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Prostate cancer metastasis to the liver is heralded by hypoenhancement on contrast-enhanced imaging, whereas small cell prostate cancer itself is ill defined in imaging and there is currently a paucity of literature describing its imaging characteristics. A 70-year-old man originally from Poland was referred to the hepatoma service for investigation of two liver lesions found during routine hepatocellular carcinoma (HCC) screening. The patient was commenced on single agent Carboplatin to treat his now de-differentiated small cell prostate cancer, to which he has responded well with interval response demonstrated on serial CT of pulmonary and liver lesions in addition to the bony disease on CT SPECT. [Extracted from the article]

Malnutrition is common in liver cirrhosis and is associated with increased rates of complications, hospitalization, and mortality. There are no consensus guidelines for malnutrition assessment in liver cirrhosis and a large number of clinicians do not routinely assess for malnutrition in patients with liver cirrhosis. This review explores the tools available for assessment of malnutrition in patients with liver cirrhosis, including nutritional screening protocols, anthropometric tools, biochemical tools, techniques analyzing body composition and functional assessments. We evaluate these tools and offer recommendations regarding their suitability for outpatient settings. In this review, we recommend the Royal Free Hospital-Nutritional Prioritising Tool for identifying patients at risk of malnutrition. Additionally, we recommend the use of the anthropometric tools Triceps Skinfold Thickness for females and Mid-Arm Muscle Circumference for males, due to differing patterns of muscle and fat malnutrition. Complementing this Bioelectrical Impedance Analysis can be utilized to assess body composition for the diagnosis of malnutrition. Biochemical markers have thus far failed to show a correlation with malnutrition. While hand grip strength is useful for detecting sarcopenia, a common complication of malnutrition, further evidence is required to validate its correlation with malnutrition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The recent Intergenerational Report (2023) highlighted that the Australian healthcare system will face increasing economic and logistical challenges, with projected growth in health spending due to an ageing population and an increasing number of chronic diseases. Shared care, a model emphasising collaboration between nursing and allied health, general practice and specialist care providers, has emerged as one solution., Objective: This paper explores the contemporary shared care landscape in Australia, highlighting the digital transformation of healthcare, the adoption of eHealth technologies, and their impact on improving patient care coordination., Discussion: The roles of shared electronic health records, secure electronic communication and consultation, electronic patient portals and telehealth in enhancing healthcare accessibility and management of chronic diseases are individually explored. Infrastructure for future inter-electronic medical record integrations are then discussed. Innovative care models combining novel technology and shared care hold promise for more efficient, patient‑centric healthcare systems. Given Australia's unique healthcare challenges, it provides the ideal environment to lead the way in the digital transformation of shared care.

Background: Prostate cancer survivorship care is essential for the early identification of cancer recurrence and progression and the monitoring of adverse effects. Prostate cancer survivorship programs have enabled care to be shared between specialists using digital healthcare platforms. We systematically reviewed the literature to examine if prostate cancer survivorship care had been successfully digitalised., Methods: English language articles were searched on PubMed, Embase, and Cochrane Libraries. The search terms included combinations of "eHealth", "digital health", "prostate cancer", "shared care", and related keywords (studies published between [1 January 1946 and 20 March 2023])., Results: Our search strategy yielded 1722 publications, of which 17 studies were included in our final review. Diverse eHealth interventions (web platforms, apps, patient portals) for digital prostate cancer shared care enabled communication, symptom management, and holistic assessment, with potential for reducing anxiety, enhancing outcomes, and increasing engagement. The studies (9 months to 5 years duration) involved participants across different care phases (16 to 3521 participants). We identified ten eHealth platforms, which provided successful symptom tracking, needs assessment, and communications. The platform-based interventions improved some aspects of communication, symptom management, and care delivery. The ongoing clinical need for a robust digital platform that caters to all domains of shared care was identified., Conclusions: eHealth will certainly play a central role in digital prostate cancer shared care, providing better health outcomes and care delivery. Future larger studies in this field should address the implementation barriers, including cost-effectiveness and primary care remuneration. It is also crucial to refine application useability and workflow, focusing on standardization and patient-centred approaches.

