Introduction: EASL guidelines of PBC advocate selection of patients in needs for second-line therapies based on the UDCA response. This means that patients in greatest need of second-line therapy must wait, at least, 12 months to start it. An alternative, untested approach is to treat high-risk patients with combination therapy from the outset. The aim of this study was develop a predictive model of UDCA response that will enable baseline selection of patients at high-risk of inadequate response.

Linked ContentThis article is linked to West et al papers. To view this article visit https://doi.org/10.1111/apt.13961.

Background and aims: The accurate identification of patients with adverse long-term outcome is of key importance in primary biliary cholangitis (PBC), particularly with the advent of novel therapies. Current prognostic tools are based on Cox models that make the assumption of proportional hazards, i.e. the hazard ratio of each variable remains constant over time. In PBC, however, this assumption may be unreliable for long-term prediction. Detecting and modeling time-dependent effects may improve accuracy compared with time-fixed (time-independent) models. The aim of this study was to identify time-dependent variables in PBC that might improve the accuracy of long-term prognostication by using data from the UK-PBC Research Cohort.

BACKGROUND:Age at presentation with primary biliary cholangitis (PBC) is associated with differential response to ursodeoxycholic acid (UDCA) therapy. Younger-presenting patients are less likely to respond to treatment and more likely to need transplant or die from the disease. PBC has a complex impact on quality of life (QoL), with systemic symptoms often having significant impact. AIM:To explain the impact of age at presentation on perceived QoL and the inter-related symptoms which impact upon it. METHODS:Using the UK-PBC cohort, symptoms were assessed using the PBC-40 and other validated tools. Data were available on 2055 patients. RESULTS:Of the 1990 patients reporting a global PBC-QoL score, 66% reported good/neutral scores and 34% reported poor scores. Each 10-year increase in age at presentation was associated with a 14% decrease in risk of poor perceived QoL (OR = 0.86, 95% CI: 0.75-0.98, P < 0.05). All symptom domains were similarly age-associated (P < 0.01). Social dysfunction was the symptom factor with the greatest impact on QoL. Median (interquartile range) PBC-40 social scores for patients with good perceived QoL were 18 (14-23) compared with 34 (29-39) for those with poor QoL. CONCLUSION:The majority of patients with primary biliary cholangitis do not feel their QoL is impaired, although impairment is reported by a sizeable minority. Age at presentation is associated with impact on perceived QoL and the symptoms impairing it, with younger patients being more affected. Social dysfunction makes the greatest contribution to QoL impairment, and it should be targeted in trials aimed at improving life quality.

Introduction: Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). However, existing definitions do not take the stage of the liver disease into account and dichotomize UDCA response and long-term risk whereas both are a continuum. We analyzed the UK-PBC Research Cohort to develop a risk score that includes markers of disease stage, as well as post-treatment liver biochemistries modeled as continuous variables.

G. Mells, M. Carbone, G. Pells, J. Newton, A. Bathgate, A. Burroughs, M. Heneghan, J. Neuberger, D. Day, S. Ducker, R. Sandford, G. Alexander, D. Jones, The UK-PBC Consortium. Academic Department of Medical Genetics, Cambridge University, Department of Hepatology, Cambridge University Hospitals, Cambridge, Institute of Cellular Medicine, NIHR Biomedical Research Centre in Ageing and Chronic Disease, Newcastle University, Newcastle-upon-Tyne, Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, Hepatology Dept, Royal Free Campus, University College London, Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, The Liver Unit, Queen Elizabeth Hospital, Birmingham, UK E-mail: greta.pells@ncl.ac.uk

