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European Journal of Radiology 142 (2021) 109884

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European Journal of Radiology


journal homepage: www.elsevier.com/locate/ejrad

Assessment of prognostic value and interreader agreement of ANALI scores


in patients with primary sclerosing cholangitis
Aristeidis Grigoriadis a, b, *, Kristina I. Ringe c, Mats Andersson a, b, Nikolaos Kartalis a, b,
Annika Bergquist d
a
Division of Radiology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
b
Department of Radiology Huddinge, Karolinska University Hospital, Stockholm, Sweden
c
Hannover Medical School, Department of Diagnostic and Interventional Radiology, Hannover, Germany
d
Division of Hepatology, Department of Upper GI Disease, Karolinska University Hospital, and Department of Medicine Huddinge, Unit of Gastroenterology and
Rheumatology, Karolinska Institutet, Stockholm, Sweden

A R T I C L E I N F O A B S T R A C T

Keywords: Purpose: ANALI-scores are two prognostic magnetic resonance imaging (MRI)-based scores developed for patients
Magnetic resonance imaging with primary sclerosing cholangitis (PSC). Our study aims to assess the interreader agreement between expert
Prognosis radiologists of the two ANALI-scores and of the radiological parameters they utilize, and to test the prognostic
Radiology
performance of the scores in our population.
Sclerosing cholangitis
Method: Three radiologists evaluated MRIs of 98 PSC-patients from a prospectively collected cohort with median
follow-up of 6.7 years. Each parameter of ANALI-scores was assessed, and the scores were calculated. Interreader
agreement was assessed with intraclass correlation coefficient (ICC). After consensus reading was reached, the
prognostic value of ANALI-scores was assessed with Cox regression, and outcome-free survival rates were
evaluated with Kaplan-Meier estimates.
Results: The ANALI-score without gadolinium had poor to moderate (ICC = 0.56, 95 %CI: 0.42–0.68) and with
gadolinium poor (ICC = 0.30, 95 %CI: 0.16–0.44) agreement. Liver deformity (ICC = 0.28, 95 %CI: 0.13–0.44)
and parenchymal enhancement heterogeneity (ICC = 0.24, 95 %CI: 0.12–0.38) had poor agreement. Portal
hypertension had poor to moderate (ICC = 0.48, 95 %CI: 0.36–0.59) and dilatation of the intrahepatic ducts had
moderate (ICC = 0.64, 95 %CI: 0.54–0.73) agreement. Hazard ratios for liver-related death, transplantation or
cirrhosis decompensation of the ANALI-scores with and without gadolinium were 3.53 (95 %CI: 1.40–8.93) and
2.25 (95 %CI: 1.56–3.24), respectively. Outcome-free survival was better for patients with low ANALI-scores.
Conclusions: The ANALI-scores show poor to moderate agreement, which challenges their usefulness in clinical
practice. They are associated with clinical outcomes, confirming the value of imaging in prognosis of PSC, but
need further multicenter evaluation.

1. Introduction counseling, and evaluation of treatment effects.


Magnetic resonance imaging/magnetic resonance chol­
Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver angiopancreatography (MRI/MRCP) is generally accepted as the mo­
disease that leads to biliary cirrhosis and liver failure, and carries an dality of choice for imaging of PSC patients [3–5]. The potential
increased risk of hepatobiliary cancer [1,2]. Liver transplantation is still prognostic value of MRI for PSC patients has been an area of interest in
the only potentially curative therapy available. There is a lack of good recent years. In 2014, a French group developed a standardized inter­
prognostic markers that could be used for patient stratification, pretation model for MRI/MRCP examinations, based on which up to half

Abbreviations: ALP, Alkaline phosphatase; CI, Confidence interval; GBCA, Gadolinium-based contrast agent; HR, Hazard ratio; ICC, Intraclass correlation coef­
ficient; INR, International normalized ratio; IHBD, Intrahepatic bile ducts; MRCP, Magnetic resonance cholangiopancreatography; MRI, Magnetic resonance imaging;
PH, Portal hypertension; PSC, Primary sclerosing cholangitis.
* Corresponding author at: Department of Radiology, Karolinska University Hospital, Hälsovägen 13, 14157, Huddinge, Sweden.
E-mail addresses: aristeidis.grigoriadis@ki.se (A. Grigoriadis), Ringe.Kristina@mh-hannover.de (K.I. Ringe), mats.n.andersson@sll.se (M. Andersson), nikolaos.
kartalis@ki.se (N. Kartalis), annika.bergquist@ki.se (A. Bergquist).

https://doi.org/10.1016/j.ejrad.2021.109884
Received 19 June 2021; Received in revised form 25 July 2021; Accepted 27 July 2021
Available online 31 July 2021
0720-048X/© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
A. Grigoriadis et al. European Journal of Radiology 142 (2021) 109884

Table 1 one patient was lost to follow-up.


