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Symptom presentations and other characteristics of colorectal cancer patients and the diagnostic performance of the UK NICE Referral Guideline for Suspected Colorectal Cancer in the South Auckland populationHsiang JC, Bai WWH, Lal D, Department of Gastroenterology, Middlemore Hospital, South Auckland, New ZealandAim: To review the presenting symptoms of colorectal cancer in the ethnically perse South Auckland populationTo evaluate the performance of both the Regional grading criteria and its NICE Guideline precursor as prediction tools for selecting colorectal cancer cases referred from primary careMethod: Retrospective review of all colorectal cancer (CRC) cases diagnosed between 2006 and January 2011. Information extracted from case note review was used to grade patients using both criteria.Results: 573 patients were included. Outpatient presenting symptoms: rectal bleeding (42.1%), change in bowel habit (25.1%), and abdominal pain (15.3%). Inpatient symptoms: abdominal pain (34.8%), rectal bleeding (32.4%), change in bowel habit (24.2%), and constipation (18.8%).41.7% of Pacific Island (PI) patients had stage IV disease compared to 23.6% of other groups combined (p<0.01). The tumour non-resection rate of Pacific Island group was 33.3% compared to 15.6% (European), 15.2% (Maori) and 8.0% (Asians), respectively (p=0.002). The age-adjusted mortality rates was: European 14.92, Maori 3.27, Pacific people 5.21, and Asian 1.05 (per 100,000)The Regional grading criteria and NICE Guideline would miss 27.7% and 33.2% of the presenting symptoms of CRC patients in the referral population.Conclusion: While rectal bleeding and change in bowel habit are frequent presenting symptoms, low-risk atypical symptoms including constipation, weight loss and abdominal pain were not uncommon.Significant proportion of Pacific Island patients present with late stage disease.Both the Regional grading criteria and NICE guideline would miss significant proportion of our study population with colorectal cancer.The 2012 Characteristics and Antibiotic Susceptibility of treatment naïve Helicobacter pylori Infections in South Auckland, New Zealand (Interim result)Hsiang JC, Selvaratnam S, Taylor SL, Tan YM, Huang J, Patrick AB. Gastroenterology Department, Middlemore Hospital, Otahuhu, Auckland, Microbiology Department, Middlemore Hospital, Otahuhu, AucklandAims: To ascertain the current prevalence of H. pylori infection in the ethnic perse population of South Auckland To assess the current antibiotic susceptibility of treatment naïve H.pyloriinfection in patients undergoing gastroscopy and provide up to date treatment recommendations Methods: Prospective study of consecutive patients undergoing gastroscopy between February 2012 and September 2012. Prevalence data was determined from all Campylobacter-Like organism (CLO) tests performed. Following informed consent CLO test was performed at routine gastroscopy. Biopsies for culture and antibiotics testing were obtained. Bacterial culture and resistance testing to common antibiotics (amoxicillin, tetracycline, clarithromycin, metronidazole and moxifloxacin) was performed. Eradication success was determined by following stool antigen clearance.Results: The prevalence of H. pylori infection among treatment naïve patients by ethnic group was: Maori (34.8%), Pacific people (31.3%) and Asian (23.8%). The interim results from 68 CLO positive patients were: Endoscopic indication- 19.1% iron deficiency anaemia, 20.6% dyspepsia, and 26.5% gastrointestinal bleeding. Antibiotic resistance: Amoxicillin 4.2% (2/48), Tetracycline 0.0% (0/48), Metronidazole 47.9% (23/48), Clarithromycin 12.5% (6/48), Moxifloxacin 7.9% (3/38 - extrapolating from levofloxacin breakpoints). Dual resistance to clarithromycin and metronidazole was 4.2%. Clearance testing: compliance 95.1% (39/41 patients) and success 76.7% (23/30). Discussion: H. pylori infection is very common among the Maori, Pacific and Asian groups. The resistance to clarithromycin and metronidazole is significant among treatment naïve patients.Conclusion: Resistance to Clarithromycin and Metronidazole has increased over historical NZ data and may contribute to low clearance rate. The current guidelines should be reviewed with respect to first-line regimensAdherence to Hepatocellular Carcinoma (HCC) Surveillance GuidelinesHsiang JC1, Bai WW1, Upton A1, Gane EJ2, Gerred SJ11Department of Gastroenterology and Hepatology, Middlemore Hospital, Auckland2New Zealand Liver Transplant Unit, Auckland City Hospital, AucklandIntroduction: Local guidelines recommend six monthly hepatic ultrasound (US) and alpha -fetoprotein (AFP) testing for patients with a high risk of developing hepatocellular carcinomna (HCC).Aim: To assess the adherence to HCC surveillance guidelines at our institution.Method: Patients with a high risk of HCC between 2007 and 2011 were identified from our clinic database. A retrospective review of electronic records was undertaken to record clinic attendance and adherence to six monthly AFP and US surveillance.Results: A total of 460 patients were identified. Cirrhosis was present in 409, severe hepatic fibrosis in 38, chronic hepatitis B and a family history of HCC in 13. European ethnicity was observed in 36%, Asian 23%, Pacific Island 20%, and Maori 12%. The aetiology of the underlying liver disease was: HBV (41%), Hepatitis C (23%), and Alcohol related liver disease (16%). The median age at diagnosis was 56 years, 62% were male. The median duration of surveillance was 3.4 years. HCC was detected in 23 patients (5%). The overall adherence rate for AFP testing and US surveillance was 79% and 59%, respectively. US adherence correlated strongly with clinic attendance but even in those attending regularly, 20% of US surveillance scans were missed.Conclusion: The poor performance of US surveillance highlights the rationale for continuing AFP testing at this time. Strategies that we have undertaken to improve US surveillance rates include: a patient education brochure, nurse specialist cirrhosis clinics, and improving clinic non-attendance procedures. We are endeavouring to organise a radiology based recall system.Predictors of serologic and clinical outcomes in childhood-acquired HBV infection in New Zealand Māori: results of 28 year longitudinal studyLim TH1, Gane EJ1, Borman B2, Moyes C,3 Cunningham C2.1Liver Unit, Auckland City Hospital, Auckland, New Zealand2Research Centre for Maōri Health and Development, Massey University, Wellington, New Zealand3The Hepatitis Foundation of New Zealand, Whakatane, New ZealandBackground: High baseline HBV DNA is associated with increased risk of liver-related complications in Asians with vertically-transmitted chronic hepatitis B virus(HBV) infection. This longitudinal study evaluates the baseline predictors for liver-related complications and serologic outcomes in 572 patients identified from a 1984 seroprevalence study with early horizontally-acquired HBV infection.Methods: Serum samples from 1984 were tested for HBeAg,HBV DNA and HBsAg level. Liver-related mortality and hepatocellular carcinoma(HCC) incidence were previously determined in these 572 HBV carriers compared to 1142 HBsAg-negative case-controls. Transient elastography(TE) was performed in 2012 in all surviving HBsAg+ inpiduals. Cox-proportional hazards models were used to determine independent baseline predictors for five long-term outcomes: severe fibrosis (TE>8KPa), HCC, liver-related mortality and HBsAg+HBeAg seroconversion.Results: After 28 years, 14HBsAg+ patients developed HCC(vs none in HBsAg- controls [P<0.001]). 11HBsAg+ patients died from liver-related causes(vs none in controls(P<0.001)). To-date, 291/515(57%) surviving HBsAg+ patients have been followed-up. 25% had elevated ALT; 12% had severe fibrosis/cirrhosis(TE>8KPa). Increasing age, Maōri ethnicity and baseline HBV DNA were predictors for liver-related death and HCC. Maōri ethnicity was a predictor for severe fibrosis. Baseline HBsAg level and gender were not predictors for long-term outcome. Since 1984,90% of HBeAg+ patients have undergone HBeAg seroconversion (median age=23yrs(range 6-66)). 31% spontaneously lost HBsAg (median age 39 yrs(range 9-80)), with higher rates in HBeAg-(44%) vs HBeAg+ patients(9%)(p<0.0001).Conclusions: In a young Maōri population with early horizontally-acquired HBV, HBV DNA, but not HBsAg-level, was associated with increased risk for liver-related complications. Higher rates of spontaneous HBeAg and HBsAg loss are seen compared to Asians HBV populations.Disclosure statement: The authors have no disclosures.CMV and EBV disease in adult liver transplant recipientsGriffiths B, Gane E, Fitt S, Munn SJ. NZLTU, Auckland Hospital, New ZealandIntroduction: Herpes virus infections are an important cause of morbidity and mortality following solid organ transplantation. NZLTU has used CMV antiviral prophylaxis in all D+/R- transplants. This audit determines the incidence of CMV disease and EBV disease.Methods: CMV and EBV D/R serostatus was collected prospectively. Pharmacy and virological data were used to identify CMV and EBV infection and disease.Results: 409 adult liver transplants were evaluated. CMV serostatus was D+/R- in 57 (12.5%), D-/R+ in 112 (27.4%), D+/R+ in 188 (46%), D-/R- in 51 (12.5%). CMV infection was detected in 47 patients (11.5%), at mean 41 weeks. There were 26 cases of CMV disease (6.4% total), diagnosed at mean 57 weeks. CMV disease developed in 16 D+/R- (28.1%), 5 D-/R+ (4.5%) and 5 D+/R+ (2.7%). Mycophenolate was associated with increased risk of CMV disease (RR 4.0; 95% CI 2.3 - 3.8; p<0.0001).EBV serostatus was D+/R- in 17 (4.8%), D-/R+ in 29 (8.3%), D+/R+ in 302 (86%), D-/R- in 3 (0.9%). Six cases of EBV-associated PTLD (1.5% total) were diagnosed at mean 86 weeks. EBV disease developed in 5 (29.4%) D+/R- and 1 (0.3%) D+/R+.Conclusion: Antiviral prophylaxis has reduced incidence and delayed onset of CMV disease in D+/R- transplants. Mycophenolate is associated with an increased risk of CMV disease. EBV D+/R- transplants have a high rate of PTLD. Better EBV prophylaxis and monitoring regimens are needed.Entecavir in Chronic Hepatitis B - “Real World” ExperienceLampen-Smith A1, Wong P2,GerredS3,Gane E11Liver Unit, Auckland City Hospital, 2Gastroenterology Department, Auckland City Hospital,3Gastroenterology Department, Middlemore Hospital.Introduction: Entecavir is an approved antiviral treatment for chronic hepatitis B1. Global registration trials demonstrated excellent safety and efficacy - serum HBV DNA undetectable in 90% after 48 weeks of treatment.2 Similar results have been reported in “real-world” experience.3Methods: This is an audit of patients at Auckland and Middlemore Hospitals treated with entecavir for at least 12 months. Patients were excluded if they had prior antiviral therapy, or a diagnosis of HCC within 12 months. Data on ALT, HBV DNA, resistance studies, ethnicity and HBeAg serology was collected. Clinic notes were reviewed for evidence of treatment adherence.Results: Entecavir was approved in 459 patients, of whom 351 have received 12 months therapy. After exclusions there were 108 HBeAg positive and 157 HBeAg negative. Twenty (18.5%) HBeAg positive patients underwent HBeAg seroconversion. Of the remaining 88 eAg positive patients, HBV DNA was suppressed to undetectable or ≤3 log in 60 (68.2%). In the 28 subjects with sub-optimal virological response, 10 were adherent and had decreasing HBV DNA whilst the remaining 18 had poor adherence/ nonattendance.Of the HBeAg negative patients, 111 (71.2%) had undetectable HBV DNA, 15 (9.6%) had levels < 3 log IU/mL. Seven (4.5%) had sub-optimal virological response, all showed poor adherence. Sequencing studies did not identify resistance mutations.Conclusion: The efficacy and safety of entecavir is in clinical practice is similar to that observed in registration studies, with 80.7% and 74.1% viral suppression in eAg negative and positive chronic hepatitis B patients respectively. Lack of response reflected poor adherence rather than entecavir resistance.References: Kim SR, et al. Recent advances in the management of chronic Hepatitis B. Hepat Mon. 2011;11(8):601-11. Lai C-L, et al. Entecavir versus Lamivudine for Patients with HBeAg-Negative Chronic Hepaititis B. N Engl J Med 2006;354:1011-20. Tsai MC, et al. A comparison of telbivudine and entecavir for chronic hepatitis B in real-world clinical practice. J Antimicrob Chemother. 