OBJECTIVE:To describe the epidemiology, healthcare utilisation and outcomes of patients presenting to emergency departments (EDs) with chronic liver disease (CLD) in Queensland, Australia. METHODS:This statewide data linkage study included adult patients with CLD-related diagnoses across 104 Queensland Health EDs between 1 January 2016 and 31 August 2023. Emergency, inpatient and mortality data were linked. Patients were stratified by cirrhosis status and decompensation. Outcome was 30-day mortality. Poisson regression assessed trends, and Cox regression evaluated mortality. RESULTS:Amongst 15,999,186 ED presentations, 23,578 (0.15%) were related to CLD, involving 11,961 patients. Presentations increased by 2% annually (IRR 1.02, 95% CI 1.02-1.03). Cirrhosis accounted for 18,735 presentations (79.5%). Overall, 20,312 presentations (86.1%) resulted in hospital admission, 918 (4.5%) were admitted to intensive care units (ICU), and 963 (4.1%) resulted in in-hospital death. Amongst patients with cirrhosis, 16,968 (90.6%) resulted in admission, 867 (5.1%) were admitted to ICU and 899 (4.8%) died in hospital. Predictors of 30-day mortality included cirrhosis (adjusted hazard ratio (aHR) 6.92, 95% CI 5.36-8.94), malignancy (aHR 3.21, 95% CI 2.90-3.55), hepatorenal syndrome (aHR 3.15, 95% CI 2.72-3.66), encephalopathy (aHR 2.03, 95% CI 1.78-2.32) and spontaneous bacterial peritonitis (aHR 1.47, 95% CI 1.20-1.80). Presentation to tertiary hospitals was associated with lower mortality (aHR 0.75, 95% CI 0.68-0.82). CONCLUSIONS:CLD-related ED presentations are increasing and place substantial demand on hospital services in Queensland. Decompensation events strongly predict mortality and healthcare utilisation. ED-initiated risk stratification and coordinated care models to improve outcomes for patients with cirrhosis require development and evaluation.

BACKGROUND AND OBJECTIVES:The role of viscoelastic haemostatic assays (VHAs) versus conventional coagulation tests (CCTs) in chronic liver disease (CLD) in the emergency department (ED) is undefined. We aimed to characterize VHA profiles and concordance with CCT. MATERIALS AND METHODS:Patients with CLD presenting to EDs (January 2016-August 2023) were included. Post-transfusion results were excluded. VHA was categorized as hypo/normo/hypercoagulable using manufacturer ranges. CCT-coagulopathy was defined as international normalized ratio (INR) >1.5, platelets <50 × 109/L or fibrinogen <1.0 g/L. RESULTS:VHA use increased over time (incidence rate ratio [IRR] 1.23, 95% confidence interval [CI]: 1.19-1.28; p < 0.001). Of 438 patients, 397 underwent rotational thromboelastometry (ROTEM) and 41 thromboelastography (TEG). ROTEM showed hypocoagulability in 275 patients (69%), normocoagulability in 84 (21%), hypercoagulability in 18 (5%) and mixed profiles in 14 (4%). Deficits were fibrinogen deficiency in 220 patients (55%), factor deficiency in 148 (37%), hyperfibrinolysis in 42 (11%) and platelet deficiency in 33 (8%). TEG showed hypocoagulability in 22 (54%), normocoagulability in 13 (32%), hypercoagulability in 3 (7%) and mixed profiles in 3 (7%). Deficits included fibrinogen deficiency in 19 patients (46%), factor deficiency in 6 (15%), hyperfibrinolysis in 5 (12%) and platelet deficiency in 3 (7%). In 120 VHA-CCT paired results, fibrinogen deficiency was detected by both in 18%, VHA alone 26%, CCT alone 2%; platelet deficiency by both 5%, VHA alone 5%, CCT alone 5%; factor deficiency by both 22%, VHA alone 3% and CCT alone 42%. CONCLUSION:Hypocoagulability from reduced fibrin-based clot strength was predominant. Marked discordance between VHA and CCT was observed in coagulation factor deficiency. CLD-specific thresholds are required to guide transfusion.

