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ObjectivesWe aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission.DesignOutcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015–2020, n=110; All India Institute of Medical Sciences, New Delhi 2018–2020, n=62).ResultsIn the 2015–2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992–1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992–1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%–11%.ConclusionsEmergency colectomy rates for ASC have halved in 25 years to 8%–15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.

Background Therapeutic drug monitoring (TDM) of infliximab (IFX) levels in inflammatory bowel disease (IBD) patients can help to guide dose adjustments or changes to therapy for selected patients in remission or with secondary loss of response (LOR). Aims To determine how IFX TDM is utilised in a real-life clinical setting and to quantify the potential for TDM to reduce the unnecessary use of IFX. Methods Data from all public IBD IFX level testing performed across Australia were prospectively collected from June 2016 to July 2017 to assess physician-reported for testing indications (induction, in remission or LOR) and associated results. The hypothetical influence of IFX TDM was based on an optimal therapeutic range of 6-10 mg/L for mucosal healing. Results Secondary LOR (reactive TDM) was the most common indication for TDM. These patients have consistently lower median IFX levels: 3.02 mg/L (IQR 1.14-6.67 mg/L) versus 5.22 mg/L (IQR 2.70-8.12 mg/L), P = 0.0001 compared with patients in remission (proactive TDM). TDM helped to identify unnecessary use of IFX in 30.6% of the TDM tests performed in luminal Crohn disease and ulcerative colitis patients, with an associated drug cost saving of $531.38 per IFX TDM test episode. Unnecessary IFX use was identified in 38.9% (96/247) of reactive IFX TDM tests performed and in 19.3% (35/181) of proactive testing. Conclusion Use of both reactive and proactive IFX TDM is cost-effective for IBD management as it informs the clinician where unnecessary use of IFX can be stopped.

BACKGROUND Although hepatitis C virus (HCV) infection is curable, treatment of difficult to access populations (DTAP) presents unique challenges. Project ECHO (PE) (Extension for Community Healthcare Outcomes) is a telementoring programme adopted to support clinicians treating DTAP. AIMS To determine if the PE model supports primary care clinicians treating HCV and to compare cohort of PE patients with those in a tertiary liver clinic (TLC). METHODS Weekly PE group video conferences were conducted. Clinical information, laboratory indices, psychosocial elements and treatment outcomes, including sustained virological response (SVR) data were recorded in the first 100 consecutive cases and retrospectively compared to 100 consecutive patients seen at a TLC from July 2016 to April 2017. RESULTS Some patient characteristics were similar between PE and TLC: gender (72% vs 75% male; P = 0.23), median age (45 vs 50; P = 0.344) and the proportion of treatment naive patients (95.0% vs 90.9%). Treatment for HCV was commenced in 78% of the PE patients and 81% of the TLC patients; 67/68 of the TLC patients and 60/61 PE patients with virological follow up who completed treatment and attended follow up have confirmed SVR. PE patients are more likely to have ongoing substance use (44% vs 17% P < 0.001), be active intravenous drug users (32% vs 17%; P < 0.001) and polysubstance abusers (26% vs 7%; P < 0.001) and were more likely to be taking opioid substitution therapy (74% vs 20%; P < 0.001). Indigenous patients were three times more greatly represented in PE (15% vs 5%; P = 0.018). CONCLUSION PE is an effective model to support primary healthcare providers treating HCV in DTAP with similar rates of treatment uptake and SVR compared to patients in TLC.

BACKGROUND Colonoscopy remains the gold standard for detection of colonic disease. An optimal evaluation depends on adequate bowel cleansing. Patients with inflammatory bowel disease (IBD), require frequent endoscopic assessment for both activity and dysplasia assessment. Two commonly used bowel preparations in Australia are Prep Kit-C (Pc) and Moviprep (Mp). Little is known about tolerability, efficacy and safety of split protocols of Mp and Pc in both IBD and non-IBD patients. AIM To primary aim was to compare the tolerability, efficacy and safety of split protocols of Mp and Pc in patients having a colonoscopy. The secondary aim was to compare the efficacy, tolerability and safety of either preparation in patients with or without IBD. METHODS Patients were randomized to Pc or Mp bowel preparation. Patients completed a questionnaire to assess tolerability. Efficacy was assessed using the Ottawa Bowel Preparation Score. Serum electrolytes and renal function were collected one week prior to colonoscopy and on the day of colonoscopy. RESULTS Of 338 patients met the inclusion criteria. Of 168 patients randomized to Mp and 170 to Pc. The efficacy of bowel preparation (mean Ottawa Bowel Preparation Score) was similar between Mp (5.4 ± 2.4) and Pc (5.1 ± 2.1) (P = 0.3). Mean tolerability scores were similar in Mp (11.84 ± 5.4) and Pc (10.99 ± 5.2; P = 0.17). 125 patients had IBD (73 had Crohn's Disease and 52 had Ulcerative colitis). Sixty-four IBD patients were allocated to Mp and 61 to Pc. In non-IBD patients, 104 were allocated to Mp and 109 to Pc. The mean tolerability score in the IBD group was lower than the non-IBD group (mean tolerability scores: IBD: 10.3 ± 5.1 and non-IBD: 12.0 ± 5.3; P = 0.01). IBD patients described more abdominal pain with Mp when compared with Pc; (Mp: 5.7 ± 4.4 vs Pc: 3.6 ± 2.6, P = 0.046). Serum magnesium level increased with Pc compared with Mp in all patients (mean increase in mmol/L: Mp: 0.03 ± 0.117 and Pc: 0.11 ± 0.106; P < 0.0001). CONCLUSION In this study, the efficacy, tolerability and safety of Mp and Pc were similar in all patients. However, patients with IBD reported lower tolerability with both preparations. Specifically, IBD patients had more abdominal pain with Mp. These results should be considered when recommending bowel preparation especially to IBD patients.