Demographic and laboratory data of study population (n = 98). The final study population comprised of 98 patients. The MRI/MRCP
Study population Normal range closest to the day of inclusion in the cohort was retrieved for evaluation.
Study design, demographic, laboratory and outcome data of study
Number of patients 98 –
Male/Female 63/35 – population are shown in Table 1.
Age in years 40 (20–79) –
Time from PSC diagnosis to MRI (years) 7.1 (0.5–25) – 2.2. MRI imaging and evaluation
IBD, n (%) 74 (76) –
Ulcerative Colitis 57 (58) –
Crohn’s Disease 16 (16) –
MRI examinations were performed using 1.5 T MRI scanners be­
Indeterminate colitis 1 (0) – tween 2012 and 2015 (Magnetom Aera and Magnetom Avanto, Siemens
Bilirubin (μmol/l) 11 (4–104) <26 Healthineers, Erlangen, Germany) with 18-channel torso phased array
ALAT (μkat/l) 0.75 (0.11–11.85) <1.1 coil and fixed spine coil. Sequences and technical parameters are shown
ASAT (μkat/l) 0.61 (0.21–7.79) <0.76
in Supplementary Table 1.
ALP (μkat/l) 1.9 (0.6–12.9) 0.7–1.9
Albumin (g/l) 39 (27–47) 36–48/36–35 Three radiologists (readers) blinded to clinical information apart
INR 1 (0.6–2.5) <1.2 from diagnosis of PSC – two from Karolinska University Hospital,
CA 19-9 (kE/l) 8 (0.3–1056) <34 Huddinge (A.G. and M.A.) and one from the Department of Diagnostic
MELD score 6 (6–17) – and Interventional Radiology, Hannover Medical School, Hannover,
Follow-up time from MRI (years) 6.7 (0.7–8.46) –
Clinical events at follow up 22 –
Germany (K.R.) with 9, 28 and 15 years of experience in abdominal
Liver Tx 12 – radiology, respectively – independently evaluated the 98 MRI exami­
Liver decompensation 6 – nations in a commercially available workstation (SECTRA PACS, IDS 7,
Liver-related death 1 – version 19.1, SECTRA AB, Linköping, Sweden). The readers were asked
Hepatobiliary cancer 3
to evaluate each of the parameters included in the ANALI scores sepa­
All values expressed as medians (range). rately, and the scores were then calculated. In line with the definitions of
ASAT, aspartate transaminase; ALAT, alanine aminotransferase; ALP, alkaline the scores, ANALI score without gadolinium = (1 × dilatation of IHBD) +
phosphatase; IBD, inflammatory bowel disease; INR, international normalized (2 × liver deformity) + (1 × PH) and ANALI score with gadolinium = (1 ×
ratio; MRI, magnetic resonance imaging; Liver-Tx, liver transplantation. liver deformity) + (1 × parenchymal enhancement heterogeneity) [6].
To assess IHBD dilatation, the readers were asked to register the diam­
of patients progressed in their disease radiologically during a 4-year eter (in millimeters) of the most dilated intrahepatic duct in left liver
follow-up [6]. It was shown that the radiological progression was lobe (segments 1–4), right anterior (segments 5 and 8), and right pos­
associated with the presence of intrahepatic bile duct (IHBD) dilatation, terior (segments 6 and 7) section, separately. The maximum registered
liver deformity, the presence of portal hypertension (PH), and hetero­ diameter for each patient was then chosen and scored as 0 if the duct
geneous enhancement in the arterial phase when gadolinium-based diameter was ≤3 mm, 1 if it was 4 mm, and 2 if it was ≥5 mm. The
intravenous contrast agent was administered. Two scores based on readers assessed the liver for signs of atrophy, lobulation of liver surface,
these radiological parameters, called ANALI score with gadolinium and or increase in the modified caudate/right lobe liver ratio [10], and liver
