Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.

To evaluate the association between single time-point quantitative liver and spleen volumes in patients with PSC and transplant-free survival, independent of Mayo risk score.

This HIPAA-compliant retrospective study included 165 PSC patients in a hospital. Total (T), and lobar (right [R], left [L], and caudate [C]) liver volumes and spleen volume (S) were measured. Adverse outcome was identified as being on liver transplantation list, transplantation or death (outcome 1), and transplantation or death (outcome 2). Cox-regression was performed to assess the predictive value of volumetric parameters to predict transplant-free survival with and without Mayo risk score. Stratified analysis by Mayo risk score categories was performed to assess the discriminative value of volumes in the model. Prediction models were developed dependent of Mayo score, based on patients demographics, lab values and volumetric measures for both defined outcomes. Kaplan-Meier curves were depicted for different liver and spleen volumes. P value <0.05 was considered statistically significant.

In this cohort (age 43 ± 17 years; 59 % men) 51 % of patients had adverse outcome. Cox-regression analysis demonstrated statistically significant association between values of T, L, R, C, S, L/T, and C/T and outcome 1; and also statistically significant association between values C, S, and C/T and outcome 2. Prediction models included age, INR, total bilirubin, AST, variceal bleeding, S, and C for outcome 1 and age, INR, total bilirubin, AST, variceal bleeding, and S for outcome 2.

Based on our observational study, quantitative liver and spleen volumes may be associated with transplant-free survival in patients with PSC and may have the potential for predicting the outcome but this should be validated by randomized clinical trial studies.

To compare liver stiffness measurement (LSM) with magnetic resonance elastography (MRE) and liver and spleen volumetry for prediction of disease severity and hepatic decompensation in primary sclerosing cholangitis (PSC).

This retrospective study was approved by the institutional review board. Magnetic resonance imaging (MRI) and MRE studies were reviewed, and mean LSM of entire liver, right lobe and left lobe, total liver, right lobe, left lobe, caudate lobe, and spleen volumes were calculated. Qualitative evaluation of lobar atrophy or hypertrophy and presence of macronodular regeneration (MNR) was recorded. Statistical analysis was performed to evaluate correlations between LSM, volumetry measurements, and Mayo risk score. Univariate and multivariate analyses were performed to predict hepatic decompensation.

A total of 266 patients with PSC were included in the study. Lobar stiffness measures were higher in the presence of relative lobe atrophy. Mean LSM was higher in the presence of MNR. Significant correlations were observed between mean LSM and volumetry measurements with a fair correlation between LSM and spleen volume (r_s = 0.526, p < 0.0001). Among the measurements, the best correlation was observed between mean LSM and Mayo risk score (r_s = 0.646, p < 0.0001). In the multivariate analyses, mean LSM and Mayo risk score were significantly associated with liver decompensation (hazard ratio, 1.18; 95%CI 1.02-1.36 and hazard ratio, 1.65; 95%CI 1.08-2.53, respectively).

LSM with MRE performs significantly better than liver and spleen volumes for prediction of both disease severity and hepatic decompensation.

Primary sclerosing cholangitis (PSC) has a variable, often progressive, course. Magnetic resonance cholangiography (MRC) is used in the diagnosis of PSC. Magnetic resonance risk scoring systems, called Anali without and with gadolinium, are used to predict disease progression, determined by radiologic factors. We aimed to assess the prognostic value of Anali scores in patients with PSC and validate our findings in a separate cohort.

We performed a retrospective study of patients with large-duct PSC (internal cohort, 119 patients in France; external cohort, 119 patients in Canada, Italy, and the United Kingdom). All the first-available MRC results were reviewed by 2 radiologists and the Anali scores were calculated as follows: Anali without gadolinium = (1× dilatation of intrahepatic bile ducts) + (2× dysmorphy) + (1× portal hypertension); Anali with gadolinium = (1× dysmorphy) + (1× parenchymal enhancement heterogeneity). The primary end point was survival without liver transplantation or cirrhosis decompensation. The prognostic value of Anali scores was assessed by Cox regression modeling.

During a total of 549 patient-years for the internal cohort and 497 patient-years for the external cohort, we recorded 2 and 8 liver transplantations, 4 and 3 liver-related deaths, and 26 and 25 cirrhosis decompensations, respectively. In the univariate analysis, factors associated with survival without liver transplantation or cirrhosis decompensation in the internal cohort were as follows: serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, alkaline phosphatase, albumin, and Anali scores. Anali scores without and with gadolinium identified patients' survival without liver transplantation or cirrhosis decompensation with a c-statistic of 0.89 (95% CI, 0.84-0.95) and 0.75 (95% CI, 0.64-0.87), respectively. Independent prognostic factors identified by multivariate analysis were Anali scores and bilirubinemia. The prognostic value of Anali scores was confirmed in the external cohort.

In internal and external cohorts, we found that Anali scores, determined from MRC, were associated with outcomes of patients with PSC. These scores might be used as prognostic factors.

To correlate total and lobar liver and spleen volume with disease severity in primary sclerosing cholangitis (PSC) as determined by Mayo risk score.

This HIPAA-compliant single center retrospective study included 147 PSC patients with available imaging studies (MRCP/CT) and laboratory data between January 2003 and January 2018. Total and lobar (right, left and caudate) liver volume and spleen volume were measured. ANOVA test was performed to assess the differences in volumes between low, intermediate and high-risk groups (Mayo risk score <0, >0 and <2, >2, respectively). Correlations between volumes and Mayo risk score were calculated. ROC analysis was performed to assess the accuracy of the variable with the strongest correlation to PSC severity to predict Mayo risk score. P value <0.05 was considered statistically significant.

The mean age of this cohort was 45 ± 17 years; 58% were men. Absolute volumes of left lobe, caudate and spleen and volume ratios of left lobe and caudate to total liver volume of the high-risk group were significantly higher compared to those of low and intermediate risk groups (p < 0.05). Left lobe to total liver volume ratio had the highest correlation to Mayo risk score (Pearson correlation coefficient 0.61, p < 0.05) and on ROC analysis it had 84.4% accuracy in detecting high-risk PSC.

In this single institution large cohort study, the left lobe to total liver volume ratio was the best quantifiable volumetric biomarker to correlate with severity of PSC as identified by Mayo risk score.