An atypical case of isolated immunoglobulin G4-related sclerosing cholangitis with a cholangiogram resembling primary sclerosing cholangitis.

An asymptomatic 77-year-old man with intrahepatic bile duct dilation was referred to our hospital. Cholangiography revealed alternations between strictures and dilated segments from the right and left hepatic ducts to the lower bile ducts, with findings of a pruned tree, beaded, shaggy appearance, and diverticulum-like outpouching. Histopathology revealed abundant immunoglobulin G4 (IgG4)-positive plasma cells (> 10 per high-power field) with an IgG4/IgG-positive cell ratio of 40-50%. After 2 weeks of steroid therapy, the cholangiography markedly improved. Because the cholangiographic findings resembled those of primary sclerosing cholangitis, steroid therapy proved useful in differentiating IgG4-related sclerosing cholangitis from primary sclerosing cholangitis.

Primary Sclerosing Cholangitis: Diagnostic Criteria.

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.

Interobserver agreement and prognostic value of image-based scoring systems in patients with primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that progresses to cirrhosis and liver failure. The Anali and Amsterdam scores are based upon imaging features on MRI and ERCP, respectively. AIMS: We aimed to compare the interobserver variability and performances of these scores. METHODS: Patients with PSC with at least 1 MRCP were included. Images were independently scored by 2 experts. Agreement and prognostic performance with a primary end point of hepatic decompensation was assessed. RESULTS: Fifty-nine patients were included (67.8% male, 86.4% IBD). Interobserver agreement for the Anali and Amsterdam scores were moderate (k = 0.49; 95% CI 0.35-0.64 and k = 0.43; 95% CI 0.30-0.56, respectively). Among the Anali components, dysmorphy (caudate/right lobe ratio > 0.9) had fair agreement (k = 0.37; 95% CI 0.14-0.60) and portal hypertension (k = 0.64, 95% CI 0.32-0.89) and intrahepatic dilation (k = 0.70; 95% CI 0.53-0.87) had substantial agreement. The Amsterdam extrahepatic and intrahepatic scores had fair agreement (k = 0.38; 95% CI 0.23-0.52) and moderate agreement (k = 0.50; 95% CI 0.34-0.67), respectively. Anali score (HR 5.90, 95% CI 1.64-21.21), total bilirubin (HR = 3.23; 95% Cl 1.06-9.91), and age (HR = 1.05; 95% CI 1.00-1.11) were independent predictors of hepatic decompensation. Mayo risk score and Anali score had good discriminative ability with c-statistics of 0.78 (CI 0.59-0.96) and 0.76 (CI 0.56-0.91). Anali score remained an independent predictor after adjusting for Mayo risk score. CONCLUSION: Anali score adds additional predictive value for hepatic decompensation in patients with PSC.

Secondary sclerosing cholangitis induced by systemic chemotherapy

There are multiple causes of secondary sclerosing cholangitis (SSC), including mechanical obstruction, ischemia, congenital abnormalities, cholangiopathy of the critically ill patient and rarely, chemotherapy (1,2). We present the case of a 52-year-old female with a history of left breast invasive ductal carcinoma treated with neoadjuvant chemotherapy (adriamycin, cyclophosphamide and paclitaxel), surgery and radiotherapy in March 2021. She was admitted in July 2022 due to painless jaundice and pruritus with marked serum cholestasis. Magnetic resonance cholangiopancreatography showed multiple strictures and dilatations involving the intra and extrahepatic bile ducts (Figure 1.A), without any extrinsic stenotic cause. Findings were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy (Figure 1.B). Biopsies were negative for malignancy and IgG4 disease. In addition, autoantibodies were negative and serum IgG4 levels were normal. Due to these findings and the history of recent chemotherapy, the patient was diagnosed with paclitaxel-induced sclerosing cholangitis, initiating treatment with ursodeoxycholic acid. Over the following two months, she suffered two episodes of Klebsiella Pneumoniae bacteraemia due to acute cholangitis. Dilatation and placement of plastic stents in both biliary trees were performed and prophylactic antibiotherapy was started. The patient had a poor evolution and was not candidate for liver transplantation on account of a recent neoplasia. She died six months later due to sepsis secondary to multiple hepatic abscesses. (AU)

Diagnosis of functional strictures in patients with primary sclerosing cholangitis using hepatobiliary contrast-enhanced MRI: a proof-of-concept study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: T1-MRC was superior to T2-MRCP for stricture diagnosis, stricture location, and prognostication. CLINICAL RELEVANCE STATEMENT: 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. KEY POINTS: • 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.

