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Treatment of primary biliary cholangitis (PBC) can improve the GLOBE score. We aimed to assess the association between changes in the GLOBE score (ΔGLOBE) and liver transplantation (LT)-free survival in patients with PBC who were treated with ursodeoxycholic acid (UDCA).Among UDCA-treated patients within the Global PBC cohort, the association between ΔGLOBE (ΔGLOBE0-1: during the first year of UDCA, ΔGLOBE1-2: during the second year) and the risk of LT or death was assessed through Cox regression analyses.Overall, 3,775 UDCA-treated patients were included; 3,424 (90.7%) were female, the median age was 54.0 (interquartile range [IQR] 45.9-62.4) years, and the median baseline GLOBE score was 0.25 (IQR -0.47 to 0.96). During a median follow-up of 7.2 (IQR 3.7-11.5) years, 730 patients reached the combined end point of LT or death. The median ΔGLOBE0-1 was -0.27 (IQR -0.56 to 0.02). Cox regression analyses, adjusted for pretreatment GLOBE score and ΔGLOBE0-12, showed that ΔGLOBE was associated with LT or death (adjusted hazard ratio 2.28, 95% confidence interval 1.81-2.87, P0.001). The interaction between baseline GLOBE score and ΔGLOBE0-1 was not statistically significant (P = 0.296). The ΔGLOBE1-2 was associated with LT or death (adjusted hazard ratio 2.19, 95% confidence interval 1.67-2.86, P0.001), independently from the baseline GLOBE score and the change in GLOBE score during the first year of UDCA.UDCA-induced changes in the GLOBE score were significantly associated with LT-free survival in patients with PBC. While the relative risk reduction of LT or death was stable, the absolute risk reduction was heavily dependent on the baseline prognosis of the patient.

INTRODUCTION: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated. RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN. DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.

Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. Methods: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983–2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10–15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. Results: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28–0.61; p

ObjectivePatients with primary biliary cholangitis (PBC) have an impaired health-related quality of life (HRQoL). Practice guidelines recommend evaluating the HRQoL in all patients with PBC. The aim of this study was to assess the reliability and validity of our Dutch translation of the PBC-40, a PBC-specific measure of the HRQoL.DesignThe PBC-40 was translated into Dutch following standardised forward–backward procedures. Participants received the Dutch PBC-40 and the RAND-36 (a validated Dutch version of the 36-Item Short Form Health Survey) through postal mail. The PBC-27 is an abridged version of the PBC-40. Internal consistency between the items within the PBC-40/PBC-27 domains was assessed by Cronbach’s alpha. In addition, score distributions were analysed on floor and ceiling effects. Construct validity was assessed by hypotheses testing using Pearson’s correlation between the PBC-40/PBC-27 domains and RAND-36 scales.Results177 patients with PBC were included. The mean age was 61.1 (SD 9.9) years and the majority of patients was female (n=164, 92.7%). From the 7080 PBC-40 items, 61 items (0.9%) were missing and 342 items (4.8%) were answered with the ‘does not apply’ option. Each PBC-40 domain had a Cronbach’s α of >0.70, with the highest in the domain fatigue (0.95). For the PBC-27, the lowest Cronbach’s α was 0.69. Floor effects were present in three domains (cognition 19.3%, itch 27.0% and social 25.0% (only for PBC-27)). No ceiling effects were observed. All domains were significantly correlated with the corresponding RAND-36 scale(s) (pConclusionOur findings demonstrate the reliability and validity of the Dutch PBC-40 and PBC-27 for the assessment of the HRQoL in patients with PBC. This PBC-specific measure can be used in Dutch-speaking patients with PBC for both research and clinical purposes.