BACKGROUND & AIMS:Liver transplantation improves survival in end-stage primary biliary cirrhosis (PBC), but the benefit for systemic symptoms including fatigue is less clear. The aim of this study was to utilise the comprehensive UK-PBC Research Cohort, including 380 post-transplant patients and 2300 non-transplanted patients, to answer key questions regarding transplantation for PBC. METHODS:Cross-sectional study of post-transplant PBC patients and case-matched non-transplanted patients. Detailed clinical information was collected, together with patient systemic symptom impact data using validated assessment tools. RESULTS:Over 25% of patients in the transplant cohort were grafted within 2 years of PBC diagnosis suggesting advanced disease at presentation. Transplanted patients were significantly younger at presentation than non-transplanted (mean 7 years) and >35% of all patients in the UK-PBC cohort who presented under 50 years had already undergone liver transplantation at the study censor point (>50% were treatment failures (post-transplant or unresponsive to UDCA)). Systemic symptom severity (fatigue and cognitive symptoms) was identical in female post-transplant patients and matched non-transplanted controls and unrelated to disease recurrence or immunosuppression type. In males, symptoms were worse in transplanted than in non-transplanted patients. CONCLUSIONS:Age at presentation is a major risk factor for progression to transplant (as well as UDCA non-response) in PBC. Although both confirmatory longitudinal studies, and studies utilising objective as well as subjective measures of function, are needed if we are to address the question definitively, we found no evidence of improved systemic symptoms after liver transplantation in PBC and patients should be advised accordingly. Consideration needs to be given to enhancing rehabilitation approaches to improve function and life quality after liver transplant for PBC.

Introduction ERCP is a safe and highly effective solution to many pancreaticobiliary problems. However, surgical options also exist. After a challenging first ERCP, it can be unclear whether surgery or repeat ERCP is preferred. The aim of this study was to identify predictive factors at first ERCP which inform this decision. Methods All ERCPs performed at one hospital (April 2008–March 2011) were analysed. Patients having more than one ERCP were evaluated in detail. Demographics, disease-specific and procedure-specific variables relating to ERCPs and any subsequent surgery were extracted. The primary outcome measure was a requirement for surgery after two or more ERCPs. Descriptive statistics and logistic regression were performed. Results 1729 ERCPs were done in 1270 patients, of which 317 patients had more than one ERCP. Of these, 140 patients were randomly sampled and analysed in detail. These form the denominator for this analysis. The primary diagnosis was gallstones in 62.8%, malignancy in 16.9% and stricture in 10.2%. Combinations of these or other diagnoses occurred in 17.6%. 74.5% of first ERCPs were urgent or emergent. Cannulation was attempted in 96.3% and successful in 81.5% of patients. The operator deemed the first ERCP to be successful in 40.6%. Multiple stones requiring a stent and planned revisit occurred in 15.2% and a large stone requiring lithotripsy in 9.8%. Repeat ERCP was deemed successful by the operator in 65.2% of cases. 40.2% went on to subsequent ERCP attempts. 31.1% of patients having a second or subsequent ERCP ended up having surgery (open biliary exploration, biliary bypass and other operations). On logistic regression, a primary diagnosis of gallstones was associated with likelihood of endoscopic success (OR (95% CI): 3.8 (1.2 to 12.3, p=0.027). In those patients with a primary diagnosis of gallstones, younger patients (OR 1.07 (1.01 to 1.12, p=0.012)) and those with sepsis at presentation (OR 5.3 (1.1 to 25.2, p=0.038)) were significantly more likely to require surgery. No other pattern was predictive of subsequent ERCP success after a first attempt. Conclusion From this analysis, there are no unequivocal clinical or technical factors which make either ERCP or surgery preferable following an incomplete first ERCP. Repeat ERCP should be considered in gallstone disease. In gallstone disease, younger or septic patients should be considered for early surgery if a first ERCP is not successful. This decision is not straightforward; multidisciplinary teamwork and communication between surgeon and endoscopist are essential. Competing interests None declared.

