These reports are provided by our award recipients and all statements are published in good faith.
OPERA-C stands for: Observational, Prospective Epidemiological Registray in Australia of HCV Liver Disease.
This is an ongoing prospective study lead by Paul Clark. It examines the clincial epidemiology of HCV in Australia, treatment uptake and outcomes in the post-DAA era through the use of a national registry for patient information and currently includes 2,585 patients over 27 active sites.
The study is now being expanded with a sub study to track patients idenitified with HCC for 5 years (an additional 3 years). Operationally the impact of this is small as there will be no new contracts and the ethics approvals (anticipated early March) and protocol amendments are considered straight forward as patient consents are considered broad enough to encompass this additional tracking.
OPERA C Poster presented at AASLD 2017.
The TOSCAR study led by Peter Angus, Stuart Roberts and Geoff McCaughan evaluated the treatment of up to 200 patients with advanced decompensated HCV liver disease who are at high risk of mortality with the combination of sofosbuvir and daclatasvir with/without ribavirin.
The interim data was presented at AASLD 2015 and AGW 2015, final data was presented at AGW 2016 and AASLD 2016. Study data was published in Alimentary Pharmacology & Therapeutics. Currently around 100 patients at 5 sites are being followed up for HCC occurance/reoccurance.
The TAPESTRY study led by Stuart Roberts, Simone Strasser, Geoff McCaughan and Amanda Nicoll focused on evaluating the efficacy and safety of Mycophenolate Mofetil (MMF) as salvage therapy in patients with Autoimmune Hepatitis who had sub-optimal outcomes to standard therapy with prednisolone with/without Azathioprine. Over 100 patients were recruited to this study making it the largest yet reported on this patient population treated with MMF. The study has been finalized and was submitted to the Journal of Clinical Gastroenterology and Hepatology with generally favorable reviews received. A subsequent revised manuscript has been resubmitted. Further studies are planned with this cohort including evaluation of predictors of response and outcomes in those who received calcineurin inhibitors.
The REV1TAL study led by John Lubel and Stuart Roberts as PI evaluated the efficacy and safety of Viekira Pak in subjects with CHC Gt1/4 infection that were treated under an AbbVie compassionate access program. Data was collected on 464 patients in this study across 20 CRN sites including 340 with cirrhosis. Data on this cohort was presented at both AASLD 2016 and EASL 2017 with final results published in the Journal Antiviral Therapy.
Outcome: In a real-world setting, treatment with PrOD in Genotype 1 HCV infection achieves excellent SVR12 rates including those with cirrhosis. Hyperbilirubinaemia is a frequent on-treatment finding but hepatic decompensation resulting in early cessation of therapy was rare.
Recipient: Jakob Begun Value: $15,000
Project Title: Measuring the impact of intestinal ultrasound in the Young Adults Health Service (IBD) at The Mater Hospital, Brisbane.
Intestinal Ultrasound (USS) is an increasingly well-validated imaging tool for the detection of complications and assessment of disease activity in IBD.Under the lead of Dr. Jakob Begun, the Young Adults Health Service (IBD) at The Mater Hospital, Brisbane has been using intestinal USS since mid-2016. The aim of the project is to further optimise the use of intestinal USS as a clinical tool in a best practice model of care at the Young Adults Health Service (IBD) at The Mater Hospital, Brisbane.
The project is a service evaluation exercise to collect metrics related to the use of intestinal USS in the Young Adults Health Service (IBD) at The Mater Hospital, Brisbane. This information will be used to inform development of a model of care that maximises the clinical utility of intestinal USS. Currently, intestinal USS is at the discretion of the treating clinician, without a clear framework within the unit to guide which patients intestinal USS is expected to benefit and without critical review of its "value add" beyond the conventional standard of care. With any introduction of a new technology into a service, it is necessary to evaluate and define the impact of that technology to understand its best application within the service to optimise patient outcome and service efficiency.
