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Epidermal growth factor (EGF) infused over 3-14 days into fetal sheep of 110-125 days gestation resulted in a number of morphological and endocrine changes. Striking hypertrophy of the skin, wool follicles and their accessory structures was seen, together with a reduction in the ratio of secondary to primary follicles and degenerative changes in wool fibres associated with shedding of fibres. Adrenal, thyroid, liver and kidney weights were increased while thymus weight was decreased. The increase in adrenal size resulted from cortical hypertrophy and was associated with increased cortisol secretion. Thyroid hypertrophy was accompanied by an increase in colloid stores, decreased plasma thyroxine and reverse triiodothyronine (T3) concentrations, unchanged plasma T3 and thyroid-binding globulin and raised thyrotropin (TSH) levels. Thyrotropin receptor affinity and content per gram of tissue were unchanged. Fetal and maternal plasma prolactin and growth hormone levels, and fetal plasma placental lactogen levels, were unchanged, although there was a significant rise in maternal plasma placental lactogen concentrations with high doses of EGF. Other maturational parameters such as switching from fetal to adult haemoglobin and liver glycogen content were unaffected.

The effects of exogenous oxytocin (OT) and estradiol-17 beta (E2) on plasma concentrations of prostaglandin (PG) E2 and 13, 14-dihydro-15-keto-PGF2 alpha (PGFM) were investigated on Day 14-15 (NP) of the estrous cycle and Days 14-16 (PI) and 21-25 (EP) of pregnancy in the ewe. Basal concentrations of PGFM were significantly elevated in utero-ovarian venous (UOV) plasma on Day 14 of pregnancy (4.05 +/- 0.81 nM, mean +/- SEM) compared to that observed on Day 14 of the cycle or Days 21-25 of pregnancy (2.29 +/- 1.3 nM and 1.06 +/- 0.56 nM, respectively). PGFM release increased significantly following intera-arterial bolus injections of 50, 500, and 5000 mU OT at 2-h intervals in all experimental groups. There was no significant difference in area and peak height of the PGFM response between the 3 groups studied. The time to peak PGFM response was, however, significantly longer in the PI group. No significant changes in concentration of PGFM were observed in any experimental group following 1-h infusions of E2 at 5, 50, and 500 pmol/min. Long-term (15-18 h) infusion of E2 at 83 pmol/min increased the peak height of the OT-induced PGFM response at both stages of gestation studied. PGE2 concentrations in UOV plasma were less than 0.05 nM in all samples studied. These results demonstrate that PG release can be induced in response to OT during the period in which ovine trophoblastic protein-1 (oTP-1) is released by the conceptus. During pregnancy, oTP-1 does not appear to inhibit the E2 induction of uterine OT receptors.

Arterial blood gases, pH and haemoglobin concentrations were monitored for 20 minutes before, during and for 120 minutes after 60 seconds of electroimmobilisation ( e-im ) at current strengths of 0 mA (control), 40 mA and 60 mA in 17 Merino ewes (36·3 ± 1·0 kg) previously prepared with unilateral carotid artery loops. e-im elicited whole body rigidity. During e-im , breathing was stopped for 50±3 seconds (40 mA) and 56 ± 2 seconds (60 mA). Arterial Po2 decreased to 43·2 ± 2·4 mmHg (5·68 ± 0·32 kPa) (40 mA) and 36·4 ± 1·8 mmHg (60 mA) while arterial Pco2 rose to 59·7 ± 1·9 mmHg (40 mA) and 69·8 ± 2·0 mmHg (60 mA). There was a significant fall in arterial pH to 7·272 ± 0·014 (40 mA) and 7·233 ± 0·011 (60 mA) during e-im and arterial haemoglobin increased by 34 ± 3 per cent and 35 ± 3 per cent at 40 mA and 60 mA, respectively. All the arterial blood gas and pH changes were significantly greater (P eim at 60 mA than at 40 mA. Multiple regression analysis indicated that (he decrease in arterial P o 2 during e-im was directly related to the latency to breathe while the changes in arterial P co 2 and pH during e-im were not. Upon cessation of 40 mA and 60 mA current, arterial P o 2 and P co 2 returned to control values within five minutes, while pH rapidly recovered by 0·15 ± 0·016 and then fell significantly (P e-im at 40 mA and 60 mA, respectively. These results indicate that in addition to muscle rigidity, e-im causes temporary apnoea with an associated acute hypoxaemia and hypercapnia, is followed by a sustained metabolic acidaemia, and the magnitude of these arterial blood gas effects increase with current strength.

