To provide a consensus statement and recommendations on MR imaging in primary sclerosing cholangitis (PSC).

The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) convened a multinational European panel of experts selected based on a literature review and their leadership in the field. A modified Delphi process was adopted to draft a list of statements. For each statement, the panelists indicated the level of agreement using a 5-point Likert scale, where 1 means "no agreement," 2 means "poor agreement," 3 means "slight agreement," 4 means "fair agreement," and 5 means "complete agreement." The median score for each statement was collected. The level of evidence was reported according to the Oxford Centre for Evidence-Based Medicine. Descriptive statistics were used to rate agreement levels and the consensus' internal reliability.

The 12 voting committee members were from Italy (n = 4, 33.4%), Austria (n = 2, 16.7%), Sweden (n = 1, 8.3%), France (n = 1, 8.3%), the United States (n = 1, 8.3%), Switzerland (n = 1, 8.3%), and Belgium (n = 2, 16.7%). The final questionnaire consisted of 55 statements. The agreement reached by the expert panel was complete for 23 statements (41.8%), fair for 16 (29.1%), slight for 15 (27.2%), and poor for 1 (1.9%). Statements that received complete agreement were used to structure a reporting template.

This statement paper recommends how and when to perform MRI in PSC patients. A structured reporting template has been created to improve quality care and communication among radiologists and clinicians.

Question A standard MR protocol and the most common imaging features to be reported are fundamental for the correct evaluation of primary sclerosing cholangitis (PSC) patients. Findings Twelve expert radiologists reported which are the most important imaging features and how and when to perform MR in PSC patients. Clinical relevance The identified statements reported in this paper and the structured reporting template are useful for radiologists and clinicians to help correctly manage PSC patients.

Our purpose was to evaluate the performance of MR imaging/cholangiography for ductal cholangiocarcinoma (CCA) diagnosis and to search for specific MR features of ductal CCA among primary sclerosing cholangitis (PSC) patients.

We retrospectively analyzed 31 patients from a single center, each with a diagnosis of PSC, and suspicion of ductal CCA. Ductal CCA had been suspected during multidisciplinary team meetings when high-grade biliary stenosis was associated with focal thickening of the biliary wall. Two radiologists blinded to clinical information and imaging history independently reviewed patients' MR examinations using a standardized model created for this study. Fisher's exact test and Student's t-test were used to analyze the population's characteristics. Fisher's exact test and the chi-square test were used to compare associations of categorical variables (each standard model's item) with the final diagnosis. Interobserver agreement was assessed by Cohen's κ coefficient.

Our population had a mean age of 42.7 ± 13.6 years and included 68% males. The final diagnosis was ductal CCA for 14 patients, and inflammatory stenosis for 17 patients. For diagnosing CCA, MR imaging/cholangiography exhibited a sensitivity of 43-50% and specificity of 70-76%, with low positive predictive (58-60%) and negative predictive (62-63%) values. Interobserver agreement ranged from κ = 0.04-0.75. Univariate analysis revealed no significant association between individual MR imaging/cholangiography features and CCA diagnosis.

MR imaging/cholangiography showed suboptimal performance for ductal CCA diagnosis among PSC patients and we did not find any specific feature to distinguish ductal CCA from inflammatory stenosis.

Question Diagnosing ductal cholangiocarcinoma in patients with primary sclerosing cholangitis remains challenging without known predictive MR imaging features. Findings MR imaging/cholangiography exhibited low sensitivity, specificity, and interobserver reliability for ductal cholangiocarcinoma diagnosis in primary sclerosing cholangitis and lacks reliability for distinguishing between benign and malignant strictures. Clinical relevance Diagnosing ductal cholangiocarcinoma in patients with primary sclerosing cholangitis remains challenging and our retrospective study demonstrates that MR imaging lacks reliability in distinguishing between benign and malignant high-grade strictures and did not find any specific MR feature of ductal CCA.

Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities.

Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA.

Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001).

We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.

To analyze the role of qualitative and quantitative 3 T MR imaging assessment as a non-invasive method for the evaluation of disease severity in patients with primary sclerosing cholangitis (PSC).

