Mayo Risk Score Research Articles

Primary biliary cholangitis is more severe in previous hepatitis B virus infection patients.

The aim of this study was to evaluate the association between previous hepatitis B virus (HBV) infection and the severity of primary biliary cholangitis (PBC). A total of 379 HBsAg-negative PBC patients were investigated between 2012 and 2017 in this study. Fifty-two of these patients underwent liver biopsy. The enrolled patients were divided into an anti-HBc-positive group and an anti-HBc-negative group; the patients with liver biopsy were further divided into early stage (stage I) and advanced stage (stages II, III, and IV) according to histological assessment. Liver fibrosis was also assessed by noninvasive prognosis scores including the Mayo Risk Score, the Newcastle model, the aspartate aminotransferase-to-platelet ratio index, the fibrosis index based on the four factors (FIB-4), and the albumin-bilirubin score. The difference in disease stage between the two groups was assessed by histological stage and noninvasive scores predicting fibrosis. The histology showed that more patients in the anti-HBc-positive group had advanced stage compared with anti-HBc-negative patients (P<0.05). Higher Mayo Risk Score, the Newcastle model, aminotransferase-to-platelet ratio index, and fibrosis index based on the four factors (all P<0.05) were obtained in all patients except for the albumin-bilirubin score (P=0.096). Previous HBV infection was associated with a worse histological stage and advanced fibrosis score of PBC. It appears that the previous HBV infection may have aggravated the PBC severity, potentially leading to poorer outcomes.

Loss of tolerance to gut immunity protein, glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis

Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn’s disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation. PAbs were more frequent in PSC(46.2%) compared to controls(healthy:0% and CLD:4.5%), [P < 0.001, for each]. Occurrence of anti-GP2 antibody was 30.8% (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4% (13/19) of anti-GP2 IgA antibodies were bound with secretory component, suggesting an active retro-transportation of anti-GP2 from the gut lumen to the mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9–99] months) and remained an independent predictor after adjusting for Mayo risk score(HR: 4.69 [1.05–21.04], P = 0.043). These results highlight the significance of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk stratification in PSC and considered as a potential therapeutic target.

Regulatory T cells with a defect in inhibition on co-stimulation deteriorated primary biliary cholangitis.

Regulatory T cells (Tregs) play an indispensable role in the progression of primary biliary cholangitis (PBC). Although Tregs could normalize costimulation in in vivo and in vitro models, it is obscure whether and how Tregs mediate these effects in PBC. Herein we focused on the quantitative and functional characteristics of Tregs in PBC. The number and proportion of Tregs, and the production of interleukin (IL)-10 were all significantly less in the PBC patients than in the healthy controls (HCs). In addition, compared to the HCs, the costimulatory CD86 of the circulation and liver were significantly higher in the patients with PBC. CD86 expression on CD1c+ cells negatively correlated with the proportion of Tregs. There was also a positive correlation between mayo risk score and the ratio of CD86/Treg. In vitro experiments showed that inhibition of CD86 expression on CD1c+ cells by Tregs was significantly weakened in the PBC patients. Furthermore, the autoantibodies from the PBC patients could promote CD86 expression on CD1c+ cells and transforming growth factor-β production by human hepatic stellate cells. Overall, Tregs declined in inhibition on co-stimulation expression in the presence of autoantibodies, which could be associated to PBC-related bile duct injury and fibrosis. This indicated that maintenance of balance of co-stimulation and Tregs could be beneficial for PBC.

Resolution of Jaundice in a Patient With Primary Biliary Cholangitis on Obeticholic Acid