The role of serology, liver function tests and imaging in screening of primary sclerosing cholangitis: the HelPSCreen score.

OBJECIVES: At present, no sensitive or specific screening test exists for primary sclerosing cholangitis (PSC). PSC screening is mainly based on elevated alkaline phosphatase (ALP) in patients with inflammatory bowel disease (IBD). We aimed to produce a screening score based on laboratory tests to predict the likelihood of PSC. Moreover, we evaluated the additional roles of liver histology and magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of PSC. MATERIALS AND METHODS: The data of 385 patients who came for their first endoscopic retrograde cholangiography (ERC) to confirm PSC diagnosis were retrieved from the PSC registry of the Helsinki University Hospital. Overall, 69 patients referred for ERC with suspected PSC, in whom PSC was excluded by ERC or liver biopsy and MRCP, served as controls. We included patients' demographics and 13 laboratory test results in the analysis. Variables with significant odds ratios were selected for multivariate logistic regression, which was used to create a novel scoring system for PSC. The presence of IBD, serum perinuclear anti-neutrophil cytoplasmic antibodies, and ALP levels demonstrated the highest predictive value for PSC. A score was assigned for each statistically significant predictor. RESULTS: The optimal cut-off point for the score was ≥3, with an AUC of 0.83 (95%CI: 0.78-0.88). The addition of liver histology or MRCP findings to the score did not add a predictive value. CONCUSIONS: In conclusion, we created a novel, simple scoring system to screen the probability of PSC. The HelPSCreen-score may help to assess the disease prevalence and to target further investigations in patients suspected of PSC.

Magnetic resonance cholangiography in the diagnosis of dominant strictures in pediatric-onset primary sclerosing cholangitis.

BACKGROUND: Magnetic resonance cholangiopancreaticography (MRCP) has become the primary imaging modality in primary sclerosing cholangitis (PSC). Endoscopic retrograde cholangiopancreaticography (ERCP) is recommended when a dominant stricture (DS) of bile ducts is suspected in MRCP. However, MRCP criteria for DS are lacking. AIMS: To evaluate the diagnostic accuracy of MRCP in the diagnosis of DS in patients with pediatric-onset PSC. METHODS: ERCP and MRCP images of patients with pediatric-onset PSC (n=36) were evaluated for the presence of DS applying the diameter-based ERCP criteria. The diagnostic accuracy of MRCP in detecting DS was calculated using ERCP as the gold standard. RESULTS: The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and accuracy of MRCP for detecting DS were 62%, 89%, 5.6, 0.43, and 81%. Most common reasons for incongruent ERCP/MRCP assessment were (1) MRCP stenosis not fulfilling the diameter criteria of ERCP, resulting in false negative MRCP evaluation, and (2) lack of filling pressure in MRCP, resulting in false positive MRCP evaluation. CONCLUSION: The high positive likelihood ratio of MRCP in detecting DS suggests that MRCP is a useful tool in the follow-up of PSC. However, diameter limits of DS should probably be less strict in MRCP than in ERCP.

Secondary Sclerosing Cholangitis due to Severe COVID-19: An Emerging Disease Entity?

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to many extrapulmonary manifestations. In this case series, we report on 7 patients developing secondary sclerosing cholangitis (SSC) after severe COVID-19 with intensive care treatment. METHODS: Between March 2020 and November 2021, 544 patient cases with cholangitis treated at a German tertiary care centre were screened for SSC. Patients found to be suffering from SSC were assigned to COVID-19 group if SSC presented after a severe course of COVID-19 and to non-COVID-19 group if not. Peak liver parameters as well as intensive care treatment factors and data generated from liver elastography were compared between both groups. RESULTS: We identified 7 patients who developed SSC after a severe course of COVID-19. In the same period, 4 patients developed SSC due to other causes. Mean values of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were higher in the COVID-19 group than in the non-COVID-19 group (GGT: 2,689 U/L vs. 1,812 U/L and ALP: 1,445 U/L vs. 1,027 U/L), whereas intensive care treatment factors were comparable in both groups. Only the mean duration of mechanical ventilation was shorter in the COVID-19 group than in the non-COVID-19 group (22.1 days vs. 36.7 days). Liver elastography indicated a fast progression to liver cirrhosis with a mean liver stiffness of 17.3 kilopascals (kPa) in less than 12 weeks in the COVID-19 group. CONCLUSIONS: Our data suggest a more severe course of SSC when caused by SARS-CoV-2. Reasons for this are probably multifactorial, including a direct cytopathogenic effect of the virus.