INTRODUCTION: Comparative data on scores that predict outcome in primary biliary cholangitis (PBC) are scarce. We aimed to assess and compare the prognostic value of the Mayo Risk Score (MRS, 1989 and 1994), UK-PBC score, and GLOBE score in a large international cohort of patients with PBC. METHODS: Ursodeoxycholic acid-treated patients from 7 centers participating in the GLOBAL PBC Study Group were included. The discriminatory performance of the scores was assessed with concordance statistics at yearly intervals up to 5 years. Model for End-stage Liver Disease was included for comparison. Prediction accuracy was assessed by comparing predicted survival and actual survival in Kaplan-Meier analyses. RESULTS: A total of 1,100 ursodeoxycholic acid-treated patients with PBC were included, with a mean (SD) age of 53.6 (12.0) years, of whom 1,003 (91%) were female. During a median follow-up of 7.6 (interquartile range 4.1-11.7) years, 42 patients underwent liver transplantation, and 127 patients died. At 1 year, the concordance statistic for Model for End-stage Liver Disease was 0.68 (95% confidence interval [CI] 0.64-0.72), 0.74 (95% CI 0.67-0.80) for the UK-PBC score, 0.76 (95% CI 0.72-0.81) for the MRS (1989 and 1994), and 0.80 (95% CI 0.76-0.84) for the GLOBE score. The GLOBE score showed superior discriminatory performance, but differences were not statistically different. For all scores, discriminatory performance increased in those with bilirubin >0.6 × ULN and advanced fibrosis estimated with Fibrosis-4. The predicted (median) minus observed 5-year transplant-free survival was +0.4% and +2.5% for the MRS (1989) and GLOBE score, respectively. DISCUSSION: All prognostic scores developed for PBC (GLOBE, UK-PBC, and MRS) demonstrated comparable discriminating performance for liver transplantation or death as well as good prediction accuracy.

BACKGROUND & AIMS: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC. METHODS: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW). RESULTS: In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1-12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1-81.2) among UDCA-treated patients and 60.7% (95% CI 58.2-63.4) among untreated patients (p

BACKGROUND: The importance of primary biliary cholangitis as an indication for liver transplantation has probably been influenced by the introduction of therapies, and changes in selection criteria and disease epidemiology.AIMS: To assess the time trends in liver transplantation for primary biliary cholangitis and to evaluate the characteristics of the patient population during the past three decades.METHODS: Patients undergoing liver transplantation from 1986 to 2015 in centres reporting to the European Liver Transplantation Registry were included. We excluded combined organ transplantations and patients RESULTS: We included 112 874 patients, of whom 6029 (5.3%) had primary biliary cholangitis. After an initial increase in the first decade, the annual number of liver transplantation for primary biliary cholangitis remained stable at around 200. The proportion of liver transplantations for primary biliary cholangitis decreased from 20% in 1986 to 4% in 2015 (P < 0.001). Primary biliary cholangitis was the only indication showing a consistent proportional decrease throughout all decades. From the first to the third decade, the age at liver transplantation increased from 54 (IQR 47-59) to 56 years (IQR 48-62) and the proportion of males increased from 11% to 15% (both P < 0.001).CONCLUSIONS: We have found a proportional decrease in primary biliary cholangitis as indication for liver transplantation. However, despite treatment with ursodeoxycholic acid and improved disease awareness, the absolute annual number of liver transplantations has stabilised.

Overall survival in primary biliary cholangitis is diminished. As patients are often asymptomatic, the disease may silently progress towards cirrhosis and liver failure. Timely diagnosis and effective treatment options are of vital importance to improve the prognosis of affected patients. Ursodeoxycholic acid is the standard of care first-line therapy and is associated with a reduced risk of liver transplantation and death. Treatment with UDCA is relevant for all patients, irrespective of disease stage or biochemical response. In case of incomplete biochemical response according to internationally accepted criteria, second-line treatment should be considered to improve long-term prognosis. Ursodeoxycholic acid has been the only accepted treatment for PBC during the last decades. Recent research, however, has identified a number of new therapeutic targets and agents, including obeticholic acid, fibrates and budesonide. While these agents all qualify as potentially beneficial second-line treatment, obeticholic acid is currently the only drug specifically approved for the treatment of PBC. Although long-term follow-up studies for these agents are mostly lacking, improvement of biochemical surrogate markers of clinical outcome induced by these drugs suggests a therapeutic benefit. The authors of this review aim to provide a summary of the results of previous and current studies evaluating medical treatments, and propose a treatment strategy based on the evidence available today.

