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Background A distinct serum metabonomic pattern has been previously revealed to be associated with various forms of liver disease. Here, we aimed to apply mass spectrometry to obtain serum metabolomic profiles from individuals with cholangiocarcinoma and benign hepatobiliary diseases to gain an insight into pathogenesis and search for potential early-disease biomarkers. Methods Serum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer. A total of 47 serum specimens from 8 cholangiocarcinoma cases, 20 healthy controls, 8 benign disease controls (bile duct strictures) and 11 patients with hepatocellular carcinoma (as malignant disease controls) were included. Data analysis was performed using univariate and multivariate statistics. Results The serum metabolome disparities between the metabolite profiles from healthy controls and patients with hepatobiliary disease were predominantly related to changes in lipid and lipid-derived compounds (phospholipids, bile acids and steroids) and amino acid metabolites (phenylalanine). A metabolic pattern indicative of inflammatory response due to cirrhosis and cholestasis was associated with the disease groups. The abundance of phospholipid metabolites was altered in individuals with liver disease, particularly cholangiocarcinoma, but no significant difference was seen between profiles from patients with benign biliary strictures and cholangiocarcinoma. Conclusion The serum metabolome in cholangiocarcinoma exhibited changes in metabolites related to inflammation, altered energy production and phospholipid metabolism. This study serves to highlight future avenues for biomarker research in large-scale studies.

BackgroundIn 2017, roughly 540 women in Sub-Saharan Africa died every day from preventable causes related to pregnancy and childbirth. To stem this public-health crisis, the WHO recommends a standard continuity of maternal healthcare, yet most women do not receive this care. Surveys suggest that illiteracy limits the uptake of the recommended care, yet little is understood about why this is so. This gap in understanding why healthcare is not sought by illiterate women compromises the ability of public health experts and healthcare providers to provide culturally relevant policy and practice. This study consequently explores the lived experiences related to care-seeking by illiterate women of reproductive age in rural Tanzania to determine why they may not access maternal healthcare services.MethodsAn exploratory, qualitative study was conducted in four communities encompassing eight focus group discussions with 81 illiterate women, 13 in-depth interviews with illiterate women and seven key-informant interviews with members of these communities who have first-hand experience with the decisions made by women concerning maternal care. Interviews were conducted in the informant’s native language. The interviews were coded, then triangulated.ResultsTwo themes emerged from the analysis: 1) a communication gap arising from a) the women’s inability to read public-health documents provided by health facilities, and b) healthcare providers speaking a language, Swahili, that these women do not understand, and 2) a dependency by these women on family and neighbors to negotiate these barriers. Notably, these women understood of the potential benefits of maternal healthcare.ConclusionsThese women knew they should receive maternal healthcare but could neither read the public-health messaging provided by the clinics nor understand the language of the healthcare providers. More health needs of this group could be met by developing a protocol for healthcare providers to determine who is illiterate, providing translation services for those unable to speak Swahili, and graphic public health messaging that does not require literacy. A failure to address the needs of this at-risk group will likely mean that they will continue to experience barriers to obtaining maternal care with detrimental health outcomes for both mothers and newborns.

Background: In 2017, an estimated 540 women in Sub-Saharan Africa died every day from preventable causes related to pregnancy and childbirth. To stem this public-health crisis, the WHO recommends a maternal and neonatal health continuity of patient care, yet most women do not meet this recommendation. Surveys suggest that illiteracy limits uptake of the proposed maternal-newborn package, yet little is known about the association between illiteracy and healthcare seeking, particularly in rural regions of low-income countries. This knowledge gap compromises the ability of public health experts and healthcare providers to provide culturally relevant policy and practice. To begin to address this gap this study explores the experiences related to care-seeking by illiterate, pregnant women in rural Tanzania.Methods: A qualitative study was conducted in four communities encompassing eight focus group discussions with 81 illiterate women, 13 interviews with illiterate women of reproductive age and seven interviews with members of these communities perceived to have some influence on women’s decisions concerning perinatal care services. Themes were coded and their relative importance determined using frequency reports and cross-tabulations. Findings: Three key themes emerged, illiterate women (1) could not read their healthcare cards or public health messaging; (2) spoke the local language, not Swahili, the language used by healthcare providers, and (3) have endeavored to develop coping strategies to overcome these obstacles. In addition, health service providers are often unaware of who is illiterate.Recommendations: More health needs of this group could be met, in the short term, by developing a protocol for health service providers to determine who is illiterate, providing translation services for those unable to speak Swahili, and graphic public health messaging that does not require literacy. In the long term, this barrier may be addressed by ensuring that all Tanzanians receive a high-quality, formal education, supporting community health workers, and recruiting healthcare providers from rural areas. A failure of to address the needs of this at-risk group will likely mean that they will continue to experience barriers to achieving the recommended continuity of patient care with detrimental health outcomes for both mothers and newborns.

