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BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Radiosurgery , Standard of Care , Humans , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Liver Neoplasms/radiotherapy , Liver Neoplasms/surgery , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/surgery , Radiosurgery/methods , Prospective Studies , Male , Female , Neoplasm Staging , Middle Aged , Randomized Controlled Trials as Topic , Aged , AdultABSTRACT
The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less (p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia.
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The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients.
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INTRODUCTION: Elimination of hepatitis C virus stands as an unresolved World Health Organization target, and is associated with complications including cirrhosis and hepatocellular carcinoma. Hepatitis C virus management has been revolutionised following the widespread availability of direct-acting antiviral agents in Australia since 2016; however, large proportions of the population remain untreated. Telehealth-based service delivery is an accessible and effective alternative, and we aimed to assess qualitative and clinical outcomes in a clinical nurse consultant-led regional telehealth model. METHODS: A prospective cohort analysis of all patients referred to a Victorian regional hospital's hepatitis C virus telehealth clinic between 1 April 2017 and 10 June 2020 was conducted. Data were collated from outpatient and electronic medical records. RESULTS: Fifty-five out of 71 referred patients were booked, with 44 patients (80%) attending at least one appointment. A history of alcohol use disorder and psychiatric comorbidity was seen in 25 (54%) and 24 (52%) patients, respectively. Twenty-one out of 24 (88%) eligible patients had direct-acting antiviral agent treatment and 14 out of 21 (67%) successfully completed the treatment. An average of 46.5â km, 54.6â min and $AUD30.70 was saved per patient for each visit. Observed benefits included: increased medical engagement, adherence to and completion of HCV treatment and cirrhosis monitoring. Telehealth-driven hepatocellular carcinoma surveillance was successful in the cirrhotic subgroup. CONCLUSION: Clinical nurse consultant-led hepatitis C virus management via telehealth allows access to marginalised regional populations. Clinical outcomes were comparable to other cohorts with additional cost-benefit, efficiency gains and carbon footprint reduction amongst a previously unreported regional Victorian hepatitis C virus population.
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BACKGROUND & AIMS: Chronic viral hepatitis is a leading cause of worldwide liver-related morbidity and mortality, despite the availability of effective treatments that reduce or prevent complications in most patients. Electronic-health (eHealth) technologies have potential to intervene along the whole cascade of care. We aimed to summarize available literature on eHealth interventions with respect to conventional screening, diagnostic and treatment outcomes in chronic hepatitis B (HBV) and hepatitis C (HCV). METHODS: We systematically reviewed MEDLINE, EMBASE, Cochrane Library and international conference abstracts, including studies published from 2009 - 2020. Overall 80 studies were included, covering electronic medical record (EMR) interventions (n=39), telemedicine (n=20), mHealth (n=5), devices (n=4), clinical decision support (n=3), web-based (n=5), social media (n=1) and electronic communication (n=3). RESULTS: Compared to standard care, EMR alerts increase screening rates in eligible populations including birth cohort screening in HCV, universal HCV screening in Emergency Departments, ethnic groups with high HBV prevalence, and HBV screening prior to immunosuppression. Direct messaging alerts to providers and automated testing may have a greater effect. No significant difference was found in sustained virological response outcomes between telemedicine and face-to-face management for community, rural and prison cohorts in HCV in the direct acting antiviral era of treatment, with higher patient satisfaction in telemedicine groups. CONCLUSIONS: EMR alerts significantly increase screening rates in eligible cohorts in both chronic HBV and HCV. Telemedicine is equally efficacious to face-to-face care in HCV treatment. Other eHealth technologies show promise; however rigorous studies are lacking.