Adult Primary Sclerosing Cholangitis (PSC) subjects have worse biliary disease at diagnosis compared to pediatric PSC subjects.

INTRODUCTION: Adult Primary Sclerosing Cholangitis (PSC) subjects have worse outcomes compared to pediatric PSC subjects. The reasons for this observation are not completely understood. METHODS: In this single-center, retrospective (2005-17) study we compared clinical information, laboratory data, and previously published MRCP-based scores between 25 pediatric (0-18 years at diagnosis) and 45 adult (19 years and above) subjects with large duct PSC at the time of diagnosis. For each subject, radiologists determined MRCP-based parameters and scores after reviewing the MRCP images. RESULTS: The median age at diagnosis for pediatric subjects was 14 years, while that of adult subjects was 39 years. At the time of diagnosis, adult subjects had a higher incidence of biliary complications like cholangitis and high-grade biliary stricture (27% vs. 6%, p = 0.003) and higher serum bilirubin (0.8 vs. 0.4 mg/dl, p = 0.01). MRCP analysis showed that adult subjects had a higher incidence of hilar lymph node enlargement (24.4% vs. 4%, p = 0.03) at diagnosis. Adult subjects had worse sum-IHD score (p = 0.003) and average-IHD score (p = 0.03). Age at diagnosis correlated with higher average-IHD (p = 0.002) and sum-IHD (p = 0.002) scores. Adult subjects had worse Anali score without contrast (p = 0.01) at diagnosis. MRCP-based extrahepatic duct parameters and scores were similar between groups. DISCUSSION: Adult PSC subjects may have higher severity of disease at diagnosis compared to pediatric subjects. Future prospective cohort studies are required to confirm this hypothesis.

Longitudinal changes in quantitative magnetic resonance imaging metrics in children and young adults with autoimmune liver disease.

PURPOSE: To assess longitudinal changes in quantitative MRI metrics in pediatric and young adult patients with autoimmune liver disease (AILD). METHODS: This prospective, IRB-approved study included 20 children and young adults (median age = 15 years) with primary sclerosing cholangitis (PSC)/autoimmune sclerosing cholangitis (ASC) and 19 (median age = 17 years) with autoimmune hepatitis (AIH). At a field strength of 1.5-T, T2*-corrected T1 mapping (cT1), 3D fast spin-echo MRCP, and 2D gradient recalled echo MR elastography (MRE) were performed at baseline, one year, and two years. cT1 and quantitative MRCP were processed using LiverMultiScan and MRCP + , respectively (Perspectum Ltd, Oxford, UK). Linear mixed models were used to assess longitudinal changes in quantitative MRI metrics. Spearman rank-order correlation was used to assess relationships between changes in quantitative MRI metrics. RESULTS: Changes in quantitative MRI metrics greater than established repeatability coefficients were measured in six (cT1) and five (MRE) patients with PSC/ASC as well as in six patients (cT1 and MRE) with AIH, although linear mixed models identified no significant changes for the subgroups as a whole. For PSC/ASC, there were positive correlations between change in liver stiffness and changes in bile duct strictures (ρ = 0.68; p = 0.005) and bile duct dilations (ρ = 0.70; p = 0.004) between baseline and Year 2. CONCLUSION: On average, there were no significant changes in quantitative MRI metrics over a two-year period in children and young adults with AILD. However, worsening cholangiopathy was associated with increasing liver stiffness by MRE in patients with PSC/ASC.

Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis.

Sclerosing cholangitis is a chronic cholestatic disease characterized by stricturing, beading, and obliterative fibrosis of the bile ducts. Sclerosing cholangitis is considered primary (PSC) if no underlying etiology is identified or secondary (SSC) if related to another identifiable cause. In this article, we will review the clinical features, pathogenesis, diagnosis, and imaging findings of PSC and SSC, with an emphasis on features that may aid in the distinction of these entities. We will also discuss various etiologies of SSC including recurrent pyogenic cholangitis, other infectious etiologies, ischemic damage, toxic insults, and immunologic, congenital, and miscellaneous causes, highlighting the unique imaging findings and clinical context of each diagnosis.