Viral hepatitis contributes to significant morbidity and mortality worldwide. While acute infection may be self-limiting, unrecognised chronic infection and under-utilisation of guideline-based approaches to therapy contribute to increasing rates of cirrhosis, hepatocellular carcinoma and death. Our aim was to review the current evidence for screening, diagnosis and treatment in hepatitis A to E. Evidence for this review was sourced from international and Australian guidelines and high-quality clinical trials. MEDLINE was searched using structured key word strategy and retrieved articles were reviewed methodically to inform a brief and up-to-date synopsis of hepatitis A to E. We share some of the recent developments in viral hepatitis, specifically the new therapies for hepatitis C. Direct-acting antiviral therapies are safe, well-tolerated and effective. Subsidies allow access for all Australians with most strains of hepatitis C. We outline evidence underpinning efficacy and safety of treatment for hepatitis B, while clarifying some of the nuances in the setting of pregnancy and immunosuppression. We provide a simplified concept to facilitate understanding of the five phases of hepatitis B; practical for real-world setting. Hepatitis A to E is a broad topic, not all aspects of these viruses can be covered in this short review. We provided suggestions for evidence based guidelines, which are a suitable supplement to this article.

Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes.Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients.Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015).Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.

AIM To assess the impact of underlying liver disease etiology on the presenting features and outcomes in a large cohort of patients with hepatocellular carcinoma (HCC). METHODS A prospective database of all patients with HCC was established from 1998 to March 2012. One thousand and seventy-eight patients were categorized into three groups, based on the etiology of their liver disease: hepatitis B virus (HBV), hepatitis C virus (HCV) and non-viral liver disease (NVLD). Overall survival was determined by Kaplan Meier analysis to time of death or last follow-up. RESULTS HCC patients with HCV (85%) were more likely to be diagnosed as part of a surveillance program, compared to HBV or NVLD (both 71%) (P < 0.001). Patients with NVLD were more likely to receive best supportive care (29%) compared to those with HBV (21%) or HCV (20%) (P < 0.02). Twelve percent of NVLD and 13% of HBV patients underwent liver transplantation compared to 21% of HCV patients (P = 0.001). Median survival from presentation was lowest in NVLD (1.7 years) when compared to HBV (2.8 years) and HCV (2.6 years) (P < 0.05). In multivariate analysis, independent predictors of survival included Child Turcotte Pugh score, size of dominant lesion, absence of vascular invasion, and management with surgical resection or liver transplantation. Patient age and the etiology of the underlying liver disease were not independent predictors of survival CONCLUSION Patients with NVLD and HCC were less likely to be enrolled in a HCC surveillance program and are less likely to have curative therapies such as liver resection and transplantation after diagnosis with HCC, when compared to patients with Hepatitis B and Hepatitis C.

Introduction: Although several staging systems exist for HCC, the most widely accepted system is the Barcelona Clinic Liver Cancer (BCLC) staging system. All patients with vascular invasion and/or distant metastases are categorized as BCLC C with similar with prognosis and treatment. The aim of this study is to compare the clinical presentation and prognosis of HCC patients who present with BCLC C. Methods: We conducted a retrospective analysis of a prospective database of patients diagnosed with HCC between January 2005 and December 2011. All patients who presented with extrahepatic metastasis (EHM) or vascular invasion (VI), consisting of either a portal venous or hepatic venous thrombus, at presentation were included for analysis. Patients with either a Child Pugh score C or ECOG performance . 2 were excluded from analysis. Demographics, tumor characteristics, treatment regimens, and survival were compared between the following groups of patients: patients with both VI and EHM (group C1), patients with VI but without EHM (group C2), and patients with EHM but without VI (group C3). Differences between groups were determined with oneway ANOVA and Chi-squared tests. Survival curves were generated using Kaplan-Meier plots.Results: Of the 448 patients diagnosed with HCC, 130 patients presented at BCLC C stage, 45 patients in group C1, 54 patients in group C2, and 31 patients in group C3. There was no difference in age, gender, race/ethnicity, presence of symptoms, or etiology of cirrhosis between the three groups of patients. Patients with both EHM and VI (Group C1) had a significantly higher AFP than the other groups (mean, 93491+/164819,19488+/-49375, and 13948+/-5248, p,0.001). These patients also had significantly worse survival than those with VI or EHM alone (2.3 mths vs. 5.9 mths, p ,0.001). Patients with VI alone (group C2) and those with EHM alone (group C3) had similar survival (5.7 vs. 6.1 mo, p= 0.62). On multivariate analysis treatment, AFP , 400 ng/ml, absence of both EHM and VI, and lack of symptoms on presentation were associated with prolonged overall survival. Conclusion: Patients with BCLC stage C tumors comprise a heterogeneous group of patients with different prognoses. Patients who present with both VI and EHM have significantly worse prognosis than those who present with VI or EHM alone.