that in a literature report de-
scribing the presence of a central dot sign on cross-sectional im-
ages in only 36% (5/14) of patients [11]. To our knowledge, this dot
sign has not been found in localized disease [18].
Patients with localized disease differ from those with diffuse CD.
The hallmark imaging signs are fusiform IHBD dilatation, which
is greater near the hilum, associated with the presence of stones
(21/21 [100%]) and segmental left liver atrophy (18/21 [86%]). These
patients were significantly older and underwent cholecystecto-
my more frequently than patients with diffuse CD (p < .001). These
results suggest a link between gallstone disease treated by chole-
cystectomy and the presence of hepatolithiasis. Intrahepatic lithia-
sis was confirmed by pathologic examination of surgical specimens
for all patients who underwent surgery (16/21 [76%]). These results
should lead us to question the existence of so-called monosegmen-
tal or unilobar CD, which has been reported to mainly affect the left
hepatic lobe. There is overlap between the imaging features of local-
ized disease and those of primary intrahepatic lithiasis [19, 20]. Even if
monosegmental or unilobar ductal plate malformations have been
reported, a substantial proportion of so-called localized CD is prob-
ably primary intrahepatic lithiasis, possibly 100% in our series [21].
This lithiasis could also have been secondary to enlarged bile ducts.
However, in our patients with diffuse biliary enlargement, lithiasis
was less frequent (16/45 [36%]) than in patients with localized dis-
ease (21/21 [100%]) (p < .001). Furthermore, lithiasis was present in
one or two segments in 7 of 45 (16%) patients with diffuse disease
compared with 18 of 21 (86%) patients with localized disease.
Most of the patients in our study had CHF-associated diffuse
CD (Caroli syndrome) as opposed to non–CHF-associated dif-
fuse CD, which differs from the findings in previous surgical stud-
AJR:216, June 2021 1537
Patients With Localized
CD (n = 45) Disease (n = 21) pa
30 (67) 5 (24) .001
15 (33) 16 (76) .001
15 (71) < .001
0 2 (10) .04
14 (31) 0 .004
0 .04
5.88 ± 3.29 3.74 ± 2.38 .03
0 .49
5 (11) 1 (5) .40
ies [22, 23]. This result occurred because we included patients
who had not undergone hepatic surgery at diagnosis. Our re-
sults show that biliary imaging features were similar in the two
subgroups. However, signs of portal hypertension and the pres-
ence of biliary hamartoma and large regenerative nodules were
seen only in CHF-associated CD [24]. It is important to note that
renal abnormalities, including renal cysts, are not helpful in dis-
criminating the two types of CD [25, 26]. As suggested by oth-
er authors [18, 27], one hypothesis is that CD with and without
associated CHF are two variants at different stages of the same
disease and that they may be forms of autosomal recessive poly-
cystic kidney disease. Although pediatric hepatobiliary university
hospital centers participated in this study, very few pediatric pa-
tients were included. This is consistent with the literature, which
describes very few reported pediatric cases [28]. However, papers
describing MRCP features in neonates [29–31] raise the question
of the sensitivity of ultrasound compared with MRCP, which is not
yet been evaluated in the literature, to our knowledge. Interest-
ingly, all our pediatric patients had CHF-associated CD [32].
Patients with CD are at high risk of development of intrahepat-
ic cholangiocarcinoma; the mean prevalence of nearly 7% in the
literature among patients with congenital IHBDs [22, 33]. In our
study, the prevalence of synchronous cholangiocarcinoma was
2% (1/45) with no significant difference between CHF-associated
and non–CHF-associated CD. The overall survival rate among pa-
tients with diffuse CD was significantly lower than that among
patients with localized disease, suggesting, once again, that it
may not be the same disease.
There are numerous other challenging discriminatory diagno-
ses, as shown by the large number (59/125 [47%]) of patients ex-
cluded from our study because of a mistaken diagnosis. Our in-
clusion criteria were based on imaging reports mentioning CD in
the conclusion, a diagnosis that can change on the basis of fur-
ther reading of imaging results, monitoring, patient history, and
a final diagnosis in a multidisciplinary meeting [34, 35].
Our study had several limitations. First, patients were includ-
ed from tertiary university centers treating patients liver disease,
which might have caused selection bias toward patients with se-
vere symptomatic CD. This could therefore have increased the
sensitivity of the funnel-shaped sign and influenced patient man-
 Lewin et al.
agement. Second, it was a retrospective study with a small num-
ber of patients. A large prospective study is needed to validate
the current results. Moreover, some patients with in both groups
(diffuse CD, 8/45 [18%]; localized CD, 5/21 [24%]) did not undergo
liver biopsy or surgery. However, other liver diseases might have
been excluded owing to the long follow-up period. In addition,
Downloaded from www.ajronline.org by 103.148.194.50 on 12/18/22 from IP address 103.148.194.50. Copyright ARRS. For personal use only; all rights reserved
because image analysis was done by consensus, we did not mea-
sure interreader variability. Finally, MRI protocols were not stan-
dardized because of the multicenter origin of patients. Neverthe-
less, all patients underwent MRCP, an inclusion criterion.
In conclusion, CHF-associated and non–CHF-associated diffuse
CD have very similar imaging features on MRCP. They exhibit typi-
cal bilobar saccular and fusiform bile duct dilatations with predom-
inantly subcapsular enlargement, including a funnel-shaped pat-
tern, which makes it possible to distinguish them from obstructive
localized biliary disease, mainly due to intrahepatic lithiasis.
Acknowledgment
We thank Aurore Vullierme for the drawing.
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