MR elastography in primary sclerosing cholangitis: a pictorial review.

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.

Impact on follow-up strategies in patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Primary sclerosing cholangitis: review for radiologists.

Primary sclerosing cholangitis is a rare chronic inflammatory disease affecting the bile ducts, which can eventually result in bile duct strictures, cholestasis and cirrhosis. Patients are often asymptomatic but may present with clinical features of cholestasis. Imaging plays an important role in the diagnosis and management. This review covers the pathophysiology, clinical features, imaging findings as well as methods of surveillance and post-transplant appearance.

Practical Guide for Radiological Diagnosis of Primary and Secondary Sclerosing Cholangitis.

Sclerosing cholangitis comprises a group of conditions that lead to chronic cholestatic disease of the bile ducts, characterized by inflammation, fibrosis, and segmental strictures of the intrahepatic and/or extrahepatic ducts, and can be classified as primary sclerosing cholangitis or secondary sclerosing cholangitis. In this review, we follow a logical step-by-step appraisal of the clinical and radiological findings of the main secondary sclerosing cholangitis groups, finally arriving at the exclusion diagnosis, which is primary sclerosing cholangitis. At the end, a practical guide is provided, aiming to facilitate the radiological approach to this complex group of diseases.

[Small duct primary sclerosing cholangitis diagnosed after fever and liver disorder: a case report].

A woman in her 10s presented to our hospital with persistent fever and liver disorder and was admitted. It was considered that her fever was due to infectious, hematological, and collagen diseases; however, these diseases were excluded. Upper and lower gastrointestinal endoscopy revealed gastritis and indicated inflammatory bowel disease involvement. Neither bile duct stricture nor bile duct wall thickening was observed in the imaging. Thus, liver biopsy was performed due to worsening liver disorder. A diagnosis of small duct primary sclerosing cholangitis was made based on the findings of edematous enlargement of the portal tracts, neutrophilic infiltration, and destruction of the interlobular bile ducts. Furthermore, liver biopsy is helpful in diagnosing unknown liver disorders, even if no abnormality in the bile duct is observed on imaging.

Algebraic topology-based machine learning using MRI predicts outcomes in primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can lead to cirrhosis and hepatic decompensation. However, predicting future outcomes in patients with PSC is challenging. Our aim was to extract magnetic resonance imaging (MRI) features that predict the development of hepatic decompensation by applying algebraic topology-based machine learning (ML). METHODS: We conducted a retrospective multicenter study among adults with large duct PSC who underwent MRI. A topological data analysis-inspired nonlinear framework was used to predict the risk of hepatic decompensation, which was motivated by algebraic topology theory-based ML. The topological representations (persistence images) were employed as input for classification to predict who developed early hepatic decompensation within one year after their baseline MRI. RESULTS: We reviewed 590 patients; 298 were excluded due to poor image quality or inadequate liver coverage, leaving 292 potentially eligible subjects, of which 169 subjects were included in the study. We trained our model using contrast-enhanced delayed phase T1-weighted images on a single center derivation cohort consisting of 54 patients (hepatic decompensation, n = 21; no hepatic decompensation, n = 33) and a multicenter independent validation cohort of 115 individuals (hepatic decompensation, n = 31; no hepatic decompensation, n = 84). When our model was applied in the independent validation cohort, it remained predictive of early hepatic decompensation (area under the receiver operating characteristic curve = 0.84). CONCLUSIONS: Algebraic topology-based ML is a methodological approach that can predict outcomes in patients with PSC and has the potential for application in other chronic liver diseases.

MR Imaging in Primary Sclerosing Cholangitis and Other Cholangitis.

Sclerosing cholangitis is characterized by irregular and ill-defined inflammation, fibrosis, and stricturing of the bile ducts and may be primary or secondary in cause. It causes progressive destruction of the biliary tree, progressive parenchymal cirrhosis, hepatic failure, and malignancy such as cholangiocarcinoma. The subtypes of sclerosing cholangitis can be broken down into primary sclerosing cholangitis (PSC), immune-mediated sclerosing cholangitis, infectious cholangitis, and ischemic cholangitis with other causes including metastatic disease and chemotherapy change. MR imaging is the gold standard test to investigate and differentiate PSC and other types of cholangitis.