A series of 26 patients, with histological diagnosis of PSC undergoing 3 T MRI and hepatological evaluation, was retrospectively enrolled. All MR examinations included diffusion-weighted imaging (DWI), T2-weighted (T2w) and T1-weighted (T1w) sequences, before and after administration of Gd-EOB-DTPA with the acquisition of both dynamic and hepato-biliary phase (HBP). Qualitative analysis was performed by assessment of liver parenchyma and biliary tract changes, also including biliary excretion of gadoxetic acid on HBP. Quantitative evaluation was conducted on liver parenchyma by measurement of apparent diffusion coefficient (ADC) and relative enhancement (RE) on 3-minute delayed phase and on HBP. Results of blood tests (ALT, ALP, GGT, total and direct bilirubin, albumin, and platelets) and transient elastography-derived liver stiffness measurements (TE-LSM) were collected and correlated with qualitative and quantitative MRI findings.

Among qualitative and quantitative findings, fibrosis visual assessment and RE had the best performance in estimating disease severity, showing a statistically significant correlation with both biomarkers of cholestasis and TE-LSM. Statistical analysis also revealed a significant correlation of gadoxetic acid biliary excretion with ALT and direct bilirubin, as well as of ADC with total bilirubin.

Qualitative and quantitative 3 T MR evaluation is a promising non-invasive method for the assessment of disease severity in patients with PSC.

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

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 ANALIGd and ANALINoGd 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. ANALINoGd, ANALIGd, and PFS were correlated with clinical scores, labs and outcomes (Cox regression analysis).

Inter-reader agreement was almost perfect (ϰ = 0.81) for PFS, but only moderate-(ϰ = 0.55) for binary ANALINoGd. For binary ANALIGd, 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), ANALINoGd (HR = 6.42, p < 0.001), ANALIGdHBP (HR = 3.66, p < 0.001) and ANALIGdAP (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).

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

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.

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.

Primary sclerosing cholangitis (PSC) is a rare, chronic liver disease with no approved therapies. The ursodeoxycholic acid (UDCA) has been widely used, although there is no evidence that the use of UDCA delays the time to liver transplant or increases survival. Several candidate drugs are currently being developed. The largest group of these new agents is represented by FXR agonists, including obeticholic acid, cilofexor, and tropifexor. Other agents that target bile acid metabolism are ASTB/IBAP inhibitors and fibroblasts growth factor (FGF)19 analogues. Cholangiocytes, the epithelial bile duct cells, play a role in PSC development. Recent studies have revealed that these cells undergo a downregulation of GPBAR1 (TGR5), a bile acid receptor involved in bicarbonate secretion and immune regulation. Additional agents under evaluation are PPARs (elafibranor and seladelpar), anti-itching agents such as MAS-related G-protein-coupled receptors antagonists, and anti-fibrotic and immunosuppressive agents. Drugs targeting gut bacteria and bile acid pathways are also under investigation, given the strong link between PSC and gut microbiota.

To describe the MR features and prognosis of patients with an uncommon complication of primary sclerosing cholangitis (PSC) characterized by a spontaneous perforation of the common bile duct (CBD) resulting in a peri-biliary collection and a pseudo-cystic appearance of the CBD.

A single-center cohort of 263 patients with PSC who had at least two MRIs between 2003 and 2022 and a minimum follow-up of 1 year was retrospectively analyzed. MRI data (characteristics of CBD perforation and MR features of PSC) and clinical data were assessed. Analysis of survival without liver transplantation according to type of PSC (classical or CBD spontaneous perforation) was performed according to the Kaplan-Meier method and the curves were compared using the Log-Rank test.

A total of nine (3.4%) PSC patients (5 males) had perforation of the CBD with a median age at diagnosis of 18 years compared to 33 years for the control group (p = 0.019). The peri-biliary collections were variable in appearance (fusiform or pedunculated), with a diameter ranging from 5 to 54 mm. All nine patients showed intra- and extra-hepatic bile duct involvement, dysmorphia, and high ANALI scores. The clinical course was characterized by numerous complications in most patients, and five patients (56%) underwent liver transplantation at a median time of 5 years from diagnosis, compared to 40 patients (16%) in the control group (p = 0.02).

The spontaneous perforation of the common bile duct is an uncommon complication of primary sclerosing cholangitis that affects young patients and is associated with a poor prognosis.

This uncommon complication of primary sclerosing cholangitis with perforation of the common bile duct resulting in a peri-biliary collection and a pseudo-cystic appearance of the common bile duct is characterized by a poor prognosis in younger patients.

• Among 263 patients with primary sclerosing cholangitis (PSC), nine patients (3.6%) had an uncommon complication characterized on MRI by perforation of the common bile duct (CBD). • This perforation of the CBD was responsible in all nine cases for the formation of a peri-biliary collection, giving a pseudo-cystic appearance to the CBD. • The spontaneous perforation of the common bile duct is an uncommon complication of primary sclerosing cholangitis that affects young patients with a poor prognosis.