2012 Mar;67(3):696-9. Prealbumin measurement as a guide to adequate nutritional supports in patients receiving parenteral nutritionHY Lee, S Larsen, S Hill, R Baskett, RS WalmsleyNorth Shore Hospital, Auckland, New ZealandPrealbumin is a visceral protein and negative acute phase reactant used as a nutritional status screening tool to detect malnutrition. Its relatively short physiological half-life of 48 to 72 hours provides a dynamic measure of protein-energy status and adequacy of nutritional support (1). A rise in prealbumin of greater than 0.04 g/L has been suggested to indicate switch from a catabolic to an anabolic state (2).Aims: To assess the use of serial measurements of serum prealbumin in patients receiving short-term parenteral nutrition (PN), to determine whether anabolism can be achieved during short-term PN and the relation between change in prealbumin and acute phase response level indicated by C-reactive protein (CRP).Methods: Retrospective review of Nutrition Support Database from May 2005 to May 2012.Results: From 494 patients identified receiving PN, 142 patients had paired prealbumin and CRP data available.Negative correlation was confirmed between CRP and prealbumin (r=-0.52). Following PN therapy the mean C-reactive protein decreased from 123 to 53 mg/L (p<0.001). Mean serum prealbumin increased from 0.12 to 0.22 g/L (p<0.001).Prealbumin rise of greater than 0.04 g/L was achieved in 72% (n=102) of patients. Mean CRP after completion of PN in this group was significantly less (42 vs 83 mg/L, p<0.001), suggesting ongoing inflammation may impede visceral protein synthesis.Conclusion: Serial prealbumin measurements in patients receiving short-term parenteral nutrition are a useful guide to the adequacy of nutritional support.An anabolic state switch can be achieved in most patients despite persistent systemic inflammatory response.References Ingenbleek Y, Young V. Clin Chem Lab Med. 2002;40:1281-1291. Bernstein L, Bachman T, Meguid M, Ament M, Baumgartner T, Kinosian B, et al. Nutrition 1995;11:169-171 The Scratch Test for identifying the lower liver edge is at least as accurate as percussion and is more effective for trainees - a randomized controlled studyHuelsen A,1,2 Fischer J,1 Hegarty J,3 Lim JY,2 Burnside MJ,2 Karim SN,2 Onyango N, 2Frampton C,4 Spencer AJ,2 Barclay ML. 1,4Departments of Gastroenterology,1 General Medicine 2 & Radiology,3 Christchurch Hospital, and Department of Medicine,4 University of Otago Christchurch, Christchurch, New Zealand.Introduction: Clinical examination of the liver requires experience to achieve accuracy. The scratch test is a simple technique to identify the lower liver edge and enhance liver palpation, and may be easier for trainees.Aims and Methods: We aimed to evaluate the accuracy of the scratch test compared to percussion at different levels of medical training. Eight examiners, from trainee intern to consultant level, were randomized to scratch or percussion testing, followed by liver palpation, on 50 subjects. Later, each examiner performed the alternative test on each subject. Confidence with each test was rated 0-3 (unsuccessful - very confident). Ultrasound scan (USS) was performed as a reference for liver location.Results: Ultrasound revealed 33/50 (66%) of livers extended below the right costal margin in the midclavicular line during quiet respiration (range 0-16cm). Of these 33, 84% and 81% were identified within 2cm of the USS location using scratch and percussion tests, respectively (p>0.05) for all examiners, but with greater accuracy for the scratch test in young trainees (86% v 80%). Ability to palpate the liver was not different following either test. Examiner confidence in the test result was significantly higher using the scratch test versus percussion, average confidence scores being 2.2 versus 1.8 (p=0.007), with a greater difference in the young trainee group (p=0.003).Conclusion: The scratch test was at least as accurate as percussion in identifying the lower liver edge. In addition, all examiners and especially the young trainees were more confident in their findings using the scratch test.Predictors of poor outcome in patients with autoimmune hepatitis: a population-based studyNgu, J.H. 1,2, Gearry, R.B. 1,2, Frampton, C.M. 2, Stedman C.A.M. 1,21 Department of Gastroenterology, Christchurch Hospital 2 University of Otago, Christchurch, New Zealand.Background/Aim: Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure and death. Identifying predictors of poor outcomes could help in devising tailored management strategies. We aimed to describe predictors of poor outcomes in the population-based AIH cohort from Canterbury.Methods: Multiple case finding methods were employed, including searches of all public and private, adult and paediatric outpatient clinics, hospital notes and pathology reports. Cases diagnosed after 1980 that fulfilled standardised diagnostic criteria were included. End of follow-up was at death, liver transplantation or the end of study (31st December 2011). The associations of putative risk factors and outcomes were analyzed using Cox proportional hazards regression. The times to event outcomes were summarized using Kaplan-Meier curves.Results: A total of 133 AIH patients were included. Independent predictors of poor liver related outcomes were incomplete normalization of ALT at 6 months (p<0.01), baseline serum albumin <36g/L (p<0.01) and age at presentation of ≤ 20 years or >60 years (p=0.01). Kaplan-Meier estimates showed 10 years adverse liver event free survival were 80% for age at presentation ≤20 years and >60 years, and 93% and 100% for age at presentation between 21-40 years and 41-60 years respectively.Conclusion: Incomplete normalization of ALT at 6 months, low serum albumin concentration at diagnosis and age at presentation of ≤ 20 years or >60 years, were significant independent predictors of poor liver related outcomes. Histological cirrhosis at diagnosis was not associated with poor prognosis and did not influence the response to initial immunosuppressive treatment.Environmental risk factors in autoimmune hepatitis: a population-based case control studyNgu, J.H. 1,2, Gearry, R.B. 1,2, Frampton, C.M. 2, Stedman C.A.M. 1,21 Department of Gastroenterology, Christchurch Hospital 2 University of Otago, Christchurch, New Zealand.Background/Aim: The precise aetiology of autoimmune hepatitis (AIH) remains unknown and likely involves a complex interaction of genetic and environmental factors. However, to date, systematic examination of association between environmental factors and AIH has yet to be performed. We aimed to perform a population-based case control study to investigate for associations between exposure to putative environmental factors and AIH.Methods: Cases were AIH patients who were alive and resided in Canterbury between 1st July 2011 and 30th June 2012. Controls were randomly selected from the Electoral Roll and were matched 2:1 to each case by age and gender. Self-reporting questionnaires that cover lifestyle factors, childhood factors and family history were used.Results: A total of 72 AIH cases and 144 controls were included. Univariate analysis showed that antibiotic (p<0.01) and being vegetarian >1 year (p=0.04) were risk factors for AIH. Alcohol consumption (p<0.01), childhood home with vegetable garden (p=0.01) and wood heating (p<0.01) were protective factors. Multivariate analysis showed that antibiotic, alcohol consumption and childhood home with wood heating were independently associated with AIH. The crude risk of AIH in first degree relatives was 0.2%.Conclusion: This is the first population-based study investigating for associations between exposure to environmental factors and AIH. We found that antibiotics were an independent risk factor, whereas alcohol consumption and childhood home with wood heating were independent protective factors for AIH. Risk of AIH in first degree relatives was low.Auckland experience with Tenofovir therapy in nucleoside/nucleotide experienced patients with Chronic Hepatitis BJohns E, Naidoo M, Gane E, New Zealand Liver Transplant Unit, AucklandThe nucleotide analogue Tenofovir is funded for patients with hepatitis B, loss of virological response (HBV DNA 20 000 IU/mL or >1 log from nadir) and proven antiviral resistance.In treatment-naïve patients 76% of HBeAg-positive and 93% of HBeAg-negative achieve viral suppression (HBV DNA <400 copies/mL or 69 IU/ml) at 48 weeks. Treatment-experienced cohorts show a similar response but questions remain over durability in patients with adefovir resistance.We report local experience in treatment-experienced patients switched to tenofovir as monotherapy or in combination with lamivudine.Results: 144 of 146 patients tolerated treatment and were analysed. 38 received combination therapy. Median follow up was 26 months (range 1-94) with 116 patients completing 12 and 75 patients 24 months of therapy. Previous treatment included lamivudine (95%), adefovir (64%) and telbivudine (12%).On intention to treat analysis 67% of HBeAg-positive, 72% of HBeAg-negative and 69% of all patients achieved viral suppression (<400 copies/mL) at 12 months, and 70%, 82% and 75% respectively at 24 months. In patients meeting PHARMAC criteria for treatment failure at commencement of therapy suppression was 56% at 12 and 75% at 24 months; results were similar in the adefovir-resistant subgroup (57% and 71%).HBeAg seroconversion occurred in 13% of patients treated for ≥ 12 months; no patient lost HBsAg.Conclusion: Our experience with tenofovir rescue therapy in patients with antiviral resistance is consistent with published series. Adefovir-resistant patients had a similar virologic response but longer follow-up is needed. The need for combination rather than monotherapy in this population needs further evaluation.Disease assessment in Crohn’s disease (CD): Data from the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) project cohorta,dFalvey, JD, aHoskin T, aMeijer B, aAshcroft A, bHampton, MB, c,eDay AS a,dGearry, RB.Departments of aMedicine, bPathology and, cPaediatrics, University of Otago Christchurch. Departments of dGastroenterology and ePaediatrics, Christchurch Hospital, Christchurch.Introduction: Colonoscopy, the gold standard for CD assessment, is not suitable for regular monitoring while clinical assessment is often inaccurate. We aimed to determine the clinical utility of three established non-invasive methods of CD assessment, the Harvey Bradshaw index (HBI), serum CRP and faecal calprotectin (FC), and one novel biomarker candidate, serum macrophage migration inhibitory factor (MIF).Methods: Patients attending for colonoscopy with known or suspected IBD were recruited to the NBIBD cohort. Cases provided full demographic and disease activity data (HBI) in addition to biological samples. Endoscopic activity was recorded using the simple endoscopic score of Crohn’s disease (SES-CD)Results: 108 cases were included. Median (IQR) SES-CD, 4 (2-12). Spearman correlation coefficients for comparison with SES-CD were: HBI r=0.24 (p=0.007); CRP, r=0.44 (p<0.0001); FC r=0.55 (p<0.0001, n=82); MIF r=0.14 (p=0.2, n=85). A trend to better diagnostic utility was observed for FC over CRP (active≡SES-CD ≥3, AUC 0.74 (p=0.0006) and AUC 0.64 (p=0.003) respectively). HBI had modest diagnostic accuracy for severe disease only (SES-CD ≥16 vs. ≤15, AUC 0.78 (p=0.0002)). Sensitivity, specificity, PPV and NPV of FC ≥125µg/g for SES-CD ≥3 disease were, 71%, 71%, 85% and 50% respectively. Neither HBI, FC nor CRP could anticipate endoscopic remission. Combining CRP (≥10mg/L) and clinical data (HBI ≥8) significantly improved PPV for the detection of moderate-severe CD (SES-CD ≥7) cf. CRP alone (PPV 73% (95%CI 51-93%) vs. 50% (95%CI 34-65%) respectively).Conclusions: Established methods of non-invasive disease assessment offer modest diagnostic utility. Novel biomarkers with greater sensitivity and specificity are urgently needed.Clinical assessment of murine Dextran Sodium Sulphate (DSS) colitis: prospective validation of a novel scoring tool.a,eFalvey JD, dMunday JS, bKeenan, JI, fDyer AE, a,eGearry, RB, cHampton, MBDepartments of Medicinea, Surgeryb and Pathologyc, University of Otago Christchurch.dInstitute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North. eDepartment of Gastroenterology, Christchurch Hospital, Christchurch. fChristchurch Animal Research Area, University of Otago, Christchurch.Introduction: Murine DSS colitis is a common research model for IBD. Histological examination of the colon provides gold standard assessment; however, non-lethal assessment is critical for disease monitoring and secondary endpoint analysis. Coopers’ murine colitis score (MCS), the current standard, correlates well with histology but has low content validity in some domains.Aims: To develop and prospectively validate a novel MCS.Methods: Developmental phase: Novel stool consistency and rectal bleeding indices were developed in order to improve content validity of these domains. Variations of the MCS were tested in post hoc analysis against histology. Validation stage: 2% DSS was provided ad libitum to 24 mice. Three mice per day (0-7) were selected randomly; disease was assessed independently by 2 observers using a proforma from which a complex MCS, a simple MCS (SMCS) and the Cooper MCS were derived. Non-invasive assessment was compared with histological activity.Results: Murine colitis scores correlated highly with histology (Spearman r=0.93, r=0.91 and r=0.91 for the simple, the complex and the Cooper MCS respectively (p<0.0001)). Correlation with histology was non-significantly greater for the novel stool score compared with Cooper stool score (r=0.86 (95%CI 0.69 - 0.94) vs. r=0.77). There was a high level of agreement (linear weighted қ=0.86 (95%CI 0.77-0.96)) and correlation (r=0.94 (95%CI 0.87-0.98) p<0.0001) between observers for the SMCS.Conclusions: A modification of the Coopers colitis score (SMCS) comprising a weight loss score, novel stool score and dichotomous rectal bleeding score, provides a valid and simple method for the non-invasive assessment of DSS colitis.Disease assessment in Ulcerative Colitis (UC): Data from the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) project cohorta,dFalvey JD, aHoskin T, aMeijer B, aAshcroft A, bHampton, MB, c,eDay AS, a,dGearry, RB.Departments of aMedicine, bPathology and,cPaediatrics University of Otago Christchurch. Departments of dGastroenterology and ePaediatrics, Christchurch Hospital, Christchurch.Introduction: Colonoscopy, the gold standard for UC assessment, is not suitable for regular monitoring while clinical assessment is frequently inaccurate. We aimed to determine the clinical utility of three established non-invasive methods of disease assessment, the simple clinical colitis activity index (SCCAI), serum CRP and faecal calprotectin (FC), and one novel biomarker candidate serum macrophage migration inhibitory factor (MIF) in the normal clinical setting.Methods: Patients attending for colonoscopy with known or suspected IBD were recruited to the NBIBD cohort. Cases with UC provided full demographic and disease activity data (SCCAI) in addition to biological samples. Endoscopic activity was recorded using the modified Baron scoreResults: 65 cases were included. Spearman r correlation coefficients for comparison with endoscopic score were: CRP, r=0.4 (p<0.0001); SCCAI r=0.44 (0.31-0.62, p=0.0002); FC r=0.55 (p<0.0001, n=51). Overall disease burden (severity*extent) correlated better with each parameter but differences were not significant. No correlation was observed between plasma MIF and endoscopic activity (r=0.11, p=0.2, n= 85). ROC analysis revealed significant diagnostic utility for SCCAI, CRP and FC (AUC 0.73 (p=0.002), AUC 0.78 (p=0.002) and AUC 0.75 (p=0.004) respectively). Optimal thresholds for distinguishing Baron ≥2 disease were (threshold (sensitivity, specificity, PPV and NPV)): SCCAI, 3.5 (59%, 88%, 72%, 81%); CRP 5mg/L (64%, 74%, 56%, 80%); FC 125 ug/g (83%, 64%, 56%, 88%). Neither CRP nor FC could reliably anticipate endoscopic remission (Baron 0).Conclusions: Established methods of non-invasive disease assessment offer modest diagnostic utility. Novel biomarkers with greater sensitivity and specificity are urgently needed.Outcomes of adalimumab therapy for Crohn’s disease from five New Zealand hospitalsSchultz M,1 Lewis-Morris T,2 Rowbotham D,3 Whiteside C,4 Bennett S,1 Thomas G,2 Inns S,4 Gearry RB2Departments of Gastroenterology, 1Dunedin, 2Christchurch, 3Auckland City, 4Hutt Valley HospitalsIntroduction: Adalimumab (ADA) is an effective therapy for the treatment of Crohn’s disease (CD). We aimed to describe the use o