The effect of protein kinase C activation and dibutyryl cyclic AMP on oxytocin secretion by ovine luteal tissue slices was investigated. Several putative regulators of luteal oxytocin secretion were also examined. Oxytocin was secreted by luteal tissue slices at a basal rate of 234·4 ± 32·8 pmol/g per h (n = 24) during 60-min incubations.Activators of protein kinase C: phorbol 12,13-dibutyrate (n = 8), phorbol 12-myristate,13-acetate (n = 4) and 1,2-didecanoylglycerol (n = 5), caused a dose-dependent stimulation of oxytocin secretion in the presence of a calcium ionophore (A23187; 0·2 μmol/l). Phospholipase C (PLC; 50–250 units/l) also caused a dose-dependent stimulation of oxytocin secretion by luteal slices. Phospholipase C-stimulated oxytocin secretion was potentiated by the addition of an inhibitor of diacylglycerol kinase (R59 022; n = 4). These data suggest that the activation of protein kinase C has a role in the stimulation of luteal oxytocin secretion. The results are also consistent with the involvement of protein kinase C in PLC-stimulated oxytocin secretion. The cyclic AMP second messenger system does not appear to be involved in the control of oxytocin secretion by the corpus luteum. Journal of Endocrinology (1990) 124, 225–232

Although the early analysts and assayers achieved quantitative results it was only much later via the atomic theory and its symbolic representation that these results can be discussed in modern terms. Quantitative analysis covers the whole of recorded history. The highlights selected for discussion are, use of the touchstone, R. Boyle's contribution to the quantitative analysis of solutions, J. Black's researches on the alkalis and J. Dalton's indroduction of symbolic notation for the composition compounds.

Cet article passe en revue les principaux facteurs a considerer pour une etude a posteriori des reactifs analytiques organiques. On donne en appendice une liste de reactifs analytiques organiques importants

A virological response to pegylated-interferon and ribavirin is typically associated with a prompt fall in serum transaminases. For some patients, transaminases rise during treatment.To assess the frequency and define factors associated with elevations of serum transaminases.A total of 169 treated patients were studied. Transaminase elevations were graded by WHO criteria - grade 0: no valuebaseline, grade 1: 1-2x baseline, grade 2: 2.1-5x baseline, grade 3:5x, grade 4: any rise with evidence of liver failure. Results 60/169 (35%) patients experienced transaminase elevations: 52 grade 1, 6 grade 2, 1 grade 3, 1 grade 4. Overall, end of treatment response and sustained virological response rates were 72% and 55%. Lower rates were observed in the grade 1 elevation group (63% and 40%) compared with patients with grade 0 (79% and 65%) and gradeor =2 elevations (85% and 71%). Grade 1 elevations tended to occur earlier during treatment than gradeor =2 elevations. Transaminase elevations were associated with greater pre-treatment body weight (P = 0.006), steatosis (P = 0.008) and poorer sustained virological response rates (P = 0.007).Transaminase elevations during treatment of chronic Hepatitis C virus with pegylated interferon and ribavirin are common but rarely severe. Mild rises may reflect ongoing viral activity in treatment non-responders. More significant rises are frequently observed despite a virological response, and may be because of an immuno-modulating effect of interferon in susceptible patients.

Introduction In PSC it has been believed that staging fibrosis is unhelpful due to the patchy nature of the condition, hence liver biopsy is rarely performed. Emerging data indicates that TE correlates well with fibrosis stage on liver histology and that both TE and the ELF test provide prognostic information in PSC. Thus far there has been no direct comparison of ELF testing and TE. Here we present a comparison of clinical scores, TE and the ELF test in patients with PSC. Method Patients with large-duct PSC had TE [Fibroscan® (Echosens): 10 valid measurements and a success rate >60% after 3 hrs fasting] and serum stored at the same visit to the Royal Free, London and the Hospital Clinic, Barcelona (Jun 2010–Feb 2015). Full patient demographics and clinical outcomes were recorded. Clinical scores of disease severity (APRI and Mayo risk score) were obtained on the day of assessment. Stored sera were tested for ELF [ADVIA Centauro® XP system (Siemens Diagnostics). Spearman–s rank correlation was used due to the non-normal distribution of measures. Results 39 [1 autoimmune overlap, 28(72%) male] PSC patients [mean (±SD): age 50(±14) yrs; age at diagnosis 42(±14) yrs; time from diagnosis of 7.8(±7.1) yrs] were evaluated. 28 patients (80%) were diagnosed with IBD: 21 ulcerative colitis, 6 Crohn’s disease, 1 indeterminate colitis. There were no significant differences in ELF, TE or age between UK and Barcelona patients. Fibroscan correlated with ELF with a Spearman–s rho 0.676 p Conclusion A significant correlation between liver stiffness measured by TE, ELF test, APRI and Mayo risk score is here demonstrated for the first time in patients with PSC. Our results suggest that while the process of fibrosis progression in PSC is poorly understood, non-invasive tests validated in other chronic liver diseases perform consistently in patients affected and should be further evaluated as tools for staging the disease, monitoring disease progression and prognosis and may provide much needed surrogate end points for clinical trials in PSC. Disclosure of interest F. Saffioti: None Declared, M. Vesterhus: None Declared, A. Telese: None Declared, G. Mazza: None Declared, D. Roccarina: None Declared, M. Rosselli: None Declared, W. Jonasson: None Declared, A. Pares: None Declared, T. Karlsen: None Declared, W. Rosenberg: None Declared, M. Pinzani: None Declared, A. Marshall: None Declared, D. Thorburn Grant/Research Support from: Boston Scientific to fund a clinical research fellow.