A prompt response to glucocorticoids is a clinical hallmark of IgG4-related disease. However, manifestations characterised by prominent tissue fibrosis on histological examination can be less responsive to glucocorticoid therapy than other types of IgG4-related disease. These manifestations include retroperitoneal fibrosis, fibrosing mediastinitis, Riedel thyroiditis, orbital pseudotumor, and hypertrophic pachymeningitis, among others. To explain this discrepancy, a preliminary distinction into proliferative and fibrotic phenotypes of IgG4-related disease has been proposed on the basis of clinical presentation, pathological features, and response to immunosuppressive therapy. Implications of this classification for patient management remain an important area of investigation. In this Series paper, we aim to dissect the pathophysiology of tissue fibrosis in IgG4-related disease and discuss how clinicians should approach the management of fibrotic manifestations of IgG4-related disease based on the most recent diagnostic and therapeutic developments.

The growing and evolving field of EUS and advanced hepatobiliary endoscopy has amplified traditional upper gastrointestinal endoscopy and unveiled novel options for remaining unsolved hepatobiliary issues, both diagnostically and therapeutically. This conceptually appealing and fascinating integration of endoscopy within the practice of hepatology is referred to as 'endo-hepatology'. Endo-hepatology focuses on the one hand on disorders of the liver parenchyma and liver vasculature and of the hepatobiliary tract on the other hand. Applications hanging under the umbrella of endohepatology involve amongst others EUS-guided liver biopsy, EUS-guided portal pressure measurement, EUS-guided portal venous blood sampling, EUS-guided coil & glue embolization of gastric varices and spontaneous portosystemic shunts as well as ERCP in the challenging context of (decompensated cirrhosis) and intraductal cholangioscopy for primary sclerosing cholangitis. Although endoscopic proficiency however does not necessarily equal in an actual straightforward end-solution for currently persisting (complex) hepatobiliary situations. Therefore, endohepatology continues to generate high-quality data to validate and standardize procedures against currently considered (best available) "golden standards" while continuing to search and trying to provide novel minimally invasive solutions for persisting hepatological stalemate situations. In the current review, we aim to critically appraise the status and potential future directions of endo-hepatology.

Imaging markers of biliary disease in primary sclerosing cholangitis (PSC) have potential for use in clinical and trial disease monitoring. Herein, we evaluate how quantitative magnetic resonance cholangiopancreatography (MRCP) metrics change over time, as per the natural history of disease.

Individuals with PSC were prospectively scanned using non-contrast MRCP. Quantitative metrics were calculated using MRCP+ post-processing software to assess duct diameters and dilated and strictured regions. Additionally, a hepatopancreatobiliary radiologist (blinded to clinical details, biochemistry and quantitative biliary metrics) reported each scan, including ductal disease assessment according to the modified Amsterdam Cholangiographic Score (MAS).

At baseline, 14 quantitative MRCP+ metrics were found to be significantly different in patients with PSC (N = 55) compared to those with primary biliary cholangitis (N = 55), autoimmune hepatitis (N = 57) and healthy controls (N = 18). In PSC specifically, baseline metrics quantifying the number of strictures and the number and length of bile ducts correlated with the MAS, transient elastography and serum ALP values (p < 0.01 for all correlations). Over a median 371-day follow-up (range: 364-462), 29 patients with PSC underwent repeat MRCP, of whom 15 exhibited quantitative changes in MRCP+ metrics. Compared to baseline, quantitative MRCP+ identified an increasing number of strictures over time (p < 0.05). Comparatively, no significant differences in biochemistry, elastography or the MAS were observed between timepoints. Quantitative MRCP+ metrics remained stable in non-PSC liver disease.

Quantitative MRCP+ identifies changes in ductal disease over time in PSC, despite stability in biochemistry, liver stiffness and radiologist-derived cholangiographic assessment (trial registration: ISRCTN39463479).

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC.

The advances of minimally invasive endoscopy-guided procedures that usually yield limited diagnostic material changed pancreaticobiliary cytopathology into one of the most challenging areas of cytopathology given the abundance of differential diagnoses to be considered when dealing with limited specimens.