BACKGROUND While the effectiveness of Helping Babies Breathe (HBB) training in Tanzania has been reported, no published studies of Essential Care for Every Baby (ECEB) and Essential Care for Small Babies (ECSB) in this setting have been found. This study compared knowledge before and after HBB, ECEB and ECSB training in Tanzania. METHODS Training was provided to future facilitators (n=16) and learners (n=24) in Tanzania. Using standardized multiple-choice questions, knowledge was assessed pre- and post-HBB and ECEB courses for both learners and facilitators, while ECSB assessment was conducted with facilitators only. A >80% score was considered to be a pass. Paired t-tests were used for hypothesis testing. RESULTS Knowledge significantly improved for both facilitators and learners on HBB and ECEB (p

BACKGROUND Liver volume (LV) can be non-invasively determined from the analysis of computed tomography (CT) images, and in patients with acute liver injury (ALI) or failure (ALF), it can reflect the balance of structural collapse with hepatic regeneration. We examined its relation to cause of liver injury, measures of liver function and histopathological findings, and utility in prediction of complications and mortality. METHODS Two hundred and seventy-three patients with ALF/ALI admitted to a specialist intensive care unit were studied. One hundred and ninety-nine patients (73%) had non-acetaminophen (NA) aetiologies and 74 (27%) had acetaminophen-induced disease. LV and proportion of predicted LV (PLV%) were determined from admission CT imaging. RESULTS LV and PLV% showed marked variation when aetiologic groups were compared (P

Background and aims Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients with Primary Sclerosing Cholangitis (PSC). We present a validation study of NKG2D polymorphisms in CC patients without PSC. Methods Seven common Single Nucleotide Polymorphisms (SNPs) of the NKG2D gene were genotyped in 164 non-PSC related CC subjects and 257 controls with HaploView. The two SNPs that were positively identified in the previous Scandinavian study, rs11053781 and rs2617167, were included. Results The seven genotyped SNPs were not associated with risk of CC. Furthermore, haplotype analysis revealed that there was no evidence to suggest that any haplotype differs in frequency between cases and controls (P > 0.1). Conclusion The common genetic variation in NKG2D does not correlate significantly with sporadic CC risk. This is in contrast to the previous positive findings in the Scandinavian study with PSC-patients. The failure to reproduce the association may reflect an important difference between the pathogenesis of sporadic CC and that of PSC-related CC. Given that genetic susceptibility is likely to be multifaceted and complex, further validation studies that include both sporadic and PSC-related CC are required.

Background Globally, eHealth has attracted considerable attention as a means of supporting maternal and perinatal health care. This article describes best practices, gains and challenges of implementing eHealth for maternal and perinatal health care in extremely remote and rural Tanzania. Methods Teleconsultation for obstetric emergency care, audio teleconferences and online eLearning systems were installed in ten upgraded rural health centres, four rural district hospitals and one regional hospital in Tanzania. Uptake of teleconsultation and teleconference platforms were evaluated retrospectively. A cross sectional descriptive study design was applied to assess performance and adoption of eLearning. Results In 2015 a total of 38 teleconsultations were attended by consultant obstetricians and 33 teleconferences were conducted and attended by 40 health care providers from 14 facilities. A total of 240 clinical cases mainly caesarean sections (CS), maternal and perinatal morbidities and mortalities were discussed and recommendations for improvement were provided. Four modules were hosted and 43 care providers were registered on the eLearning system. For a period of 18–21 months total views on the site, weekly conference forum, chatroom and learning resources ranged between 106 and 1,438. Completion of learning modules, acknowledgment of having acquired and utilized new knowledge and skills in clinical practice were reported in 43–89% of 20 interviewed health care providers. Competencies in using the eLearning system were demonstrated in 62% of the targeted users. Conclusions E-Health presents an opportunity for improving maternal health care in underserved remote areas in low-resource settings by broadening knowledge and skills, and by connecting frontline care providers with consultants for emergency teleconsultations.