Introduction 30% of the UK population has NAFLD. A significant minority (10%) will have NASH of whom 15% will develop cirrhosis. Recognising this subpopulation at risk can be difficult as patients are often asymptomatic. Non-invasive tests (NIT) of liver fibrosis including FIB4 and the Enhanced Liver Fibrosis (ELF) panel have been validated in NAFLD and provide opportunities to devise risk stratification pathways. We reviewed GP referrals with a final diagnosis of NAFLD to three London hospitals to assess the potential role of NIT in new pathways. Method All new GP referrals to the Royal Free, Whittington and University College London hospitals with a final diagnosis of NAFLD between 1/4/12 and 31/3/13 had their electronic records assessed. Demographic, clinical, laboratory and outcome data were collected. The potential impact of the use of FIB4 was evaluated. Prospectively FIB4 and ELF are being used to stratify patients prior to referral. Results Over 1 year, 191 patients with a final diagnosis of NAFLD were referred by GP’s. 130 had sufficient data to calculate FIB-4 values. 87 patients (67%) had FIB4 3.25 (high risk of advanced liver disease). FIB4 was indeterminate (1.30–3.25) in 40 (31%) who would be stratified with ELF in the new pathway (Figure 1). Twenty (15%) had a liver biopsy. 10 (8%) had FIB4 3.25 and 5 had indeterminate FIB4 scores (1.30–3.25). Conclusion New approaches to tackle the increasing burden of NAFLD are required. Patients at low risk of advanced fibrosis should have their risk factors managed in primary care, whilst those at high risk need specialist input. Existing methods are ineffective in stratifying patients. Applying FIB4, 67% of referrals could have been avoided but the majority of cirrhotic patients would not have been identified. We have initiated a novel primary care pathway integrating the use of FIB4 and ELF (to categorise FIB-4 indeterminate cases) to stratify patients for management in primary or secondary care. Within the 1st year, over 400 patients have entered the pathway and data from clinical and cost effectiveness analysis are due in mid 2015. Disclosure of interest None Declared.

Introduction Acute portal mesenteric vein thrombosis, when extensive, is associated with catastrophic complications of gut infarction, short bowel syndrome, PN dependence and death. The absence of a satisfactory therapeutic regimen has prompted the recommendation for alternative therapies (Hepatology 2010;51:210–218). Based on the safety profile of prolonged low dose tPA in children with extensive deep vein thrombosis, we have developed a ward-based TPA protocol to be used in patients with acute splanchnic vein thrombosis and symptoms/radiological signs of gut ischaemia. This treatment algorithm was approved by RFH DTC. Method Alteplase is commenced at a dose of 0.05 mg/kg/hr in patients with acute splanchnic vein thrombosis, after informed consent and an MDT decision involving surgery/radiology/hepatology. The standard contraindications to tPA apply. Monitoring involves 12 hrly FBC, clotting, fibrinogen. Thromboelastography/ROTEM were included as exploratory investigations. t-PA may be continued for 72 h. Contrast enhanced CT is performed at 48 h, or earlier if clinically indicated. TIPS is indicated if thrombus/symptoms persist at 72 h. Results To-date, 6 patients have been treated with this regimen. Aetiology of thrombosis was Chiari malformation (1) previously undiagnosed JAK2+ve MPD (2) local sepsis (1) and unknown (2) (see Table 1). Three patients had complete radiologic normalisation of their splanchnic circulation, 2 of whom also required TIPS due to persistent PVT. Two patients re-permeated their SMV with complete resolution of clinical symptoms and radiological signs of gut ischaemia, but with persistent PV thrombus. One patient did not have a radiological response, although their pain resolved. No patient required surgery for gut ischaemia. All patients survived and were discharged with normal enteric function. Two patients had their infusion interrupted; one for an arterial line puncture site bleed, and one for worsening gut symptoms (infusion re-started). Conclusion This early experience suggests that systemic tPA in patients with acute PMVT and symptoms/signs of gut ischaemia can be used to achieve resolution of thrombus and symptoms and avoid catastrophic complications of gut infarction. We propose that tPA is of value in a multi-modality approach to the management of acute splanchnic vein thrombosis. Disclosure of interest None Declared.

