Disease severity prognostication in primary sclerosing cholangitis: a validation of the Anali scores and comparison with the potential functional stricture

Abstract

Objectives: Our aim was twofold. First, to validate Anali scores with and without gadolinium (ANALI_Gd and ANALI_NoGd) in primary sclerosing cholangitis (PSC) patients. Second, to compare the ANALIs prognostic ability with the recently-proposed potential functional stricture (PFS).

Materials and methods: This retrospective study included 123 patients with a mean age of 41.5 years, who underwent gadoxetic acid-enahnced MRI (GA-MRI). Five readers independently evaluated all images for calculation of ANALI_Gd and ANALI_NoGd scores based upon following criteria: intrahepatic bile duct change severity, hepatic dysmorphia, liver parenchymal heterogeneity, and portal hypertension. In addition, hepatobiliary contrast excretion into first-order bile ducts was evaluated on 20-minute hepatobiliary-phase (HBP) images to assess PFS. Inter- and intrareader agreement were calculated (Fleiss´and Cohen kappas). Kaplan-Meier curves were generated for survival analysis. ANALI_NoGd, ANALI_Gd, and PFS were correlated with clinical scores, labs and outcomes (Cox regression analysis).

Results: Inter-reader agreement was almost perfect (ϰ = 0.81) for PFS, but only moderate-(ϰ = 0.55) for binary ANALI_NoGd. For binary ANALI_Gd, the agreement was slightly better on HBP (ϰ = 0.64) than on arterial-phase (AP) (ϰ = 0.53). Univariate Cox regression showed that outcomes for decompensated cirrhosis, orthotopic liver transplantation or death significantly correlated with PFS (HR (hazard ratio) = 3.15, p < 0.001), ANALI_NoGd (HR = 6.42, p < 0.001), ANALI_GdHBP (HR = 3.66, p < 0.001) and ANALI_GdAP (HR = 3.79, p < 0.001). Multivariate analysis identified the PFS, all three ANALI scores, and Revised Mayo Risk Score as independent risk factors for outcomes (HR 3.12, p < 0.001; 6.12, p < 0.001; 3.56, p < 0.001;3.59, p < 0.001; and 4.13, p < 0.001, respectively).

Conclusion: ANALI_NoGd and GA-MRI-derived ANALI scores and PFS could noninvasively predict outcomes in PSC patients.

Clinical relevance statement: The combined use of Anali scores and the potential functional stricture (PFS), both derived from unenhanced-, and gadoxetic acid enhanced-MRI, could be applied as a diagnostic and prognostic imaging surrogate for counselling and monitoring primary sclerosing cholangitis patients.

Key points: Primary sclerosing cholangitis patients require radiological monitoring to assess disease stability and for the presence and type of complications. A contrast-enhanced MRI algorithm based on potential functional stricture and ANALI scores risk-stratified these patients. Unenhanced ANALI score had a high negative predictive value, indicating some primary sclerosing cholangitis patients can undergo non-contrast MRI surveillance.

Keywords: Cholangiopancreatography (prognosis); Cholangitis (sclerosing); Constriction (pathologic); Contrast media; Magnetic resonance imaging (functional).

Fig. 1

Flowchart Between 2007 and 2022, 8564 patients underwent a standardized 3.0 Tesla contrast-enhanced MRI of the liver. Of these, 1312 patients were excluded because they were imaged using a contrast agent other than gadoxetic acid. A diagnosis other than sclerosing cholangitis further eliminated 7016 patients. Among patients with sclerosing cholangitis, additional exclusion occurred due to: secondary sclerosing cholangitis (SSC) (70), either overlap syndrome and/or small-duct PSC (14), incomplete HBP (10), previous OLT (11), age under 18 years (3), and prior malignancy (5)