Cholangiocarcinoma is a fatal cancer of the biliary epithelium and has an incidence that is increasing worldwide. Survival beyond a year of diagnosis is less than 5%, and therapeutic options are few. Known risk factors include biliary diseases such as primary sclerosing cholangitis and parasitic infestation of the biliary tree, but most cases are not associated with any of these underlying diseases. Numerous in vitro and in vivo models, as well as novel analytical techniques for human samples, are helping to delineate the many pathways implicated in this disease, albeit at a frustratingly slow pace. As yet, however, none of these studies has been translated into improved patient outcome and, overall, the pathophysiology of cholangiocarcinoma is still poorly understood. There remains an urgent need for new approaches and models to improve management of this insidious and devastating disease. In this review, we take a bedside-to-bench approach to discussing cholangiocarcinoma and outline research opportunities for the future in this field.

Background Discriminatory metabolic profiles have been described in urinary 1 H nuclear magnetic resonance (NMR) spectroscopy studies of African patients with hepatocellular carcinoma (HCC). This study aimed to assess similarities in a UK cohort, where there is a greater etiological diversity. Methods Urine from cirrhosis and HCC patients was analyzed using a 600MHz 1 H NMR system. Multivariate analysis and median group MR spectra comparison identified metabolite alterations between groups. Metabolite identification was achieved through literature reference and statistical total correlation spectroscopy. Diagnostic accuracy was compared to serum alpha-fetoprotein (AFP). Results Of the 52 patients recruited, 13 samples from HCC and 25 from cirrhosis patients were selected. At 200IUmL −1 , diagnostic sensitivity of AFP was 27%. Multivariate analysis of urinary spectra generated diagnostic models with a sensitivity/specificity of 53.6%/96%. p-Cresol sulfate ( P =0.04), creatinine ( P =0.03), citrate ( P =0.21) and hippurate ( P =0.52) were reduced in the HCC patients. Carnitine ( P =0.31) and formate ( P =0.44) were elevated. Conclusion Diagnostic sensitivity was lower than previous African studies, but still outperformed serum AFP. Reduced creatinine, citrate and hippurate and elevated carnitine are comparable with the African studies. p-Cresol sulfate alteration is a novel finding and may indicate an altered sulfonation capacity of the liver in patients with HCC.

Increased occurrence of drought and dry spells during the growing season have resulted in increased interest in protection of tropical water catchment areas. In Mgeta, a water catchment area in the Uluguru Mountains in Tanzania, water used for vegetable and fruit production is provided through canals from the Uluguru South Forest Reserve. The clearing of forest land for cultivation in the steep slopes in the area is causing severe land degradation, which is threatening the water catchment area, livelihoods, and food security of the local communities, as well as the major population centers in the lowlands. In this paper, the economic performance of a traditional cropping-livestock system with East African (EA)-goats and pigs and extensive vegetable production is compared with a more sustainable and environmentally friendly crop-dairy goat production system. A linear programming (LP) crop-livestock model, maximizing farm income considering the environmental constraints in the area was applied for studying the economic performance of dairy goats in the production system. The model was worked out for the rainy and dry seasons and the analysis was conducted for a basic scenario representing the current situation, based on the variability in the 30 years period from 1982-2012, and in a scenario of both lower crop yields and increased crop variability due to climate change. Data obtained from a sample of 60 farmers that were interviewed using a questionnaire was used to develop and parameterize the model. The study found that in the steep slopes of the area, a crop-dairy goat system with extensive use of grass and multipurpose trees (MPTs) would do better than the traditional vegetable gardening with the EA goat production system. The crop-dairy goat system was superior both in the basic and in a climate change scenario since the yield variation of the grass and MPTs system was less affected compared to vegetable crops due to more tree cover and the use of perennial grasses. However, the goat milk production in the area was constrained by inadequate feeding and lack of an appropriate breeding program. Hence, farmers should enhance goat milk production by supplementing with more concentrate feed and by implementing goat-breeding principles. Moreover, policy measures to promote such a development are briefly discussed. Keywords: dairy goats, climate change, risk analysis, Tanzania, production system