ANALI score without gadolinium, were developed. In a subsequent deformity was scored as absent (0) or present (1). Portal hypertension
study, the prognostic value of these scores was assessed and then vali­ was registered as absent (0) or present (1) when portosystemic shunts
dated in cohorts from different centers [7]. High scores were found to be were found. Absence (0) or presence (1) of parenchymal enhancement
associated with poorer prognosis. The risk of developing liver-related heterogeneity was evaluated in the arterial phase of enhancement.
death, liver transplantation or liver decompensation was 25 times Laboratory data and clinical events, including liver transplantation,
higher for patients with high ANALI scores without gadolinium and 13 death, cirrhosis decompensation or occurrence of hepatobiliary cancer,
times higher for patients with high ANALI scores with gadolinium than and indication for liver transplantation were collected for all patients.
in patients with low ANALI scores. MELD score was also calculated.
Although the two ANALI scores seem promising, their interreader
agreement has not been evaluated to date. Interpretation of MRI ex­ 2.3. Outcomes
aminations of patients with PSC is challenging, as shown by two recent
studies [8,9]. Agreement therefore needs to be assessed before the Outcomes were decompensation of liver cirrhosis (encephalopathy,
ANALI scores can be utilized in clinical practice. ascites, first bleeding of esophageal varices), liver transplantation or
The aim of this study is two-fold, namely to both assess the inter­ liver related death. Hepatobiliary cancers were noted but not considered
reader agreement between expert radiologists of the two ANALI scores as a primary outcome, if patients were still alive at the end of the study,
and of the radiological parameters they utilize, and to test the prognostic in accordance with original study [7].
performance of the scores in our population.
2.4. Statistical analysis
2. Materials and methods
Patient clinical and laboratory data were described as medians or
2.1. Study population absolute numbers and percentages. Interreader agreement was assessed
for each parameter and for the two ANALI scores separately by means of
For this regional ethical review board-approved study, we retrieved intraclass correlation coefficient (ICC) using a two-way random effects
140 consecutive patients with large duct PSC from a prospective model based on absolute agreement and individual measurements
observational study between 2012 and 2020. Inclusion criteria were [11,12]. ICC values <0.50 indicated poor agreement, values between
large duct PSC and at least one MRI/MRCP using gadoxetic acid (Pri­ 0.50 and 0.75 moderate agreement, between 0.75 and 0.90 good
movist/Eovist, Bayer Healthcare) contrast agent according to a stan­ agreement and above 0.90 excellent agreement [12]. 95% confidence
dardized protocol dedicated to patients with PSC. Exclusion criteria intervals (CI) were also calculated for each ICC value.
were MRI/MRCP performed with another protocol (n = 33), small duct For outcome-free survival analysis, cases of disagreement were
PSC (n = 2), and prior hepatobiliary cancer or liver transplantation (n = resolved in a consensus reading between all three readers unanimously.
2). One patient was excluded due to incomplete MRI/MRCP, three pa­ Data were censored and analyzed in a similar way as in the original
tients had no MRI/MRCP performed after inclusion in the cohort, and study [7], at the date of last follow-up alive, or at the time of liver-

