Comparing the resource implications of old and new colorectal adenoma surveillance guidelines in Australia.

BACKGROUND: The latest update to the Australian adenoma surveillance guideline in 2018 introduced a novel risk stratification system with updated surveillance recommendations. The resource implications of adopting this new system are unclear. AIMS: To quanitfy the resource demands of adopting new over old adenoma surveillance guidelines. METHODS: We studied data from 2443 patients undergoing colonoscopies, in which a clinically significant lesion was identified in their latest, or previous procedure(s) across five Australian hospitals. We excluded procedures with inflammatory bowel disease, new or prior history of colorectal cancer or resection, inadequate bowel preparation and incomplete procedures. Old and new Australian surveillance intervals were calculated according to the number, size and histological characteristics of lesions identified. We used these data to compare the rate of procedures according to each guideline. RESULTS: Based on the procedures for 766 patients, the new surveillance guidelines significantly increased the number of procedures allocated an interval of 1 year (relative risk (RR): 1.57, P = 0.009) and 10 years (RR: 3.83, P < 0.00001) and reduced those allocated to half a year (RR: 0.08, P = 0.00219), 3 years (RR: 0.51, P < 0.00001) and 5 years (RR: 0.59, P < 0.00001). Overall, this reduced the relative number of surveillance procedures by 21% over 10 years (25.92 vs 32.78 procedures/100 patient-years), which increased to 22% after excluding patients 75 or older at the time of surveillance (19.9 vs 25.65 procedures/100 patient-years). CONCLUSION: The adoption of the latest Australian adenoma surveillance guidelines can reduce demand for surveillance colonoscopy by more than a fifth (21-22%) over 10 years.

Assessment of hepatitis B virus infection and interhost cellular responses using intrahepatic cholangiocyte organoids.

The intrahepatic cholangiocyte organoids (ICOs) model was evaluated for host differences in hepatitis B virus (HBV) infection, cellular responses, antiviral and immunomodulator responses. Twelve ICOs generated from liver resections and biopsies were assessed for metabolic markers and functional HBV entry receptor expression throughout differentiation. Structural changes relevant to HBV infection were characterized using histology, confocal, and electron microscopy examinations. Optimal ICO culture conditions for HBV infection using HepAD38 (genotype D) and plasma-derived HBV (genotype B and C) were described. HBV infection was confirmed using HBcAg immunostaining, qRT-PCR (RNA, covalently closed circular DNA [cccDNA], extracellular DNA) and ELISA (HBsAg and HBeAg). Drug response to antiviral and immunosuppressive agent, and cellular responses (interferon-stimulated genes [ISG]) to interferon-α and viral mimic (PolyI:C) were assessed. ICOs underwent metabolic and structural remodeling following differentiation. Optimal HBV infection was achieved in well-differentiated ICOs using spinoculation, with time and donor-dependent increase in HBV RNA, cccDNA, extracellular DNA, HBeAg and HBsAg. Donor-dependent drug responsiveness to entry inhibitor and JAK inhibitor was observed. Despite having a robust ISG response to interferon-α and PolyI:C, HBV infection in ICOs did not upregulate ISGs. Human ICOs support HBV infection and replication with donor-dependent variation in viral dynamics and cellular responses. These features can be utilized for the development of personalized drug testing platform for antivirals.

Assessment of HBV infection and inter-host cellular responses using intrahepatic cholangiocyte organoids.

Intrahepatic cholangiocyte organoids (ICOs) model was evaluated for host differences in hepatitis B virus (HBV) infection, cellular responses, antiviral, and immunomodulator responses. Twelve ICOs generated from liver resections and biopsies were assessed for metabolic markers and functional HBV entry receptor expression throughout differentiation. Structural changes relevant to HBV infection were characterized using histology, confocal, and electron microscopy examinations. Optimal ICO culture conditions for HBV infection using HepAD38 (genotype D) and plasma derived HBV (genotype B & C) were described. HBV infection was confirmed using HBcAg immunostaining, qRT-PCR (RNA, cccDNA, extracellular DNA), and ELISA (HBsAg and HBeAg). Drug response to antiviral and immunosuppressive agent, and cellular responses (interferon-stimulated genes [ISG]) to interferon-α and viral mimic (PolyI:C) were assessed. ICOs underwent metabolic and structural remodeling following differentiation. Optimal HBV infection was achieved in well-differentiated ICOs using spinoculation, with time and donor dependent increase in HBV RNA, cccDNA, extracellular DNA, HBeAg, and HBsAg. Donor dependent drug-responsiveness to entry inhibitor and JAK inhibitor was observed. Despite having a robust ISG response to interferon-α and PolyI:C, HBV infection in ICOs did not upregulate ISGs. Human ICOs support HBV infection and replication with donor dependent variation in viral dynamics and cellular responses. These features can be utilized for development of personalized drug testing platform for antivirals.