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC.

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.

Background: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable., Methods: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates., Results: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172)., Conclusions: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

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.

Introduction: Despite the availability of effective, subsidised hepatitis B treatment, linkage to care and treatment rates remain very low globally. In Australia, specially trained primary care physicians (general practitioner, GPs) can prescribe hepatitis B treatment, however, most hepatitis B care occurs in specialist clinics. Increasing hepatitis B management by GPs in primary care clinics is essential to achieve national hepatitis B linkage to care and treatment targets by 2030.This pilot study determines the feasibility, acceptability and effectiveness of Simply B, a novel GP hepatitis B e-support package designed to increase hepatitis B management by GPs in primary care clinics., Methods and Analysis: This study will be conducted in three parts:Part A: A prospective open-label pilot intervention study, comparing the proportion of people with hepatitis B who are managed by their GP in primary care clinics before, 12 months and 24 months after implementation of the Simply B electronic hepatitis B support package.Part B: A nested qualitative health services feasibility study using semistructured interviews and thematic analysisPart C: Cost-effectiveness analysis., Ethics and Dissemination: This study has received ethics approval by St Vincent's Hospital. Data management and analysis will be centralised through the Department of Gastroenterology, St Vincent's Hospital., Trial Registration Number: NCT05614466., Competing Interests: Competing interests: JH has received investigator-initiated research funding (Gilead Australia Fellowship 2017, 2019) and speaker fees (2017) from Gilead Sciences, and speaker fees and investigator-initiated research funding from Eisai (2020, 2021)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Necroptosis is a highly inflammatory mode of cell death that has been implicated in causing hepatic injury including steatohepatitis/ nonalcoholic steatohepatitis (NASH); however, the evidence supporting these claims has been controversial. A comprehensive, fundamental understanding of cell death pathways involved in liver disease critically underpins rational strategies for therapeutic intervention. We sought to define the role and relevance of necroptosis in liver pathology., Methods: Several animal models of human liver pathology, including diet-induced steatohepatitis in male mice and diverse infections in both male and female mice, were used to dissect the relevance of necroptosis in liver pathobiology. We applied necroptotic stimuli to primary mouse and human hepatocytes to measure their susceptibility to necroptosis. Paired liver biospecimens from patients with NASH, before and after intervention, were analyzed. DNA methylation sequencing was also performed to investigate the epigenetic regulation of RIPK3 expression in primary human and mouse hepatocytes., Results: Identical infection kinetics and pathologic outcomes were observed in mice deficient in an essential necroptotic effector protein, MLKL, compared with control animals. Mice lacking MLKL were indistinguishable from wild-type mice when fed a high-fat diet to induce NASH. Under all conditions tested, we were unable to induce necroptosis in hepatocytes. We confirmed that a critical activator of necroptosis, RIPK3, was epigenetically silenced in mouse and human primary hepatocytes and rendered them unable to undergo necroptosis., Conclusions: We have provided compelling evidence that necroptosis is disabled in hepatocytes during homeostasis and in the pathologic conditions tested in this study., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia., Methods: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes., Results: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8-9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%)., Conclusions: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS., (© 2022. The Author(s).)