Primary biliary cholangitis (PBC) is a slowly progressive chronic cholestatic liver disease that, in a subgroup of patients, may result in liver failure or death. The definition of specific risk profiles, i.e. risk stratification, is of critical importance for the identification of these subgroups and thereby the targeting of care. Over the last few years large multicentre cohort studies have improved our knowledge regarding factors associated with progressive disease. Stratification based on biochemical response to ursodoxycholic acid provides a readily available measure to identify groups that might benefit from additional therapies to further improve prognosis. In addition, serum total bilirubin and alkaline phosphatase are now considered the most robustly validated biomarkers of long-term outcome in PBC and are used as endpoints in clinical trials. The GLOBE score and UK-PBC risk score enable us to quantify the risk of future events for the individual patient, allowing more individualized risk prediction. In this review, we discuss both established prognostic factors and newly developed tools to estimate prognosis in PBC, highlighting their strengths, limitations and applicability in clinical practice.

The GLOBAL Primary Biliary Cholangitis (PBC) Study Group and United Kingdom-PBC (UK-PBC) Consortium have demonstrated that dichotomous response criteria are not as accurate as continuous equations at predicting mortality or liver transplantation in PBC. The aim of this analysis was to assess the clinical utility of the GLOBE and UK-PBC risk scores using data from POISE, a phase 3 trial investigating obeticholic acid (OCA) in patients with PBC. Data (N = 216) at baseline and month 12 were used to calculate the GLOBE and UK-PBC risk scores to assess the projected change in risk with OCA versus placebo. Additionally, the benefit of OCA was assessed in patients not meeting the POISE primary endpoint. Both the GLOBE and UK-PBC risk scores predicted a significant reduction in long-term risk of death and liver transplantation after OCA treatment (P < 0.0001). The differences in the relative risk reduction from baseline in the 10-year event risk after 1 year for OCA 10 mg versus placebo was 26% (GLOBE) and 37% (UK-PBC). The scores also predicted a significantly decreased risk in patients treated with OCA who did not meet POISE response criteria after 1 year of treatment compared to an increased risk with placebo (P < 0.0001). Conclusion: This analysis demonstrates the use of the GLOBE and UK-PBC risk scores to assess risk reduction of a cohort treated with OCA. While validation of this risk reduction in studies with clinical outcomes is needed, this study highlights the potential use of these scores in individualizing risk prediction in PBC both in clinical practice and therapeutic trials. (Hepatology Communications 2018;2:683-692).

Linked Content This article is linked to Harms et al and Gerussi et al papers. To view these articles, visit https://doi-org.eur.idm.oclc.org/10.1111/apt.15060 and https://doi-org.eur.idm.oclc.org/10.1111/apt.15095. We would like to thank Gerussi et al1 for their interest in our study and for highlighting valid remarks and questions that our paper raises.2 Rightfully, the authors state that “non‐response” to first‐line therapy leaves patients prone to the need for liver transplantation (LT). Although—as previously proposed3—we believe the term “non‐response” should be avoided and should rather be replaced with “incomplete response” given that these patients do in fact still benefit from ursodeoxycholic acid (UDCA) treatment, we would like to stress that our in‐depth analyses in the Dutch population show that a minority of patients with primary biliary cholangitis (PBC) that are initially classified as “complete responders” after the first year of therapy, eventually also undergoes LT. This might be explained by the fact that some patients should actually be reclassified as “incomplete responders” when re‐evaluating the response status during follow‐up, as recently shown by Goet et al.4 Secondly, the authors suggest that, in addition to epidemiological changes and a reduced rate of biochemical response in males, diagnostic delay might impact the increasing proportion of males transplanted for PBC. However, it seems unlikely that diagnostic delay in males has worsened over the past decades, leaving this as an implausible explanation for our finding. Another comment was that potential under‐reporting of autoimmune variant syndrome in PBC might impact our findings. Although research on the incidence and prevalence of such variant syndromes is limited, and studies on the impact of concomitant autoimmune hepatitis on long‐term outcome are conflicting,5, 6 exploring this further could indeed improve therapeutic strategies for this subgroup of patients with PBC, with a potential reduction in LTs as a result. Overall, we agree with Gerussi et al that our study stresses the unmet need of effective second‐line therapies in PBC that reduce progression to liver failure, and the correct implementation of such drugs in clinical practice. As new potentially effective therapies including obeticholic acid and fibrates currently brighten the therapeutic horizon, we propose to renew this study after a decade or so, hopefully to find a renewed reduction in the absolute number of LTs for PBC.