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Hepatitis C, Chronic , Telemedicine , Antiviral Agents , Electronics , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Humans , Mass ScreeningABSTRACT
BACKGROUND: A unique model of care was adopted in Australia following introduction of universal subsidised direct-acting antiviral (DAA) access in 2016 in order to encourage rapid scale-up of treatment. Community-based medical practitioners and integrated hepatitis nurses initiated DAA treatment with remote hepatitis specialist approval of the planned treatment without physical review. AIMS: To evaluate outcomes of community-based treatment of hepatitis C virus (HCV) through this remote consultation process in the first 12 months of this model of care. METHODS: A retrospective chart review of patients undergoing community-based HCV treatment from general practitioners and integrated hepatitis nurse consultants through the remote consultation model in three state jurisdictions in Australia from 1 March 2016 to 28 February 2017. RESULTS: Sustained virological response at 12 weeks (SVR12) was confirmed in 383 (65.1%) of 588 subjects intended for treatment with a median follow-up time of 12 months (interquartile range 9-14 months). The SVR12 test was not performed in 159 (27.0%) of 588 and 307 (52.2%) of 588 did not have liver biochemistry rechecked following treatment. Subjects who completed follow up exhibited high SVR12 rates (383/392; 97.7%). Nurse-led treatment was associated with higher confirmation of SVR12 (73.7% vs 62.4%; P = 0.01) and liver biochemistry testing post treatment (57.5% vs 45.0%; P = 0.01). CONCLUSIONS: Community-based management of HCV through remote specialist consultation may be an effective model of care. Failure to check SVR12, recheck liver biochemistry and appropriate surveillance in patients with cirrhosis may emerge as significant issues requiring further support, education and refinement of the model to maximise effectiveness of future elimination efforts.
Subject(s)
General Practitioners , Hepatitis C, Chronic , Hepatitis C , Remote Consultation , Antiviral Agents/therapeutic use , Australia/epidemiology , Hepacivirus , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Humans , Retrospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Hepatitis C, Chronic , Hepatitis C , Aged , Antiviral Agents/therapeutic use , Australia/epidemiology , Cost-Benefit Analysis , Female , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Male , Markov Chains , Middle Aged , National Health Programs , Quality-Adjusted Life Years , Retrospective Studies , South Australia/epidemiologyABSTRACT
Background and study aims Endocuff Vision improves adenoma detection rates in patients without inflammatory bowel disease. This study aimed to investigate the safety and feasibility of Endocuff Vision-assisted high-definition white light endoscopy (HDWLE) with dye-spray chromoendoscopy for detection of dysplasia in patients with ulcerative colitis. Patients and methods Patients with clinically inactive ulcerative colitis due for dysplasia surveillance were recruited. Procedural endpoints included safety, cecal intubation rate (CIR), terminal ileum intubation rate (TIR), withdrawal time, polyp detection rate, dysplasia detection rate (DDR), and sessile serrated lesion detection rate. Results Twenty-five patients (9 female, median age 57 [range 28â-â82] years) were studied. Endocuff Vision-assisted HDWLE was completed in all participants, with a CIR of 100â%, in a median 4 minutes (range 2â-â16), and a TIR of 88% in a median of 6.5 minutes (range 3â-â19). Median withdrawal time was 18 minutes (range 10â-â55), including application of dye-spray, biopsies and polypectomy. The Mayo Endoscopic subscore was 0 in 11, 1 in 9, and 2 in 5 patients. The DDR was 24â% (6 patients had a total of 12 dysplastic lesions) and sessile serrated lesion detection rate was 12â% (3 patients had a total of 4 sessile serrated polyps). No serious adverse events occurred, with one patient developing clinically insignificant minor mucosal bleeding. Conclusion Endocuff Vision-assisted HDWLE is feasible and safe in patients with ulcerative colitis undergoing dysplasia surveillance. Further studies are required to assess superiority of this technique compared with standard high-definition white light endoscopy with chromoendoscopy.
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AIMS: To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy. METHODS: A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded. RESULTS: Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance. 64/89 (72%) had Crohn's disease, 38 (43%) were males, median age at switch was 40y (range 17-78), median IBD duration 6y (0-29). Median follow-up was 1.9y (0-5). Reasons for switching to co-therapy included fatigue (37%), hepatotoxicity (23%), nausea (23%), arthralgia (10%), headache (12%) and hypersensitivity reaction (4%). Overall, 66 (74%) patients remained on co-therapy until most recent review and achieved a clinical response. High rates of overcoming intolerance (62-100%) occurred with co-therapy for all reasons above, although fatigue was less amenable to switching than non-fatigue indications (62% vs 91%, pâ¯=â¯<0.001). Of 34 patients not escalated to biologics with endoscopic data, 15 were in remission (44%) at most recent review. CONCLUSION: Low-dose thiopurine combined with allopurinol appears safe and effective in overcoming intolerances to thiopurine monotherapy in many cases.
