Much has changed since the last guideline of 2008, both in endoscopy and in the practice of obtaining informed consent, and it is vital that all endoscopists who are responsible for performing invasive and increasingly risky procedures are aware of the requirements for obtaining valid consent. This guideline is restricted to GI endoscopy but we cover elective and acute or emergency procedures. Few clinical trials have been carried out in relation to informed consent but most areas are informed by guidance from the General Medical Counsel (GMC) and/or are enshrined in legislation. Following an iterative voting process a series of recommendations have been drawn up that cover the majority of situations that will be encountered by endoscopists. This is not exhaustive and where doubt exists we have described where legal advice is likely to be required. This document relates to the law and endoscopy practice in the UK-where there is variation between the four devolved countries this is pointed out and endoscopists must be aware of the law where they practice. The recommendations are divided into consent for patients with and without capacity and we provide sections on provision of information and the consent process for patients in a variety of situations. This guideline is intended for use by all practitioners who request or perform GI endoscopy, or are involved in the pathway of such patients. If followed, we hope this document will enhance the experience of patients attending for endoscopy in UK units.

RNA virus genome replication requires initiation at the precise terminus of the template RNA. To investigate the nucleotide requirements for initiation of hepatitis C virus (HCV) positive-strand RNA replication, a hammerhead ribozyme was inserted at the 59 end of an HCV subgenomic replicon, allowing the generation of replicons with all four possible nucleotides at position 1. This analysis revealed a preference for a purine nucleotide at this position for initiation of RNA replication. The sequence requirements at positions 2-4 in the context of the J6/JFH-1 virus were also examined by selecting replication-competent virus from a pool containing randomized residues at these positions. There was strong selection for both the wild-type cytosine at position 2, and the wild-type sequence at positions 2-4 (CCU). An adenine residue was well tolerated at positions 3 and 4, which suggests that efficient RNA replication is less dependent on these residues.Hepatitis C virus (HCV) has a positive-sense RNA genome of 9.5 kb that comprises a single ORF which is flanked by highly structured untranslated regions (UTRs) that are required for both RNA replication and protein translation. The polyprotein is cleaved into ten polypeptides; structural proteins at the amino terminus and non-structural proteins at the carboxy terminus. Use of the subgenomic replicon system (Lohmann et al., 1999) has shown that non-structural proteins NS3-NS5B are both necessary and sufficient for replication of an RNA molecule containing the 59 and 39 UTRs. In vitro studies have shown that the purified viral RNA-dependent RNA polymerase, NS5B, can initiate transcription by a de novo mechanism using a template from the 39 end of either the positive or negative strands, as well as synthetic RNA templates (Luo et al., 2000;Zhong et al., 2000;Shim et al., 2002). Furthermore, using the HCV 39 UTR as template, ATP was most efficiently used for initiation, followed by GTP and CTP, whereas no initiation was observed with UTP (Zhong et al., 2000). However, a further study revealed that NS5B could utilize all four nucleotides for initiation if they complemented the 39-terminal nucleotide of the template RNA (Shim et al., 2002). Although important in determining the biochemical details of polymerase function, these studies do not address how NS3-NS5B protein complexes recognize the appropriate RNA template and initiate RNA replication within cells. Two recent studies have addressed this question by analysing requirements for initiation of positive-strand synthesis (Luo et al., 2003;Cai et al., 2004) using the replicon system. However, these studies did not analyse all four possible terminal nucleotides, and requirements at positions +2 to +4 (prior to the start of a highly conserved stem-loop comprising nucleotides +5 to +20) were not examined, although a deletion of nucleotides +1 to +4 resulted in a non-viable replicon.To obtain a complete set of data pertaining to the terminal requirements for HCV RNA replication, we inserted a hammerhead ribozyme directly ups...

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Background/Aims People with Spondyloarthritis (SpA), especially those with psoriatic disease (PsD) [psoriasis (PsO) and psoriatic arthritis (PsA)], are at higher risk of non-alcoholic fatty liver disease (NAFLD) due to increased prevalence of metabolic syndrome, obesity, hypertension, dyslipidaemia and disease-specific factors such as duration/ severity of psoriasis. There is significant concern that both synthetic and biological DMARDs (including methotrexate) may worsen liver function in PsD patients with NAFLD. The Leeds Teaching Hospitals Trust (LTHT) NAFLD pathway uses three screening tools (ELF, FIB-4 and fibroscanning) to identify those needing further investigation/ treatment by hepatology. However, the pathway is not validated in PsD. Our aim was to survey the prevalence of liver disease in our PsD population and explore the performance of our hepatology referral pathway. Methods We audited consecutive patients referred from the Leeds Specialist SpA service at LTHT with persistently abnormal ALT, whom the consultant Rheumatologist felt required Hepatology referral for suspected NAFLD. Data collected were: age, sex, BMI, history of diabetes, ALT, AST, platelets, albumin, hepatitis B and C, ELF score, FIB-4 score, fibroscan score, abdominal ultrasound, liver biopsy result and final hepatology diagnosis (NAFLD, fibrosis/cirrhosis or other). Results 72 patients were included; 84.2% had PsD (61/72), and 15.8% (11/62) had ‘Other’ forms of SpA (including axial spondyloarthritis, enteropathic arthritis, etc). Baseline characteristics, drug treatment and liver biochemistry/virology were similar between PsD and Other arthritis groups (Table 1) except for age which was lower in the Other. The average ELF scores were similar between PsD and Other, however FIB-4 scores were higher in PsD, and was associated with higher rates of fibrosis/cirrhosis (Table 1). FIB-4 >1.3, but not ELF>9.5, was statistically significantly associated with a high fibroscan score (p = 0.038 and p = 0.443 respectively). Conclusion PsD patients had higher rates of significant fibrosis/cirrhosis compared with patients with Other SpAs. FIB-4 was better than ELF for identifying which PsD patients required fibroscan and further investigation to exclude significant fibrosis/ cirrhosis. These findings will now be validated in a larger prospective study. Disclosure S.R. Harrison: None. U. Nandasoma: None. R. Parker: None. C. Chimakurthi: None. P. Laws: None. A. Barr: None. C. Vandevelde: None. H. Marzo-Ortega: None. J. Freeston: None.