We describe a few challenging examples of potential pitfalls in pancreatobiliary cytopathology evaluation collected from a busy academic hospital (tertiary) center. Case 1 illustrates the challenges in handling paucicellular specimens from pancreatic solid lesions in which differential diagnoses may include acinar cell carcinoma, neuroendocrine tumors, adenocarcinoma, or even benign pancreatic tissue, among others. Case 2 illustrates the pitfalls in evaluating limited specimens from patients with chronic pancreatitis, specially when distinguishing exuberant reactive atypia from dysplastic changes is mandatory. Case 3 illustrates pitfalls in distinguishing malignancy from reactive changes in biliary brushing specimens from patients with primary sclerosing cholangitis. Finally, cases 4 and 5 highlight the importance of including the possibility of pancreatic metastasis in the differential diagnoses of some pancreatic lesions.

Over time, there has been an increasing demand for pathologists to render diagnoses on limited specimens obtained through minimally invasive procedures which can be frequently challenging even for the most experienced professionals. In many difficult cases, salvaging additional material for a cell block can turn out to be extremely helpful given the possibility of utilizing additional ancillary tests for diagnostic confirmation.

Biliary abnormalities in children are uncommon, and the spectrum of biliary disorders is broader than in adult patients. Unlike in adults, biliary disorders in children are rarely neoplastic and are more commonly rhabdomyosarcoma rather than cholangiocarcinoma. Pediatric biliary disorders may be embryologic or congenital, such as anatomic gallbladder anomalies, anomalous pancreaticobiliary tracts, various cholestatic processes, congenital cystic lesions, or genetic conditions. They may also be benign, such as biliary filling anomalies, biliary motility disorders, and biliary inflammatory and infectious disorders. Distinguishing these entities with a single imaging modality is challenging. US is the primary imaging modality for initial evaluation of biliary abnormalities in children, due to its wide availability, lack of ionizing radiation, and low cost and because it requires no sedation. Other examinations such as MRI, CT, and nuclear medicine examinations may provide anatomic and functional information to narrow the diagnosis further. Hepatobiliary-specific contrast material with MRI can provide better assessment of biliary anatomy on delayed images than can traditional MRI contrast material. MR cholangiopancreatography (MRCP) allows visualization of the intra- and extrahepatic biliary ducts, which may not be possible with endoscopic retrograde cholangiopancreatography (ERCP). Suspected biliary atresia requires multiple modalities for diagnosis and timely treatment. Determining the type of choledochal cyst calls for a combination of initial US and MRCP. Many benign and malignant biliary masses require biopsy for definitive diagnosis. Knowledge of the imaging appearances of different pediatric biliary abnormalities is necessary for appropriate imaging workup, providing a diagnosis or differential diagnosis, and guiding appropriate management. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Cholangiocarcinoma (CCA) is a deadly complication observed in the setting of primary sclerosing cholangitis (PSC). When symptoms develop and CCA is diagnosed, it is usually at an advanced stage. Median survival is less than 12 months. Early identification of CCA leads to improved outcomes. Although diagnostic tests have excellent specificity, they are plagued by low sensitivity. No surveillance strategies have been widely agreed upon, but most societies recommend measurement of serum carbohydrate antigen 19-9 and MRCP every 6 to 12 months in patients with PSC. Advances in understanding of the genetic factors that lead to CCA are awaited.

Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy.

Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO).

The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells.

Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.

Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by inflammation and fibrosis of intra- and/or extrahepatic bile ducts leading to the formation of multifocal strictures alternated to bile duct dilatations. The diagnosis of the most common subtype of the disease, the large duct PSC, is based on the presence of elevation of cholestatic indices, the association of typical cholangiographic findings assessed by magnetic resonance cholangiography and the exclusion of causes of secondary sclerosing cholangitis. Liver biopsy is not routinely applied for the diagnosis of large duct PSC but is mandatory in the case of suspicion of small duct PSC or overlap with autoimmune hepatitis.

PSC strictures are routinely diagnosed on T2-MRCP as dominant- (DS) or high-grade stricture (HGS). However, high inter-observer variability limits their utility. We introduce the "potential functional stricture" (PFS) on T1-weighted hepatobiliary-phase images of gadoxetic acid-enhanced MR cholangiography (T1-MRC) to assess inter-reader agreement on diagnosis, location, and prognostic value of PFS on T1-MRC vs. DS or HGS on T2-MRCP in PSC patients, using ERCP as the gold standard.