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A. Grigoriadis et al. European Journal of Radiology 142 (2021) 109884

Table 2 normalized ratio (INR) and alkaline phosphatase (ALP) [13–25]. For
Intraclass correlation coefficient (ICC) with 95% confidence intervals (CI) (in assessment of survival rates, patients were categorized in groups of low
parentheses) of intrahepatic bile duct dilatation, liver deformity, parenchymal and high scores, ≤ 2 and >2 for the score without gadolinium and ≤1
enhancement heterogeneity, presence of portal hypertension and ANALI scores and >1 for the score with gadolinium, respectively. Kaplan-Meier esti­
with and without gadolinium. mates were calculated and the curves were compared with log-rank test,
Parameter ICC (95% CI) when applicable. P-value <0.05 was considered significant. STATA
IHBD† dilatation 0.64 (0.54–0.73) v15.1 statistical package was used for statistical analysis.
Liver deformity 0.28 (0.13–0.44)
Parenchymal enhancement heterogeneity 0.24 (0.12–0.38) 3. Results
Portal hypertension 0.48 (0.36–0.59)
ANALI score with gadolinium 0.30 (0.16–0.44)
ANALI score without gadolinium 0.56 (0.42–0.68) 3.1. Clinical characteristics

IHBD, intrahepatic bile ducts.
The study population consisted of 98 patients with large duct PSC, 63
(64%) males and the median age at inclusion was 40 years (range
related death, liver transplantation, and cirrhosis decompensation, 20–79) and median duration of PSC till MRI was 7.1 years (range
whichever came first. Univariate Cox proportional hazards regression 0.5–25). During median follow-up of 6.7 years, 19 patients (19%)
analysis was performed to evaluate association between outcomes and developed outcomes. Twelve (12%) patients underwent liver trans­
the ANALI scores, MELD score and laboratory parameters. Multivariate plantation (ten patients due to liver decompensation and two due to
analysis with adjustment for age and sex was also performed. Some of high-grade dysplasia), six (6%) patients developed liver decompensa­
the variables included in the analyses were tested previously and have tion, and one patient died of end-stage liver disease. Three additional
shown prognostic value. These include bilirubin, albumin, international patients developed hepatobiliary cancer and were still alive at the end of

Fig. 1. Axial T2-weighted image (a), coronal


maximum intensity projection from 3D
MRCP (b) and T1-weighted images with fat
suppression after contrast injection in arte­
rial phase (c and d) and portal venous phase
(e and f) of a 36 years-old patient with PSC.
ANALI score with and without gadolinium
was calculated as 1, 2, 0, and 4, 3, 0 for
readers A, B, and C, respectively. Reader A
and B evaluated the liver as deformed
whereas reader C as normal. Maximal duct
diameter was registered as being ≥5 mm, 4
mm and ≤3 mm by reader A, B, and C,
respectively. Reader B registered paren­
chymal enhancement heterogeneity as pre­
sent whereas the other two readers as absent.
The only variable that all readers agreed
upon was absence of portal hypertension
(absence of esophageal varices and porto­
systemic collaterals in upper abdomen in e
and f).

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A. Grigoriadis et al. European Journal of Radiology 142 (2021) 109884

Fig. 2. Axial (a) and coronal (b) T2-


weighted images, coronal maximum in­
tensity projection from 3D MRCP (c) and T1-
weighted images with fat suppression after
contrast injection in arterial (d) and portal
venous phase (e and f) of a 66 years-old pa­
tient with PSC. ANALI score with and
without gadolinium was calculated as 1 and
5 by all readers, respectively. All readers
registered the same values for all individual
parameters of the scores. The liver was
registered as deformed [enlarged segment 4
and lateral segment (asterisks in a), lobula­
tion of liver surface (arrows in a and b)],
maximal duct diameter as being ≥5 mm
(dashed arrow in c), parenchymal enhance­
ment heterogeneity as absent (d), portal hy­
pertension as present [arrowheads pointing
at esophageal varices in (e) and recanalized
paraumbilical veins in (f)].

study period (one cholangiocarcinoma, one gallbladder cancer and one gadolinium. The distribution of the scores in the study population after
hepatocellular carcinoma), but these events were not included as out­ consensus reading is shown in Supplementary Figs. 1 and 2. Median
comes in survival analysis according to the study definition. MELD score was 6 (range 6–17).

3.2. Assessment of interreader agreement 3.3. Prognostic performance of the scores

Interreader agreement for each variable individually and for the two Only one patient with ANALI score without gadolinium between
ANALI scores with and without gadolinium are shown in Table 2. The 0 and 2 and no patient with ANALI score with gadolinium 0 developed
ANALI score without gadolinium had poor to moderate interreader outcomes. In the univariate Cox regression analysis, the two ANALI
agreement (ICC = 0.56, 95% CI: 0.42–0.68), whereas the score with scores, MELD score and all laboratory tests were significantly associated
gadolinium had poor agreement (ICC = 0.30, 95% CI: 0.16–0.44) with outcomes and remained significant even after adjusting for sex and
(Figs. 1 and 2). The parameters of the two scores exhibited agreement age (Table 3). The ANALI score without gadolinium demonstrated a
varying from poor to moderate, with parenchymal enhancement het­ hazard ratio (HR) of 2.25 (95% CI, 1.56–3.24), and the score with
erogeneity having the lowest agreement (ICC = 0.24, poor, 95% CI: gadolinium had a HR of 3.53 (95% CI, 1.40–8.93) in the univariate
0.12–0.38) and dilatation of the intrahepatic ducts the highest (ICC = analysis. The only laboratory parameter with HR higher than the two
0.64, moderate, 95% CI: 0.54–0.73). Liver deformity, which is used in scores was INR with a HR of 6.16 (95% CI, 1.91– 19.89). MELD score had
both scores, had poor agreement (ICC = 0.28, 95% CI: 0.13–0.44), and a HR of 1.54 (95% CI, 1.34– 1.76). Outcome-free survival was signifi­
evaluation of portal hypertension had poor to moderate agreement (ICC cantly better for patients with low ANALI scores as shown in the Kaplan-
= 0.48, 95% CI: 0.36–0.59). After consensus reading, the median value Meier estimates in Fig. 3 and in Supplementary Figs. 3 and 4. P-value for
was 2 for the ANALI score without gadolinium and 1 for the score with log-rank test for the score with gadolinium was P = 0.017. Log-rank test