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Symptom presentations and other characteristics of colorectal cancer patients and the diagnostic performance of the UK NICE Referral Guideline for Suspected Colorectal Cancer in the South Auckland populationHsiang JC, Bai WWH, Lal D, Department of Gastroenterology, Middlemore Hospital, South Auckland, New ZealandAim: To review the presenting symptoms of colorectal cancer in the ethnically perse South Auckland populationTo evaluate the performance of both the Regional grading criteria and its NICE Guideline precursor as prediction tools for selecting colorectal cancer cases referred from primary careMethod: Retrospective review of all colorectal cancer (CRC) cases diagnosed between 2006 and January 2011. Information extracted from case note review was used to grade patients using both criteria.Results: 573 patients were included. Outpatient presenting symptoms: rectal bleeding (42.1%), change in bowel habit (25.1%), and abdominal pain (15.3%). Inpatient symptoms: abdominal pain (34.8%), rectal bleeding (32.4%), change in bowel habit (24.2%), and constipation (18.8%).41.7% of Pacific Island (PI) patients had stage IV disease compared to 23.6% of other groups combined (p<0.01). The tumour non-resection rate of Pacific Island group was 33.3% compared to 15.6% (European), 15.2% (Maori) and 8.0% (Asians), respectively (p=0.002). The age-adjusted mortality rates was: European 14.92, Maori 3.27, Pacific people 5.21, and Asian 1.05 (per 100,000)The Regional grading criteria and NICE Guideline would miss 27.7% and 33.2% of the presenting symptoms of CRC patients in the referral population.Conclusion: While rectal bleeding and change in bowel habit are frequent presenting symptoms, low-risk atypical symptoms including constipation, weight loss and abdominal pain were not uncommon.Significant proportion of Pacific Island patients present with late stage disease.Both the Regional grading criteria and NICE guideline would miss significant proportion of our study population with colorectal cancer.The 2012 Characteristics and Antibiotic Susceptibility of treatment naïve Helicobacter pylori Infections in South Auckland, New Zealand (Interim result)Hsiang JC, Selvaratnam S, Taylor SL, Tan YM, Huang J, Patrick AB. Gastroenterology Department, Middlemore Hospital, Otahuhu, Auckland, Microbiology Department, Middlemore Hospital, Otahuhu, AucklandAims: To ascertain the current prevalence of H. pylori infection in the ethnic perse population of South Auckland To assess the current antibiotic susceptibility of treatment naïve H.pyloriinfection in patients undergoing gastroscopy and provide up to date treatment recommendations Methods: Prospective study of consecutive patients undergoing gastroscopy between February 2012 and September 2012. Prevalence data was determined from all Campylobacter-Like organism (CLO) tests performed. Following informed consent CLO test was performed at routine gastroscopy. Biopsies for culture and antibiotics testing were obtained. Bacterial culture and resistance testing to common antibiotics (amoxicillin, tetracycline, clarithromycin, metronidazole and moxifloxacin) was performed. Eradication success was determined by following stool antigen clearance.Results: The prevalence of H. pylori infection among treatment naïve patients by ethnic group was: Maori (34.8%), Pacific people (31.3%) and Asian (23.8%). The interim results from 68 CLO positive patients were: Endoscopic indication- 19.1% iron deficiency anaemia, 20.6% dyspepsia, and 26.5% gastrointestinal bleeding. Antibiotic resistance: Amoxicillin 4.2% (2/48), Tetracycline 0.0% (0/48), Metronidazole 47.9% (23/48), Clarithromycin 12.5% (6/48), Moxifloxacin 7.9% (3/38 - extrapolating from levofloxacin breakpoints). Dual resistance to clarithromycin and metronidazole was 4.2%. Clearance testing: compliance 95.1% (39/41 patients) and success 76.7% (23/30). Discussion: H. pylori infection is very common among the Maori, Pacific and Asian groups. The resistance to clarithromycin and metronidazole is significant among treatment naïve patients.Conclusion: Resistance to Clarithromycin and Metronidazole has increased over historical NZ data and may contribute to low clearance rate. The current guidelines should be reviewed with respect to first-line regimensAdherence to Hepatocellular Carcinoma (HCC) Surveillance GuidelinesHsiang JC1, Bai WW1, Upton A1, Gane EJ2, Gerred SJ11Department of Gastroenterology and Hepatology, Middlemore Hospital, Auckland2New Zealand Liver Transplant Unit, Auckland City Hospital, AucklandIntroduction: Local guidelines recommend six monthly hepatic ultrasound (US) and alpha -fetoprotein (AFP) testing for patients with a high risk of developing hepatocellular carcinomna (HCC).Aim: To assess the adherence to HCC surveillance guidelines at our institution.Method: Patients with a high risk of HCC between 2007 and 2011 were identified from our clinic database. A retrospective review of electronic records was undertaken to record clinic attendance and adherence to six monthly AFP and US surveillance.Results: A total of 460 patients were identified. Cirrhosis was present in 409, severe hepatic fibrosis in 38, chronic hepatitis B and a family history of HCC in 13. European ethnicity was observed in 36%, Asian 23%, Pacific Island 20%, and Maori 12%. The aetiology of the underlying liver disease was: HBV (41%), Hepatitis C (23%), and Alcohol related liver disease (16%). The median age at diagnosis was 56 years, 62% were male. The median duration of surveillance was 3.4 years. HCC was detected in 23 patients (5%). The overall adherence rate for AFP testing and US surveillance was 79% and 59%, respectively. US adherence correlated strongly with clinic attendance but even in those attending regularly, 20% of US surveillance scans were missed.Conclusion: The poor performance of US surveillance highlights the rationale for continuing AFP testing at this time. Strategies that we have undertaken to improve US surveillance rates include: a patient education brochure, nurse specialist cirrhosis clinics, and improving clinic non-attendance procedures. We are endeavouring to organise a radiology based recall system.Predictors of serologic and clinical outcomes in childhood-acquired HBV infection in New Zealand Māori: results of 28 year longitudinal studyLim TH1, Gane EJ1, Borman B2, Moyes C,3 Cunningham C2.1Liver Unit, Auckland City Hospital, Auckland, New Zealand2Research Centre for Maōri Health and Development, Massey University, Wellington, New Zealand3The Hepatitis Foundation of New Zealand, Whakatane, New ZealandBackground: High baseline HBV DNA is associated with increased risk of liver-related complications in Asians with vertically-transmitted chronic hepatitis B virus(HBV) infection. This longitudinal study evaluates the baseline predictors for liver-related complications and serologic outcomes in 572 patients identified from a 1984 seroprevalence study with early horizontally-acquired HBV infection.Methods: Serum samples from 1984 were tested for HBeAg,HBV DNA and HBsAg level. Liver-related mortality and hepatocellular carcinoma(HCC) incidence were previously determined in these 572 HBV carriers compared to 1142 HBsAg-negative case-controls. Transient elastography(TE) was performed in 2012 in all surviving HBsAg+ inpiduals. Cox-proportional hazards models were used to determine independent baseline predictors for five long-term outcomes: severe fibrosis (TE>8KPa), HCC, liver-related mortality and HBsAg+HBeAg seroconversion.Results: After 28 years, 14HBsAg+ patients developed HCC(vs none in HBsAg- controls [P<0.001]). 11HBsAg+ patients died from liver-related causes(vs none in controls(P<0.001)). To-date, 291/515(57%) surviving HBsAg+ patients have been followed-up. 25% had elevated ALT; 12% had severe fibrosis/cirrhosis(TE>8KPa). Increasing age, Maōri ethnicity and baseline HBV DNA were predictors for liver-related death and HCC. Maōri ethnicity was a predictor for severe fibrosis. Baseline HBsAg level and gender were not predictors for long-term outcome. Since 1984,90% of HBeAg+ patients have undergone HBeAg seroconversion (median age=23yrs(range 6-66)). 31% spontaneously lost HBsAg (median age 39 yrs(range 9-80)), with higher rates in HBeAg-(44%) vs HBeAg+ patients(9%)(p<0.0001).Conclusions: In a young Maōri population with early horizontally-acquired HBV, HBV DNA, but not HBsAg-level, was associated with increased risk for liver-related complications. Higher rates of spontaneous HBeAg and HBsAg loss are seen compared to Asians HBV populations.Disclosure statement: The authors have no disclosures.CMV and EBV disease in adult liver transplant recipientsGriffiths B, Gane E, Fitt S, Munn SJ. NZLTU, Auckland Hospital, New ZealandIntroduction: Herpes virus infections are an important cause of morbidity and mortality following solid organ transplantation. NZLTU has used CMV antiviral prophylaxis in all D+/R- transplants. This audit determines the incidence of CMV disease and EBV disease.Methods: CMV and EBV D/R serostatus was collected prospectively. Pharmacy and virological data were used to identify CMV and EBV infection and disease.Results: 409 adult liver transplants were evaluated. CMV serostatus was D+/R- in 57 (12.5%), D-/R+ in 112 (27.4%), D+/R+ in 188 (46%), D-/R- in 51 (12.5%). CMV infection was detected in 47 patients (11.5%), at mean 41 weeks. There were 26 cases of CMV disease (6.4% total), diagnosed at mean 57 weeks. CMV disease developed in 16 D+/R- (28.1%), 5 D-/R+ (4.5%) and 5 D+/R+ (2.7%). Mycophenolate was associated with increased risk of CMV disease (RR 4.0; 95% CI 2.3 - 3.8; p<0.0001).EBV serostatus was D+/R- in 17 (4.8%), D-/R+ in 29 (8.3%), D+/R+ in 302 (86%), D-/R- in 3 (0.9%). Six cases of EBV-associated PTLD (1.5% total) were diagnosed at mean 86 weeks. EBV disease developed in 5 (29.4%) D+/R- and 1 (0.3%) D+/R+.Conclusion: Antiviral prophylaxis has reduced incidence and delayed onset of CMV disease in D+/R- transplants. Mycophenolate is associated with an increased risk of CMV disease. EBV D+/R- transplants have a high rate of PTLD. Better EBV prophylaxis and monitoring regimens are needed.Entecavir in Chronic Hepatitis B - “Real World” ExperienceLampen-Smith A1, Wong P2,GerredS3,Gane E11Liver Unit, Auckland City Hospital, 2Gastroenterology Department, Auckland City Hospital,3Gastroenterology Department, Middlemore Hospital.Introduction: Entecavir is an approved antiviral treatment for chronic hepatitis B1. Global registration trials demonstrated excellent safety and efficacy - serum HBV DNA undetectable in 90% after 48 weeks of treatment.2 Similar results have been reported in “real-world” experience.3Methods: This is an audit of patients at Auckland and Middlemore Hospitals treated with entecavir for at least 12 months. Patients were excluded if they had prior antiviral therapy, or a diagnosis of HCC within 12 months. Data on ALT, HBV DNA, resistance studies, ethnicity and HBeAg serology was collected. Clinic notes were reviewed for evidence of treatment adherence.Results: Entecavir was approved in 459 patients, of whom 351 have received 12 months therapy. After exclusions there were 108 HBeAg positive and 157 HBeAg negative. Twenty (18.5%) HBeAg positive patients underwent HBeAg seroconversion. Of the remaining 88 eAg positive patients, HBV DNA was suppressed to undetectable or ≤3 log in 60 (68.2%). In the 28 subjects with sub-optimal virological response, 10 were adherent and had decreasing HBV DNA whilst the remaining 18 had poor adherence/ nonattendance.Of the HBeAg negative patients, 111 (71.2%) had undetectable HBV DNA, 15 (9.6%) had levels < 3 log IU/mL. Seven (4.5%) had sub-optimal virological response, all showed poor adherence. Sequencing studies did not identify resistance mutations.Conclusion: The efficacy and safety of entecavir is in clinical practice is similar to that observed in registration studies, with 80.7% and 74.1% viral suppression in eAg negative and positive chronic hepatitis B patients respectively. Lack of response reflected poor adherence rather than entecavir resistance.References: Kim SR, et al. Recent advances in the management of chronic Hepatitis B. Hepat Mon. 2011;11(8):601-11. Lai C-L, et al. Entecavir versus Lamivudine for Patients with HBeAg-Negative Chronic Hepaititis B. N Engl J Med 2006;354:1011-20. Tsai MC, et al. A comparison of telbivudine and entecavir for chronic hepatitis B in real-world clinical practice. J Antimicrob Chemother. 