Six blinded readers independently reviewed 129 MRIs to diagnose and locate stricture, if present. DS/HGS was determined on T2-MRCP. On T1-MRC, PFS was diagnosed if no GA excretion was seen in the CBD, hilum or distal RHD, or LHD. If excretion was normal, "no functional stricture" (NFS) was diagnosed. T1-MRC diagnoses (NFS = 87; PFS = 42) were correlated with ERCP, clinical scores, labs, splenic volume, and clinical events. Statistical analyses included Kaplan-Meier curves and Cox regression.

Interobserver agreement was almost perfect for NFS vs. PFS diagnosis, but fair to moderate for DS and HGS. Forty-four ERCPs in 129 patients (34.1%) were performed, 39 in PFS (92.9%), and, due to clinical suspicion, five in NFS (5.7%) patients. PFS and NFS diagnoses had 100% PPV and 100% NPV, respectively. Labs and clinical scores were significantly worse for PFS vs. NFS. PFS patients underwent more diagnostic and therapeutic ERCPs, experienced more clinical events, and reached significantly more endpoints (p < 0.001) than those with NFS. Multivariate analysis identified PFS as an independent risk factor for liver-related events.

T1-MRC was superior to T2-MRCP for stricture diagnosis, stricture location, and prognostication.

Because half of PSC patients will develop clinically-relevant strictures over the course of the disease, earlier more confident diagnosis and correct localization of functional stricture on gadoxetic acid-enhanced MRI may optimize management and improve prognostication.

• There is no consensus regarding biliary stricture imaging features in PSC that have clinical relevance. • Twenty-minute T1-weighted MRC images correctly classified PSC patients with potential (PFS) vs with no functional stricture (NFS). • T1-MRC diagnoses may reduce the burden of diagnostic ERCPs.

Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with liver transplantation (LT) as the only curative therapy. Some regions use body-weight-loss as standard-exception criteria for organ allocation but data on the impact of body composition on survival of patients with PSC is scarce.

Abdominal MRI of PSC patients were quantitatively analyzed for intramuscular fat fraction (IMFF) as surrogate of myosteatosis. Clinical and laboratory data were retrieved from patient records. Primary outcome was transplant-free survival (TFS).

116 PSC patients were included. Median age was 38 (18-71) years with 74 (64%) male patients. 15 (13%) patients had significant weigh loss. IMFF was significantly associated with survival. Multivariate regression analysis showed IMFF ≥ 15% as independent predictor for TFS (p = 0.032, HR 3.215 CI 1.104-9.366), but not significant weight loss (p = 0.618).

IMFF is independently associated with TFS in patients with PSC and may identify patients with more urgent need for LT. NCT03584204.

Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC), accounting for 2-8% of cases and being the leading cause of death in these patients. The majority of PSC-associated CCAs (PSC-CCA) develop within the first few years after PSC diagnosis. Older age and male sex, as well as concomitant inflammatory bowel disease (IBD) or high-grade biliary stenosis, are some of the most relevant risk factors. A complex combination of molecular mechanisms involving inflammatory pathways, direct cytopathic damage, and epigenetic and genetic alterations are involved in cholangiocytes carcinogenesis. The insidious clinical presentation makes early detection difficult, and the integration of biochemical, radiological, and histological features does not always lead to a definitive diagnosis of PSC-CCA. Surveillance is mandatory, but current guideline strategies failed to improve early detection and consequently a higher patient survival rate. MicroRNAs (miRNAs), gene methylation, proteomic and metabolomic profile, and extracellular vesicle components are some of the novel biomarkers recently applied in PSC-CCA detection with promising results. The integration of these new molecular approaches in PSC diagnosis and monitoring could contribute to new diagnostic and surveillance strategies.

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines' Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.

Primary sclerosing cholangitis (PSC) is a chronic and progressive immune-mediated cholangiopathy causing biliary tree inflammation and scarring, leading to liver cirrhosis and end-stage liver disease. Diagnosis of PSC is challenging due to its nonspecific symptoms and overlap with other liver diseases. Despite the rising incidence of PSC, there is no proven medical therapy that can alter the natural history of the disease. While liver transplantation (LT) is the most effective approach for managing advanced liver disease caused by PSC, post-transplantation recurrence of PSC remains a challenge. Therefore, ongoing research aims to develop better therapies for PSC, and continued efforts are necessary to improve outcomes for patients with PSC. This article provides an overview of PSC's pathogenesis, clinical presentation, and management options, including LT trends and future aspects. It also highlights the need for improved therapeutic options and ethical considerations in providing equitable access to LT for patients with PSC. Additionally, the impact of liver transplant on the quality of life and psychological outcomes of patients with PSC is discussed. Ongoing research into PSC's pathogenesis and post-transplant recurrence is crucial for improved understanding of the disease and more effective treatment options.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibroinflammatory damage to the biliary tree, typically in the setting of inflammatory bowel disease, with an increased risk of liver failure and cholangiocarcinoma. A complex pathophysiology, heterogeneity in clinical features, and the rare nature of the disease have contributed to the lack of effective therapy to date. However, recent innovations in the characterization and prognostication of patients with PSC, in addition to new tools for medical management and emerging pharmacologic agents, give rise to the potential for meaningful progress in the next several years. This review summarizes current concepts in PSC and highlights particular areas in need of further study.