Introduction The optimal pharmaceutical treatment of primary sclerosing cholangitis (PSC) remains controversial. We performed a systematic review and network meta-analysis of different pharmacological interventions for the treatment of patients with PSC. Method We included randomised controlled trials (RCTs) of various pharmacological interventions compared with each other or with placebo in patients with PSC. We conducted network meta-analyses following the National Institute for Health and Care Excellence Decision Support Unit guidance to compare multiple interventions simultaneously for each of the primary (mortality, adverse events, health-related quality of life (HRQoL)) and secondary outcomes (decompensated cirrhosis, liver transplantation, malignancies) and only included trials in which participants could receive any of the interventions being assessed (transitivity assumption). We conducted a Bayesian network meta-analysis and calculated the odds ratios (OR), rate ratios, or hazard ratios with 95% credible intervals or Bayesian confidence intervals (CrI) for assessing the effect of treatment. We used three different non-informative priors and ensured that the results converged prior to calculation of posterior probabilities for Bayesian network meta-analysis. Results We included 22 RCTs on different treatment regimens for PSC, comprising of 1111 patients. There was no statistically significant difference in the mortality at 1-year, 5-years or at maximal follow-up between any of the treatments and placebo. There was no statistically significant difference in the proportion of patients with any adverse event, serious adverse events, liver decompensation, liver transplant, any malignancy, cholangiocarcinoma, or colorectal cancer at maximal follow-up or in the HRQoL between any of the treatments and placebo. Penicillamine was associated with higher number of total adverse events compared to placebo (rate ratio 1.93; 95% CrI 1.07 to 3.49) and to low-dose ursodeoxycholic acid (rate ratio 2.38; 95% CrI 1.02 to 5.56). There was no statistically significant difference in the total number of serious adverse events between any of the treatments and placebo. Conclusion None of the current therapies for primary sclerosing cholangitis are effective. Disclosure of interest K. Gurusamy: None Declared, F. Saffioti: None Declared, C. Toon: None Declared, B. Davidson: None Declared, E. Tsochatzis: None Declared, D. Thorburn Grant/Research Support from: Boston Scientific to fund a clinical research fellow.

Introduction Cystic lesions of the pancreas (CLP) are being detected with increasing frequency. Current methods of stratifying risk of malignant transformation are imperfect. The aim of this study was therefore to determine the incidence of high-risk lesions and define clinical and radiological features that predict malignancy in a large cohort of patients with CLP managed by surgery or surveillance. Method A retrospective cohort study from January 2000 to December 2013 of patients over 18 years of age with a confirmed CLP evaluated in a tertiary referral hepatobiliary centre. Results Of the 1,090 patients diagnosed with a CLP during the study period, 768 patients were included in the study. A total of 141 patients were referred for immediate pancreatic resection, 570 entered surveillance while 57 had a malignant CLP which was unresectable at diagnosis (N=47) or were unfit for surgery (N=10). In those who underwent immediate resection, malignancy was present in 38% (54/141). During follow-up 2% (10/570) of those entering a surveillance programme underwent malignant transformation, although most instances were after discharge from active surveillance. Only two patients in the surveillance cohort underwent surgery, of which only one case was curative. Clinical and radiological features associated with a high-risk CLP included older age, associated symptoms, presence of a solid component or a dilated main pancreatic duct. Larger size did not correlate consistently with malignant transformation, particularly in IPMNs where the median size of benign lesions was larger than malignant IPMNs (30mm (range: 11–130) vs. 23mm (range: 15–56)). Conclusion The sensitivity of diagnostic tests leading to immediate surgery for high risk CLP (malignant or mucinous CLP) was 92%, with a specificity of just 5%. Surveillance of CLP without high-risk features was associated with a low incidence of cancer development. This study supports the stratification of CLP based on worrisome clinical and radiological features. Disclosure of interest None Declared.