ObjectiveThe clinical benefit of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has never been reported in absolute measures. The aim of this study was to assess the number needed to treat (NNT) with UDCA to prevent liver transplantation (LT) or death among patients with PBC.MethodsThe NNT was calculated based on the untreated LT-free survival and HR of UDCA with respect to LT or death as derived from inverse probability of treatment weighting-adjusted Cox proportional hazard analyses within the Global PBC Study Group database.ResultsWe included 3902 patients with a median follow-up of 7.8 (4.1–12.1) years. The overall HR of UDCA was 0.46 (95% CI 0.40 to 0.52) and the 5-year LT-free survival without UDCA was 81% (95% CI 79 to 82). The NNT to prevent one LT or death within 5 years (NNT5y) was 11 (95% CI 9 to 13). Although the HR of UDCA was similar for patients with and without cirrhosis (0.33 vs 0.31), the NNT5y was 4 (95% CI 3 to 5) and 20 (95% CI 14 to 34), respectively. Among patients with low alkaline phosphatase (ALP) (≤2× the upper limit of normal (ULN)), intermediate ALP (2–4× ULN) and high ALP (>4× ULN), the NNT5y to prevent one LT or death was 26 (95% CI 15 to 70), 11 (95% CI 8 to 17) and 5 (95% CI 4 to 8), respectively.ConclusionThe absolute clinical efficacy of UDCA with respect to LT or death varied with baseline prognostic characteristics, but was high throughout. These findings strongly emphasise the incentive to promptly initiate UDCA treatment in all patients with PBC and may improve patient compliance.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group). METHODS: We collected demographic and clinical data from 785 patients (89% female) with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results from biochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years). RESULTS: PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis 3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02). CONCLUSIONS: Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects. ispartof: GASTROENTEROLOGY vol:156 issue:1 pages:96-+ ispartof: location:United States status: published

BACKGROUND & AIMS: Patients usually receive a diagnosis of primary biliary cholangitis (PBC) at an early stage, based on biochemical analyses. We investigated the proportion of patients who progress to moderate or advanced PBC and factors associated with progression and patient survival. METHODS: We obtained data from 1615 patients (mean age, 55.4 y) with early stage PBC (based on their normal levels of albumin and bilirubin), collected at the time of initial evaluation or treatment, from the Global PBC Study Group database (comprising patients at 19 liver centers in North American and European countries). We collected data from health care evaluations on progression to moderate PBC (abnormal level of bilirubin or albumin) or advanced-stage PBC (abnormal level of both). The median follow-up time was 7.9 years. The composite end point was decompensation, hepatocellular carcinoma, liver transplantation, or death. RESULTS: Of the 1615 patients identified with early stage PBC, 904 developed moderate PBC and 201 developed advanced disease over the study period. The proportions of patients who transitioned to moderate PBC at 1, 3, and 5 years were 12.9%, 30.2%, and 45.8%. The proportions of these patients who then transitioned to advanced PBC at 1, 3, and 5 years later were 3.4%, 12.5%, and 16.0%, respectively. During the follow-up period, 236 patients had a clinical event. The proportions of patients with moderate PBC and event-free survival were 97.9%, 95.1%, and 91.5% at 1, 3, and 5 years, respectively, and the proportions of patients with advanced PBC and event-free survival were 90.6%, 71.2%, and 58.3% at 1, 3, and 5 years later, respectively. Variables associated with transition from early to moderate PBC included baseline levels of bilirubin, albumin, and alkaline phosphatase; aspartate to alanine aminotransferase ratio; platelet count; and treatment with ursodeoxycholic acid. Transitions from early to moderate PBC and from moderate to advanced PBC were associated with higher probabilities of a clinical event (time-dependent hazard ratios, 3.0; 95% CI, 2.0-4.5; and 4.6; 95% CI, 3.5-6.2). CONCLUSIONS: Approximately half of patients with early stage PBC progress to a more severe stage within 5 years. Progression is associated with an increased risk of a clinical event, so surveillance is important for patients with early stage PBC. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:18 issue:3 pages:684-+ ispartof: location:United States status: published