To develop, train, and validate a multiview deep convolutional neural network (DeePSC) for the automated diagnosis of primary sclerosing cholangitis (PSC) on two-dimensional MR cholangiopancreatography (MRCP) images.

This retrospective study included two-dimensional MRCP datasets of 342 patients (45 years ± 14 [SD]; 207 male patients) with confirmed diagnosis of PSC and 264 controls (51 years ± 16; 150 male patients). MRCP images were separated into 3-T (n = 361) and 1.5-T (n = 398) datasets, of which 39 samples each were randomly chosen as unseen test sets. Additionally, 37 MRCP images obtained with a 3-T MRI scanner from a different manufacturer were included for external testing. A multiview convolutional neural network was developed, specialized in simultaneously processing the seven images taken at different rotational angles per MRCP examination. The final model, DeePSC, derived its classification per patient from the instance expressing the highest confidence in an ensemble of 20 individually trained multiview convolutional neural networks. Predictive performance on both test sets was compared with that of four licensed radiologists using the Welch t test.

DeePSC achieved an accuracy of 80.5% ± 1.3 (sensitivity, 80.0% ± 1.9; specificity, 81.1% ± 2.7) on the 3-T and 82.6% ± 3.0 (sensitivity, 83.6% ± 1.8; specificity, 80.0% ± 8.9) on the 1.5-T test set and scored even higher on the external test set (accuracy, 92.4% ± 1.1; sensitivity, 100.0% ± 0.0; specificity, 83.5% ± 2.4). DeePSC outperformed radiologists in average prediction accuracy by 5.5 (P = .34, 3 T) and 10.1 (P = .13, 1.5 T) percentage points.

Automated classification of PSC-compatible findings based on two-dimensional MRCP was achievable and demonstrated high accuracy on internal and external test sets.Keywords: Neural Networks, Deep Learning, Liver Disease, MRI, Primary Sclerosing Cholangitis, MR Cholangiopancreatography Supplemental material is available for this article. © RSNA, 2023.

Gallbladder enlargement is common in patients with primary sclerosing cholangitis (PSC). The gallbladder may confer hepatoprotection against bile acid overload, through the sequestration and cholecystohepatic shunt of bile acids. The aim of this study was to assess the potential impact of the gallbladder on disease features and bile acid homeostasis in PSC.

Patients with PSC from a single tertiary center who underwent liver MRI with three-dimensional cholangiography and concomitant analyses of serum bile acids were included. Gallbladder volume was measured by MRI and a cut-off of 50 ml was used to define gallbladder enlargement. Bile acid profiles and PSC severity, as assessed by blood tests and MRI features, were compared among patients according to gallbladder size (enlarged vs. normal-sized) or presence (removed vs. conserved). The impact of cholecystectomy was also assessed in the Abcb4 knockout mouse model of PSC.

Sixty-one patients with PSC, all treated with ursodeoxycholic acid (UDCA), were included. The gallbladder was enlarged in 30 patients, whereas 11 patients had been previously cholecystectomized. Patients with enlarged gallbladders had significantly lower alkaline phosphatase, a lower tauro-vs. glycoconjugate ratio and a higher UDCA vs. total bile acid ratio compared to those with normal-sized gallbladders. In addition, gallbladder volume negatively correlated with the hydrophobicity index of bile acids. Cholecystectomized patients displayed significantly higher aspartate aminotransferase and more severe bile duct strictures and dilatations compared to those with conserved gallbladder. In the Abcb4 knockout mice, cholecystectomy caused an increase in hepatic bile acid content and in circulating secondary bile acids, and an aggravation in cholangitis, inflammation and liver fibrosis.

Altogether, our findings indicate that the gallbladder fulfills protective functions in PSC.

