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Background: Optimal management of cirrhosis is complex, and patients often lack knowledge and skills, which can affect self-management. We assessed patient knowledge about cirrhosis and examined whether knowledge was associated with clinical outcomes, healthcare service use, and healthcare costs. A cross-sectional ‘knowledge survey’ was conducted during 2018-2We assessed patient knowledge about cirrhosis and explore whether knowledge was associated with clinical outcomes, healthcare service use, and costs. METHODS: Patients with cirrhosis (n=123) completed a ‘knowledge survey’. We calculated the proportion of correct answers to eight questions deemed to be “key knowledge” about cirrhosis by an expert panel, and dichotomized patients as ‘good knowledge’/‘poor knowledge’. Clinical data, healthcare costs, and health-related quality of life (SF-36) were available. RESULTS: 58.5% of patients had ‘good knowledge’ about cirrhosis. Higher education level was associated with higher odds of having ‘good knowledge’ about cirrhosis (adjusted-OR=5.55, 95%CI 2.40-12.84). Compared to patients with ‘poor knowledge’, those with ‘good knowledge’ had a higher health status in the SF-36 physical functioning domain (p=0.011), fewer cirrhosis-related admissions (adjusted incidence rate ratio [IRR]=0.59, 95%CI 0.35-0.99) and emergency presentations (adj-IRR=0.34, 95%CI 0.16-0.72), and more planned one-day cirrhosis admissions (adj-IRR=3.96, 95%CI 1.46-10.74). The total cost of cirrhosis admissions was lower for patients with ‘good knowledge’ (adj-IRR=0.30, 95%CI 0.29-0.30).Conclusion: Poor disease knowledge is associated with increased use and total cost of healthcare services. Targeted educational interventions to improve patient knowledge may be an effective strategy to promote a more cost-effective use of healthcare services.

Objective: To measure progress towards Australia's National Hepatitis B Strategy 2014–17 targets, and assess geographic variation in disease burden and access to care for those living with chronic hepatitis B (CHB). Methods: Data were generated from routinely collected sources, including risk-group prevalence and population data, infectious diseases notifications, Medicare records, and immunisation registry data, and assessed nationally and according to geographic area for 2013–15. Results: CHB prevalence in 2015 was 239,167 (1.0%), with 62% of those affected having been diagnosed (target 80%). Treatment uptake was 6.1% (target 15%), and only 15.3% of people with CHB received guideline-based care. CHB prevalence ranged within Australia's 31 Primary Health Networks (PHNs) from 1.77% (NT) to 0.56% (Grampians & Barwon South West VIC). No PHN reached the 15% treatment target, with uptake highest in South Western Sydney (13.7%). Immunisation coverage reached the 95% target in three PHNs. Conclusions: The CHB burden in Australia is significant and highly geographically focused, with notable disparities in access to care across Australia. Implications for public health: Efforts to improve progress toward National Strategy targets should focus on priority areas where the prevalence of CHB is substantial but access to treatment and care remains low.

Objective Endoplasmic reticulum aminopeptidase 1 (ERAP‐1) and ERAP‐2, encoded on chromosome 5q15, trim endogenous peptides for HLA‐mediated presentation to the immune system. Polymorphisms in ERAP1 and/or ERAP2 are strongly associated with several immune‐mediated diseases with specific HLA backgrounds, implicating altered peptide handling and presentation as prerequisites for autoreactivity against an arthritogenic peptide. Given the thorough characterization of disease risk–associated polymorphisms that alter ERAP activity, this study aimed instead to interrogate the expression effect of chromosome 5q15 polymorphisms to determine their effect on ERAP isoform and protein expression. Methods RNA sequencing and genotyping across chromosome 5q15 were performed to detect genetic variants in ERAP1 and ERAP2 associated with altered total gene and isoform‐specific expression. The functional implication of a putative messenger RNA splice‐altering variant on ERAP‐1 protein levels was validated using mass spectrometry. Results Polymorphisms associated with ankylosing spondylitis (AS) significantly influenced the transcript and protein expression of ERAP‐1 and ERAP‐2. Disease risk–associated polymorphisms in and around both genes were also associated with increased gene expression. Furthermore, key risk‐associated ERAP1 variants were associated with altered transcript splicing, leading to allele‐dependent alternate expression of 2 distinct isoforms and significant differences in the type of ERAP‐1 protein produced. Conclusion In accordance with studies demonstrating that polymorphisms that increase aminopeptidase activity predispose to immune disease, the increased risk also attributed to increased expression of ERAP1 and ERAP2 supports the notion of using aminopeptidase inhibition to treat AS and other ERAP‐associated conditions.

Ankylosing spondylitis (AS) is a common immune-mediated arthropathy primarily affecting the spine and pelvis. Most AS patients have subclinical intestinal inflammation, suggesting the gut microbiome and the immune response play a role in pathogenesis. Susceptibility to AS is primarily genetic, and at least 114 susceptibility variants have been identified to date. We applied bioinformatic methods utilizing epigenetic and gene and protein expression data to identify the cell types through which AS-associated variants operate. Variants were enriched in transcriptionally regulated regions in monocytes, CD4+ and CD8+ T cells, natural killer cells, regulatory T cells and B cells and mucosa from the small intestine, sigmoid colon and rectum. Weak signals were detected in bone cells, consistent with bone disease being a secondary manifestation. RNA sequencing of blood cells from AS patients and controls identified differentially expressed genes. Interrogation of expression databases showed that the upregulated genes were enriched in monocytes and downregulated genes were enriched in CD8+ T cells and natural killer cells. Gene Ontology term enrichment analysis identified microbes and the gut in the aetiology of AS. These findings identify the key immune cell types that drive the disease, and further highlight the involvement of the gut microbiome in the pathogenesis of AS.

We compared quantitative RT-PCR (qRT-PCR), RNA-seq and capture sequencing (CaptureSeq) in terms of their ability to assemble and quantify long noncoding RNAs and novel coding exons across 20 human tissues. CaptureSeq was superior for the detection and quantification of genes with low expression, showed little technical variation and accurately measured differential expression. This approach expands and refines previous annotations and simultaneously generates an expression atlas.

Introduction Ankylosing spondylitis (AS) is unique in its pathology where inflammation commences at the entheses before progressing to an osteoproliferative phenotype generating excessive bone formation that can result in joint fusion. The underlying mechanisms of this progression are poorly understood. Recent work has suggested that changes in Wnt signalling, a key bone regulatory pathway, may contribute to joint ankylosis in AS. Using the proteoglycan-induced spondylitis (PGISp) mouse model which displays spondylitis and eventual joint fusion following an initial inflammatory stimulus, we have characterised the structural and molecular changes that underlie disease progression. Methods PGISp mice were characterised 12 weeks after initiation of inflammation using histology, immunohistochemistry (IHC) and expression profiling. Results Inflammation initiated at the periphery of the intervertebral discs progressing to disc destruction followed by massively excessive cartilage and bone matrix formation, as demonstrated by toluidine blue staining and IHC for collagen type I and osteocalcin, leading to syndesmophyte formation. Expression levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints, were reduced by 49% and 63% respectively in the spine PGISp compared with control mice (P < 0.05) with SOST inhibition confirmed by IHC. Microarray profiling showed genes involved in inflammation and immune-regulation were altered. Further, a number of genes specifically involved in bone regulation including other members of the Wnt pathway were also dysregulated. Conclusions This study implicates the Wnt pathway as a likely mediator of the mechanism by which inflammation induces bony ankylosis in spondyloarthritis, raising the potential that therapies targeting this pathway may be effective in preventing this process.