Accurate differentiation between benign and malignant causes of biliary obstruction remains challenging and reliable biomarkers are urgently needed. Bile is a potential source of such biomarkers. Our aim was to apply a proteomic approach to identify a potential biomarker in bile that differentiates between malignant and benign disease, and to assess its diagnostic accuracy. Neutrophil gelatinase-associated lipocalin (NGAL) is multi-functional protein, released from activated neutrophils, with roles in inflammation, immune function, and carcinogenesis. It has not previously been described in bile.Bile, urine, and serum were collected prospectively from 38 patients undergoing endoscopic retrograde cholangiopancreatography ("discovery" cohort); 22 had benign and 16 had malignant pancreatobiliary disease. Initially, label-free proteomics and immunoblotting were performed in samples from a subset of these patients. Enzyme-linked immunosorbent assay was then performed for NGAL as a potential biomarker on all samples in this cohort. The diagnostic performance of biliary NGAL was then validated in a second, independent group ("validation" cohort) of 21 patients with pancreatobiliary disease (benign n=14, malignant n=7).NGAL levels were significantly raised in bile from the malignant disease group, compared with bile from the benign disease group in the discovery cohort (median 1,556 vs. 480 ng/ml, P=0.007). Biliary NGAL levels had a receiver operating characteristic area under curve of 0.76, sensitivity 94%, specificity 55%, positive predictive value 60%, and negative predictive value 92% for distinguishing malignant from benign causes. Biliary NGAL was independent of serum biochemistry and carbohydrate antigen 19-9 (CA 19-9) in differentiating between underlying benign and malignant disease. No significant differences in serum and urine NGAL levels were found between benign and malignant disease. Combining biliary NGAL and serum CA 19-9 improved diagnostic accuracy for malignancy (sensitivity 85%, specificity 82%, positive predictive value 79%, and negative predictive value 87%). The diagnostic accuracy of biliary NGAL was confirmed in the second independent validation cohort.NGAL in bile is a novel potential biomarker to help distinguish benign from malignant biliary obstruction.

Background The currently available tumour markers used in the management of patients with colorectal metastases are of limited value. Tumour M2-pyruvate kinase (TuM2-PK), a tumour-associated isoenzyme of pyruvate kinase, is elevated in patients with gastrointestinal cancer. This study has measured TuIVI2-PK levels in patients before and after resection of colorectal liver metastases (CLM).Materials and methods Fifty patients with CLM and no local residual disease had TuM2-PK levels measured before liver resection. In 20 patients, TuM2-PK levels were repeated at 2 weeks, 5 weeks and 5 months after resection. Plasma levels were analysed by enzyme-linked immunosorbent assay (ScheBo, Giessen, Germany). Carcinoembryonic antigen (CEA) and CA19-9 levels were measured at the same time periods by electrochemiluminescence immunoassay. CEA, CA19-9 and TuM2-PK levels were compared with the tumour number, volume, differentiation and stage. Cut-off values used for TuM2-PK, CEA and CA19-9 were 15 IU/ml, 10 ng/ml and 391 U/ml, respectively.Results TuM2-PK was elevated in 68%, CEA in 62% and CA19-9 in 40% of patients with CLM. TuM2-PK+CEA was elevated in 88% and TuM2-PK + CA19-9 in 78% of patients. A significant correlation was observed between tumour volume and CEA (r= 0.34, P< 0.05) and CA19-9 (r= 0.49, P

Summary Background Chronic biochemical cholestasis has been shown to be associated with a fivefold increase in histologically advanced liver disease in patients receiving home parenteral nutrition. Aims To investigate prevalence of chronic biochemical cholestasis in home parenteral nutrition patients and examine factors influencing its occurrence. Methods Records of all patients receiving home parenteral nutrition for >6 months treated at a single centre were reviewed and plasma biochemistry recorded. Logistic regression analysis was employed to identify factors associated with prevalence of chronic biochemical cholestasis. Results Records of 113 patients were reviewed. The point prevalence of chronic biochemical cholestasis was 24%, increasing to 28% if patients receiving parenteral fluid and electrolytes only were excluded. In multivariate analysis, presence of colon in continuity was associated with a significantly lower prevalence of chronic biochemical cholestasis, while total parenteral calorie intake was associated with a higher prevalence of chronic biochemical cholestasis. No association was seen between small intestinal lengths or between parenteral lipid intake and chronic biochemical cholestasis in multivariate analysis. Conclusions Chronic biochemical cholestasis is common in patients receiving home parenteral nutrition. High parenteral calorie intake and lack of a colon in continuity with small intestine are independently associated with an increased risk of chronic biochemical cholestasis.