In patients with primary sclerosing cholangitis (PSC), gallbladder status impacts on bile acid homeostasis and disease features. We found evidence of lessened bile acid toxicity in patients with PSC and enlarged gallbladders and of increased disease severity in those who were previously cholecystectomized. In the Abcb4 knockout mouse model of PSC, cholecystectomy causes an aggravation of cholangitis and liver fibrosis. Overall, our results suggest that the gallbladder plays a protective role in PSC.

Progress of cholangitis to cholangiosepsis is a frequent observation in patients with secondary sclerosing cholangitis in critically ill patients (SSC-CIP). Adequate biliary drainage may reduce episodes of cholangiosepsis and therefore stabilize liver function and improve survival. The primary objective of the BISCIT study is to demonstrate that scheduled biliary interventions will reduce incidence of cholangiosepsis, liver transplantation, or death in patients with SSC-CIP.

A total of 104 patients will be randomized at ten study sites. Patients with SSC-CIP, confirmed by endoscopic retrograde cholangiography (ERC), will be randomized 1:1 either in the intervention group which will be treated with scheduled biliary interventions (i.e., therapeutic ERC) every 8 weeks for 6 months or in the control group which will receive standard of care. The randomization will be stratified by center. The composite primary efficacy endpoint is defined as (1) occurrence of death, (2) necessity of liver transplantation, or (3) occurrence of cholangiosepsis within 6 months following randomization.

Prospective evaluation of endoscopic treatment procedures is urgently needed to establish an evidence-based therapeutic treatment algorithm in SSC-CIP. A positive trial result could change the current standard of care for patients with SSC-CIP. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications.

The trial was registered at ClinicalTrials.gov (NCT05396755, date of registration: May 31, 2022, last update: May 31, 2022).

The evidence for hepatobiliary tumour surveillance in patients with primary sclerosing cholangitis (PSC) is scarce. In this study, we aimed to prospectively evaluate cholangiocarcinoma (CCA) surveillance with yearly MRI with cholangiopancreatography (MRI/MRCP) in a nationwide cohort.

In total, 512 patients with PSC from 11 Swedish hospitals were recruited. The study protocol included yearly clinical follow-ups, liver function tests and contrast-enhanced MRI/MRCP and carbohydrate antigen (CA) 19-9. Patients with severe/progressive bile duct changes on MRI/MRCP were further investigated with endoscopic retrograde cholangiopancreatography. Patients were followed for 5 years or until a diagnosis of CCA, liver transplantation (LT) and/or death. Risk factors associated with CCA were analysed with Cox regression.

Eleven patients (2%) were diagnosed with CCA, and two (0.5%) with high-grade bile duct dysplasia. Severe/progressive bile duct changes on MRI/MRCP were detected in 122 patients (24%), of whom 10% had an underlying malignancy. The primary indication for LT (n = 54) was biliary dysplasia in nine patients (17%) and end-stage liver disease in 45 patients (83%), of whom three patients (7%) had unexpected malignancy in the explants. The median survival for patients with CCA was 13 months (3-22 months). Time to diagnosis of high-grade dysplasia and/or hepatobiliary malignancy was significantly associated with severe/progressive bile duct changes on MRI/MRCP (hazard ratio 10.50; 95% CI 2.49-44.31) and increased levels of CA19-9 (hazard ratio 1.00; 95% CI 1.00-1.01).

In an unselected cohort of patients with PSC, yearly CA19-9 and MRI/MRCP surveillance followed by ERCP was ineffective in detecting cancer early enough to support long-term survival. Given the low occurrence of CCA, studies on individualised strategies for follow-up and improved diagnostic methods for PSC-related CCA are warranted.

A prospective nationwide 5-year study was conducted to evaluate yearly cholangiocarcinoma surveillance using MRI and CA19-9 in patients with primary sclerosing cholangitis. Only 2% of the patients were diagnosed with cholangiocarcinoma during follow-up and their prognosis remained poor despite surveillance. This surveillance strategy failed to detect cancer early enough to support long-term survival. Therefore, individualised strategies and improved diagnostic methods will be required to improve the early detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.

Magnetic resonance cholangiopancreatography (MRCP) has become the reference examination for the exploration of the biliary tract and has replaced endoscopic cholangiography for the analysis of the biliary tract because of its equivalent performance and its noninvasive character.