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A. Grigoriadis et al. European Journal of Radiology 142 (2021) 109884

Table 3
Risk estimates for clinical outcomes (liver-related death, liver transplantation or cirrhosis decompensation) of ANALI scores, MELD
score and laboratory parameters.
Parameter HR† (CI 95%) P-value HRadj‡ (CI 95%) P-value

ANALI without gadolinium 2.25 (1.56–3.24) 0.000 2.37 (1.60–3.50) 0.000


ANALI with gadolinium 3.53 (1.40–8.93) 0.008 3.62 (1.38–9.49) 0.009
MELD score 1.54 (1.34–1.76) 0.000 1.66 (1.40–1.97) 0.000
Albumin 0.76 (0.68–0.85) 0.000 0.73 (0.65–0.83) 0.000
Bilirubin 1.06 (1.04–1.08) 0.000 1.07 (1.05–1.09) 0.000
ALP§ 1.31 (1.16–1.47) 0.000 1.32 (1.16–1.49) 0.000
INR¶ 6.16 (1.91–19.89) 0.002 6.53 (1.83–23.38) 0.004
ASAT†† 1.49 (1.20–1.85) 0.000 1.50 (1.20–1.87) 0.000
ALAT‡‡ 1.23 (1.05–1.45) 0.010 1.24 (1.05–1.46) 0.010
GGT§§ 1.08 (1.02–1.16) 0.028 1.08 (1.01–1.15) 0.033

HR, hazard ratio.

HRadj, Adjusted hazard ratio for sex and age.
§
ALP, alkaline phosphatase.

INR, international normalized ratio.
††
ASAT, aspartate transaminase.
‡‡
ALAT, alanine aminotransferase.
§§
GGT, gamma-glutamyl transferase

was not performed for the score without gadolinium due to the low definition of IHBD dilatation in the ANALI scores has stringent cut-offs
number of outcomes in the low-score group (n = 1). (≤3 mm, 4 mm and ≥5 mm) which may, at least partly, explain the
poor to moderate agreement found for this parameter. Small differences
4. Discussion in the acquired measurements of ductal diameter may lead to change in
category and, thus, disagreement between readers. IHBD dilatation had
Our study shows that both ANALI scores with and without gadolin­ the highest agreement and seems to be the most promising. It can be
ium have poor to moderate interreader agreement. Despite disagree­ hypothesized that a wider range and/or fewer categories may improve
ment between readers, these scores were able to predict clinical agreement. The relatively poor agreement of the individual parameters
outcomes in consensus reader setting. included in the ANALI scores explains the poor agreement of the score
From the four parameters used in the scores, two (liver deformity and with gadolinium and the poor to moderate agreement of the score
parenchymal enhancement heterogeneity) have poor agreement, one without gadolinium. This is more pronounced for the score with gado­
(portal hypertension) has poor to moderate agreement and one (IHBD linium, which utilizes two parameters that both show poor agreement,
dilatation) has moderate agreement. Evaluation of liver deformity is namely liver deformity and parenchymal enhancement heterogeneity.
quite subjective since, apart from the more objective calculation of the Poor agreement between readers in the evaluation of MRI of patients
caudate to right lobe ratio, it relies mainly on qualitative findings, such with PSC is well known. The results of our study are in line with two
as nodularity of surface and atrophy. This may explain the poor agree­ previously performed studies evaluating interreader agreement of MRI/
ment. Similarly, a clear definition is lacking for the parameter paren­ MRCP examinations in patients with PSC, although these studies did not
chymal enhancement heterogeneity, and its evaluation depends on specifically evaluate the parameters assessed here [8,9]. Altogether, it
reader perception. Portosystemic shunts are easy to assess on imaging can be concluded that evaluation of the MRI/MRCP of patients with PSC
when they are large, but can be hard to identify when only small varices is challenging. Before an imaging parameter can be considered a
are present, especially if no contrast agent is administered. The biomarker suitable for a prognostic model for patients with PSC in

Fig. 3. Kaplan-Meier curves for outcome-free survival


for ANALI score with (blue lines) and without (black
lines) gadolinium (consensus reading) in study popula­
tion. Solid lines represent patients with low ANALI
scores (score ≤2 without gadolinium and ≤1 with
gadolinium) and the dashed lines patients with high
ANALI scores (score >2 without gadolinium and >1
with gadolinium). Outcome was defined as liver trans­
plantation, liver-related death or cirrhosis decompen­
sation. (For interpretation of the references to colour in
this figure legend, the reader is referred to the web
version of this article.)