Objectives: In this era of near universal ursodeoxycholic acid (UDCA) treatment for primary biliary cholangitis (PBC), progression to cirrhosis still occurs in an important proportion of patients. The aim of this study was to describe the incidence of cirrhosis-associated complications in patients with PBC and assess risk factors and impact on survival. Methods: Cohorts of UDCA-treated patients from 16 European and North-American liver centers were included. We used Cox proportional hazards assumptions and Kaplan-Meier estimates. Results: During 8.1 years' median follow-up, 278 of 3,224 patients developed ascites, variceal bleeding, and/or encephalopathy (incidence rate of 9.7 cases/1,000 patient years). The overall cumulative incidence was 9.1% after 10 years of follow-up, but decreased over time to 5.8% after the year 2000. Earlier calendar year of diagnosis (P0.54 after 12 months of UDCA had a 10-year complication rate of 37.4%, as compared to 3.2% in biochemical responders with an APRI ≤0.54. The 10-year transplantation-free survival after a complication was 9% (time-dependent hazard ratio 21.5; 20.1-22.8). Prognosis after variceal bleeding has improved over time. Conclusions: In this large international cohort, up to 15% of UDCA-treated PBC patients developed major non-neoplastic, cirrhosis-associated hepatic complications within 15 years, but cumulative incidence has decreased over time. Biochemical non-response to UDCA and APRI were independent risk factors for these complications. Subsequent long-term outcome after complications is generally poor, but has improved over the past decades.

Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSC-related death and liver transplantation), 2 (liver transplantation), and 3 (liver-related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow-up was 142 months. During follow-up, 31 patients died (20 PSC-related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver-related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49-6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17-3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10-2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10-1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19-5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09-3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22-3.77). Interobserver agreement was moderate for Nakanuma stage (κ = 0.56) and substantial for Nakanuma component fibrosis (κ = 0.67), Ishak stage (κ = 0.64), and Ludwig stage (κ = 0.62). Conclusion: We confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system—incorporating features of chronic biliary disease—again showed the strongest predictive value. (Hepatology 2017;65:907-919).

In many countries, including the Netherlands, a substantial number of patients visit the Emergency Department (ED) without a referral by a general practitioner. The goal of this study was to determine the characteristics and motivations of self-referred patients (SRPs) at the ED. The secondary objective was to explore SRPs' opinion about copayments.A survey, in seven different languages was performed among SRPs from October 2011 until January 2012 at an academic ED in the Netherlands. Patients were included on 21 day-, 21 evening-, and 21 nightshifts during week and weekend days equally. Patient characteristics, motivations, complaints, diagnosis, and the opinion regarding copayments were examined.A total of 436 SRPs were included (response rate 82%). Forty-seven percent of the ED population was self-referred. SRPs were mainly male (58%), between 18 and 35 years (54%), Dutch (67%), single without children (42%), and low-educated (73%). The most commonly presented complaints were of musculoskeletal origin (35%). Expected need for additional medical care (e.g., X-rays, blood tests) was the reason to visit the ED for 28% of the SRPs. Around 30% of the SRPs were not prepared to pay for an ED visit. Fifty percent of SRPs were prepared to pay up to 25 or 50 EUR. Highly educated patients were willing to pay more than patients with a low level of education (p 0.05).SRPs (47% of the total ED population) are often young men with musculoskeletal complaints. They are convinced that additional medical tests are necessary. About 70% of the SRPs are willing to make a copayment, half of the SRPs with a maximum between 25 EUR and 50 EUR. As highly educated SRPs are prepared to pay more, introducing copayments might influence equity in health care accessibility.