Based on the International Primary Sclerosing Cholangitis (PSC) Study Group recommendations for MR imaging in PSC, two protocols can be distinguished for the imaging of biliary tract: a basic protocol and a more complete protocol. It is essential to know the main pitfalls in order not to wrongly describe biliary anomalies. In addition to the excellent performance of MR imaging with MRCP in analyzing the anatomy and the anomalies of the biliary tree, complementary techniques have recently been developed. Several MR prognostic factors have been described. New hepato-specific contrast agents are now available for assessment of the general and segmental liver function. MR Elastography and Diffusion-weighted MR sequences are accurate to evaluate the degree of hepatic fibrosis. Finally, images obtained in MRCP can be postprocessed by a software that will analyze and model the biliary tree in order to quantitatively evaluate the biliary system.

Magnetic resonance imaging with its recent developments becomes by now an essential tool for the evaluation of biliary diseases.

Early and differential diagnosis of perihilar cholangiocarcinoma (PHCCA) is highly challenging. This study aimed to evaluate whether volatile organic compounds (VOCs) in bile samples could be emerging diagnostic biomarkers for PHCCA. We collected 200 bile samples from patients with PHCCA and benign biliary diseases (BBD), including a 140-patient training cohort and an 60-patient test cohort. Gas chromatography-ion mobility spectrometry (GC-IMS) was used for VOCs detection. The predictive models were constructed using machine learning algorithms. Our analysis detected 19 VOC substances using GC-IMS in the bile samples and resulted in the identification of three new VOCs, 2-methoxyfuran, propyl isovalerate, and diethyl malonate that were found in bile. Unsupervised hierarchical clustering analysis supported that VOCs detected in the bile could distinguish PHCCA from BBD. Twelve VOCs defined according to 32 signal peaks had significant statistical significance between BBD and PHCCA, including four up-regulated VOCs in PHCCA, such as 2-ethyl-1-hexanol, propyl isovalerate, cyclohexanone, and acetophenone, while the rest eight VOCs were down-regulated. ROC curve analysis revealed that machine learning models based on VOCs could help diagnosing PHCCA. Among them, SVM provided the highest AUC of 0·966, with a sensitivity and specificity of 93·1% and 100%, respectively. The diagnostic model based on different VOC spectra could be a feasible method for the differential diagnosis of PHCCA.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor, with a median survival of only 13 months. Surgical resection remains the only curative therapy; however, at first detection, only one-third of patients are at an early enough stage for this approach to be effective, thus rendering early diagnosis as an efficient approach to improving survival. Therefore, the identification of higher-risk patients, whose risk is correlated with genetic and pre-cancerous conditions, and the employment of non-invasive-screening modalities would be appropriate. For several at-risk patients, such as those suffering from primary sclerosing cholangitis or fibropolycystic liver disease, the use of periodic (6-12 months) imaging of the liver by ultrasound (US), magnetic Resonance Imaging (MRI)/cholangiopancreatography (MRCP), or computed tomography (CT) in association with serum CA19-9 measurement has been proposed. For liver cirrhosis patients, it has been proposed that at-risk iCCA patients are monitored in a similar fashion to at-risk HCC patients. The possibility of using Artificial Intelligence models to evaluate higher-risk patients could favor the diagnosis of these entities, although more data are needed to support the practical utility of these applications in the field of screening. For these reasons, it would be appropriate to develop screening programs in the research protocols setting. In fact, the success of these programs reauires patient compliance and multidisciplinary cooperation.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary ductal inflammation and fibrosis causing both intrahepatic and extrahepatic biliary strictures and dilatation. There is currently no effective medical treatment and the disease leads to cirrhosis and liver failure, with patients often requiring liver transplantation in end-stage disease. Liver fibrosis is one of the most important factors in determining patient outcome in PSC, and the diagnosis and monitoring of fibrosis are vital to patient care. MRI with magnetic resonance cholangiopancreatography is the non-invasive imaging modality of choice in PSC and is useful for the evaluation of parenchymal and biliary changes. Biliary ductal abnormalities, however, cannot always predict the presence of liver fibrosis and alternative means are needed. MR Elastography (MRE) is the most accurate non-invasive method for assessing liver fibrosis and is particularly helpful in PSC due to unique hepatic manifestations. Like other non-invasive modalities, MRE measures liver stiffness as an indirect method for assessing fibrosis. Given the ability of MRE to assess liver fibrosis and the importance of fibrosis in PSC patients, MRE can reliably predict patient outcome. In this pictorial review, we will review MR findings of PSC, with an emphasis on MRE, and demonstrate scenarios where MRE is particularly helpful in evaluating PSC patients.

Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.

We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.

A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.

Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.