Primary biliary cholangitis (PBC) is an autoimmune disease marked by destruction of small intralobular bile ducts. Without medical therapy, patients can develop cholestatic liver disease, cirrhosis, and even liver failure. First line therapy with ursodeoxycholic acid (UDCA) is often effective, but up to 35% of patients will experience a suboptimal response. Obeticholic acid (OCA) has been recently approved for use in patients with inadequate response to UDCA alone. In prior trials, the addition of OCA has been associated with significant improvement in alkaline phosphatase (ALP) but only minimal reduction in total bilirubin (Tbil). With this case, we present a patient with inadequate response to UDCA who demonstrated remarkable improvement with marked reduction in ALP and resolution of jaundice after the addition of OCA. A 62 year old female presented with jaundice and labs revealed elevated liver-associated enzymes (LAEs), notably ALP 912 and Tbil 3.9. PBC was diagnosed based on positive AMA and liver biopsy findings. Histology also noted stage 3 hepatic fibrosis. She was started on UDCA 500mg twice daily with initial improvement in ALP but not Tbil (Figure 1). MRCP revealed a questionable focal biliary stricture, although endoscopic stenting did not lead to biochemical improvement and no stricture was seen on subsequent imaging. Repeat liver biopsy confirmed PBC and excluded overlap of autoimmune hepatitis. Due to persistent jaundice, the patient was started on OCA 5mg daily in conjunction to her UDCA. After six months, ALP has slowly declined to 279, and other LAEs have normalized with Tbil 0.8. OCA is a novel agent farnesoid X receptor agonist and has direct anti-cholestatic and anti-fibrotic effects. The addition of OCA to UDCA is associated with a 20-25% reduction in ALP. While our patient had an expected decline in ALP, the more remarkable finding has been the complete resolution of her hyperbilirubinemia with the combination of UDCA and low dose OCA. Her Mayo risk score declined from intermediate to low risk of death (7.8 to 5.7). This unexpected clinical improvement has allowed us to continue medical management while deferring liver transplant evaluation. More long-term data are needed to determine whether OCA impacts overall and transplant-free survival in patients with PBC.

Does neutrophil-to-lymphocyte ratio predict 1-year mortality in patients with primary biliary cholangitis? Results from a retrospective study with validation cohort

ObjectivesNeutrophil-to-lymphocyte ratio (NLR) has been used to predict prognosis in various liver diseases, but its role in primary biliary cholangitis (PBC) is not clarified. We aimed to investigate the prognostic...

Elevated trimethylamine-N-oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients with normal liver function.

Trimethylamine-N-oxide (TMAO) is produced in the liver from trimethylamine, which is exclusively generated by gut bacteria. The objective of this article is to investigate the relationship between TMAO and primary sclerosing cholangitis (PSC) and its clinical characteristics. Serum TMAO was measured in 305 PSC patients, 90 ulcerative colitis patients and 99 healthy controls. In PSC patients with normal liver function (n = 197), TMAO was higher in patients reaching liver transplantation or death during follow-up than those who did not, with an optimal TMAO cut-off of 4.1 µM (AUC = 0.64, p < 0.001). PSC patients with high TMAO (>4.1 µM, n = 77) exhibited shorter transplantation-free survival than patients with low TMAO (n = 120, log-rank test: p < 0.0001). High TMAO (>4.1 µM) was associated with reduced transplantation-free survival (HR 1.87, p = 0.011), independently of the Mayo risk score (HR 1.74, p < 0.001). Overall, PSC patients demonstrated reduced TMAO values compared with ulcerative colitis and healthy controls, mainly caused by PSC patients with reduced liver function (INR > 1.2), suggesting impaired oxidation of trimethylamine to TMAO. PSC patients with and without inflammatory bowel disease had similar TMAO levels. In PSC patients with normal liver function, elevated TMAO was associated with shorter transplantation-free survival, potentially reflecting clinically relevant metabolic changes resulting from dietary interactions with the gut microbiota.

Risk factors for recurrence of primary biliary cholangitis after liver transplantation in female patients: A Japanese multicenter retrospective study.

Primary biliary cholangitis (PBC) is diagnosed mainly in female individuals, and risk factors for PBC recurrence (rPBC) after liver transplantation (LT) from cadaveric donors have been reported. We conducted a retrospective multicenter study of rPBC in female patients after living‐donor LT (LDLT). A total of 388 female patients undergoing LDLT for end‐stage PBC were enrolled, and the effects of preoperative and operative factors were evaluated. Postoperative factors were evaluated in 312 patients who survived for more than 1 year post‐LDLT. rPBC was defined as abnormal hepatic enzyme levels with typical histological findings in liver biopsies. Fifty‐eight patients (14.9%) developed rPBC with a median of 4.6 (0.8‐14.5) years post‐LT. Cox hazard analysis (P < 0.05) showed that younger recipient age (hazard ratio, 0.95; 95% confidence interval, 0.920‐0.982), shorter operative time (1.00; 0.995‐0.999), higher serum immunoglobulin M level (1.00; 1.001‐1.002), donor sex mismatch (2.45; 1.268‐4.736), human leukocyte antigen B60 (2.56; 1.336‐4.921) and DR8 (1.98; 1.134‐3.448), and initial treatment with cyclosporine A (3.14; 1.602‐6.138) were significantly associated with rPBC. The frequencies of Child‐Turcotte‐Pugh class C (0.46; 0.274‐0.775), the model of end‐stage liver disease score (0.96; 0.914‐0.998), and updated Mayo risk score (1.02; 1.005‐1.033) were significantly lower in rPBC. Posttransplantation use of steroids decreased and that of antimetabolites increased the frequency of rPBC. Conclusion: The timing of LT, recipient conditions, donor characteristics, and immunosuppressive medications may be associated with rPBC in LT recipients. (Hepatology Communications 2017;1:394–405)