Jakob Begun - email@example.com
Recipient: Mark Ward Value: $15,000
Project Title: A virtual clinic to coordinate compassionate intensified biologic therapy in patients with inflammatory bowel disease - cost analysis and effectiveness compared to standard of care.
A substantial proportion of patients with inflammatory bowel disease treated with anti-TNF agents develop secondary loss of response to these therapies. Therapeutic drug monitoring (measuring drug levels, and where appropriate, anti-drug antibodies) can help identify which patients may respond to dose intensification. Dose intensification is not currently supported by the PBS but is accessible through compassionate programs offered by pharmaceutical companies. Current service models to deliver compassionate intensified anti-TNF therapy are inadequate; they are resource intensive, lack protocols to identify suitable patients and to monitor response to intensified therapy and lead to an inconsistent delivery of care.
This award will support research into a novel model of care in this setting, namely a virtual clinic, which has been in use at our institution since 2015. The aims of this study are to assess the cost effectiveness of our virtual clinic, compared to standard of care, in managing patients with secondary loss of response to anti-TNF therapy who undergo dose intensification and to investigate whether treating-to-target via a virtual clinic improves patients' outcomes.
For further information:
Mark Ward - M.Ward@alfred.org.au
Recipient: John Lubel Value: $50,000
Project Title: Screening is caring: Community-based non-invasive diagnosis and treatment strategies for hepatitis C to reduce liver disease burden
The CATCH project has been incredibly successful, culminating in an editorialised publication in the Journal of Hepatology late last year. This journal is one of the top liver journals with an impact factor of 15. The front cover of the Journal was also dedicated to the topic of community screening. This was a major achievement of the project and with ongoing support we will continue to publish in high impact peer-reviewed journals.
Our first PhD student, Stephen Bloom, has also passed his PhD in the last few weeks week and our second PhD student is in the end of her second year.
Work is progressing well with the project, but there is still much more work to do. We are now entering the 3-5 year follow-up period as well as bio-chemical assessment of samples taken longitudinally through the patient's journey with viral hepatitis.
Publications under peer review
Bloom S, Liew D, Roberts S, Lubel J, Kemp W. Cost effectiveness of community non-invasive techniques to triage hepatitis C for hepatocellular carcinoma surveillance. J Hepatol. 2018
For further information:
John Lubel - firstname.lastname@example.org
Recipient: Dr Robert Bryant Value: $60,000
Establishing an IBD gastrointestinal ultrasound service in South Australia
Inflammatory bowel diseases (IBD), encompassing ulcerative colitis and Crohn’s disease, are lifelong inflammatory conditions of the gut. The cause of IBD is incompletely understood, but is thought to relate to susceptible genetics, changes in the gut microbiome, and immune dysfunction. Rates of IBD are increasing dramatically worldwide, and it is estimated that as many as one in 250 Australians are affected.
Therapeutic advances over the past two decades have shifted the goal posts of IBD therapy. The target of IBD treatment is now to heal the bowel, which has been shown to improve outcomes for people with IBD. Treatment strategies in IBD now require objective evidence of disease activity to guide management decisions, which has led to an increasing requirement for expensive and invasive investigations such as colonoscopy.
Advances in sonographic imaging have expanded the use of ultrasound in many areas of clinical practice. Gastrointestinal ultrasound is an emerging technique that has been shown to be accurate in assessing IBD as compared to endoscopy and other types of imaging, and holds advantages of being non-invasive, inexpensive, and lacking in radiation. Furthermore, gastrointestinal ultrasound can be performed in the clinic without any patient preparation, to expedite management decisions.