Introduction There is limited outcome data on patients undergoing liver transplantation (LT) while receiving opiate replacement therapy (ORT). In 2008 the UK transplant centres adopted consensus guidelines for the assessment and management of patients on ORT prior to LT. We report the collated UK experience of LT in patients receiving ORT. Methods All UK transplant centres submitted retrospective data, using a standardised proforma. Results 75 LT assessments were undertaken between 2001 and 2010 in patients using ORT, 36 pre and 39 post introduction of national guidelines. 51/75 (68%) were listed. Detailed information on aetiology was available for 44 patients listed. 38/44 (86%) were male, median age was 47 (32-61). Aetiology of liver disease was Hepatitis C virus (HCV) in 27/44 (61%), HCV and alcohol in 14/44 (32%) and alcohol in 3/44 (7%). 13/44 patients had hepatocellular carcinoma. Pre-2008 14/28 (50%) underwent formal substance misuse assessment prior to listing, compared to 13/14 (93%) post-2008. 42/44 patients injected (39/42 heroin) and 2/44 inhaled/smoked illicit drugs for a median duration of 15 years. The median abstinence from illicit drug use and duration of ORT were both 60 months. ORT was methadone in 40/44, buprenorphine 2/44, dihydrocodeine 1/44 and methadone combined with diamorphine (1/44). The median dose of methadone was 40 mg at assessment and 50mg after LT. 29/51 (57%) listed received LT, 12/51 (24%) died or deteriorated, 5/44 (11%) were delisted for substance misuse, 1/51 improved and was removed from the list and 4/51 remain active. Median ITU and total hospital stay was 2 and 16.5 days respectively. Overall survival after LT was 86% at 1 year, 76% at 3 years and 62% at 5 years. Details of subsequent substance misuse post LT were available for 18/29 patients: 9/18 (50%) reported illicit drug use. Return to illicit drug use after LT was not associated with reduced survival (66% vs 78%; p>0.05). Conclusion To date only a minority of patients assessed in the UK on ORT have undergone LT (29/75), however outcomes are acceptable given the indications. The introduction of guidelines has improved the rates of formal drug misuse assessment and while return to substance misuse is common, this does not adversely affect survival.

This paper reports the important results of the RESPOND-2 trial and is accompanied in the same issue by the report of the SPRINT-2 trial investigating the use of boceprevir for untreated chronic hepatitis C virus (HCV) genotype 1 infection.The RESPOND-2 trial recruited 403 patients who had either no response to interferon previously or had no circulating virus at the end of treatment but then relapsed within the first 24 weeks of stopping therapy.

Background and Aims: Chronic hepatitis B virus (HBV) is an important health problem in the UK with an estimated 180,000 to 325,000 people infected and at risk of long-term liver sequelae.We aim to establish a national database of chronic HBV patients for long-term follow-up to provide comprehensive data on natural history, clinical management and virological characteristics of chronic HBV.Methods: Adult patients with chronic HBV under active follow-up in 15 UK centres were eligible for enrolment.Demographic, clinical and laboratory data were collected.HBV DNA amplification and direct sequencing were undertaken in a subset of patients.Results: 637 individuals are currently registered in the cohort.Median age is 41 years (IQR 33-51years) and 57% are male.Predominant ethnicities are white (27%), Chinese (21%), black African (18%) and Pakistani (12%).The majority (85%; n = 557) were born outside of the UK.20% (115/569) are HBeAg positive and 80% (448/560) anti-HBe positive.HBV DNA was detected in 74%.Over a third (35%; 215/613) are currently on antiviral nucleos(t)ide analogues or interferon and 14% (77/543) had been previously.Analysis of the subset sequenced (n = 188) indicated 14%, 21%, 27%, 29%, and 8.5% to be genotypes A to E respectively, with 0.5% genotype G.Most common genotypes were A (44%) and D (47%) in whites, B (40%) and C (50%) in Chinese, D (90%) in Pakistanis, and A (23%) and E (46%) in black Africans.61% had mutations in the precore region only, associated with the inhibition of HBeAg synthesis.9% of the samples carried T1762/A1764 mutations on analysis of the basal core promoter (BCP) region.A further 8% carried both precore and BCP mutations.Of 47 samples currently on/or previously on nucleos(t)ides, 19% bore antiviral resistance mutations.Conclusions: In patients enrolled in our national HBV cohort, genotypic distribution and ethnicity data confirms immigrant populations are most at risk of HBV infection.One fifth had mutations associated with antiviral resistance demonstrating the potential utility of this database to monitor emergence of resistance in clinical practice which may differ from trial data.We aim to recruit into the cohort approximately 5,000 patients for long-term prospective follow-up.