Ursodeoxycholic Acid Therapy in Patients with Primary Biliary Cholangitis with Limited Liver Transplantation Availability

IntroductionThere is little information on survival rates of patients with primary biliary cholangtis (PBC) in developing countries. This is particularly true in Latin America, where the number of liver transplants performed remains extremely low for patients with advanced liver disease who fulfill criteria for liver transplantation. The goal of this study was to compare survival rate of patients with PBC in developing countries who were treated with ursodeoxycholic acid (UDCA) versus survival of patients who received other treatments (OT) without UDCA, prescribed before the UDCA era. Material and MethodsA retrospective study was performed, including records of 78 patients with PBC in the liver unit in a third level referral hospital in Mexico City. Patients were followed for five years from initial diagnosis until death related to liver disease or to the end of the study. Patients received UDCA (15 mg/kg/per day) (n = 41) or OT (n = 37) before introduction of UDCA in Mexico. ResultsResponse to treatment was higher in the group that received UDCA. In the five years of follow-up, survival rates were significantly higher in the UDCA group than in the OT group. The hazard ratio of death was higher in the OT group vs. UDCA group, HR 8.78 (95% CI, 2.52-30.61); Mayo Risk Score and gender were independently associated with the risk of death. ConclusionsThe study confirms that the use of UDCA in countries with a limited liver transplant program increases survival in comparison to other treatments used before the introduction of UDCA.

Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis

Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We aimed to identify novel protein biomarkers of disease severity and prognosis in primary sclerosing cholangitis (PSC). Using a bead-based array targeting 63 proteins, we profiled a derivation panel of Norwegian endoscopic retrograde cholangiography bile samples (55 PSC, 20 disease controls) and a Finnish validation panel (34 PSC, 10 disease controls). Selected identified proteins were measured in serum from two Norwegian PSC cohorts (n=167 [1992-2006] and n=138 [2008-2012]), inflammatory bowel disease (n=96) and healthy controls (n=100). In the bile derivation panel, the levels of 14 proteins were different between PSC patients and controls (p<0.05); all were confirmed in the validation panel. Twenty-four proteins in the bile derivation panel were significantly (p<0.05) different between PSC patients with mild compared to severe cholangiographic changes (modified Amsterdam criteria); this was replicated for 18 proteins in the validation panel. Interleukin (IL)-8, matrix metallopeptidase (MMP)9/lipocalin (LCN)2-complex, S100A8/9, S100A12 and tryptophan hydroxylase (TPH)2 in the bile were associated with both a PSC diagnosis and grade of cholangiographic changes. Stratifying PSC patients according to tertiles of serum IL-8, but not MMP9/LCN2 and S100A12, provided excellent discrimination for transplant-free survival both in the serum derivation and validation cohort. Furthermore, IL-8 was associated with transplant-free survival in multivariable analyses in both serum panels independently of age and disease duration, indicating an independent influence on PSC progression. However, the Enhanced Liver Fibrosis (ELF®) test and Mayo risk score proved to be stronger predictors of transplant-free survival. Based on assaying of biliary proteins, we have identified novel biliary and serum biomarkers as indicators of severity and prognosis in PSC. Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We have identified inflammatory proteins including calprotectin and IL-8 as important indicators of disease severity and prognosis in bile and serum from patients with primary sclerosing cholangitis.