2012 Mar;67(3):696-9. Prealbumin measurement as a guide to adequate nutritional supports in patients receiving parenteral nutritionHY Lee, S Larsen, S Hill, R Baskett, RS WalmsleyNorth Shore Hospital, Auckland, New ZealandPrealbumin is a visceral protein and negative acute phase reactant used as a nutritional status screening tool to detect malnutrition. Its relatively short physiological half-life of 48 to 72 hours provides a dynamic measure of protein-energy status and adequacy of nutritional support (1). A rise in prealbumin of greater than 0.04 g/L has been suggested to indicate switch from a catabolic to an anabolic state (2).Aims: To assess the use of serial measurements of serum prealbumin in patients receiving short-term parenteral nutrition (PN), to determine whether anabolism can be achieved during short-term PN and the relation between change in prealbumin and acute phase response level indicated by C-reactive protein (CRP).Methods: Retrospective review of Nutrition Support Database from May 2005 to May 2012.Results: From 494 patients identified receiving PN, 142 patients had paired prealbumin and CRP data available.Negative correlation was confirmed between CRP and prealbumin (r=-0.52). Following PN therapy the mean C-reactive protein decreased from 123 to 53 mg/L (p<0.001). Mean serum prealbumin increased from 0.12 to 0.22 g/L (p<0.001).Prealbumin rise of greater than 0.04 g/L was achieved in 72% (n=102) of patients. Mean CRP after completion of PN in this group was significantly less (42 vs 83 mg/L, p<0.001), suggesting ongoing inflammation may impede visceral protein synthesis.Conclusion: Serial prealbumin measurements in patients receiving short-term parenteral nutrition are a useful guide to the adequacy of nutritional support.An anabolic state switch can be achieved in most patients despite persistent systemic inflammatory response.References Ingenbleek Y, Young V. Clin Chem Lab Med. 2002;40:1281-1291. Bernstein L, Bachman T, Meguid M, Ament M, Baumgartner T, Kinosian B, et al. Nutrition 1995;11:169-171 The Scratch Test for identifying the lower liver edge is at least as accurate as percussion and is more effective for trainees - a randomized controlled studyHuelsen A,1,2 Fischer J,1 Hegarty J,3 Lim JY,2 Burnside MJ,2 Karim SN,2 Onyango N, 2Frampton C,4 Spencer AJ,2 Barclay ML. 1,4Departments of Gastroenterology,1 General Medicine 2 & Radiology,3 Christchurch Hospital, and Department of Medicine,4 University of Otago Christchurch, Christchurch, New Zealand.Introduction: Clinical examination of the liver requires experience to achieve accuracy. The scratch test is a simple technique to identify the lower liver edge and enhance liver palpation, and may be easier for trainees.Aims and Methods: We aimed to evaluate the accuracy of the scratch test compared to percussion at different levels of medical training. Eight examiners, from trainee intern to consultant level, were randomized to scratch or percussion testing, followed by liver palpation, on 50 subjects. Later, each examiner performed the alternative test on each subject. Confidence with each test was rated 0-3 (unsuccessful - very confident). Ultrasound scan (USS) was performed as a reference for liver location.Results: Ultrasound revealed 33/50 (66%) of livers extended below the right costal margin in the midclavicular line during quiet respiration (range 0-16cm). Of these 33, 84% and 81% were identified within 2cm of the USS location using scratch and percussion tests, respectively (p>0.05) for all examiners, but with greater accuracy for the scratch test in young trainees (86% v 80%). Ability to palpate the liver was not different following either test. Examiner confidence in the test result was significantly higher using the scratch test versus percussion, average confidence scores being 2.2 versus 1.8 (p=0.007), with a greater difference in the young trainee group (p=0.003).Conclusion: The scratch test was at least as accurate as percussion in identifying the lower liver edge. In addition, all examiners and especially the young trainees were more confident in their findings using the scratch test.Predictors of poor outcome in patients with autoimmune hepatitis: a population-based studyNgu, J.H. 1,2, Gearry, R.B. 1,2, Frampton, C.M. 2, Stedman C.A.M. 1,21 Department of Gastroenterology, Christchurch Hospital 2 University of Otago, Christchurch, New Zealand.Background/Aim: Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure and death. Identifying predictors of poor outcomes could help in devising tailored management strategies. We aimed to describe predictors of poor outcomes in the population-based AIH cohort from Canterbury.Methods: Multiple case finding methods were employed, including searches of all public and private, adult and paediatric outpatient clinics, hospital notes and pathology reports. Cases diagnosed after 1980 that fulfilled standardised diagnostic criteria were included. End of follow-up was at death, liver transplantation or the end of study (31st December 2011). The associations of putative risk factors and outcomes were analyzed using Cox proportional hazards regression. The times to event outcomes were summarized using Kaplan-Meier curves.Results: A total of 133 AIH patients were included. Independent predictors of poor liver related outcomes were incomplete normalization of ALT at 6 months (p<0.01), baseline serum albumin <36g/L (p<0.01) and age at presentation of ≤ 20 years or >60 years (p=0.01). Kaplan-Meier estimates showed 10 years adverse liver event free survival were 80% for age at presentation ≤20 years and >60 years, and 93% and 100% for age at presentation between 21-40 years and 41-60 years respectively.Conclusion: Incomplete normalization of ALT at 6 months, low serum albumin concentration at diagnosis and age at presentation of ≤ 20 years or >60 years, were significant independent predictors of poor liver related outcomes. Histological cirrhosis at diagnosis was not associated with poor prognosis and did not influence the response to initial immunosuppressive treatment.Environmental risk factors in autoimmune hepatitis: a population-based case control studyNgu, J.H. 1,2, Gearry, R.B. 1,2, Frampton, C.M. 2, Stedman C.A.M. 1,21 Department of Gastroenterology, Christchurch Hospital 2 University of Otago, Christchurch, New Zealand.Background/Aim: The precise aetiology of autoimmune hepatitis (AIH) remains unknown and likely involves a complex interaction of genetic and environmental factors. However, to date, systematic examination of association between environmental factors and AIH has yet to be performed. We aimed to perform a population-based case control study to investigate for associations between exposure to putative environmental factors and AIH.Methods: Cases were AIH patients who were alive and resided in Canterbury between 1st July 2011 and 30th June 2012. Controls were randomly selected from the Electoral Roll and were matched 2:1 to each case by age and gender. Self-reporting questionnaires that cover lifestyle factors, childhood factors and family history were used.Results: A total of 72 AIH cases and 144 controls were included. Univariate analysis showed that antibiotic (p<0.01) and being vegetarian >1 year (p=0.04) were risk factors for AIH. Alcohol consumption (p<0.01), childhood home with vegetable garden (p=0.01) and wood heating (p<0.01) were protective factors. Multivariate analysis showed that antibiotic, alcohol consumption and childhood home with wood heating were independently associated with AIH. The crude risk of AIH in first degree relatives was 0.2%.Conclusion: This is the first population-based study investigating for associations between exposure to environmental factors and AIH. We found that antibiotics were an independent risk factor, whereas alcohol consumption and childhood home with wood heating were independent protective factors for AIH. Risk of AIH in first degree relatives was low.Auckland experience with Tenofovir therapy in nucleoside/nucleotide experienced patients with Chronic Hepatitis BJohns E, Naidoo M, Gane E, New Zealand Liver Transplant Unit, AucklandThe nucleotide analogue Tenofovir is funded for patients with hepatitis B, loss of virological response (HBV DNA 20 000 IU/mL or >1 log from nadir) and proven antiviral resistance.In treatment-naïve patients 76% of HBeAg-positive and 93% of HBeAg-negative achieve viral suppression (HBV DNA <400 copies/mL or 69 IU/ml) at 48 weeks. Treatment-experienced cohorts show a similar response but questions remain over durability in patients with adefovir resistance.We report local experience in treatment-experienced patients switched to tenofovir as monotherapy or in combination with lamivudine.Results: 144 of 146 patients tolerated treatment and were analysed. 38 received combination therapy. Median follow up was 26 months (range 1-94) with 116 patients completing 12 and 75 patients 24 months of therapy. Previous treatment included lamivudine (95%), adefovir (64%) and telbivudine (12%).On intention to treat analysis 67% of HBeAg-positive, 72% of HBeAg-negative and 69% of all patients achieved viral suppression (<400 copies/mL) at 12 months, and 70%, 82% and 75% respectively at 24 months. In patients meeting PHARMAC criteria for treatment failure at commencement of therapy suppression was 56% at 12 and 75% at 24 months; results were similar in the adefovir-resistant subgroup (57% and 71%).HBeAg seroconversion occurred in 13% of patients treated for ≥ 12 months; no patient lost HBsAg.Conclusion: Our experience with tenofovir rescue therapy in patients with antiviral resistance is consistent with published series. Adefovir-resistant patients had a similar virologic response but longer follow-up is needed. The need for combination rather than monotherapy in this population needs further evaluation.Disease assessment in Crohn’s disease (CD): Data from the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) project cohorta,dFalvey, JD, aHoskin T, aMeijer B, aAshcroft A, bHampton, MB, c,eDay AS a,dGearry, RB.Departments of aMedicine, bPathology and, cPaediatrics, University of Otago Christchurch. Departments of dGastroenterology and ePaediatrics, Christchurch Hospital, Christchurch.Introduction: Colonoscopy, the gold standard for CD assessment, is not suitable for regular monitoring while clinical assessment is often inaccurate. We aimed to determine the clinical utility of three established non-invasive methods of CD assessment, the Harvey Bradshaw index (HBI), serum CRP and faecal calprotectin (FC), and one novel biomarker candidate, serum macrophage migration inhibitory factor (MIF).Methods: Patients attending for colonoscopy with known or suspected IBD were recruited to the NBIBD cohort. Cases provided full demographic and disease activity data (HBI) in addition to biological samples. Endoscopic activity was recorded using the simple endoscopic score of Crohn’s disease (SES-CD)Results: 108 cases were included. Median (IQR) SES-CD, 4 (2-12). Spearman correlation coefficients for comparison with SES-CD were: HBI r=0.24 (p=0.007); CRP, r=0.44 (p<0.0001); FC r=0.55 (p<0.0001, n=82); MIF r=0.14 (p=0.2, n=85). A trend to better diagnostic utility was observed for FC over CRP (active≡SES-CD ≥3, AUC 0.74 (p=0.0006) and AUC 0.64 (p=0.003) respectively). HBI had modest diagnostic accuracy for severe disease only (SES-CD ≥16 vs. ≤15, AUC 0.78 (p=0.0002)). Sensitivity, specificity, PPV and NPV of FC ≥125µg/g for SES-CD ≥3 disease were, 71%, 71%, 85% and 50% respectively. Neither HBI, FC nor CRP could anticipate endoscopic remission. Combining CRP (≥10mg/L) and clinical data (HBI ≥8) significantly improved PPV for the detection of moderate-severe CD (SES-CD ≥7) cf. CRP alone (PPV 73% (95%CI 51-93%) vs. 50% (95%CI 34-65%) respectively).Conclusions: Established methods of non-invasive disease assessment offer modest diagnostic utility. Novel biomarkers with greater sensitivity and specificity are urgently needed.Clinical assessment of murine Dextran Sodium Sulphate (DSS) colitis: prospective validation of a novel scoring tool.a,eFalvey JD, dMunday JS, bKeenan, JI, fDyer AE, a,eGearry, RB, cHampton, MBDepartments of Medicinea, Surgeryb and Pathologyc, University of Otago Christchurch.dInstitute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North. eDepartment of Gastroenterology, Christchurch Hospital, Christchurch. fChristchurch Animal Research Area, University of Otago, Christchurch.Introduction: Murine DSS colitis is a common research model for IBD. Histological examination of the colon provides gold standard assessment; however, non-lethal assessment is critical for disease monitoring and secondary endpoint analysis. Coopers’ murine colitis score (MCS), the current standard, correlates well with histology but has low content validity in some domains.Aims: To develop and prospectively validate a novel MCS.Methods: Developmental phase: Novel stool consistency and rectal bleeding indices were developed in order to improve content validity of these domains. Variations of the MCS were tested in post hoc analysis against histology. Validation stage: 2% DSS was provided ad libitum to 24 mice. Three mice per day (0-7) were selected randomly; disease was assessed independently by 2 observers using a proforma from which a complex MCS, a simple MCS (SMCS) and the Cooper MCS were derived. Non-invasive assessment was compared with histological activity.Results: Murine colitis scores correlated highly with histology (Spearman r=0.93, r=0.91 and r=0.91 for the simple, the complex and the Cooper MCS respectively (p<0.0001)). Correlation with histology was non-significantly greater for the novel stool score compared with Cooper stool score (r=0.86 (95%CI 0.69 - 0.94) vs. r=0.77). There was a high level of agreement (linear weighted қ=0.86 (95%CI 0.77-0.96)) and correlation (r=0.94 (95%CI 0.87-0.98) p<0.0001) between observers for the SMCS.Conclusions: A modification of the Coopers colitis score (SMCS) comprising a weight loss score, novel stool score and dichotomous rectal bleeding score, provides a valid and simple method for the non-invasive assessment of DSS colitis.Disease assessment in Ulcerative Colitis (UC): Data from the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) project cohorta,dFalvey JD, aHoskin T, aMeijer B, aAshcroft A, bHampton, MB, c,eDay AS, a,dGearry, RB.Departments of aMedicine, bPathology and,cPaediatrics University of Otago Christchurch. Departments of dGastroenterology and ePaediatrics, Christchurch Hospital, Christchurch.Introduction: Colonoscopy, the gold standard for UC assessment, is not suitable for regular monitoring while clinical assessment is frequently inaccurate. We aimed to determine the clinical utility of three established non-invasive methods of disease assessment, the simple clinical colitis activity index (SCCAI), serum CRP and faecal calprotectin (FC), and one novel biomarker candidate serum macrophage migration inhibitory factor (MIF) in the normal clinical setting.Methods: Patients attending for colonoscopy with known or suspected IBD were recruited to the NBIBD cohort. Cases with UC provided full demographic and disease activity data (SCCAI) in addition to biological samples. Endoscopic activity was recorded using the modified Baron scoreResults: 65 cases were included. Spearman r correlation coefficients for comparison with endoscopic score were: CRP, r=0.4 (p<0.0001); SCCAI r=0.44 (0.31-0.62, p=0.0002); FC r=0.55 (p<0.0001, n=51). Overall disease burden (severity*extent) correlated better with each parameter but differences were not significant. No correlation was observed between plasma MIF and endoscopic activity (r=0.11, p=0.2, n= 85). ROC analysis revealed significant diagnostic utility for SCCAI, CRP and FC (AUC 0.73 (p=0.002), AUC 0.78 (p=0.002) and AUC 0.75 (p=0.004) respectively). Optimal thresholds for distinguishing Baron ≥2 disease were (threshold (sensitivity, specificity, PPV and NPV)): SCCAI, 3.5 (59%, 88%, 72%, 81%); CRP 5mg/L (64%, 74%, 56%, 80%); FC 125 ug/g (83%, 64%, 56%, 88%). Neither CRP nor FC could reliably anticipate endoscopic remission (Baron 0).Conclusions: Established methods of non-invasive disease assessment offer modest diagnostic utility. Novel biomarkers with greater sensitivity and specificity are urgently needed.Outcomes of adalimumab therapy for Crohn’s disease from five New Zealand hospitalsSchultz M,1 Lewis-Morris T,2 Rowbotham D,3 Whiteside C,4 Bennett S,1 Thomas G,2 Inns S,4 Gearry RB2Departments of Gastroenterology, 1Dunedin, 2Christchurch, 3Auckland City, 4Hutt Valley HospitalsIntroduction: Adalimumab (ADA) is an effective therapy for the treatment of Crohn’s disease (CD). We aimed to describe the use o