Cost effectiveness of treatment models of care for hepatitis C: the South Australian state-wide experience.

AIM: The objective was to study the long-term (lifetime) cost effectiveness of four different hepatitis C virus (HCV) treatment models of care (MOC) with directly acting antiviral drugs. METHODS: A cohort Markov model-based probabilistic cost-effectiveness analysis (CEA) was undertaken extrapolating to up to 30 years from cost and outcome data collected from a primary study involving a real-life Australian cohort. In this study, noncirrhotic patients treated for HCV from 1 March 2016 to 28 February 2017 at four major public hospitals and liaising sites in South Australia were studied retrospectively. The MOC were classified depending on the person providing patient workup, treatment and monitoring into MOC1 (specialist), MOC2 (mixed specialist and hepatitis nurse), MOC3 (hepatitis nurse) and MOC4 (general practitioner, GP). Incremental costs were estimated from the Medicare perspective. Incremental outcomes were estimated based on the quality-adjusted life years (QALY) gained by achieving a sustained virological response. A cost-effectiveness threshold of Australian dollar 50 000 per QALY gained, the implicit criterion used for assessing the cost-effectiveness of new pharmaceuticals and medical services in Australia was assumed. Net monetary benefit (NMB) estimates based on this threshold were calculated. RESULTS: A total of 1373 patients, 64% males, mean age 50 (SD ±11) years, were studied. In the CEA, MOC4 and MOC2 clearly dominated MOC1 over 30 years with lower costs and higher QALYs. Similarly, NMB was the highest in MOC4, followed by MOC2. CONCLUSION: Decentralized care using GP and mixed consultant nurse models were cost-effective ways of promoting HCV treatment uptake in the setting of unrestricted access to new antivirals.

Clinical factors leading to a change in management in chronic hepatitis B patients managed in a tertiary setting.

BACKGROUND: Newer antiviral agents for chronic hepatitis B (CHB) are highly effective, with minimal risks of complications and development of resistance. AIM: To identify the proportion of patients with CHB on treatment who will not require alteration of management and the clinical factors of those who will require closer monitoring. METHODS: Patients with CHB who were on entecavir and/or tenofovir between January 2011 and December 2016 were retrospectively studied. According to the initial treatment plan provided by the managing physician, any deviation in the interval of follow up, choice of investigations and alteration of medical therapy were considered a change in CHB management. We also evaluated the predictability of these changes, factors associated with higher frequency of change and the additional cost of managing stable patients with CHB in a tertiary setting. RESULTS: Of the patients, 75.7% (n = 87/115) did not have a change in CHB management; 85.6% of the changes in management were predictable based on liver function tests, hepatitis B virus DNA polymerase chain reaction levels and liver ultrasound. Interpreter use (OR (95% CI) = 2.41 (1.01-5.76)), liver cirrhosis (OR (95% CI) = 4.11 (1.44-11.75)) and immunosuppression (OR (95% CI) = 3.81 (1.2-12.06)) were associated risk factors. Overall, there was an incremental annual cost of AU$60 166 to manage patients who did not require alteration of their CHB management in our institution. CONCLUSION: The majority of stable CHB patients on highly potent antiviral treatment do not require alteration of management. While additional investigations are required, this study highlights the potential for a shared primary care approach in highly selected CHB patients.

Saving costs through a coordinated care model for patients with hepatocellular cancer.

BACKGROUND: In keeping with recent trends, patients with hepatocellular cancer have had their care managed by a dedicated Nurse Coordinator at our tertiary Australian hospital since 2010. To date, there are few data to justify the cost-effectiveness of this approach. AIMS: To quantify the potential cost saved through the employment of a Nurse Coordinator in the management of patients with hepatocellular carcinoma at a single tertiary-level Australian hospital. METHODS: A retrospective audit of patients managed by the Nurse Coordinator between 2010 and 2015 was conducted. Consensus reports from previous meetings were reviewed, and nurse-initiated radiological procedures and encounters were identified. Clinical activities were prospectively evaluated over a 1-month period in July-August 2015. The equivalent annual number of outpatient medical encounters spared was calculated. Using the national average cost of each gastroenterology outpatient encounter, a total annual cost was determined and was compared against the cost of funding the position. RESULTS: The activity of the Nurse Coordinator resulted in an equivalent of at least 175 outpatient encounters being spared per year, with a minimum annual cost saving of $85 750. A total of 113 encounters resulted from the independent delivery and initiation of multidisciplinary team meeting plans; 10 were attributed to nurse-led patient education, and 52 were equated to weekly clinical activities. This represented a net annual saving of $17 050. CONCLUSION: The incorporation of the Nurse Coordinator in the care pathway of patients with hepatocellular cancer is associated with a reduction in medical outpatient load and, consequently, a significant annual cost saving.