Fig. 2

No functional stricture (NFS). OLT for HD. A 36 years-old male PSC patient. Axial (a) T2- weighted images, coronal maximum intensity projection from 3D MRCP (b) and post-contrast T1- weighted images with fat suppression in arterial (c, axial) portal venous phase (d, coronal) and HBP (e, coronal and f, axial). ANALI scores with and without gadoxetic acid in the arterial and HB phases were the same for all five readers (A-E): 2 in the ANALI_GdAP, 2 in the ANALI_GdHBP, and 5 in the ANALI_NoGd. In other words, all readers graded duct dilatation ≥ 5 mm, liver dysmorphy (i.e., liver contour lobulation (⇥ in a) ± increased caudate-to-right liver lobe ratio (* in a)) as 1, portal hypertension with collateral vessels (⇥ in d) ±, splenomegaly (* in d) as 1, and heterogeneous parenchymal enhancement as 1 (⇥ in c and f). All 5 readers called no functional stricture (NFS) since contrast in the intra- and extrahepatic bile ducts on the HBP image indicates excretion (⇥ in e)

Fig. 3

No functional stricture (NFS). OLT for HD. A 55 years-old male PSC patient. Coronal maximum intensity projection from 3D MRCP (a), axial T2-weighted image (b) and post-contrast T1-weighted images with fat suppression in arterial phase (c, axial) and portal venous (d, coronal) and HB phase (e, axial and f, coronal). ANALI_GdAP, ANALI_GdHBP, and ANALI_NoGd.scores were calculated by all 5 readers. Readers A-E graded gadoxetic acid-enhanced AP images as 2, and HBP images as 2. In other words, all readers registered parenchymal enhancement heterogeneity as present in the AP (⇥ in c), as well as in the HBP (⇥ in e). But on non-contrast images, ANALI_NoGd scores were 4,4,3,3,2 for readers A, B, C, D, and E, respectively. Reader A, B and D scored the IHBD as 1 (4 mm, ⇥ in a), Reader C and E as 0 (≤ 3 mm, ⇥ in d in a). Reader A, C, and D rated the liver as deformed = 1 (⇥ in d in b), whereas readers B and E judged the liver as normal = 0. Reader E scored no signs of portal hypertension = 0, whereas, due to collateral vessels (⇥ in d), all other readers scored PH as = 1. All 5 readers called no functional stricture (NFS) since contrast excretion is seen within the intra- and extrahepatic bile ducts in the HBP (⇥ in d, f)

Fig. 4

Functional stricture (FS). OLT for HD. A 59 years-old male PSC patient. Coronal maximum intensity projection from 3D MRCP (a), Post-contrast T1-weighted images with fat suppression in arterial phase (b, axial), portal venous (c, coronal) and HB phase (d, axial and e, coronal). Also, ERCP (f, coronal) and 4-week follow-up coronal T1-VIBE HBP, after ERCP (g). Potential functional stricture (PFS) was diagnosed by all five readers due to the absent contrast excretion in the HBP ( ↑ in e). ERCP the following day confirmed a FS which was dilated (⇥ in f). Follow-up HBP shows normal excretion (⇥ in g), i.e., NFS, now. All five readers scored the ANALI_GdHBP as 2 (⇥ in d) because the parenchymal enhancement was rated as heterogeneous and liver dysmorphy was judged present (➞in b). However, for the ANALI_GdAP, readers A, C and E scored the parenchymal enhancement as heterogeneous (⇥in b), i.e., 1 while readers B and D scored the enhancement as homogeneous, i.e., 0. This means the overall ANALI_GdAP scores were 2, 1, 2, 1, 2 for readers A, B, C, D, and E, respectively. For the ANALI_NoGd, readers A, B, C, D, and E assigned scores of 3,2,5,3, and 2, respectively. For the individual parameters, IHBD were scored as 0, 0,2 [maximal duct diameter as ≥ 3 mm (⇥ in a)], 0,0, respectively. All readers felt that liver dysmorphia [enlarged caudate lobe (* in b), lobulated liver surface (➞ in b)] was present, i.e., 1. All but reader B felt that PH was present due to collateral vessels (⇥ in c)

Fig. 5

a–d Kaplan Maier curves for adverse outcome-free survival for the low- vs high-risk PSC patients based upon ANALI_NoGd, ≤ 2 and > 2 (a), ANALI_GdAP, ≤ 1 and > 1 (b), ANALI_GdHBP, ≤ 1 and > 1 (c), and PFS vs NFS (d)