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Symptom presentations and other characteristics of colorectal cancer patients and the diagnostic performance of the UK NICE Referral Guideline for Suspected Colorectal Cancer in the South Auckland populationHsiang JC, Bai WWH, Lal D, Department of Gastroenterology, Middlemore Hospital, South Auckland, New ZealandAim: To review the presenting symptoms of colorectal cancer in the ethnically perse South Auckland populationTo evaluate the performance of both the Regional grading criteria and its NICE Guideline precursor as prediction tools for selecting colorectal cancer cases referred from primary careMethod: Retrospective review of all colorectal cancer (CRC) cases diagnosed between 2006 and January 2011. Information extracted from case note review was used to grade patients using both criteria.Results: 573 patients were included. Outpatient presenting symptoms: rectal bleeding (42.1%), change in bowel habit (25.1%), and abdominal pain (15.3%). Inpatient symptoms: abdominal pain (34.8%), rectal bleeding (32.4%), change in bowel habit (24.2%), and constipation (18.8%).41.7% of Pacific Island (PI) patients had stage IV disease compared to 23.6% of other groups combined (p<0.01). The tumour non-resection rate of Pacific Island group was 33.3% compared to 15.6% (European), 15.2% (Maori) and 8.0% (Asians), respectively (p=0.002). The age-adjusted mortality rates was: European 14.92, Maori 3.27, Pacific people 5.21, and Asian 1.05 (per 100,000)The Regional grading criteria and NICE Guideline would miss 27.7% and 33.2% of the presenting symptoms of CRC patients in the referral population.Conclusion: While rectal bleeding and change in bowel habit are frequent presenting symptoms, low-risk atypical symptoms including constipation, weight loss and abdominal pain were not uncommon.Significant proportion of Pacific Island patients present with late stage disease.Both the Regional grading criteria and NICE guideline would miss significant proportion of our study population with colorectal cancer.The 2012 Characteristics and Antibiotic Susceptibility of treatment naïve Helicobacter pylori Infections in South Auckland, New Zealand (Interim result)Hsiang JC, Selvaratnam S, Taylor SL, Tan YM, Huang J, Patrick AB. Gastroenterology Department, Middlemore Hospital, Otahuhu, Auckland, Microbiology Department, Middlemore Hospital, Otahuhu, AucklandAims: To ascertain the current prevalence of H. pylori infection in the ethnic perse population of South Auckland To assess the current antibiotic susceptibility of treatment naïve H.pyloriinfection in patients undergoing gastroscopy and provide up to date treatment recommendations Methods: Prospective study of consecutive patients undergoing gastroscopy between February 2012 and September 2012. Prevalence data was determined from all Campylobacter-Like organism (CLO) tests performed. Following informed consent CLO test was performed at routine gastroscopy. Biopsies for culture and antibiotics testing were obtained. Bacterial culture and resistance testing to common antibiotics (amoxicillin, tetracycline, clarithromycin, metronidazole and moxifloxacin) was performed. Eradication success was determined by following stool antigen clearance.Results: The prevalence of H. pylori infection among treatment naïve patients by ethnic group was: Maori (34.8%), Pacific people (31.3%) and Asian (23.8%). The interim results from 68 CLO positive patients were: Endoscopic indication- 19.1% iron deficiency anaemia, 20.6% dyspepsia, and 26.5% gastrointestinal bleeding. Antibiotic resistance: Amoxicillin 4.2% (2/48), Tetracycline 0.0% (0/48), Metronidazole 47.9% (23/48), Clarithromycin 12.5% (6/48), Moxifloxacin 7.9% (3/38 - extrapolating from levofloxacin breakpoints). Dual resistance to clarithromycin and metronidazole was 4.2%. Clearance testing: compliance 95.1% (39/41 patients) and success 76.7% (23/30). Discussion: H. pylori infection is very common among the Maori, Pacific and Asian groups. The resistance to clarithromycin and metronidazole is significant among treatment naïve patients.Conclusion: Resistance to Clarithromycin and Metronidazole has increased over historical NZ data and may contribute to low clearance rate. The current guidelines should be reviewed with respect to first-line regimensAdherence to Hepatocellular Carcinoma (HCC) Surveillance GuidelinesHsiang JC1, Bai WW1, Upton A1, Gane EJ2, Gerred SJ11Department of Gastroenterology and Hepatology, Middlemore Hospital, Auckland2New Zealand Liver Transplant Unit, Auckland City Hospital, AucklandIntroduction: Local guidelines recommend six monthly hepatic ultrasound (US) and alpha -fetoprotein (AFP) testing for patients with a high risk of developing hepatocellular carcinomna (HCC).Aim: To assess the adherence to HCC surveillance guidelines at our institution.Method: Patients with a high risk of HCC between 2007 and 2011 were identified from our clinic database. A retrospective review of electronic records was undertaken to record clinic attendance and adherence to six monthly AFP and US surveillance.Results: A total of 460 patients were identified. Cirrhosis was present in 409, severe hepatic fibrosis in 38, chronic hepatitis B and a family history of HCC in 13. European ethnicity was observed in 36%, Asian 23%, Pacific Island 20%, and Maori 12%. The aetiology of the underlying liver disease was: HBV (41%), Hepatitis C (23%), and Alcohol related liver disease (16%). The median age at diagnosis was 56 years, 62% were male. The median duration of surveillance was 3.4 years. HCC was detected in 23 patients (5%). The overall adherence rate for AFP testing and US surveillance was 79% and 59%, respectively. US adherence correlated strongly with clinic attendance but even in those attending regularly, 20% of US surveillance scans were missed.Conclusion: The poor performance of US surveillance highlights the rationale for continuing AFP testing at this time. Strategies that we have undertaken to improve US surveillance rates include: a patient education brochure, nurse specialist cirrhosis clinics, and improving clinic non-attendance procedures. We are endeavouring to organise a radiology based recall system.Predictors of serologic and clinical outcomes in childhood-acquired HBV infection in New Zealand Māori: results of 28 year longitudinal studyLim TH1, Gane EJ1, Borman B2, Moyes C,3 Cunningham C2.1Liver Unit, Auckland City Hospital, Auckland, New Zealand2Research Centre for Maōri Health and Development, Massey University, Wellington, New Zealand3The Hepatitis Foundation of New Zealand, Whakatane, New ZealandBackground: High baseline HBV DNA is associated with increased risk of liver-related complications in Asians with vertically-transmitted chronic hepatitis B virus(HBV) infection. This longitudinal study evaluates the baseline predictors for liver-related complications and serologic outcomes in 572 patients identified from a 1984 seroprevalence study with early horizontally-acquired HBV infection.Methods: Serum samples from 1984 were tested for HBeAg,HBV DNA and HBsAg level. Liver-related mortality and hepatocellular carcinoma(HCC) incidence were previously determined in these 572 HBV carriers compared to 1142 HBsAg-negative case-controls. Transient elastography(TE) was performed in 2012 in all surviving HBsAg+ inpiduals. Cox-proportional hazards models were used to determine independent baseline predictors for five long-term outcomes: severe fibrosis (TE>8KPa), HCC, liver-related mortality and HBsAg+HBeAg seroconversion.Results: After 28 years, 14HBsAg+ patients developed HCC(vs none in HBsAg- controls [P<0.001]). 11HBsAg+ patients died from liver-related causes(vs none in controls(P<0.001)). To-date, 291/515(57%) surviving HBsAg+ patients have been followed-up. 25% had elevated ALT; 12% had severe fibrosis/cirrhosis(TE>8KPa). Increasing age, Maōri ethnicity and baseline HBV DNA were predictors for liver-related death and HCC. Maōri ethnicity was a predictor for severe fibrosis. Baseline HBsAg level and gender were not predictors for long-term outcome. Since 1984,90% of HBeAg+ patients have undergone HBeAg seroconversion (median age=23yrs(range 6-66)). 31% spontaneously lost HBsAg (median age 39 yrs(range 9-80)), with higher rates in HBeAg-(44%) vs HBeAg+ patients(9%)(p<0.0001).Conclusions: In a young Maōri population with early horizontally-acquired HBV, HBV DNA, but not HBsAg-level, was associated with increased risk for liver-related complications. Higher rates of spontaneous HBeAg and HBsAg loss are seen compared to Asians HBV populations.Disclosure statement: The authors have no disclosures.CMV and EBV disease in adult liver transplant recipientsGriffiths B, Gane E, Fitt S, Munn SJ. NZLTU, Auckland Hospital, New ZealandIntroduction: Herpes virus infections are an important cause of morbidity and mortality following solid organ transplantation. NZLTU has used CMV antiviral prophylaxis in all D+/R- transplants. This audit determines the incidence of CMV disease and EBV disease.Methods: CMV and EBV D/R serostatus was collected prospectively. Pharmacy and virological data were used to identify CMV and EBV infection and disease.Results: 409 adult liver transplants were evaluated. CMV serostatus was D+/R- in 57 (12.5%), D-/R+ in 112 (27.4%), D+/R+ in 188 (46%), D-/R- in 51 (12.5%). CMV infection was detected in 47 patients (11.5%), at mean 41 weeks. There were 26 cases of CMV disease (6.4% total), diagnosed at mean 57 weeks. CMV disease developed in 16 D+/R- (28.1%), 5 D-/R+ (4.5%) and 5 D+/R+ (2.7%). Mycophenolate was associated with increased risk of CMV disease (RR 4.0; 95% CI 2.3 - 3.8; p<0.0001).EBV serostatus was D+/R- in 17 (4.8%), D-/R+ in 29 (8.3%), D+/R+ in 302 (86%), D-/R- in 3 (0.9%). Six cases of EBV-associated PTLD (1.5% total) were diagnosed at mean 86 weeks. EBV disease developed in 5 (29.4%) D+/R- and 1 (0.3%) D+/R+.Conclusion: Antiviral prophylaxis has reduced incidence and delayed onset of CMV disease in D+/R- transplants. Mycophenolate is associated with an increased risk of CMV disease. EBV D+/R- transplants have a high rate of PTLD. Better EBV prophylaxis and monitoring regimens are needed.Entecavir in Chronic Hepatitis B - “Real World” ExperienceLampen-Smith A1, Wong P2,GerredS3,Gane E11Liver Unit, Auckland City Hospital, 2Gastroenterology Department, Auckland City Hospital,3Gastroenterology Department, Middlemore Hospital.Introduction: Entecavir is an approved antiviral treatment for chronic hepatitis B1. Global registration trials demonstrated excellent safety and efficacy - serum HBV DNA undetectable in 90% after 48 weeks of treatment.2 Similar results have been reported in “real-world” experience.3Methods: This is an audit of patients at Auckland and Middlemore Hospitals treated with entecavir for at least 12 months. Patients were excluded if they had prior antiviral therapy, or a diagnosis of HCC within 12 months. Data on ALT, HBV DNA, resistance studies, ethnicity and HBeAg serology was collected. Clinic notes were reviewed for evidence of treatment adherence.Results: Entecavir was approved in 459 patients, of whom 351 have received 12 months therapy. After exclusions there were 108 HBeAg positive and 157 HBeAg negative. Twenty (18.5%) HBeAg positive patients underwent HBeAg seroconversion. Of the remaining 88 eAg positive patients, HBV DNA was suppressed to undetectable or ≤3 log in 60 (68.2%). In the 28 subjects with sub-optimal virological response, 10 were adherent and had decreasing HBV DNA whilst the remaining 18 had poor adherence/ nonattendance.Of the HBeAg negative patients, 111 (71.2%) had undetectable HBV DNA, 15 (9.6%) had levels < 3 log IU/mL. Seven (4.5%) had sub-optimal virological response, all showed poor adherence. Sequencing studies did not identify resistance mutations.Conclusion: The efficacy and safety of entecavir is in clinical practice is similar to that observed in registration studies, with 80.7% and 74.1% viral suppression in eAg negative and positive chronic hepatitis B patients respectively. Lack of response reflected poor adherence rather than entecavir resistance.References: Kim SR, et al. Recent advances in the management of chronic Hepatitis B. Hepat Mon. 2011;11(8):601-11. Lai C-L, et al. Entecavir versus Lamivudine for Patients with HBeAg-Negative Chronic Hepaititis B. N Engl J Med 2006;354:1011-20. Tsai MC, et al. A comparison of telbivudine and entecavir for chronic hepatitis B in real-world clinical practice. J Antimicrob Chemother. 