P410 Vedolizumab is safe and effective for IBD, but has no effect on liver biochemistry in patients with concurrent PSC

Background: Blocking of lymphocyte trafficking is a potential mechanism to alter the disease course of primary sclerosing cholangitis (PSC). We studied the effect of the selective α4β7 integrin antibody, vedolizumab, on liver biochemistry and inflammatory bowel disease (IBD) activity in patients with IBD and PSC (IBD-PSC). Methods: We reviewed electronic medical records of adult patients who had an established diagnosis of IBD-PSC from five tertiary centers. We assessed baseline patient and disease characteristics and treatment exposures. The primary outcome was change in serum alkaline phosphatase at weeks 14 and 30. Secondary outcomes included changes in other liver biochemistries, the Mayo Risk Score for PSC and IBD clinical and endoscopic remission. We also performed a safety analysis for the development of adverse events including liver-related complications. Results: We identified 34 patients with IBD-PSC. Nine (26%) had a history of orthotopic liver transplant, 7 were on stable doses of ursodeoxycholic acid (UDCA) and 2 patients commenced UDCA during the study period. Median follow-up was 9 (IQR: 7–16) months; 28 (92%) had at least 6 months of clinical follow-up. Serum alkaline phosphatase activities did not significantly decrease with vedolizumab therapy (median 268 (IQR: 105–551) IU/L at baseline versus 249 (IQR: 183–634) IU/L, p=0.9899 at week 30). Of the 18 patients with an abnormal alkaline phosphatase at baseline (>120IU/L), 11 (61%) had improvement with treatment. In these patients, alkaline phosphatase trended down from 475 IU/L (IQR: 241–757) at baseline to 283 IU/L (IQR: 207–658), p=0.267 at week 30 but none of these normalized (Figure 1). Median alkaline phosphatase changes remained similar when patients exposed to UDCA were excluded. Of the 8 patients (31%) with normal alkaline phosphatase at baseline, 4 (50%) had a subsequent increase to abnormal levels by week 30, from a baseline median of 98 IU/L (IQR: 77–102) to 146 IU/L (IQR: 90–203), p=0.036 at week 30 (Figure 2). No significant changes in other liver biochemistries or the Mayo PSC Risk Score were demonstrated at week 30. 55% of Crohn's disease and 21% of ulcerative colitis patients achieved clinical remission at week 30. Seven patients (21%) ceased vedolizumab therapy; one for a deterioration in liver biochemistry thought to be a drug reaction and six for IBD primary non-response. Two patients developed ascending cholangitis but continued vedolizumab. Conclusions: Vedolizumab therapy in patients with IBD-PSC has little overall effect on liver biochemistry, but is safe and does improve IBD clinical activity. Treatment earlier in the disease course of PSC and assessment of longer-term exposure of lymphocyte trafficking blockade in IBD-PSC remains of interest.

Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease characterized by a breakdown of immune tolerance to mitochondrial and nuclear antigens, causing injury to the biliary epithelial cells. Fatigue is the commonest reported symptom in PBC and has a negative impact on patients' perceived quality of life, often through social isolation. It is unrelated to the severity of liver disease and appears unresponsive to current therapies, including ursodeoxycholic acid and transplantation. Fatigue in PBC is complex, with numerous associated peripheral and central nervous system (CNS) features. Initially, cholestasis causes degenerative CNS change affecting areas of the brain regulating autonomic dysfunction and sleep, and these changes lead directly to some manifestations of fatigue and the associated cognitive impairment. The aim of the study was to examine global cerebral blood flow with brain perfusion scintigraphy SPECT in well-defined group of PBC Caucasian patients with verbally reported fatigue. Twenty consecutive PBC female patients (median age 58.9, ranges 38-80; 4 cirrhotic) with mean duration of the disease 3.3 years, were prospectively enrolled into the study. Fatigue Impact Scale (FIS) questionnaire was administered to every patients at the moment of brain examination. Brain perfusion scintigraphy SPECT was performed after intravenous injection of 760-800 MBq of technetium99m labeled exametazime (99mTc –HMPAO). Then patients were examined using double head gamma camera system, and data were analyzed with dedicated nuclear medicine software. In analyzed cohort the median FIS score was 70.5 points (ranges 21-160), which was higher than previously reported. There were no correlation between age of patients at the SPECT/FIS examination, duration of the disease, the presence of liver cirrhosis, Mayo Risk Score, and FIS domains: Cognitive, Physical and Social, as well as with brain blood flow. However, positive correlation between Cognitive dimension of FIS measure and right frontal lobe perfusion impairment assessed with SPECT technic (p<0.05) was found. The results of this study showed that right lobe perfusion impairment might impact brain function in PBC. Cognitive dimension was stage-independent symptom in analyzed cohort, and cognitive impairment might be, in turn, associated with functional brain lesion.

Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis.