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A. Grigoriadis et al. European Journal of Radiology 142 (2021) 109884

clinical practice, a good interreader agreement has to be established. CRediT authorship contribution statement
Despite the shortcomings of disagreement between readers, these
scores seem useful if consensus between readers can be achieved. We Aristeidis Grigoriadis: Conceptualization, Data curation, Formal
demonstrated that both ANALI scores are significantly associated with analysis, Investigation, Methodology, Project administration, Software,
outcomes. The risk of developing outcome increased by 2.3 times for Supervision, Validation, Visualization, Writing - original draft. Kristina
each incremental increase of the score without gadolinium, and by 3.5 I. Ringe: Conceptualization, Data curation, Formal analysis, Method­
times for each incremental increase of the score with gadolinium. Both ology, Supervision, Validation. Mats Andersson: Conceptualization,
scores had a higher HR compared to the MELD score (HR, 1.5). These Data curation, Methodology, Project administration, Validation. Niko­
results are similar to those found in the study by Lemoinne et al. [7], laos Kartalis: Conceptualization, Data curation, Formal analysis,
where the HRs of the score with and without gadolinium were 2.9 and Investigation, Methodology, Project administration, Supervision, Vali­
2.5, respectively. In our study, contrast agent was administered to all dation. Annika Bergquist: Conceptualization, Data curation, Formal
patients, unlike in the study by Lemoinne et al. [7] where there was a analysis, Investigation, Methodology, Project administration, Supervi­
selection who were administered contrast agent (mostly patients with sion, Validation, Visualization, Resources.
more severe disease). This may, at least partly, explain the higher HR of
3.5 for the ANALI score with gadolinium found in our study. Interest­ Appendix A. Supplementary material
ingly, INR demonstrated the highest HR point estimate (HR, 6.16)
among all variables evaluated. However, confidence intervals of INR HR Supplementary data to this article can be found online at https://doi.
were quite wide (95 %CI, 1.91–19.89), indicating low precision, which org/10.1016/j.ejrad.2021.109884.
may explain this result.
Our study has limitations. The number of outcomes is relatively small References
(n = 19) despite a median follow-up time of 6.7 years. We defined
clinical outcomes in accordance with the original study with the aim to [1] A. Bergquist, A. Ekbom, R. Olsson, D. Kornfeldt, L. Lööf, Å. Danielsson,
R. Hultcrantz, S. Lindgren, H. Prytz, H. Sandberg-Gertzén, S. Almer, F. Granath,
evaluate the ANALI scores in the same manner as the developers of the U. Broomé, Hepatic and extrahepatic malignancies in primary sclerosing
scores. The composite endpoint was liver transplantation, cirrhosis cholangitis, J. Hepatol. 36 (3) (2002) 321–327.
decompensation or liver-related death (including death from chol­ [2] J.K. Dyson, U. Beuers, D.E.J. Jones, A.W. Lohse, M. Hudson, Primary sclerosing
cholangitis, Lancet 391 (10139) (2018) 2547–2559.
angiocarcinoma) but not cholangiocarcinoma. The rationale behind this [3] R. Chapman, J. Fevery, A. Kalloo, D.M. Nagorney, K.M. Boberg, B. Shneider, G.
can be questioned and it can be argued that cholangiocarcinoma should J. Gores, American Association for the Study of Liver, Diagnosis and management
be included among the outcomes. However, we chose to use the same of primary sclerosing cholangitis, Hepatology 51 (2) (2010) 660–678.
[4] European Association for the Study of the, EASL Clinical Practice Guidelines:
outcomes as the score developers to make the fairest comparison and management of cholestatic liver diseases, J. Hepatol. 51(2) (2009) 237-67.
validation. It is also unlikely that using the combined endpoint including [5] C. Schramm, J. Eaton, K.I. Ringe, S. Venkatesh, J. Yamamura, M.R.I.w.g.o.t.
hepatobiliary cancers would have changed our findings since only three IPSCSG, Recommendations on the use of magnetic resonance imaging in PSC-A
position statement from the International PSC Study Group, Hepatology 66 (5)
cancer patients were alive at follow-up. Another limitation is lack of
(2017) 1675–1688.