Introduction There is an excess mortality associated with weekend medical admissions for many conditions and poorer surgical outcomes with night-time (NT) operating. Due to the time critical nature of organ retrieval for liver transplantation many transplants occur ‘out-of-hours’. We sought to identify if there was an impact upon transplant survival (a composite outcome of graft failure or death) with weekend (5pm Friday to 8am Monday) or NT (7 pm to 7 am) liver transplantation. Method Data on 8338 liver only transplants were obtained from the UK Transplant Registry, as at 04/01/2015. These included only those with adult NHS group 1 recipients (aged 17 or more) transplanted in the UK from solid organ deceased donors from 1 January 2000 to 31 December 2014. Cox proportional hazard models were created controlling for variables with a statistical impact on survival such as renal support, ventilation status, sepsis, graft appearance, CIT, donor type, split liver and transplant year. Results There was a significant reduction in the hazard of the composite outcome of graft failure or death at 30 days (adjusted hazard ratio: 0.79, 95% CI: 0.67–0.93, p-value: 0.01), 90 days (0.83, 0.72–0.95, 0.01), 1 year (0.87, 0.77–0.97, 0.02) and 3 years (0.89, 0.80–0.99, 0.03) associated with weekend transplantation but not with NT transplantation. However, when the analysis was conditioned to only those patients alive and with a functioning graft at 30 days post transplantation, the weekend effect was no longer significant at both 1 year (0.96, 0.81–1.133, 0.62) and 3 years (0.96, 0.85–1.10, 0.59). Conclusion We have demonstrated a significant reduction in death or graft failure associated with liver transplantation at weekends of 10–20%, which is pertinent only to the early post-operative transplant survival. American studies have shown no change in outcomes with weekend liver transplantation but a possible increase in early mortality with nighttime operating in one small study. The reasons for reduced adverse outcomes with weekend transplantation are unclear. It may represent a “lead-in” effect as patients transplanted at the weekend will be in intensive care for the first days following surgery, where service provision is similar 7 days a week, and step down to level one care during the week rather than at weekends. Other factors may include transplanting teams being risk adverse at weekends and more likely to decline marginal organs for grafting and prioritising less complex cases for weekend working. This is a novel and interesting finding that requires deeper analysis of the data set and prospective monitoring. Disclosure of interest None Declared.

Introduction Liver disease is the third largest cause of premature death in the United Kingdom (UK) and currently accounts for 2% of deaths in England, but there is little strategy to improve care for those dying from it, as well as a lack of research in this area. Understanding of the views of health care professionals (HCP) on how care can be improved for patients dying from cirrhosis is poor. Aim To conduct a national survey of primary, secondary and tertiary care providers to explore current attitudes and practices, to identify future training needs, ideas for service improvement and research priorities. Method An online questionnaire survey was emailed to a maximum of 6,181 HCPs working in hepatology and gastroenterology (liver), general practice (GP) and specialist palliative care (SPC) across the UK. Results 517 HCP responded: 195 from liver, 46 from GPs and 273 from SPC (response rates 4%, 23% and 10% respectively; overall response rate 8%). Nearly all liver and SPC professionals felt that SPC had a role in the care of patients with cirrhosis. Liver professionals tended to refer to SPC whilst patients were in hospital but overall numbers were low, with only 14% (22/161) and 6% (9/61) of liver professionals referring more than 20 patients/year from in-patient and out-patient care respectively. Patients with cirrhosis only made up a median 1% of the SPC workload. All HCPs wanted further training in: managing liver-related symptoms (SPC), symptom control and end of life issues (liver and GP). Open responses were received from 221 participants. Two main research priorities were identified by all three health professional groups: better symptom control (in particular how best to manage recurrent ascites, opioid pharmacology in liver disease and optimal management of pruritus and encephalopathy), and prognostication. Conclusion Although all HCPs recognised the important role of SPC in caring for dying patients with cirrhosis, they all needed further training and uptake of skills to improve their confidence. We recommend a focus on improved understanding of the needs of patients with cirrhosis and their families, identification of better ways in communicating with patients at risk of death, smoother links across care boundaries, and enhanced training for all staff groups. Disclosure of interest None Declared.