AIMTo assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients.METHODSSera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various anti-microbial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls.RESULTSA total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA pos vs neg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level.CONCLUSIONPresence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.

HOVON 104; Results of First 25 Patients from a Multicenter, Multinational, Prospective Phase II Study of Bortezomib Based Induction Treatment Followed By Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Al Amyloidosis

HOVON 104; Results of First 25 Patients from a Multicenter, Multinational, Prospective Phase II Study of Bortezomib Based Induction Treatment Followed By Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Al Amyloidosis

A Triple Blinded, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Oral Vancomycin in Primary Sclerosing Cholangitis: a Pilot Study.

Recent studies have suggested the therapeutic effect of antimicrobial agents on primary sclerosing cholangitis (PSC). Therefore, we aimed to evaluate the efficacy of oral vancomycin in patients with PSC. A triple blinded, randomized, placebo-controlled trial was performed on 29 patients (2015-2016) in the Imam Khomeini Hospital, Tehran, Iran (NCT02605213). Patients were divided into two groups by simple randomization method: placebo 11 (37.9%)/vancomycin 18 (62.1%) and were treated with oral vancomycin (125 mg, four times a day) for 12 weeks. All patients in both groups simultaneously underwent treatment with ursodeoxycholic acid (UDCA, 300 mg, three times a day) before and during the study. Patients' laboratory data and clinical symptoms were recorded at the beginning, first and third month after starting treatment, and the response to treatment was analyzed. 29 patients with a mean age of 36.27+/-10.60 years were included in the study. Primary endpoints were accomplished in the vancomycin group showing a significant decline in the mean level of PSC Mayo risk score (decrease rate 3rd month - baseline = -322.03%, p=0.026) during follow up time. Moreover, the analysis of the level of alkaline phosphatase (ALP) in the vancomycin group showed a significant decrease in the third month of treatment as compared to its level in the first month (mean difference 3rd month -1st month = -142.92, Decrease rate= -18.24%, p=0.02). Among secondary endpoints, erythrocyte sedimentation rate (p=0.005), gamma-glutamyl transpeptidase (p=0.02) and patients' symptoms including fatigue, pruritus, diarrhea and anorexia showed a significant decrease in the vancomycin group. This study demonstrated an acceptable efficacy of vancomycin in the treatment of PSC.

Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases.

Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and liver injury. We aimed to investigate whether ATX is an indicator of cholestatic liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1–60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with liver biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as a predictor of survival.

Early Peribiliary Hyperenhancement on MRI in Patients with Primary Sclerosing Cholangitis: Significance and Association with the Mayo Risk Score.

The aims of this study are to assess any relationship between peribiliary hyperenhancement on MRI in patients with primary sclerosing cholangitis (PSC) and their Mayo risk score and to assess which timing of peribiliary hyperenhancement correlates best with the Mayo risk score. In this HIPAA-compliant, IRB-approved retrospective study, 101 patients who underwent MRI for known or suspected PSC were identified. Of those, 62 patients (mean age 48 years; 40 males) were diagnosed with PSC by a hepatologist based on findings on MRI, ERCP, and/or liver biopsy, and comprise the final cohort. Data were recorded on whether peribiliary hyperenhancement was present, the post-contrast phase and the extent of involvement. The components to calculate the Mayo risk score were recorded. Statistical analysis was performed using the student T test, Fisher's exact test, and the Kaplan-Meier estimate. Of 62 patients, 41 (66.1%) patients had a low-Mayo risk score (<0), 14 (22.6%) had an intermediate-risk score (≤2 and >0), and 7 (11.3%) had a high-risk score (>2). On MRI, 29 (46.8%) patients demonstrated arterial peribiliary hyperenhancement. Both the presence and extent of peribiliary hyperenhancement showed significant associations with Mayo risk score (p<0.01). Using the combined end point of liver transplantation or death, there was a statistically significant difference in survival times between those with and those without arterial peribiliary hyperenhancement (p<0.05). The presence of arterial peribiliary hyperenhancement in patients with PSC on MRI is associated with higher Mayo risk scores and may suggest a poorer prognosis.