The GESA IBD Clinician Establishment Award will be used to establish the first adult gastrointestinal ultrasound service in South Australia at The Queen Elizabeth Hospital. Dr Bryant has gained expertise in Gastrointestinal Ultrasound through training at the Adelaide Women’s and Children’s Hospital and a dedicated fellowship in Milan Italy. The Award will be used to purchase the necessary ultrasound equipment to establish the service, as well as facilitate further research evaluating the accuracy of gastrointestinal ultrasound in IBD as compared to other tools including endoscopy. The patient experience of gastrointestinal ultrasound will also be assessed, as well as the capacity for ultrasound to improve illness-related knowledge and perceptions. The study will form an essential role in informing local clinicians of the value of gastrointestinal ultrasound in IBD practice.
For further information:
Dr Robert Bryant - email@example.com
Recipient: Dr. William Connell Value: $125,000
The management of IBD is increasingly complex and specialised. At the same time, its prevalence is among the highest in the world. A report commissioned by the Crohn's and Colitis Association of Australia has previously identified a disparity in the level of IBD care across the
country, with some rural patients having reduced access to best practice management.
In mid 2015, a monthly satellite Complex IBD clinic was developed in Bendigo, a regional Victorian city that services much of central and North Western Victoria. Using a model of care established by the IBD Service at St Vincent's Hospital, Melbourne, the Clinic is designed to complement the pre-existing structure of IBD care provided by the region's gastroenterologists, surgeons and GP's. Regardless of health insurance status, patients with complex IBD needs are seen together in consultation by their local gastroenterologist, A/Prof Leslie Fisher, and a visiting IBD physician,
Dr Bill Connell. Where necessary, patients are offered access to multidisciplinary facilities at St Vincent's Hospital, including IBD nurses (via Telehealth or IBD Help line), colorectal surgeons, psychologists, and dieticians. A local biological infusion centre was established to cater for the increasing demand for access to biologic medications.
The service has improved access of local patients with complex IBD to best practice management according to Evidence Based Medicine guidelines, as well as addressing each individual's holistic needs. In January 2017, the new Bendigo Hospital was opened, and it is intended that the service will eventually expand to include greater coverage for the region's IBD community and at the same time up skill new health care practitioners who are interested in establishing an autonomous service of its own.
For further information:
Dr. William Connell - William.CONNELL@svha.
Recipient: Emily Wright Value: $60,000
Stricture Definition and Treatment (STRIDENT) Study: Solving the commonest and most neglected complication of Inflammatory Bowel Disease
Intestinal strictures are the most common complication of Inflammatory Bowel Disease (IBD), accounting for substantial morbidity and cost. Surgical management is often required. Despite this, stricture evolution and assessment is poorly understood and there is little controlled data to guide clinical management. The Stricture Definition and Treatment (STRIDENT) study is a prospective, randomised controlled trial (RCT), for patients with IBD related symptomatic strictures. Patients receive optimised standard drug treatment versus high dose drug therapy, including high dose anti-TNF treatment (adalimumab) intensified progressively to eliminate inflammation.
This study addresses the current key issues in IBD management including the use of disease biomarkers and non-invasive imaging to better characterise and predict disease behaviour and the role of high dose anti-TNF drug therapy to better control inflammation. This study examines the role of novel bedside imaging techniques, bedside Intestinal Ultrasound (IUS) to better monitor inflammation and predict response to treatment. Bedside IUS is an emerging modality in IBD and offers safe, reliable, inexpensive and non-invasive assessment of bowel inflammation.
This is the first RCT of stricture management in inflammatory bowel disease, and the only trial to examine the efficacy of high-dose anti-TNF therapy in strictures. It will determine an evidence based treatment algorithm for patients with this common, but often neglected, complication of IBD. The results of this study will address this need and will directly impact on the treatment received by patients, transforming stricture management, and clinical and patient-reported outcomes.
For further information:
Emily Wright - Emily.Wright@svha.org.au
Recipient: Rupert Leong Value: $75,000
Inflammatory Bowel Diseases: Intestinal Mucosal Protein Biomarker Discovery and Barrier Function Assessment Using Confocal Laser Endomicroscopy
The GESA AbbVie IBD Clinical Research Grant was used to support a joint research program combining endoscopic Confocal Laser Endomicroscopy (eCLE) and mass spectrometry techniques in the evaluation of intestinal permeability in Inflammatory Bowel Disease (IBD).