Introduction Pancreatic enzyme insufficiency (PEI) is a well-recognised cause of malnutrition in pancreatic cancer (PC). Pancreatic enzyme replacement therapy (PERT) in the form of enteric coated pancreatin microspheres is recommended in these patients with symptoms of PEI to prevent weight loss and malnutrition and improve quality of life. Given that the probability of PEI is high in PC (80–90%), PERT is recommended without the use of formal diagnostic tests. The optimal starting dose of PERT is 40–50000 lipase units per main meal. The aim of this study was to evaluate the use of PERT in PC patients, to ascertain if these patients were given the appropriate PERT dose and to determine whether dietician review was associated with more and better PERT use. Method A single centre retrospective analysis of patients diagnosed with PC in 2014 in a tertiary hospital specialising in the treatment of patients with hepato-pancreato-biliary (HPB) diseases. We identified 80 patients with PC. Information was collected from electronic patient records regarding the patients’ symptoms of PEI, evidence of PERT use, the dose prescribed and whether the patients were seen by a dietician. Fisher’s exact test was used to calculate whether (a) dietician review was associated with higher rate of PERT use and (b) dietician review was associated with higher rate of appropriate PERT dosing. Results Symptoms of PEI (abdominal pain, weight loss or steatorrhoea) were recorded in 57.5% of PC patients (46/80). PERT was prescribed in the minority of patients [41.3% (33/80)] with appropriate dosing given to the majority of patients when prescribed [66.7% (22/33)]. A dietician was involved in the care of less than half [43.8% (35/80)] of patients. However, referral to a dietician was strongly associated with PERT use with 60% (21/35) of patients being referred given PERT compared to only 26.7% (12/45) of patients who were not (p = 0.003). Dietician involvement was also associated with more appropriate PERT use with 85% (17/20) of patients given appropriate doses compared to 45.5% (5/11); (p = 0.038) when started without dietician review. Conclusion In this audit, we demonstrated that while symptoms of PEI were present in the majority of patients, the minority of patients were given PERT. The minority of patients were seen by a dietician but when assessed were more likely to receive PERT at the appropriate dosage, which may account for the low rate of PERT in the cohort as a whole. This study highlights the lack of awareness of the problem of PEI in PC patients amongst managing physicians. This could lead to a missed opportunity to reduce symptoms and improve quality of life in patients with a simple intervention. A referral to the dietician was shown to benefit these patients. Disclosure of interest None Declared.

Perchlorate (0–75 μg) can be determined spectrophotometrically at 292 nm after extraction of protriptylinium perchlorate into ethyl acetate. The effects of pH and diverse anions are reported. The system has been applied to the determination of perchlorate in samples of potassium chlorate after prior selective destruction of chlorate.

Summary Background: Hepatitis C virus infection is more common in patients with inflammatory bowel disease than in general population. Limited data are available as to the safety and efficacy of α-interferon therapy for chronic active hepatitis C in patients with concomitant inflammatory bowel disease. Aim: To evaluate the efficacy and safety of α-interferon monotherapy in patients with chronic active hepatitis C and inactive or mildly active inflammatory bowel disease. Methods: A total of 513 consecutive inflammatory bowel disease patients at a single centre were tested for antibodies to hepatitis C virus (anti-hepatitis C virus) between 1995 and 2000. Twenty-one patients had detectable anti-hepatitis C virus Ab and were hepatitis C virus-RNA positive with histologically proved chronic active hepatitis. Each of these patients, whose inflammatory bowel disease was in clinical remission or mildly active, was sex- and age-matched to three controls with similar histological grade and stage of chronic hepatitis C virus but without inflammatory bowel disease; and all were treated with human leucocyte α-interferon 6 million units given thrice weekly for 12 months. Responses to treatment were classified as follows: complete response – persistently normal alanine aminotransferase and viral clearance (hepatitis C virus-RNA–ve) at the end-of-treatment, incomplete response – alanine aminotransferase normalization without viral clearance (hepatitis C virus-RNA+ve), and sustained response – alanine aminotransferase normalization and hepatitis C virus clearance 12 months after the end-of-treatment. Results: Twenty-one patients with chronic active hepatitis C and inflammatory bowel disease (10 with Crohn's disease and 11 with ulcerative colitis) and 63 sex- and age-matched controls with chronic hepatitis C virus alone received α-interferon monotherapy. Response rates to interferon were similar for inflammatory bowel disease patients compared with controls [CR 42% vs. 35% and SR 24% vs. 18% (P, not significant), respectively]. None of the 21 inflammatory bowel disease patients had severe adverse effects and the mild ones observed were comparable with those seen in the control group. No patients developed an inflammatory bowel disease relapse during the interferon treatment period or in the 12 months thereafter. Conclusions: The biochemical and virological response to a 12-month human leucocyte α-interferon treatment in patients with chronic active hepatitis C are similar to that observed in matched controls with chronic hepatitis C virus without inflammatory bowel disease. Adverse effects are similar in both groups of patients and unrelated to the underlying inflammatory bowel condition. This provides hepatologists with evidence that α-interferon can be safely administered to patients with chronic hepatitis C virus and inflammatory bowel disease provided that the inflammatory bowel condition is in clinical remission.