assessment of the intrareader agreement of the ANALI scores, but we [6] A. Ruiz, S. Lemoinne, F. Carrat, C. Corpechot, O. Chazouilleres, L. Arrive,
chose to focus on evaluating the interreader agreement. Radiologic course of primary sclerosing cholangitis: assessment by three-
dimensional magnetic resonance cholangiography and predictive features of
progression, Hepatology 59 (1) (2014) 242–250.
5. Conclusions [7] S. Lemoinne, N. Cazzagon, S. El Mouhadi, P.J. Trivedi, A. Dohan, A. Kemgang,
K. Ben Belkacem, C. Housset, Y. Chretien, C. Corpechot, G. Hirschfield, A. Floreani,
R. Motta, B. Gallix, A. Barkun, J. Barkun, O. Chazouillères, L. Arrivé, Simple
In conclusion, our study shows that both the individual parameters Magnetic Resonance Scores Associate With Outcomes of Patients With Primary
utilized in the ANALI scores and the scores as such have poor to mod­ Sclerosing Cholangitis, Clin. Gastroenterol. Hepatol. 17 (13) (2019) 2785–2792.e3.
erate agreement, which calls into question their usefulness in everyday [8] A. Grigoriadis, F. Morsbach, N. Voulgarakis, K. Said, A. Bergquist, N. Kartalis,
Inter-reader agreement of interpretation of radiological course of bile duct changes
clinical practice. The association between ANALI scores and clinical between serial follow-up magnetic resonance imaging/3D magnetic resonance
outcomes confirm the value of MRI in the prognostication of PSC pa­ cholangiopancreatography of patients with primary sclerosing cholangitis, Scand.
tients but the ANALI scores need further fine-optimization and broad J. Gastroenterol. 55 (2) (2020) 228–235.
[9] R. Zenouzi, T. Liwinski, J. Yamamura, C. Weiler-Normann, M. Sebode, S. Keller, A.
multicenter evaluation.
W. Lohse, C. Schramm, P.S.C.S.G. International, Follow-up magnetic resonance
imaging/3D-magnetic resonance cholangiopancreatography in patients with
6. Statement of financial support primary sclerosing cholangitis: challenging for experts to interpret, Aliment.
Pharmacol. Ther. 48(2) (2018) 169–178.
[10] H. Awaya, D.G. Mitchell, T. Kamishima, G. Holland, K. Ito, T. Matsumoto,
This study has received funding by Stockholm County Council and Cirrhosis: modified caudate-right lobe ratio, Radiology 224 (3) (2002) 769–774.
Cancer Research Funds of Radiumhemmet. [11] P.E. Shrout, J.L. Fleiss, Intraclass correlations: uses in assessing rater reliability,
Psychol. Bull. 86 (2) (1979) 420–428.
[12] T.K. Koo, M.Y. Li, A Guideline of Selecting and Reporting Intraclass Correlation
7. Ethics approval statement Coefficients for Reliability Research, J. Chiropr. Med. 15 (2) (2016) 155–163.
[13] S. Al Mamari, J. Djordjevic, J.S. Halliday, R.W. Chapman, Improvement of serum
alkaline phosphatase to <1.5 upper limit of normal predicts better outcome and
This study is approved by the institutional review board, Regionala reduced risk of cholangiocarcinoma in primary sclerosing cholangitis, J. Hepatol.
Etikprövningsnämnden (EPN) Stockholm, D-nr 2011/824-31/2 and 58 (2) (2013) 329–334.
[14] K.M. Boberg, G. Rocca, T. Egeland, A. Bergquist, U. Broomé, L. Caballeria,
2018/1494-31/3. The study conforms to declaration of Helsinki.
R. Chapman, R. Hultcrantz, S. Mitchell, A. Pares, F. Rosina, E. Schrumpf, Time-
dependent Cox regression model is superior in prediction of prognosis in primary
8. Patient consent statement sclerosing cholangitis, Hepatology 35 (3) (2002) 652–657.
[15] U. Broome, R. Olsson, L. Loof, G. Bodemar, R. Hultcrantz, A. Danielsson, H. Prytz,
H. Sandberg-Gertzen, S. Wallerstedt, G. Lindberg, Natural history and prognostic
According to ethics approval every patient has given informed con­ factors in 305 Swedish patients with primary sclerosing cholangitis, Gut 38 (4)
sent to participate in the study. (1996) 610–615.
[16] E.M. de Vries, J. Wang, M.M. Leeflang, K. Boonstra, R.K. Weersma, U.H. Beuers, R.
B. Geskus, C.Y. Ponsioen, Alkaline phosphatase at diagnosis of primary sclerosing
9. Disclosures and conflicts of interest cholangitis and 1 year later: evaluation of prognostic value, Liver Int. 36 (12)
(2016) 1867–1875.
[17] E.R. Dickson, P.A. Murtaugh, R.H. Wiesner, P.M. Grambsch, T.R. Fleming,
Professor Annika Bergquist has received research grant from Gilead. J. Ludwig, N.F. LaRusso, M. Malinchoc, R.W. Chapman, M.M. Kaplan, et al.,
Associate Professor Nikolaos Kartalis is a speaker for Bayer.