Objective outcomes of this grant are:
Our research focused on identifying two methods of studying intestinal permeability – an invasive method that Leong developed using endoscopic Confocal Laser Endomicroscopy (eCLE) and a new non-invasive serum biomarker by UNSW Mass Spectrometry Facility led by Wasinger. The development of a new non-invasive biomarker is critical towards further research on this mechanism. eCLE, being invasive, lacks the capacity to generate high and rapid throughput. As such we aimed to develop non-invasive methods of studying intestinal permeability. Compromised epithelial cell integrity in the gastrointestinal tract is linked to dysfunction of the mucosal barrier.
We found that ongoing intestinal permeability defects underlie ongoing bowel symptoms even when the mucosal is no longer inflamed. We used a discovery and targeted proteomic approach to interrogate the differences in leaky gut patients suffering from IBD based on their confocal endomicroscopy score (CLE leakiness score). Quantitative proteomic profiling was performed using serums by label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Functional annotation analysis of detected proteins and Multiple Reaction Monitoring (MRM) was used to verify findings. Proteins of interest were analysed in high and low leak patients and found to differ significantly. Increased circulation of Epithelial Barrier Component (EBC) proteins are associated with intestinal complications, confirming epithelial defects at the in-vivo proteome-level and suggesting viability of monitoring intestinal injury by serological tests. Modulated proteins in patients with ongoing intestinal damage may be able to predict for the development of complications and predict for the need to escalate treatment.
Our research helps to explain the disconnect seen in clinical trials where patients have mucosal healing but have not entered clinical remission. The importance of this finding is to generate an alternative “treat-to-target” strategy of recovery of intestinal barrier function, rather than aiming for mucosal healing alone. The recovery of the barrier function may be important to prevent further flares of IBD in the future.
For further information:
Rupert W Leong - Rupert.Leong@sswahs.
Valerie Wasinger - firstname.lastname@example.org
Recipient: Anthony Catto-Smith Value: $75,000
Cardiovascular Phenotype in Children with Chronic Inflammatory Disease (CUPID study)
The reduction of cardiovascular disease (CVD), the leading cause of mortality and the most expensive disease group in Australia, is a National Health Priority. Atherosclerosis, the pathology underlying CVD is a chronic inflammatory condition that starts in early life.
In adults, there is increasing evidence that Inflammatory Bowel Disease (IBD) is associated with an adverse cardiovascular phenotype. Children with IBD theoretically also carry increased cardiovascular risk in addition to the potential life-long consequences of the underlying disease.
The CUPID study aims to increase the understanding of the relationship between paediatric IBD and cardiovascular risk, facilitating the development of preventative strategies and identification of populations who would benefit most. In CUPID we are assessing intermediate cardiovascular phenotypes – non-invasive measures of arterial structure and function that are thought to predict later cardiovascular risk and disease. This study involves close collaboration between the Gastroenterology Department, Royal Children’s Hospital, Melbourne and the Infection and Immunity Group, Murdoch Childrens Research Institute.
CUPID is a cross-sectional case-control study investigating the cardiovascular intermediate phenotypes of children with established IBD, including non-invasive macro- and micro-vascular assessment, and biomarkers of inflammation and adverse cardiovascular status. It is, as far as we are aware, the most detailed cardiovascular assessment of children with IBD to date. We’re aiming for 80 patients with Crohn’s disease or ulcerative colitis of at least 6 months duration aged 7-18 years, and 80 age-and sex matched controls.
Currently we have 66 children with IBD and 66 healthy comparison participants. Each of the 66 IBD patients and 66 comparison participants have had fasting plasma glucose, lipid profile, high sensitivity C-reactive protein, carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (cIMT), abdominal aorta intima-media thickness (aIMT), and retinal vascular calibre performed. Recruitment is nearing completion and analysis of the above measures has commenced.