This review will discuss the immediate- and long-term success, complications and overall benefits of self-expandable metal stents (SEMSs) in malignant or benign obstruction of the oesophagus, stomach and duodenum. Over recent years, indications such as benign disease have expanded, as has SEMS diversity with self-expandable plastic stents (SEPSs) or fully covered and biodegradable stents, for example.SEMSs have been increasingly used in malignant upper gastrointestinal obstruction with many reports confirming efficacy, despite a significant complication rate. Fully covered stents are increasingly used for a variety of benign oesophageal disease, but their place in gastric outlet obstruction is still unclear. Covered and uncovered stents have different functional characteristics and stent type must be selected on an individual basis. Biodegradable stents show promise and the outcome of experience in larger patient cohorts is eagerly awaited.This area is an evolving field, in which the clinician requires up-to-date knowledge of therapeutic options to make individualized treatment choices in difficult clinical circumstances. Technical and clinical success for oesophageal or gastroduodenal SEMSs are then above 90%. Minor complications are common, but serious complications seldom occur. Biodegradable stents may be useful, especially when stenting is needed for a short period of time.

Introduction Pancreatobiliary malignancies are amongst the commonest causes of cancer-related death worldwide and usually present with biliary obstruction. Accurate differentiation between benign and malignant causes of obstruction is likely to improve outcome in pancreatobiliary disease and reliable biomarkers are urgently needed. Bile is a potential source of such biomarkers due to its anatomical proximity to the site of pathology. Our aim was to apply a proteomic approach to identify potential biomarkers in bile which could differentiate between malignant and benign disease. Methods Bile, urine and serum were collected prospectively from 59 patients undergoing ERCP (endoscopic retrograde cholangiopancreatography) for benign (n = 36) or malignant (n = 23) pancreatobiliary disease at our centre. Initially, label-free proteomics and immunoblotting were performed in a sub-set of patients. Candidate biomarkers were selected on the basis of increased abundance of peptide fragments, and immunoblotting performed on an expanded cohort. ELISA was then performed for our potential biomarker on all samples in bile, blood and urine. Results Neutrophil gelatinase associated lipocalin (NGAL) levels were significantly raised in bile from the malignant disease group, compared to bile from the benign disease group (median 1839 ng/mL vs 472 ng/mL, p Conclusion NGAL in bile is a novel potential biomarker to distinguish benign from malignant biliary obstruction, particularly in combination with serum tumour markers.

Introduction Cholangiocarcinoma (CCA) is a primary biliary ductal cancer which is often difficult to diagnose and which carries a poor prognosis. New diagnostic tests are urgently needed to improve patient outcome. Bile is a rich source of potential novel biomarkers for CCA, due to its intimate proximity to the malignant lesion. However, there are no biliary biomarkers for CCA currently available. MicroRNAs (miRNAs) are key post-transcriptional regulators, and influence tumorogenesis. Studies on cell lines and tissue have identified several potential miRNA signatures for CCA, and recently miR-9 was identified as elevated in bile from CCA compared with benign disease 1 . In this study we aimed to measure specific miRNA expression in bile from patients with CCA, gallstone disease and pancreatic adenocarcinoma (PA) and to assess their performance in differentiating these causes of biliary obstruction. Methods Bile was collected at endoscopic retrograde cholangiopancreatography (ERCP) from patients with CCA (n = 6), PA (n = 10) and gallstones (n = 8; benign control). Bile was prepared as previously described1 and total RNA was isolated using TRIzol (Invitrogen, Paisley, UK). Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) was performed using Taqman mature miRNA primers and probes (Applied Biosystems, Cheshire, UK). Expression of oncomiR-21, miR-155 and miR-106a was measured. Cycle passing threshold (Ct) was recorded and normalised to RNU6B expression. Relative expression was calculated as 2Ct_miRNA-Ct_RNU6B. PCR reactions were carried out in duplicate. Results MiR-106a and oncomiR-21 were highly expressed in bile from patients with CCA compared to those with gallstones. MiR-155 was not significantly upregulated in malignancy. In discriminating CCA from benign disease, miR-106a had sensitivity and specificity of 83.3% [95% CI 36–100] and 88% [95% CI 47–100] respectively, with an AUC of 0.83 (cut-off level > 6.05). OncomiR-21 was also upregulated in the bile of both tumour types, but was not as reliable. Neither miRNA discriminated significantly between PA and CCA. Conclusion MiRNA can be reliably isolated from bile pellets. Both miR-106a and oncomiR-21 are potential novel biliary biomarkers for CCA, and could improve differentiation of benign from malignant disease at ERCP. Further work is required to validate these findings in a larger cohort and against other disease groups, and to investigate possible correlations between miRNA profile and disease course. Disclosure of Interest None Declared Reference Shigehara K, Yokomuro S, Ishibashi O, et al. Real-time PCR-based analysis of the human bile microRNAome identifies miR-9 as a potential diagnostic biomarker for biliary tract cancer. PloS one . 2011; 6(8):e23584.