176 PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PILOT STUDY EVALUATING EFFICACY AND SAFETY OF INTRAVENOUS SILIBININ IN PATIENTS WITH HCV RECURRENCE ON THE GRAFT AFTER LIVER TRANSPLANTATION M. Rendina, M. D’Amato, A. Castellaneta, N.M. Castellaneta, N. Brambilla, G. Giacovelli, L. Rovati, S.F. Rizzi, M. Zappimbulso, R. Bringiotti, A. Di Leo. Gastroenterology, University of Bari, Bari, Clinical Research, Rottapharm SpA, Milan, Italy E-mail: mariarendina@virgilio.it

Bismuth (0–300 μg) can be determined spectrophotometrically at 482 nm after its extraction as protriptylinium tetraiodobismuthate(III) into chloroform. The effects of reagent conditions and diverse ions are reported. The system has been applied to the determination of bismuth in pharmaceutical samples.

Rhenium (0–20 μg) may be determined as perrhenate spectrophotometrically at 362 nm after its extraction at pH 4 with amiloride hydrochloride into 4-methyl-2-pentanone. The relative standard deviation for 7 determinations of 10 μg of perrhenate is 1.5%. The effects of pH and diverse ions are reported. Only perchlorate, periodate and iodide interfere seriously. The system has been applied to the determination of rhenium on alumina and on carbon catalysts.

Chromium(VI) ($500 μg dichromate) can be determined spectrophotometrically at 365 nm after its extraction as protriptylinium dichromate into acetone-chloroform (1:1, vv). The effects of acidity, diverse ions and masking studies are reported. The relative standard deviation for determination of 200 μg of dichromate is 0.9% (n = 7). The system has been applied to the Spectrophotometric determination of chromium in steels (0.03–4%).

Background: The risk of a surgeon acquiring the hepatitis C virus (HCV) through occupational exposure is dependant on the prevalence of HCV infection in the patient population, the probability of a percutaneous injury transmitting HCV, and the incidence of percutaneous injury during surgery. Aims: To estimate the prevalence of HCV infection in the adult surgical patient population in North Glasgow and thereafter estimate the risk of HCV transmission to surgeons through occupational exposure. Methods: The prevalence of HCV infection was estimated through the unlinked anonymous testing of samples from male surgical patients, aged 16–49 years, in two North Glasgow hospitals from 1996 to 1997, and adjusting these data for age and sex. Using published estimates of the incidence of percutaneous injury during surgery and percutaneous injury transmitting HCV, the risk of occupational transmission of HCV to surgeons was then derived. Results: The estimated prevalence of anti-HCV infection for all adult patients in the two hospitals combined was 1.4% (cardiothoracic/cardiology 0.8%, orthopaedics/rheumatology 1.4%, general surgery/ENT 2.0%). The estimated probability of HCV transmission from an HCV infected patient to an uninfected surgeon was 0.001–0.032% per annum (0.035–1.12% risk over a 35 year professional career). Conclusions: The risk of an individual surgeon acquiring HCV through occupational exposure is low, even in an area with an extremely high prevalence of HCV among its injecting drug using population. Surgeons however should be encouraged to observe universal precautions and present for assessment after needlestick injuries to protect themselves and their patients from this insidious infection.

A sensitive system is reported for the determination of tin in copper-based alloys by flame atomic absorption spectrophotometry. Use of a slotted quartz atom trap coupled with hydride generation improved the sensitivity by a factor of 200, compared with that obtained using conventional flame AAS. The determination of tin in a series of reference samples demonstrates the usefulness of the system for the analysis of metallurgical samples.

A sensitive system is described for the determination of antimony in copper-based alloys by flame atomic absorption spectrophotometry. The use of a slotted tube quartz atom trap improves precision and reduces the characteristic concentration by factors of 3 and 1.6 compared with the use of conventional flame AAS. Interferences are minimised by coating the internal surfaces of the STAT with copper.