Subject(s)
Allopurinol/administration & dosage , Azathioprine/administration & dosage , Immunosuppressive Agents/administration & dosage , Inflammatory Bowel Diseases/drug therapy , Adolescent , Adult , Aged , Allopurinol/adverse effects , Australia , Azathioprine/adverse effects , Chemical and Drug Induced Liver Injury , Drug Therapy, Combination , Fatigue , Female , Humans , Immunosuppressive Agents/adverse effects , Linear Models , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
INTRODUCTION: Despite decades of research and a detailed knowledge of the immunopathological basis of coeliac disease (CD), adherence to a lifelong gluten-free diet (GFD) remains the single proven and available treatment. The increasing prevalence of CD combined with variable adherence to the GFD in a significant proportion of patients demands new therapeutic strategies. AREAS COVERED: Trial registries, clinicaltrials.gov, pharmaceutical company website searches as well as published data from PubMed and conference proceedings were used to extract the most recent outcomes for CD therapeutics. This article aims to review the available therapies from a pathophysiological approach, and propose future directions in this interesting yet largely unfulfilled area of research. EXPERT OPINION: Increasingly, the GFD is being challenged by its availability, palatability, practicality and now even efficacy in some populations. Whilst the causative antigens have been well described, it is clear that treatment based on the removal of these immunostimulatory peptides from the diet is far more complex than early experience in CD treatment implied. Despite burgeoning interest and research in experimental therapies for CD over the past twenty years, the only therapy showing promise as a true alternative to a GFD is that of the induction of tolerance via a vaccine.
Subject(s)
Celiac Disease/drug therapy , Drug Design , Drugs, Investigational/therapeutic use , Animals , Celiac Disease/diet therapy , Celiac Disease/physiopathology , Diet, Gluten-Free , Drugs, Investigational/pharmacology , Humans , Immune Tolerance , Patient Compliance , Vaccines/administration & dosage , Vaccines/immunologyABSTRACT
BACKGROUND: The hyperdense artery sign (HAS) on CT brain scan is an assumed radiological marker of acute intra-arterial thrombotic occlusion. However, the relationship between HAS between time of stroke onset has not been adequately investigated, leading to uncertainty regarding its validity as a marker of acute ischaemia. We attempted to determine if the presence of the hyperdense artery sign is associated with time from stroke onset. METHODS: Retrospective cross-sectional study conducted in a tertiary referral centre. Consecutive patients with acute ischaemic stroke and confirmed middle cerebral arterial occlusion on initial CT angiogram from 2007-2011 were included. Visual estimation and manual measurement of Hounsfield units of affected and corresponding non-affected artery on non-contrast CT was completed and mean density was calculated from four separate readings. Primary outcome measures were Time from stroke onset and HAS on both visual estimation and the ratio of mean value in Hounsfield Units (HU) of affected to non-affected artery. RESULTS: One hundred and fifty-four subjects with confirmed arterial occlusion on CT Angiogram were included in the study. There were no significant differences in age distribution or vascular risk factor presence between subjects with or without HAS. Subjects with HAS were less likely to be male (50.9% vs 70.8%, p = 0.02).) HAS was found in 106 (68.8%) of all subjects. Median NIHSS score at presentation was significantly higher in the HAS group (17 vs 12, p = 0.02). No statistically significant association between HAS and stroke onset time or density ratio between affected and non-affected artery was detected overall within either the first 24-h or on subgroup analysis of those in the first 4.5-h. A small subgroup of three patients with stroke onset greater than 24-h all had absent HAS. CONCLUSIONS: No evidence of a correlation between time of stroke onset and presence of a HAS within the first 24-h post acute ischaemic stroke was identified. The HAS was associated with a higher NIHSS score at presentation.