Background: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), as it can delay histological progression, improve long-term outcome and is extremely safe and well tolerated. However, UDCA is not always sufficient and the prognosis of patients inadequately responding to treatment is worse compared with the general population. Reliable identification of so-called non-responders is of key importance, not only for selecting patients who could benefit from additional, second-line therapy, but also for identifying those individuals who are at low risk of developing end-stage disease and in whom UDCA mono-therapy can be safely continued. Several laboratory surrogate endpoints for the long-term response to UDCA have been proposed, including the Barcelona, Paris, Toronto and Rotterdam criteria. All these criteria have limitations and the superiority of one over the other has not been firmly established. Key Messages: Recently the Global PBC Study Group developed a new prognostic tool by studying a large, representative and multinational cohort of 4,119 UDCA-treated patients. In a random sample of 2,488 cases, a risk score - the GLOBE score - was developed, predictive of transplantation-free survival. This risk score comprises age, and bilirubin, albumin, alkaline phosphatase and platelet count obtained after 1 year therapy, and has a performance (C statistic 0.81, 95% CI 0.79-0.83) that is markedly better than that of previously proposed response criteria. Comparable performance was found in an independent validation cohort of 1,631 cases (C statistic 0.82, 95% CI 0.79-0.84). A web app will allow the easy use of the score in clinical practice.

BACKGROUND & AIMS: Approaches to risk stratification for patients with primary biliary cirrhosis (PBC) are limited, single-center based, and often dichotomous. We aimed to develop and validate a better model for determining prognoses of patients with PBC. METHODS: We performed an international, multicenter meta-analysis of 4119 patients with PBC treated with ursodeoxycholic acid at liver centers in 8 European and North American countries. Patients were randomly assigned to derivation (n = 2488 [60%]) and validation cohorts (n = 1631 [40%]). A risk score (GLOBE score) to predict transplantation-free survival was developed and validated with univariate and multivariable Cox regression analyses using clinical and biochemical variables obtained after 1 year of ursodeoxycholic acid therapy. Risk score outcomes were compared with the survival of age-, sex-, and calendar time-matched members of the general population. The prognostic ability of the GLOBE score was evaluated alongside those of the Barcelona, Paris-1, Rotterdam, Toronto, and Paris-2 criteria. RESULTS: Age (hazard ratio = 1.05; 95% confidence interval [CI]: 1.04-1.06; P 0.30 had significantly shorter times of transplant-free survival than matched healthy individuals (P

Background In many countries, including the Netherlands, a substantial number of patients visit the Emergency Department (ED) without a referral by a general practitioner. The goal of this study was to determine the characteristics and motivations of self-referred patients (SRPs) at the ED. The secondary objective was to explore SRPs’ opinion about copayments. Methods A survey, in seven different languages was performed among SRPs from October 2011 until January 2012 at an academic ED in the Netherlands. Patients were included on 21 day-, 21 evening-, and 21 nightshifts during week and weekend days equally. Patient characteristics, motivations, complaints, diagnosis, and the opinion regarding copayments were examined. Results A total of 436 SRPs were included (response rate 82%). Forty-seven percent of the ED population was self-referred. SRPs were mainly male (58%), between 18 and 35 years (54%), Dutch (67%), single without children (42%), and low-educated (73%). The most commonly presented complaints were of musculoskeletal origin (35%). Expected need for additional medical care (e.g., X-rays, blood tests) was the reason to visit the ED for 28% of the SRPs. Around 30% of the SRPs were not prepared to pay for an ED visit. Fifty percent of SRPs were prepared to pay up to 25 or 50 EUR. Highly educated patients were willing to pay more than patients with a low level of education (p Conclusions SRPs (47% of the total ED population) are often young men with musculoskeletal complaints. They are convinced that additional medical tests are necessary. About 70% of the SRPs are willing to make a copayment, half of the SRPs with a maximum between 25 EUR and 50 EUR. As highly educated SRPs are prepared to pay more, introducing copayments might influence equity in health care accessibility.

were independent variables related to ATX activity. In terms of HRQoL, serum ATX was associated with fatigue (r = 0.218; p =0.02) in PBC-40 as well as fatigue (r = 0.217; p =0.02), cognitive (r = 0.207; p =0.03) and emotional (r = 0.202; p =0.03) domains of the PBC27 questionnaire. No correlations were found with generic SF-36 domains, except for physical functioning (r = 0.204; p =0.03). Conclusions: In patients with PBC, serum ATX is not only associated with pruritus but may also be involved in impairment of further aspects of patients’ quality of life and liver dysfunction. Thus, ATX inhibitors could be of potential benefit not only in the treatment of pruritus but also other incapacitating symptoms related to chronic cholestasis.