Evaluation of Biliary Calprotectin as a Biomarker in Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts with limited therapeutic options except liver transplantation. Reliable biomarkers to predict the disease course are unavailable, and currently employed disease activity scores such as the Mayo risk score (MRS) have limitations. The present study aims to evaluate biliary calprotectin as a marker of disease activity and prognosis in PSC.This is a monocentric retrospective observational study. Calprotectin concentrations were measured by an enzyme-linked immunosorbent assay in bile samples collected by endoscopic retrograde cholangiography from 106 PSC patients and 20 controls. Biliary calprotectin concentrations were compared between the 2 groups. In PSC patients, results were evaluated with regard to the presence of dominant bile duct stenoses, bile microbiology, MRS, survival free of liver transplantation, and necessity for bile duct interventions in the further disease course.Median (interquartile ranges) biliary calprotectin concentrations were higher in PSC patients than in controls (3646 ng/mL, 249–9748 vs 116 ng/mL, 104–655; P < 0.001). In the PSC cohort, higher biliary calprotectin concentrations were associated with the presence of microbes in bile (P = 0.02), the occurrence of dominant bile duct stenosis at any time in the disease course (P = 0.005), and the necessity for future bile duct interventions (P = 0.02). Patients with biliary calprotectin concentrations above a cut-off of 11,610 ng/mL displayed significantly shorter transplantation-free survival than those with biliary calprotectin concentrations ≤11,610 ng/mL (P < 0.001). Univariate Cox regression analysis revealed high biliary calprotectin concentration (>11,610 ng/mL) as a risk factor of shorter transplantation-free survival of PSC patients (P < 0.001) beside high plasma alkaline phosphatase (ALP) concentration (>142.5 U/L) (P = 0.006), high MRS (≥2) (P < 0.001), and nonsterility of bile (P = 0.03). Multivariate analysis identified only MRS (P = 0.002) and ALP concentration (P = 0.04) as independent risk factors.Our data strongly suggest that biliary calprotectin may be a valuable additional marker for disease activity and a predictor of outcome in PSC, so that further studies for evaluation of calprotectin in this disease are warranted.

Sa1573 Liver Stiffness (LS) Measured by Magnetic Resonance Elastography (MRE) is a Better Predictor of Hepatic Decompensation or Liver transplantation (LT) in Patients With Primary Sclerosing Cholangitis (PSC) than Model for End-Stage Liver Disease (MELD) Score or PSC Mayo Risk Score (MRS)

Sa1573 Liver Stiffness (LS) Measured by Magnetic Resonance Elastography (MRE) is a Better Predictor of Hepatic Decompensation or Liver transplantation (LT) in Patients With Primary Sclerosing Cholangitis (PSC) than Model for End-Stage Liver Disease (MELD) Score or PSC Mayo Risk Score (MRS)

Patients with large-duct primary sclerosing cholangitis and Crohn's disease have a better outcome than those with ulcerative colitis, or without IBD.

Approximately 20% of primary sclerosing cholangitis (PSC) patients with concomitant inflammatory bowel disease (IBD) have Crohn's disease (CD). To compare PSC/CD with other PSC patients. Retrospective study of 240 PSC patients diagnosed between 1975 and 2012 (median follow-up 12 years). Activity of PSC at diagnosis was assessed by liver biopsy, Mayo risk and ERC scores. Survival without liver transplantation, number of transplantations and liver-related death were endpoints. Sixty-three per cent of patients had IBD: 105 UC, 32 CD and 14 IBD unclassified (IBDu). IBD was diagnosed before PSC in 50%. The yearly development of PSC after diagnosing IBD was similar in UC, CD or IBDu. Small-duct PSC was present in 28% of PSC/CD compared to 3% of PSC/UC. Small-duct PSC had a markedly better survival than large-duct PSC: no patient developed cholangiocarcinoma or liver-related death, but colorectal cancer occurred in three patients. In large-duct PSC, a more favourable outcome was evident in patients with CD. The liver disease was less progressive: one patient underwent liver transplantation compared to 28% and liver-related deaths were absent compared to 7% in the other PSC groups. The prevalence of PSC with concomitant Crohn's disease is relatively rare, but the outcome is more benign than PSC with UC or without IBD. Approximately one-fourth has small-duct PSC. In large-duct PSC/CD, liver disease is less aggressive and the outcome is much better. The outcome of PSC patients with UC resembled that of PSC without IBD.

Impact of previous cyst-enterostomy on patients' outcome following resection of bile duct cysts.

To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts (BDC) resection. A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cyst-enterostomy (CE) were compared. Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136). This is the large series to show that previous CE is associated with poorer short- and long-term results after Todani types I and IVb BDC resection.