2012 Mar;67(3):696-9. Prealbumin measurement as a guide to adequate nutritional supports in patients receiving parenteral nutritionHY Lee, S Larsen, S Hill, R Baskett, RS WalmsleyNorth Shore Hospital, Auckland, New ZealandPrealbumin is a visceral protein and negative acute phase reactant used as a nutritional status screening tool to detect malnutrition. Its relatively short physiological half-life of 48 to 72 hours provides a dynamic measure of protein-energy status and adequacy of nutritional support (1). A rise in prealbumin of greater than 0.04 g/L has been suggested to indicate switch from a catabolic to an anabolic state (2).Aims: To assess the use of serial measurements of serum prealbumin in patients receiving short-term parenteral nutrition (PN), to determine whether anabolism can be achieved during short-term PN and the relation between change in prealbumin and acute phase response level indicated by C-reactive protein (CRP).Methods: Retrospective review of Nutrition Support Database from May 2005 to May 2012.Results: From 494 patients identified receiving PN, 142 patients had paired prealbumin and CRP data available.Negative correlation was confirmed between CRP and prealbumin (r=-0.52). Following PN therapy the mean C-reactive protein decreased from 123 to 53 mg/L (p<0.001). Mean serum prealbumin increased from 0.12 to 0.22 g/L (p<0.001).Prealbumin rise of greater than 0.04 g/L was achieved in 72% (n=102) of patients. Mean CRP after completion of PN in this group was significantly less (42 vs 83 mg/L, p<0.001), suggesting ongoing inflammation may impede visceral protein synthesis.Conclusion: Serial prealbumin measurements in patients receiving short-term parenteral nutrition are a useful guide to the adequacy of nutritional support.An anabolic state switch can be achieved in most patients despite persistent systemic inflammatory response.References Ingenbleek Y, Young V. Clin Chem Lab Med. 2002;40:1281-1291. Bernstein L, Bachman T, Meguid M, Ament M, Baumgartner T, Kinosian B, et al. Nutrition 1995;11:169-171 The Scratch Test for identifying the lower liver edge is at least as accurate as percussion and is more effective for trainees - a randomized controlled studyHuelsen A,1,2 Fischer J,1 Hegarty J,3 Lim JY,2 Burnside MJ,2 Karim SN,2 Onyango N, 2Frampton C,4 Spencer AJ,2 Barclay ML. 1,4Departments of Gastroenterology,1 General Medicine 2 & Radiology,3 Christchurch Hospital, and Department of Medicine,4 University of Otago Christchurch, Christchurch, New Zealand.Introduction: Clinical examination of the liver requires experience to achieve accuracy. The scratch test is a simple technique to identify the lower liver edge and enhance liver palpation, and may be easier for trainees.Aims and Methods: We aimed to evaluate the accuracy of the scratch test compared to percussion at different levels of medical training. Eight examiners, from trainee intern to consultant level, were randomized to scratch or percussion testing, followed by liver palpation, on 50 subjects. Later, each examiner performed the alternative test on each subject. Confidence with each test was rated 0-3 (unsuccessful - very confident). Ultrasound scan (USS) was performed as a reference for liver location.Results: Ultrasound revealed 33/50 (66%) of livers extended below the right costal margin in the midclavicular line during quiet respiration (range 0-16cm). Of these 33, 84% and 81% were identified within 2cm of the USS location using scratch and percussion tests, respectively (p>0.05) for all examiners, but with greater accuracy for the scratch test in young trainees (86% v 80%). Ability to palpate the liver was not different following either test. Examiner confidence in the test result was significantly higher using the scratch test versus percussion, average confidence scores being 2.2 versus 1.8 (p=0.007), with a greater difference in the young trainee group (p=0.003).Conclusion: The scratch test was at least as accurate as percussion in identifying the lower liver edge. In addition, all examiners and especially the young trainees were more confident in their findings using the scratch test.Predictors of poor outcome in patients with autoimmune hepatitis: a population-based studyNgu, J.H. 1,2, Gearry, R.B. 1,2, Frampton, C.M. 2, Stedman C.A.M. 1,21 Department of Gastroenterology, Christchurch Hospital 2 University of Otago, Christchurch, New Zealand.Background/Aim: Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure and death. Identifying predictors of poor outcomes could help in devising tailored management strategies. We aimed to describe predictors of poor outcomes in the population-based AIH cohort from Canterbury.Methods: Multiple case finding methods were employed, including searches of all public and private, adult and paediatric outpatient clinics, hospital notes and pathology reports. Cases diagnosed after 1980 that fulfilled standardised diagnostic criteria were included. End of follow-up was at death, liver transplantation or the end of study (31st December 2011). The associations of putative risk factors and outcomes were analyzed using Cox proportional hazards regression. The times to event outcomes were summarized using Kaplan-Meier curves.Results: A total of 133 AIH patients were included. Independent predictors of poor liver related outcomes were incomplete normalization of ALT at 6 months (p<0.01), baseline serum albumin <36g/L (p<0.01) and age at presentation of ≤ 20 years or >60 years (p=0.01). Kaplan-Meier estimates showed 10 years adverse liver event free survival were 80% for age at presentation ≤20 years and >60 years, and 93% and 100% for age at presentation between 21-40 years and 41-60 years respectively.Conclusion: Incomplete normalization of ALT at 6 months, low serum albumin concentration at diagnosis and age at presentation of ≤ 20 years or >60 years, were significant independent predictors of poor liver related outcomes. Histological cirrhosis at diagnosis was not associated with poor prognosis and did not influence the response to initial immunosuppressive treatment.Environmental risk factors in autoimmune hepatitis: a population-based case control studyNgu, J.H. 1,2, Gearry, R.B. 1,2, Frampton, C.M. 2, Stedman C.A.M. 1,21 Department of Gastroenterology, Christchurch Hospital 2 University of Otago, Christchurch, New Zealand.Background/Aim: The precise aetiology of autoimmune hepatitis (AIH) remains unknown and likely involves a complex interaction of genetic and environmental factors. However, to date, systematic examination of association between environmental factors and AIH has yet to be performed. We aimed to perform a population-based case control study to investigate for associations between exposure to putative environmental factors and AIH.Methods: Cases were AIH patients who were alive and resided in Canterbury between 1st July 2011 and 30th June 2012. Controls were randomly selected from the Electoral Roll and were matched 2:1 to each case by age and gender. Self-reporting questionnaires that cover lifestyle factors, childhood factors and family history were used.Results: A total of 72 AIH cases and 144 controls were included. Univariate analysis showed that antibiotic (p<0.01) and being vegetarian >1 year (p=0.04) were risk factors for AIH. Alcohol consumption (p<0.01), childhood home with vegetable garden (p=0.01) and wood heating (p<0.01) were protective factors. Multivariate analysis showed that antibiotic, alcohol consumption and childhood home with wood heating were independently associated with AIH. The crude risk of AIH in first degree relatives was 0.2%.Conclusion: This is the first population-based study investigating for associations between exposure to environmental factors and AIH. We found that antibiotics were an independent risk factor, whereas alcohol consumption and childhood home with wood heating were independent protective factors for AIH. Risk of AIH in first degree relatives was low.Auckland experience with Tenofovir therapy in nucleoside/nucleotide experienced patients with Chronic Hepatitis BJohns E, Naidoo M, Gane E, New Zealand Liver Transplant Unit, AucklandThe nucleotide analogue Tenofovir is funded for patients with hepatitis B, loss of virological response (HBV DNA 20 000 IU/mL or >1 log from nadir) and proven antiviral resistance.In treatment-naïve patients 76% of HBeAg-positive and 93% of HBeAg-negative achieve viral suppression (HBV DNA <400 copies/mL or 69 IU/ml) at 48 weeks. Treatment-experienced cohorts show a similar response but questions remain over durability in patients with adefovir resistance.We report local experience in treatment-experienced patients switched to tenofovir as monotherapy or in combination with lamivudine.Results: 144 of 146 patients tolerated treatment and were analysed. 38 received combination therapy. Median follow up was 26 months (range 1-94) with 116 patients completing 12 and 75 patients 24 months of therapy. Previous treatment included lamivudine (95%), adefovir (64%) and telbivudine (12%).On intention to treat analysis 67% of HBeAg-positive, 72% of HBeAg-negative and 69% of all patients achieved viral suppression (<400 copies/mL) at 12 months, and 70%, 82% and 75% respectively at 24 months. In patients meeting PHARMAC criteria for treatment failure at commencement of therapy suppression was 56% at 12 and 75% at 24 months; results were similar in the adefovir-resistant subgroup (57% and 71%).HBeAg seroconversion occurred in 13% of patients treated for ≥ 12 months; no patient lost HBsAg.Conclusion: Our experience with tenofovir rescue therapy in patients with antiviral resistance is consistent with published series. Adefovir-resistant patients had a similar virologic response but longer follow-up is needed. The need for combination rather than monotherapy in this population needs further evaluation.Disease assessment in Crohn’s disease (CD): Data from the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) project cohorta,dFalvey, JD, aHoskin T, aMeijer B, aAshcroft A, bHampton, MB, c,eDay AS a,dGearry, RB.Departments of aMedicine, bPathology and, cPaediatrics, University of Otago Christchurch. Departments of dGastroenterology and ePaediatrics, Christchurch Hospital, Christchurch.Introduction: Colonoscopy, the gold standard for CD assessment, is not suitable for regular monitoring while clinical assessment is often inaccurate. We aimed to determine the clinical utility of three established non-invasive methods of CD assessment, the Harvey Bradshaw index (HBI), serum CRP and faecal calprotectin (FC), and one novel biomarker candidate, serum macrophage migration inhibitory factor (MIF).Methods: Patients attending for colonoscopy with known or suspected IBD were recruited to the NBIBD cohort. Cases provided full demographic and disease activity data (HBI) in addition to biological samples. Endoscopic activity was recorded using the simple endoscopic score of Crohn’s disease (SES-CD)Results: 108 cases were included. Median (IQR) SES-CD, 4 (2-12). Spearman correlation coefficients for comparison with SES-CD were: HBI r=0.24 (p=0.007); CRP, r=0.44 (p<0.0001); FC r=0.55 (p<0.0001, n=82); MIF r=0.14 (p=0.2, n=85). A trend to better diagnostic utility was observed for FC over CRP (active≡SES-CD ≥3, AUC 0.74 (p=0.0006) and AUC 0.64 (p=0.003) respectively). HBI had modest diagnostic accuracy for severe disease only (SES-CD ≥16 vs. ≤15, AUC 0.78 (p=0.0002)). Sensitivity, specificity, PPV and NPV of FC ≥125µg/g for SES-CD ≥3 disease were, 71%, 71%, 85% and 50% respectively. Neither HBI, FC nor CRP could anticipate endoscopic remission. Combining CRP (≥10mg/L) and clinical data (HBI ≥8) significantly improved PPV for the detection of moderate-severe CD (SES-CD ≥7) cf. CRP alone (PPV 73% (95%CI 51-93%) vs. 50% (95%CI 34-65%) respectively).Conclusions: Established methods of non-invasive disease assessment offer modest diagnostic utility. Novel biomarkers with greater sensitivity and specificity are urgently needed.Clinical assessment of murine Dextran Sodium Sulphate (DSS) colitis: prospective validation of a novel scoring tool.a,eFalvey JD, dMunday JS, bKeenan, JI, fDyer AE, a,eGearry, RB, cHampton, MBDepartments of Medicinea, Surgeryb and Pathologyc, University of Otago Christchurch.dInstitute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North. eDepartment of Gastroenterology, Christchurch Hospital, Christchurch. fChristchurch Animal Research Area, University of Otago, Christchurch.Introduction: Murine DSS colitis is a common research model for IBD. Histological examination of the colon provides gold standard assessment; however, non-lethal assessment is critical for disease monitoring and secondary endpoint analysis. Coopers’ murine colitis score (MCS), the current standard, correlates well with histology but has low content validity in some domains.Aims: To develop and prospectively validate a novel MCS.Methods: Developmental phase: Novel stool consistency and rectal bleeding indices were developed in order to improve content validity of these domains. Variations of the MCS were tested in post hoc analysis against histology. Validation stage: 2% DSS was provided ad libitum to 24 mice. Three mice per day (0-7) were selected randomly; disease was assessed independently by 2 observers using a proforma from which a complex MCS, a simple MCS (SMCS) and the Cooper MCS were derived. Non-invasive assessment was compared with histological activity.Results: Murine colitis scores correlated highly with histology (Spearman r=0.93, r=0.91 and r=0.91 for the simple, the complex and the Cooper MCS respectively (p<0.0001)). Correlation with histology was non-significantly greater for the novel stool score compared with Cooper stool score (r=0.86 (95%CI 0.69 - 0.94) vs. r=0.77). There was a high level of agreement (linear weighted қ=0.86 (95%CI 0.77-0.96)) and correlation (r=0.94 (95%CI 0.87-0.98) p<0.0001) between observers for the SMCS.Conclusions: A modification of the Coopers colitis score (SMCS) comprising a weight loss score, novel stool score and dichotomous rectal bleeding score, provides a valid and simple method for the non-invasive assessment of DSS colitis.Disease assessment in Ulcerative Colitis (UC): Data from the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) project cohorta,dFalvey JD, aHoskin T, aMeijer B, aAshcroft A, bHampton, MB, c,eDay AS, a,dGearry, RB.Departments of aMedicine, bPathology and,cPaediatrics University of Otago Christchurch. Departments of dGastroenterology and ePaediatrics, Christchurch Hospital, Christchurch.Introduction: Colonoscopy, the gold standard for UC assessment, is not suitable for regular monitoring while clinical assessment is frequently inaccurate. We aimed to determine the clinical utility of three established non-invasive methods of disease assessment, the simple clinical colitis activity index (SCCAI), serum CRP and faecal calprotectin (FC), and one novel biomarker candidate serum macrophage migration inhibitory factor (MIF) in the normal clinical setting.Methods: Patients attending for colonoscopy with known or suspected IBD were recruited to the NBIBD cohort. Cases with UC provided full demographic and disease activity data (SCCAI) in addition to biological samples. Endoscopic activity was recorded using the modified Baron scoreResults: 65 cases were included. Spearman r correlation coefficients for comparison with endoscopic score were: CRP, r=0.4 (p<0.0001); SCCAI r=0.44 (0.31-0.62, p=0.0002); FC r=0.55 (p<0.0001, n=51). Overall disease burden (severity*extent) correlated better with each parameter but differences were not significant. No correlation was observed between plasma MIF and endoscopic activity (r=0.11, p=0.2, n= 85). ROC analysis revealed significant diagnostic utility for SCCAI, CRP and FC (AUC 0.73 (p=0.002), AUC 0.78 (p=0.002) and AUC 0.75 (p=0.004) respectively). Optimal thresholds for distinguishing Baron ≥2 disease were (threshold (sensitivity, specificity, PPV and NPV)): SCCAI, 3.5 (59%, 88%, 72%, 81%); CRP 5mg/L (64%, 74%, 56%, 80%); FC 125 ug/g (83%, 64%, 56%, 88%). Neither CRP nor FC could reliably anticipate endoscopic remission (Baron 0).Conclusions: Established methods of non-invasive disease assessment offer modest diagnostic utility. Novel biomarkers with greater sensitivity and specificity are urgently needed.Outcomes of adalimumab therapy for Crohn’s disease from five New Zealand hospitalsSchultz M,1 Lewis-Morris T,2 Rowbotham D,3 Whiteside C,4 Bennett S,1 Thomas G,2 Inns S,4 Gearry RB2Departments of Gastroenterology, 1Dunedin, 2Christchurch, 3Auckland City, 4Hutt Valley HospitalsIntroduction: Adalimumab (ADA) is an effective therapy for the treatment of Crohn’s disease (CD). We aimed to describe the use o