Background: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort., Methods: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE)., Findings: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12., Conclusions: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective The aims of this study were to: (1) identify the characteristics of patients with chronic hepatitis B (CHB) who do not attend their hospital liver clinic appointments; and (2) raise awareness among general practitioners (GP) of alternative pathways to care for CHB in order to prevent long-term complications of CHB (liver cancer and cirrhosis). Methods This prospective study was conducted between May 2018 and January 2019 at one site of a tertiary referral hospital in western Melbourne. Patients with minimal liver complications who did not attend their first two initial appointments were included in the study, in addition to referring GPs of new CHB patients to the liver clinic who had minimal liver complications (characterised by minimal fibrosis (<7kPa)) and no liver comorbidities (including cirrhosis and/or hepatocellular carcinoma). GPs of patients who failed to attend the liver clinic as a new patient were sent an alternative discharge letter that included information on alternative pathways to care in the community for their patients. A follow-up survey to referring GPs was conducted afterwards for feedback. Demographic data was also collected for included patients. Results Thirty patients with non-complicated CHB were included in the study (median age 32.5 years). Patients were from 11 different countries and six regions. The mean wait time from referral to clinic date was 424 days (SD 218.9). Only four GPs responded to the letter, with non-responding GPs surveyed primarily not participating due to having over 1 year of no contact from the patient or hospital. Conclusion This study showed that there were long waiting lists for CHB referrals and alerting GPs to alternative pathways after patients failed to attend appointments was ineffective. There needs to be improved coordination between tertiary and primary services to provide timely and effective care for patients with CHB. What is known about this topic? There are 239000 Australians living with CHB: most recent estimates indicate that only 62% have been diagnosed, 15% are being monitored and 6% of those requiring treatment are receiving antiviral therapy. The complications of CHB (liver cancer and cirrhosis) can be averted by routine monitoring and timely commencement of highly effective oral antiviral therapy. In Australia, both GPs and specialists in gastroenterology and infectious diseases are involved in the management of CHB patients, but most prescribing occurs in specialist services. The current specialist-centred model of CHB care has been described as neither practical nor sustainable given the limited resources and capacity of specialist services, and the challenges for people with CHB to access public hospitals for routine care. What does this paper add? Non-attending patients were a primarily young population. The median wait time for a clinic appointment in this hospital setting was 424 days, with some patients waiting ≥800 days for an appointment. This extensive wait time for a largely asymptomatic condition may have affected attendance rates. Although this particular intervention to engage GPs in collaborative care had limited results, it is clear that management of CHB by GPs, transparency in wait lists and adequate resourcing of specialist services would help alleviate the referral burden on hospitals. What are the implications for practitioners? GPs should be aware that waiting lists for liver clinic appointments can be extensive in public hospital settings due to the high referral burden and limited resources of these services. Alternative pathways to care, such as GPs trained to prescribe Schedule 100 drugs, are an effective means of alleviating this burden while also ensuring CHB patients are seen in a timely manner and receive routine monitoring.

Chronic hepatitis B (CHB) is a major health problem worldwide and is associated with significant long-term morbidity and mortality. The hepatitis B virus (HBV) is a hepatotropic virus that is capable of integrating in the host nucleus permanently resulting in lifelong infection. To date, there is no definitive cure for HBV, as our current treatments cannot eradicate the viral reservoir that has integrated in the liver. Elucidating the immunopathogenesis is key to finding a therapeutic target for HBV as the virus is not in itself cytopathic but the immune response to the virus causes the majority of the cellular injury. In most cases, the virus reaches a state of equilibrium with low viral replication constrained by host immunity. Multiple cytokines have been implicated in the pathogenesis of CHB. Tumor necrosis factor (TNF) has emerged as a key player; on one hand it can facilitate immune-mediated virological control but on the other hand it can cause collateral hepatocyte damage, cirrhosis and possibly promote hepatocellular carcinoma. In this review, we discuss the current understanding of the immunopathogenesis of HBV, focusing on TNF and whether it can be harnessed in therapeutic strategies to cure HBV infection., Competing Interests: The Walter and Eliza Hall Institute of Medical Research have a research license agreement with TetraLogic Pharmaceuticals (Malvern, PA, USA), the manufactures of the cIAP antagonist birinapant. Tetralogic has filed a PCT on behalf of The Walter and Eliza Hall Institute of Medical Research. MP provides consultative advice to, and was on the scientific advisory board of, TetraLogic Pharmaceuticals. The remaining authors declare no conflict of interest.