For further information:
Professor Anthony G Catto-Smith - email@example.com
Image: Assessment of the carotid artery by ultrasound
Recipient: Laurence Britton Value: $ 55,287
Laurence Britton is a Gastroenterologist based in Brisbane at the Princess Alexandra and Greenslopes Private Hospitals. His PhD studies have been supported by the GESA Biomedical Postgraduate Research Scholarship 2014. His PhD is being undertaken under the supervision of Prof Darrell Crawford and Dr Kim Bridle at the Gallipoli Medical Research Foundation, University of Queensland at Greenslopes in Brisbane.
Laurence’s thesis is titled “Interactions Between Iron and Fat in Non-alcoholic Fatty Liver Disease”. His studies have focussed on the role of iron in dysregulation of adipose tissue and liver function, in particular with regards to the development of insulin resistance. During his studies, Laurence has developed a cell culture model of iron loading in human adipocytes using differentiated Simpson-Golabi-Behmel Syndrome (SGBS) pre-adipocytes. He has been able to detect a number of differentially expressed proteins in the secretome of these cells in response to iron using a mass spectroscopy technique known as stable isotope labelling with amino acids in cell culture (SILAC). Human studies have examined the association between insulin resistance and hepatic iron concentration and the effect of venesection on serum adipokines.
He has made oral presentations of his work at the American Association for the Study of Liver Diseases (AASLD) annual meeting in Washington D.C. in 2013 and also at the conference of the World Gastroenterology Association (Gastro 2015) in Brisbane.
Recipient: Sujievvan Chandran Value: $80,114
Research projects on oesophagogastric cancer, endoscopic devices in the upper gastrointestinal tract and the role of endoscopy in the prevention of colorectal cancer
Thank you to GESA for supporting my research project as the inaugural winner of the GESA Postgraduate Clinical Research Scholarship for 2014. I have successfully completed seven research projects that were subsequently published. Our research topic examined novel approaches to the endoscopic management of gastrointestinal disorders. The three areas we focused on were oesophagogastric cancer, endoscopic devices in the upper gastrointestinal tract and finally the role of endoscopy in the prevention of colorectal cancer.
In the area of oesophagogastric cancer we investigated the utility of EUS guided fiducial placement and a novel endoscopic marker inserted at the margins of the tumour to allow for Image-Guided Radiotherapy (IGRT). Our experience suggested that our novel marker allows for improved tumour localization and IGRT, which is currently being assessed in other areas including bladder cancer at our institution.
Endoscopic devices examined in the upper GI tract included a novel fully covered self-expanding metal stent (FCSEMS) for the management of pancreatic fluid collections across 13 centres nationally and a multi-centre diagnostic non-randomized single blind study assessing a novel oesophageal capsule for triaging upper GI bleeding.
Finally in the area of colonoscopy we completed the first nationwide assessment of colonoscopy practices. I undertook a multi-center prospective study on right sided adenoma detection with retroflexion versus forward view colonoscopy and assessed the role of real time optical diagnosis of polyp histology in predicting appropriate surveillance intervals.
I am grateful for the support provided by GESA through this scholarship without which the numerous research projects would not have been possible. Our research was supported by a large number of units across Australia who contributed to many of the studies described above. Finally I would like to thank the endoscopy unit at Austin Health and in particular Dr. Rhys Vaughan and Dr. Marios Efthymiou for their guidance through this time.
For further information:
Sujievvan Chandran - firstname.lastname@example.org
Recipient: Jane Andrews Value: $125,000
Clinical Correlates of Mental Health Issues in Outpatients with Inflammatory Bowel Disease under Routine Care
For further information:
Taryn Lores - email@example.com
GESA Research Stories is a new feature for GESA members to promote their research. To be included, please forward your research story to firstname.lastname@example.org.