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Symptom presentations and other characteristics of colorectal cancer patients and the diagnostic performance of the UK NICE Referral Guideline for Suspected Colorectal Cancer in the South Auckland populationHsiang JC, Bai WWH, Lal D, Department of Gastroenterology, Middlemore Hospital, South Auckland, New ZealandAim: To review the presenting symptoms of colorectal cancer in the ethnically perse South Auckland populationTo evaluate the performance of both the Regional grading criteria and its NICE Guideline precursor as prediction tools for selecting colorectal cancer cases referred from primary careMethod: Retrospective review of all colorectal cancer (CRC) cases diagnosed between 2006 and January 2011. Information extracted from case note review was used to grade patients using both criteria.Results: 573 patients were included. Outpatient presenting symptoms: rectal bleeding (42.1%), change in bowel habit (25.1%), and abdominal pain (15.3%). Inpatient symptoms: abdominal pain (34.8%), rectal bleeding (32.4%), change in bowel habit (24.2%), and constipation (18.8%).41.7% of Pacific Island (PI) patients had stage IV disease compared to 23.6% of other groups combined (p<0.01). The tumour non-resection rate of Pacific Island group was 33.3% compared to 15.6% (European), 15.2% (Maori) and 8.0% (Asians), respectively (p=0.002). The age-adjusted mortality rates was: European 14.92, Maori 3.27, Pacific people 5.21, and Asian 1.05 (per 100,000)The Regional grading criteria and NICE Guideline would miss 27.7% and 33.2% of the presenting symptoms of CRC patients in the referral population.Conclusion: While rectal bleeding and change in bowel habit are frequent presenting symptoms, low-risk atypical symptoms including constipation, weight loss and abdominal pain were not uncommon.Significant proportion of Pacific Island patients present with late stage disease.Both the Regional grading criteria and NICE guideline would miss significant proportion of our study population with colorectal cancer.The 2012 Characteristics and Antibiotic Susceptibility of treatment naïve Helicobacter pylori Infections in South Auckland, New Zealand (Interim result)Hsiang JC, Selvaratnam S, Taylor SL, Tan YM, Huang J, Patrick AB. Gastroenterology Department, Middlemore Hospital, Otahuhu, Auckland, Microbiology Department, Middlemore Hospital, Otahuhu, AucklandAims: To ascertain the current prevalence of H. pylori infection in the ethnic perse population of South Auckland To assess the current antibiotic susceptibility of treatment naïve H.pyloriinfection in patients undergoing gastroscopy and provide up to date treatment recommendations Methods: Prospective study of consecutive patients undergoing gastroscopy between February 2012 and September 2012. Prevalence data was determined from all Campylobacter-Like organism (CLO) tests performed. Following informed consent CLO test was performed at routine gastroscopy. Biopsies for culture and antibiotics testing were obtained. Bacterial culture and resistance testing to common antibiotics (amoxicillin, tetracycline, clarithromycin, metronidazole and moxifloxacin) was performed. Eradication success was determined by following stool antigen clearance.Results: The prevalence of H. pylori infection among treatment naïve patients by ethnic group was: Maori (34.8%), Pacific people (31.3%) and Asian (23.8%). The interim results from 68 CLO positive patients were: Endoscopic indication- 19.1% iron deficiency anaemia, 20.6% dyspepsia, and 26.5% gastrointestinal bleeding. Antibiotic resistance: Amoxicillin 4.2% (2/48), Tetracycline 0.0% (0/48), Metronidazole 47.9% (23/48), Clarithromycin 12.5% (6/48), Moxifloxacin 7.9% (3/38 - extrapolating from levofloxacin breakpoints). Dual resistance to clarithromycin and metronidazole was 4.2%. Clearance testing: compliance 95.1% (39/41 patients) and success 76.7% (23/30). Discussion: H. pylori infection is very common among the Maori, Pacific and Asian groups. The resistance to clarithromycin and metronidazole is significant among treatment naïve patients.Conclusion: Resistance to Clarithromycin and Metronidazole has increased over historical NZ data and may contribute to low clearance rate. The current guidelines should be reviewed with respect to first-line regimensAdherence to Hepatocellular Carcinoma (HCC) Surveillance GuidelinesHsiang JC1, Bai WW1, Upton A1, Gane EJ2, Gerred SJ11Department of Gastroenterology and Hepatology, Middlemore Hospital, Auckland2New Zealand Liver Transplant Unit, Auckland City Hospital, AucklandIntroduction: Local guidelines recommend six monthly hepatic ultrasound (US) and alpha -fetoprotein (AFP) testing for patients with a high risk of developing hepatocellular carcinomna (HCC).Aim: To assess the adherence to HCC surveillance guidelines at our institution.Method: Patients with a high risk of HCC between 2007 and 2011 were identified from our clinic database. A retrospective review of electronic records was undertaken to record clinic attendance and adherence to six monthly AFP and US surveillance.Results: A total of 460 patients were identified. Cirrhosis was present in 409, severe hepatic fibrosis in 38, chronic hepatitis B and a family history of HCC in 13. European ethnicity was observed in 36%, Asian 23%, Pacific Island 20%, and Maori 12%. The aetiology of the underlying liver disease was: HBV (41%), Hepatitis C (23%), and Alcohol related liver disease (16%). The median age at diagnosis was 56 years, 62% were male. The median duration of surveillance was 3.4 years. HCC was detected in 23 patients (5%). The overall adherence rate for AFP testing and US surveillance was 79% and 59%, respectively. US adherence correlated strongly with clinic attendance but even in those attending regularly, 20% of US surveillance scans were missed.Conclusion: The poor performance of US surveillance highlights the rationale for continuing AFP testing at this time. Strategies that we have undertaken to improve US surveillance rates include: a patient education brochure, nurse specialist cirrhosis clinics, and improving clinic non-attendance procedures. We are endeavouring to organise a radiology based recall system.Predictors of serologic and clinical outcomes in childhood-acquired HBV infection in New Zealand Māori: results of 28 year longitudinal studyLim TH1, Gane EJ1, Borman B2, Moyes C,3 Cunningham C2.1Liver Unit, Auckland City Hospital, Auckland, New Zealand2Research Centre for Maōri Health and Development, Massey University, Wellington, New Zealand3The Hepatitis Foundation of New Zealand, Whakatane, New ZealandBackground: High baseline HBV DNA is associated with increased risk of liver-related complications in Asians with vertically-transmitted chronic hepatitis B virus(HBV) infection. This longitudinal study evaluates the baseline predictors for liver-related complications and serologic outcomes in 572 patients identified from a 1984 seroprevalence study with early horizontally-acquired HBV infection.Methods: Serum samples from 1984 were tested for HBeAg,HBV DNA and HBsAg level. Liver-related mortality and hepatocellular carcinoma(HCC) incidence were previously determined in these 572 HBV carriers compared to 1142 HBsAg-negative case-controls. Transient elastography(TE) was performed in 2012 in all surviving HBsAg+ inpiduals. Cox-proportional hazards models were used to determine independent baseline predictors for five long-term outcomes: severe fibrosis (TE>8KPa), HCC, liver-related mortality and HBsAg+HBeAg seroconversion.Results: After 28 years, 14HBsAg+ patients developed HCC(vs none in HBsAg- controls [P<0.001]). 11HBsAg+ patients died from liver-related causes(vs none in controls(P<0.001)). To-date, 291/515(57%) surviving HBsAg+ patients have been followed-up. 25% had elevated ALT; 12% had severe fibrosis/cirrhosis(TE>8KPa). Increasing age, Maōri ethnicity and baseline HBV DNA were predictors for liver-related death and HCC. Maōri ethnicity was a predictor for severe fibrosis. Baseline HBsAg level and gender were not predictors for long-term outcome. Since 1984,90% of HBeAg+ patients have undergone HBeAg seroconversion (median age=23yrs(range 6-66)). 31% spontaneously lost HBsAg (median age 39 yrs(range 9-80)), with higher rates in HBeAg-(44%) vs HBeAg+ patients(9%)(p<0.0001).Conclusions: In a young Maōri population with early horizontally-acquired HBV, HBV DNA, but not HBsAg-level, was associated with increased risk for liver-related complications. Higher rates of spontaneous HBeAg and HBsAg loss are seen compared to Asians HBV populations.Disclosure statement: The authors have no disclosures.CMV and EBV disease in adult liver transplant recipientsGriffiths B, Gane E, Fitt S, Munn SJ. NZLTU, Auckland Hospital, New ZealandIntroduction: Herpes virus infections are an important cause of morbidity and mortality following solid organ transplantation. NZLTU has used CMV antiviral prophylaxis in all D+/R- transplants. This audit determines the incidence of CMV disease and EBV disease.Methods: CMV and EBV D/R serostatus was collected prospectively. Pharmacy and virological data were used to identify CMV and EBV infection and disease.Results: 409 adult liver transplants were evaluated. CMV serostatus was D+/R- in 57 (12.5%), D-/R+ in 112 (27.4%), D+/R+ in 188 (46%), D-/R- in 51 (12.5%). CMV infection was detected in 47 patients (11.5%), at mean 41 weeks. There were 26 cases of CMV disease (6.4% total), diagnosed at mean 57 weeks. CMV disease developed in 16 D+/R- (28.1%), 5 D-/R+ (4.5%) and 5 D+/R+ (2.7%). Mycophenolate was associated with increased risk of CMV disease (RR 4.0; 95% CI 2.3 - 3.8; p<0.0001).EBV serostatus was D+/R- in 17 (4.8%), D-/R+ in 29 (8.3%), D+/R+ in 302 (86%), D-/R- in 3 (0.9%). Six cases of EBV-associated PTLD (1.5% total) were diagnosed at mean 86 weeks. EBV disease developed in 5 (29.4%) D+/R- and 1 (0.3%) D+/R+.Conclusion: Antiviral prophylaxis has reduced incidence and delayed onset of CMV disease in D+/R- transplants. Mycophenolate is associated with an increased risk of CMV disease. EBV D+/R- transplants have a high rate of PTLD. Better EBV prophylaxis and monitoring regimens are needed.Entecavir in Chronic Hepatitis B - “Real World” ExperienceLampen-Smith A1, Wong P2,GerredS3,Gane E11Liver Unit, Auckland City Hospital, 2Gastroenterology Department, Auckland City Hospital,3Gastroenterology Department, Middlemore Hospital.Introduction: Entecavir is an approved antiviral treatment for chronic hepatitis B1. Global registration trials demonstrated excellent safety and efficacy - serum HBV DNA undetectable in 90% after 48 weeks of treatment.2 Similar results have been reported in “real-world” experience.3Methods: This is an audit of patients at Auckland and Middlemore Hospitals treated with entecavir for at least 12 months. Patients were excluded if they had prior antiviral therapy, or a diagnosis of HCC within 12 months. Data on ALT, HBV DNA, resistance studies, ethnicity and HBeAg serology was collected. Clinic notes were reviewed for evidence of treatment adherence.Results: Entecavir was approved in 459 patients, of whom 351 have received 12 months therapy. After exclusions there were 108 HBeAg positive and 157 HBeAg negative. Twenty (18.5%) HBeAg positive patients underwent HBeAg seroconversion. Of the remaining 88 eAg positive patients, HBV DNA was suppressed to undetectable or ≤3 log in 60 (68.2%). In the 28 subjects with sub-optimal virological response, 10 were adherent and had decreasing HBV DNA whilst the remaining 18 had poor adherence/ nonattendance.Of the HBeAg negative patients, 111 (71.2%) had undetectable HBV DNA, 15 (9.6%) had levels < 3 log IU/mL. Seven (4.5%) had sub-optimal virological response, all showed poor adherence. Sequencing studies did not identify resistance mutations.Conclusion: The efficacy and safety of entecavir is in clinical practice is similar to that observed in registration studies, with 80.7% and 74.1% viral suppression in eAg negative and positive chronic hepatitis B patients respectively. Lack of response reflected poor adherence rather than entecavir resistance.References: Kim SR, et al. Recent advances in the management of chronic Hepatitis B. Hepat Mon. 2011;11(8):601-11. Lai C-L, et al. Entecavir versus Lamivudine for Patients with HBeAg-Negative Chronic Hepaititis B. N Engl J Med 2006;354:1011-20. Tsai MC, et al. A comparison of telbivudine and entecavir for chronic hepatitis B in real-world clinical practice. J Antimicrob Chemother. 