Background: Chronic hepatitis C virus (HCV) infection is frequently associated with elevated markers of iron stores. Recessively inherited mutations in the HFE gene are responsible for iron accumulation in most cases of hereditary haemochromatosis and may have a role in HCV infection. They may also be associated with progressive liver fibrosis although this remains controversial. Aims: To assess the prevalence of HFE mutations in Scottish HCV infected patients and to explore the effect of the carrier state on serum and liver iron stores, and the severity of liver disease. Patients: A total of 164 patients with antibodies to HCV who underwent liver biopsy were assessed prospectively. Methods: Each patient was screened for HFE mutations (Cys282Tyr and His63Asp). Iron markers were assessed in serum (ferritin, transferrin saturation) and on liver biopsy (stainable iron, liver iron concentration (LIC) and hepatic iron index). Results: There were 67 (41%, 26 Cys282Tyr, 33 His63Asp, eight compound) heterozygotes. Forty four (28%) patients had elevated serum iron markers, 24 (15%) had stainable liver iron, and five (3%) had elevated LICs. Carriage of HFE mutations was not associated with any clinical, biochemical, virological, or pathological features, including accumulation of liver iron. Elevated serum iron markers were associated with male sex, increased alcohol consumption, and increased liver inflammation and fibrosis. Patients with elevated LICs were older, acquired HCV infection earlier, and had more liver inflammation. Conclusions: Patients with chronic HCV infection frequently have elevated serum iron markers although elevated LICs are uncommon. Elevated serum iron studies and LICs occur in patients with more severe liver disease. Carriage of HFE mutations, although frequently observed in these HCV infected patients, does not have a role in the accumulation of iron or the progression of liver disease in HCV infection.

Introduction Transjugular intrahepatic portosystemic shunt (TIPS) insertion is established as an important intervention in the management of refractory ascites. We conducted a retrospective analysis of a large series of patients undergoing TIPS insertion for this indication. Aim The aims of this study were to describe the series of patients undergoing TIPS insertion for refractory ascites at the Royal Free Hospital particularly with regards to survival and procedural success. Method A retrospective analysis of the Royal Free Hospital radiology database was conducted to identify all patients who underwent all TIPS procedures between January 1991 and January 2011. Patient records were used to subsequently identify those patients in whom refractory ascites was the principal indication for TIPS insertion and to characterise this patient cohort. Patients were excluded if hydrothorax was the primary indication for TIPS insertion. All patients underwent baseline EEG/echocardiography and cross sectional imaging as part of their pre-procedural work up. Patients were requiring regular paracentesis and were either diuretic insensitive or intolerant. Results 1073 TIPS-related procedures were conducted at the Royal Free Hospital between January 1991 and January 2011. Of these, 159 patients underwent TIPS insertion for refractory ascites. Within this patients cohort, the underlying aetiology of cirrhosis was: alcohol 56.0% (89/159), hepatitis C 12.6% (20/159), cryptogenic 8.8%(14/159) and other causes 22.6% (36/159). 29% (46/159) of the patients were female, 71% (113/159) were male. The mean age at the time of TIPS insertion was 54.3 (±0.94) yrs. The mean pre-TIPS MELD score was 15.26 (±0.57) with a mean pre-TIPS EEG frequency of 7.51 Hz (±0.20). The mean post-procedural portal pressure gradient was 11.0 mm Hg (±0.57). Six month, 12 month and 2-year survival post-TIPS insertion was 78%, 50% and 50% respectively. At 6 months, 63% of patients had no or minimal ascites, 29% had moderate volume ascites and only 8% had persistent large volume ascites. At 12 months, 69% of patients had no or minimal ascites, 21% had moderate volume ascites and 10% had persistent ascites requiring paracentesis. Conclusion In a carefully selected group of patients, TIPS is an effective intervention in the management of refractory ascites.

of 73% (56/77). No deaths occurred; no clinically meaningful differences were observed in frequencies of serious adverse events (AEs), AEs leading to discontinuation, or grade 3/4 AST/ALT elevations in patients with or without cirrhosis. Conclusions: All-oral DCV+ASV treatment exhibited similarly high SVR rates and no clinically relevant differences in safety/tolerability in cirrhotic and non-cirrhotic patients with HCV genotype 1b infection.

A flow-injection manifold has been developed for the spectrophotometric determination of manganese(VII) at 548 nm after extraction into chloroform of the ion-associate, benzyltributylammonium permanganate. The carrier stream was a pH 6 buffer containing 10% (w/v) ammonium fluoride and the reagent stream was 0.10% (w/v) benzyltributylammonium chloride. The injection rate was 20 h −1 . The calibration graph is linear up to 25 μg ml −1 and the detection limit (3 × baseline noise) is 0.91 μg ml −1 Mn(VII), based on 250-μl injection volumes. The system has been aplied to the determination of manganese in steels and a cupro-nickel alloy.