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A. Grigoriadis et al. European Journal of Radiology 142 (2021) 109884

Primary sclerosing cholangitis: refinement and validation of survival models, [23] P.P. Stanich, E. Björnsson, A.A. Gossard, F. Enders, R. Jorgensen, K.D. Lindor,
Gastroenterology 103 (6) (1992) 1893–1901. Alkaline phosphatase normalization is associated with better prognosis in primary
[18] P.S. Kamath, R.H. Wiesner, M. Malinchoc, W. Kremers, T.M. Therneau, C. sclerosing cholangitis, Dig. Liver Dis. 43 (4) (2011) 309–313.
L. Kosberg, G. D’Amico, E.R. Dickson, W.R. Kim, A model to predict survival in [24] J.J. Tischendorf, H. Hecker, M. Kruger, M.P. Manns, P.N. Meier, Characterization,
patients with end-stage liver disease, Hepatology 33 (2) (2001) 464–470. outcome, and prognosis in 273 patients with primary sclerosing cholangitis: A
[19] T.H. Karlsen, T. Folseraas, D. Thorburn, M. Vesterhus, Primary sclerosing single center study, Am. J. Gastroenterol. 102 (1) (2007) 107–114.
cholangitis - a comprehensive review, J. Hepatol. 67 (6) (2017) 1298–1323. [25] T.J. Weismuller, P.J. Trivedi, A. Bergquist, M. Imam, H. Lenzen, C.Y. Ponsioen, K.
[20] W.R. Kim, T.M. Therneau, R.H. Wiesner, J.J. Poterucha, J.T. Benson, Holm, D. Gotthardt, M.A. Farkkila, H.U. Marschall, D. Thorburn, R.K. Weersma, J.
M. Malinchoc, N.F. Larusso, K.D. Lindor, E.R. Dickson, A revised natural history Fevery, T. Mueller, O. Chazouilleres, K. Schulze, K.N. Lazaridis, S. Almer, S.P.
model for primary sclerosing cholangitis, Mayo Clin. Proc. 75 (7) (2000) 688–694. Pereira, C. Levy, A. Mason, S. Naess, C.L. Bowlus, A. Floreani, E. Halilbasic, K.K.
[21] L. Lindström, R. Hultcrantz, K.M. Boberg, I. Friis–Liby, A. Bergquist, Association Yimam, P. Milkiewicz, U. Beuers, D.K. Huynh, A. Pares, C.N. Manser, G.N. Dalekos,
between reduced levels of alkaline phosphatase and survival times of patients with B. Eksteen, P. Invernizzi, C.P. Berg, G.I. Kirchner, C. Sarrazin, V. Zimmer, L. Fabris,
primary sclerosing cholangitis, Clin. Gastroenterol. Hepatol. 11 (7) (2013) F. Braun, M. Marzioni, B.D. Juran, K. Said, C. Rupp, K. Jokelainen, M. Benito de
841–846. Valle, F. Saffioti, A. Cheung, M. Trauner, C. Schramm, R.W. Chapman, T.H.
[22] C. Rupp, A. Rossler, E. Halibasic, P. Sauer, K.H. Weiss, K. Friedrich, A. Wannhoff, Karlsen, E. Schrumpf, C.P. Strassburg, M.P. Manns, K.D. Lindor, G.M. Hirschfield,
A. Stiehl, W. Stremmel, M. Trauner, D.N. Gotthardt, Reduction in alkaline B.E. Hansen, K.M. Boberg, P.S.C.S.G. International, Patient Age, Sex, and
phosphatase is associated with longer survival in primary sclerosing cholangitis, Inflammatory Bowel Disease Phenotype Associate With Course of Primary
independent of dominant stenosis, Aliment. Pharmacol. Ther. 40 (11-12) (2014) Sclerosing Cholangitis, Gastroenterology 152(8) (2017) 1975–1984e8.
1292–1301.

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