2012 Mar;67(3):696-9. Prealbumin measurement as a guide to adequate nutritional supports in patients receiving parenteral nutritionHY Lee, S Larsen, S Hill, R Baskett, RS WalmsleyNorth Shore Hospital, Auckland, New ZealandPrealbumin is a visceral protein and negative acute phase reactant used as a nutritional status screening tool to detect malnutrition. Its relatively short physiological half-life of 48 to 72 hours provides a dynamic measure of protein-energy status and adequacy of nutritional support (1). A rise in prealbumin of greater than 0.04 g/L has been suggested to indicate switch from a catabolic to an anabolic state (2).Aims: To assess the use of serial measurements of serum prealbumin in patients receiving short-term parenteral nutrition (PN), to determine whether anabolism can be achieved during short-term PN and the relation between change in prealbumin and acute phase response level indicated by C-reactive protein (CRP).Methods: Retrospective review of Nutrition Support Database from May 2005 to May 2012.Results: From 494 patients identified receiving PN, 142 patients had paired prealbumin and CRP data available.Negative correlation was confirmed between CRP and prealbumin (r=-0.52). Following PN therapy the mean C-reactive protein decreased from 123 to 53 mg/L (p<0.001). Mean serum prealbumin increased from 0.12 to 0.22 g/L (p<0.001).Prealbumin rise of greater than 0.04 g/L was achieved in 72% (n=102) of patients. Mean CRP after completion of PN in this group was significantly less (42 vs 83 mg/L, p<0.001), suggesting ongoing inflammation may impede visceral protein synthesis.Conclusion: Serial prealbumin measurements in patients receiving short-term parenteral nutrition are a useful guide to the adequacy of nutritional support.An anabolic state switch can be achieved in most patients despite persistent systemic inflammatory response.References Ingenbleek Y, Young V. Clin Chem Lab Med. 2002;40:1281-1291. Bernstein L, Bachman T, Meguid M, Ament M, Baumgartner T, Kinosian B, et al. Nutrition 1995;11:169-171 The Scratch Test for identifying the lower liver edge is at least as accurate as percussion and is more effective for trainees - a randomized controlled studyHuelsen A,1,2 Fischer J,1 Hegarty J,3 Lim JY,2 Burnside MJ,2 Karim SN,2 Onyango N, 2Frampton C,4 Spencer AJ,2 Barclay ML. 1,4Departments of Gastroenterology,1 General Medicine 2 & Radiology,3 Christchurch Hospital, and Department of Medicine,4 University of Otago Christchurch, Christchurch, New Zealand.Introduction: Clinical examination of the liver requires experience to achieve accuracy. The scratch test is a simple technique to identify the lower liver edge and enhance liver palpation, and may be easier for trainees.Aims and Methods: We aimed to evaluate the accuracy of the scratch test compared to percussion at different levels of medical training. Eight examiners, from trainee intern to consultant level, were randomized to scratch or percussion testing, followed by liver palpation, on 50 subjects. Later, each examiner performed the alternative test on each subject. Confidence with each test was rated 0-3 (unsuccessful - very confident). Ultrasound scan (USS) was performed as a reference for liver location.Results: Ultrasound revealed 33/50 (66%) of livers extended below the right costal margin in the midclavicular line during quiet respiration (range 0-16cm). Of these 33, 84% and 81% were identified within 2cm of the USS location using scratch and percussion tests, respectively (p>0.05) for all examiners, but with greater accuracy for the scratch test in young trainees (86% v 80%). Ability to palpate the liver was not different following either test. Examiner confidence in the test result was significantly higher using the scratch test versus percussion, average confidence scores being 2.2 versus 1.8 (p=0.007), with a greater difference in the young trainee group (p=0.003).Conclusion: The scratch test was at least as accurate as percussion in identifying the lower liver edge. In addition, all examiners and especially the young trainees were more confident in their findings using the scratch test.Predictors of poor outcome in patients with autoimmune hepatitis: a population-based studyNgu, J.H. 1,2, Gearry, R.B. 1,2, Frampton, C.M. 2, Stedman C.A.M. 1,21 Department of Gastroenterology, Christchurch Hospital 2 University of Otago, Christchurch, New Zealand.Background/Aim: Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure and death. Identifying predictors of poor outcomes could help in devising tailored management strategies. We aimed to describe predictors of poor outcomes in the population-based AIH cohort from Canterbury.Methods: Multiple case finding methods were employed, including searches of all public and private, adult and paediatric outpatient clinics, hospital notes and pathology reports. Cases diagnosed after 1980 that fulfilled standardised diagnostic criteria were included. End of follow-up was at death, liver transplantation or the end of study (31st December 2011). The associations of putative risk factors and outcomes were analyzed using Cox proportional hazards regression. The times to event outcomes were summarized using Kaplan-Meier curves.Results: A total of 133 AIH patients were included. Independent predictors of poor liver related outcomes were incomplete normalization of ALT at 6 months (p<0.01), baseline serum albumin <36g/L (p<0.01) and age at presentation of ≤ 20 years or >60 years (p=0.01). Kaplan-Meier estimates showed 10 years adverse liver event free survival were 80% for age at presentation ≤20 years and >60 years, and 93% and 100% for age at presentation between 21-40 years and 41-60 years respectively.Conclusion: Incomplete normalization of ALT at 6 months, low serum albumin concentration at diagnosis and age at presentation of ≤ 20 years or >60 years, were significant independent predictors of poor liver related outcomes. Histological cirrhosis at diagnosis was not associated with poor prognosis and did not influence the response to initial immunosuppressive treatment.Environmental risk factors in autoimmune hepatitis: a population-based case control studyNgu, J.H. 1,2, Gearry, R.B. 1,2, Frampton, C.M. 2, Stedman C.A.M. 1,21 Department of Gastroenterology, Christchurch Hospital 2 University of Otago, Christchurch, New Zealand.Background/Aim: The precise aetiology of autoimmune hepatitis (AIH) remains unknown and likely involves a complex interaction of genetic and environmental factors. However, to date, systematic examination of association between environmental factors and AIH has yet to be performed. We aimed to perform a population-based case control study to investigate for associations between exposure to putative environmental factors and AIH.Methods: Cases were AIH patients who were alive and resided in Canterbury between 1st July 2011 and 30th June 2012. Controls were randomly selected from the Electoral Roll and were matched 2:1 to each case by age and gender. Self-reporting questionnaires that cover lifestyle factors, childhood factors and family history were used.Results: A total of 72 AIH cases and 144 controls were included. Univariate analysis showed that antibiotic (p<0.01) and being vegetarian >1 year (p=0.04) were risk factors for AIH. Alcohol consumption (p<0.01), childhood home with vegetable garden (p=0.01) and wood heating (p<0.01) were protective factors. Multivariate analysis showed that antibiotic, alcohol consumption and childhood home with wood heating were independently associated with AIH. The crude risk of AIH in first degree relatives was 0.2%.Conclusion: This is the first population-based study investigating for associations between exposure to environmental factors and AIH. We found that antibiotics were an independent risk factor, whereas alcohol consumption and childhood home with wood heating were independent protective factors for AIH. Risk of AIH in first degree relatives was low.Auckland experience with Tenofovir therapy in nucleoside/nucleotide experienced patients with Chronic Hepatitis BJohns E, Naidoo M, Gane E, New Zealand Liver Transplant Unit, AucklandThe nucleotide analogue Tenofovir is funded for patients with hepatitis B, loss of virological response (HBV DNA 20 000 IU/mL or >1 log from nadir) and proven antiviral resistance.In treatment-naïve patients 76% of HBeAg-positive and 93% of HBeAg-negative achieve viral suppression (HBV DNA <400 copies/mL or 69 IU/ml) at 48 weeks. Treatment-experienced cohorts show a similar response but questions remain over durability in patients with adefovir resistance.We report local experience in treatment-experienced patients switched to tenofovir as monotherapy or in combination with lamivudine.Results: 144 of 146 patients tolerated treatment and were analysed. 38 received combination therapy. Median follow up was 26 months (range 1-94) with 116 patients completing 12 and 75 patients 24 months of therapy. Previous treatment included lamivudine (95%), adefovir (64%) and telbivudine (12%).On intention to treat analysis 67% of HBeAg-positive, 72% of HBeAg-negative and 69% of all patients achieved viral suppression (<400 copies/mL) at 12 months, and 70%, 82% and 75% respectively at 24 months. In patients meeting PHARMAC criteria for treatment failure at commencement of therapy suppression was 56% at 12 and 75% at 24 months; results were similar in the adefovir-resistant subgroup (57% and 71%).HBeAg seroconversion occurred in 13% of patients treated for ≥ 12 months; no patient lost HBsAg.Conclusion: Our experience with tenofovir rescue therapy in patients with antiviral resistance is consistent with published series. Adefovir-resistant patients had a similar virologic response but longer follow-up is needed. The need for combination rather than monotherapy in this population needs further evaluation.Disease assessment in Crohn’s disease (CD): Data from the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) project cohorta,dFalvey, JD, aHoskin T, aMeijer B, aAshcroft A, bHampton, MB, c,eDay AS a,dGearry, RB.Departments of aMedicine, bPathology and, cPaediatrics, University of Otago Christchurch. Departments of dGastroenterology and ePaediatrics, Christchurch Hospital, Christchurch.Introduction: Colonoscopy, the gold standard for CD assessment, is not suitable for regular monitoring while clinical assessment is often inaccurate. We aimed to determine the clinical utility of three established non-invasive methods of CD assessment, the Harvey Bradshaw index (HBI), serum CRP and faecal calprotectin (FC), and one novel biomarker candidate, serum macrophage migration inhibitory factor (MIF).Methods: Patients attending for colonoscopy with known or suspected IBD were recruited to the NBIBD cohort. Cases provided full demographic and disease activity data (HBI) in addition to biological samples. Endoscopic activity was recorded using the simple endoscopic score of Crohn’s disease (SES-CD)Results: 108 cases were included. Median (IQR) SES-CD, 4 (2-12). Spearman correlation coefficients for comparison with SES-CD were: HBI r=0.24 (p=0.007); CRP, r=0.44 (p<0.0001); FC r=0.55 (p<0.0001, n=82); MIF r=0.14 (p=0.2, n=85). A trend to better diagnostic utility was observed for FC over CRP (active≡SES-CD ≥3, AUC 0.74 (p=0.0006) and AUC 0.64 (p=0.003) respectively). HBI had modest diagnostic accuracy for severe disease only (SES-CD ≥16 vs. ≤15, AUC 0.78 (p=0.0002)). Sensitivity, specificity, PPV and NPV of FC ≥125µg/g for SES-CD ≥3 disease were, 71%, 71%, 85% and 50% respectively. Neither HBI, FC nor CRP could anticipate endoscopic remission. Combining CRP (≥10mg/L) and clinical data (HBI ≥8) significantly improved PPV for the detection of moderate-severe CD (SES-CD ≥7) cf. CRP alone (PPV 73% (95%CI 51-93%) vs. 50% (95%CI 34-65%) respectively).Conclusions: Established methods of non-invasive disease assessment offer modest diagnostic utility. Novel biomarkers with greater sensitivity and specificity are urgently needed.Clinical assessment of murine Dextran Sodium Sulphate (DSS) colitis: prospective validation of a novel scoring tool.a,eFalvey JD, dMunday JS, bKeenan, JI, fDyer AE, a,eGearry, RB, cHampton, MBDepartments of Medicinea, Surgeryb and Pathologyc, University of Otago Christchurch.dInstitute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North. eDepartment of Gastroenterology, Christchurch Hospital, Christchurch. fChristchurch Animal Research Area, University of Otago, Christchurch.Introduction: Murine DSS colitis is a common research model for IBD. Histological examination of the colon provides gold standard assessment; however, non-lethal assessment is critical for disease monitoring and secondary endpoint analysis. Coopers’ murine colitis score (MCS), the current standard, correlates well with histology but has low content validity in some domains.Aims: To develop and prospectively validate a novel MCS.Methods: Developmental phase: Novel stool consistency and rectal bleeding indices were developed in order to improve content validity of these domains. Variations of the MCS were tested in post hoc analysis against histology. Validation stage: 2% DSS was provided ad libitum to 24 mice. Three mice per day (0-7) were selected randomly; disease was assessed independently by 2 observers using a proforma from which a complex MCS, a simple MCS (SMCS) and the Cooper MCS were derived. Non-invasive assessment was compared with histological activity.Results: Murine colitis scores correlated highly with histology (Spearman r=0.93, r=0.91 and r=0.91 for the simple, the complex and the Cooper MCS respectively (p<0.0001)). Correlation with histology was non-significantly greater for the novel stool score compared with Cooper stool score (r=0.86 (95%CI 0.69 - 0.94) vs. r=0.77). There was a high level of agreement (linear weighted қ=0.86 (95%CI 0.77-0.96)) and correlation (r=0.94 (95%CI 0.87-0.98) p<0.0001) between observers for the SMCS.Conclusions: A modification of the Coopers colitis score (SMCS) comprising a weight loss score, novel stool score and dichotomous rectal bleeding score, provides a valid and simple method for the non-invasive assessment of DSS colitis.Disease assessment in Ulcerative Colitis (UC): Data from the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) project cohorta,dFalvey JD, aHoskin T, aMeijer B, aAshcroft A, bHampton, MB, c,eDay AS, a,dGearry, RB.Departments of aMedicine, bPathology and,cPaediatrics University of Otago Christchurch. Departments of dGastroenterology and ePaediatrics, Christchurch Hospital, Christchurch.Introduction: Colonoscopy, the gold standard for UC assessment, is not suitable for regular monitoring while clinical assessment is frequently inaccurate. We aimed to determine the clinical utility of three established non-invasive methods of disease assessment, the simple clinical colitis activity index (SCCAI), serum CRP and faecal calprotectin (FC), and one novel biomarker candidate serum macrophage migration inhibitory factor (MIF) in the normal clinical setting.Methods: Patients attending for colonoscopy with known or suspected IBD were recruited to the NBIBD cohort. Cases with UC provided full demographic and disease activity data (SCCAI) in addition to biological samples. Endoscopic activity was recorded using the modified Baron scoreResults: 65 cases were included. Spearman r correlation coefficients for comparison with endoscopic score were: CRP, r=0.4 (p<0.0001); SCCAI r=0.44 (0.31-0.62, p=0.0002); FC r=0.55 (p<0.0001, n=51). Overall disease burden (severity*extent) correlated better with each parameter but differences were not significant. No correlation was observed between plasma MIF and endoscopic activity (r=0.11, p=0.2, n= 85). ROC analysis revealed significant diagnostic utility for SCCAI, CRP and FC (AUC 0.73 (p=0.002), AUC 0.78 (p=0.002) and AUC 0.75 (p=0.004) respectively). Optimal thresholds for distinguishing Baron ≥2 disease were (threshold (sensitivity, specificity, PPV and NPV)): SCCAI, 3.5 (59%, 88%, 72%, 81%); CRP 5mg/L (64%, 74%, 56%, 80%); FC 125 ug/g (83%, 64%, 56%, 88%). Neither CRP nor FC could reliably anticipate endoscopic remission (Baron 0).Conclusions: Established methods of non-invasive disease assessment offer modest diagnostic utility. Novel biomarkers with greater sensitivity and specificity are urgently needed.Outcomes of adalimumab therapy for Crohn’s disease from five New Zealand hospitalsSchultz M,1 Lewis-Morris T,2 Rowbotham D,3 Whiteside C,4 Bennett S,1 Thomas G,2 Inns S,4 Gearry RB2Departments of Gastroenterology, 1Dunedin, 2Christchurch, 3Auckland City, 4Hutt Valley HospitalsIntroduction: Adalimumab (ADA) is an effective therapy for the treatment of Crohn’s disease (CD). We aimed to describe the use o

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