Introduction Better biomarkers are urgently needed to assist accurate diagnosis and appropriate treatment of malignant biliary obstruction, as, although malignancy is a common cause of obstructive jaundice, current diagnostic techniques often fail to differentiate benign from malignant disease. Molecular analysis of bile has recently produced promising candidate biomarkers. Previous work from our group found that biliary neutrophil gelatinase-associated lipocalin (NGAL), a small extracellular 25-kDa protein with several biological functions, differentiates obstructive jaundice from malignancy from that in benign disease. The mechanism of NGAL in hepatopancreatobiliary (HPB) malignancy is unknown, although in other systems it promotes neoplastic diffusion by complexing and stabilising matrix metalloproteinase-9 (MMP9), enabling local invasion. Aims (1) To investigate possible biliary complexing of MMP9 and NGAL as a mechanism of tumorigenesis. (2) To validate our previous findings of biliary NGAL as a novel biomarker of malignancy in biliary obstruction. Methods Bile samples were collected from 77 patients undergoing ERCP (n=77, 22 with malignant disease and 55 with benign disease) at Imperial College London. ELISA was used to quantify levels of MMP9/NGAL complexes and of NGAL and MMP9 occurring independently in bile. Pearson9s correlation analysis was used to determine the relationship between NGAL, MMP9 and NGAL/MMP9 complex levels, and statistical significance assessed by the Mann–Whitney U test. Results Biliary NGAL levels were significantly higher in malignant biliary obstruction compared to benign disease (median 1555 ng/ml vs 402 ng/ml, p=0.003), giving a ROC AUC of 0.74. Biliary MMP9 and NGAL/MMP9 complex levels were not different between these groups (p=0.527, p=0.760). Unbound biliary NGAL and MMP9 levels correlated poorly (r 2 =0.03, p>0.05). Unbound NGAL correlated poorly with complex (r 2 =0.07, p>0.05) whereas unbound MMP9 correlated with NGAL/MMP9 complex level (r 2 =0.73, p Conclusion This study is novel in confirming the presence of MMP9 in bile, alone and in complex with NGAL. However, although NGAL was increased in malignancy, MMP9 and MMP9/NGAL complex were not, suggesting that NGAL acts independently of MMP9 in endobiliary HPB malignancy. Mechanisms remain to be elucidated. This study also supports previous reports of NGAL as a novel and independent bile biomarker of malignant biliary obstruction. Competing interests None declared.

Introduction We have previously demonstrated that the level of neutrophil gelatinase-associated lipocalin (NGAL) is increased in the bile of patients with pancreatobiliary malignancy. NGAL is expressed by activated neutrophils and many other cell types and is thought to have bacteriostatic, pro-proliferative and pro-metastatic functions. NGAL can be detected in the blood plasma. We hypothesised that the plasma NGAL level is elevated in patients with cholangiocarcinoma (CC) compared with patients with primary sclerosing cholangitis (PSC), and with healthy volunteers. Methods Plasma samples were collected from 97 patients with confirmed CC, 62 patients with PSC and no CC and 82 healthy controls. Plasma NGAL quantification was performed in duplicate on plasma from each subject using a Quantikine ELISA kit (R&D Systems, Minneapolis, Minnesota, USA). CC and healthy control cohorts were compared using the Student t test and receiver operator characteristic (ROC) analysis. Differences between CC and PSC cohorts were then sought. Pearson9s correlation analysis was used to assess relationships between the levels of NGAL and other plasma markers. Results Median NGAL concentrations (range) in CC, PSC and healthy controls were 92 ng/ml (14–644), 83 (43–171) and 64 (29–132) respectively. NGAL levels were significantly higher in plasma from CC patients compared with healthy controls (p 2 =0.14), white cell count (r 2 =0.09), bilirubin (r 2 =0.01), ALP (r 2 =0.02) or creatinine (r 2 =0.03). There was moderate correlation between NGAL and Ca19-9 concentrations (r 2 =0.38). Conclusion NGAL is expressed at significantly higher concentrations in the plasma of patients with CC compared to plasma from healthy controls and from subjects with PSC. This finding appears to be independent of renal impairment, cholestasis or systemic inflammatory response, suggesting that NGAL may represent a novel plasma biomarker of CC. Competing interests None declared.