Objective Non-alcoholic fatty liver disease (NAFLD) is estimated to affect a third of Australian adults, and its prevalence is predicted to rise, increasing the burden on the healthcare system. The LOCal Assessment and Triage Evaluation of Non-Alcoholic Fatty Liver Disease (LOCATE-NAFLD) trialled a community-based fibrosis assessment service using FibroScan to reduce the time to diagnosis of high-risk NAFLD and improve patient outcomes.Methods We conducted a 1:1 parallel randomised trial to compare two alternative models of care for NAFLD diagnosis and assessment. Participants had suspected NAFLD and were referred to a hepatology clinic in one of three major hospitals in South-East Queensland. Eligible consenting participants were randomised to receive usual care or the intervention (LOCATE). Participants in the intervention arm received a FibroScan outside of the hospital setting, with results provided to their primary care provider and the referring hepatologist. All participants were followed up 12 months after randomisation to measure their clinical and patient-reported outcomes.Results 97 participants were recruited from October 2020 to December 2022. Of the 50 participants randomised to the intervention arm, one failed to attend their appointment, and of the 48 (98%) who had a FibroScan 13 (27%) had a liver stiffness measurement of 8.0 kPa or greater. The HR for the time to diagnosis of high risk was 1.28 (95% CI 0.59 to 2.79), indicating a faster average time to diagnosis with the intervention, but failing to conclusively demonstrate a faster time. The intervention did greatly reduce the time to FibroScan by almost 1 year (median difference 0.92 years, 95% CI 0.56 to 1.45). Other clinical outcomes showed minimal changes.Conclusion The LOCATE model shows potential for impact, particularly in reducing waiting times for patients at high risk of developing severe liver disease due to NAFLD. A larger sample and longer follow-ups are needed to measure additional clinical outcomes.Trial registration number ACTRN12620000158965.

Abstract Introduction Stereotactic body radiation therapy (SBRT) is associated with high local control rates in hepatocellular carcinoma (HCC). This study reports the outcomes of SBRT compared to surgical resection (SR) and percutaneous ablation (PA) for treatment‐naïve, solitary HCCs ≤3 cm. Methods This was a retrospective study of patients with BCLC stage 0/A HCC with a single ≤3 cm lesion, treated with curative intent between 2016 and 2020. SBRT was used for patients considered unsuitable for SR or PA. The co‐primary endpoints were progression‐free survival (PFS) and overall survival (OS). The secondary endpoints were treatment‐related clinical toxicity rates and local control (LC) rates. Results There were 112 patients included in this study. SBRT was delivered in 36 patients (32.1%), 51 had PA (45.5%) and 25 underwent SR (22.3%). Median follow‐up was 23 months (range, 3–60 months) from diagnosis. The 3‐year PFS and OS were 67% and 69% following SBRT, 55% and 80% following PA, and 85% and 100% following SR, respectively. Patients in the SR cohort had significantly better 3‐year PFS and OS compared to SBRT and PA groups (p = 0.03 and p = 0.04, respectively). There was no significant difference in PFS (p = 0.15) or OS (p = 0.23) between SBRT and PA treated patients. The 3‐year LC rate for the entire cohort was 98%. Conclusions In patients with treatment‐naïve, early‐stage solitary HCCs ≤3 cm, SBRT was associated with comparable PFS, OS and LC outcomes to PA. SBRT should be considered as a curative intent therapy to avoid treatment stage migration in this favourable prognostic cohort of patients.

Background: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD).Methods: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model.Results: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p<0.01). 31.2% (95% CI: 23.8-39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: -0.6,95% CI: -0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0-23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2-34.8) had a loss of response to biologics.Conclusions: Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.

Background:Psychosocial, lifestyle and practical needs are not routinely attended to during outpatient hepatology management, and little is known about the type and effectiveness of support services accessed by patients with cirrhosis. We quantified the type and use of community and allied health services in patients with cirrhosis.Methods:The study included 562 Australian adults with a diagnosis of cirrhosis. Health service use was assessed via questionnaire and via linkage to the Australian Medicare Benefits Schedule. Patient needs were assessed using the Supportive Needs Assessment tool for Cirrhosis (SNAC).Results:Although most patients (85.9%) used at least one community/allied health service for support with their liver disease, many reported requiring additional help with psychosocial (67.4%), lifestyle (34.3%) or practical needs (21.9%) that were not met by available services, or patients did not access services. A multidisciplinary care plan or case conference (in the 12 months prior to recruitment) was accessed by 48% of patients, 56.2% reported the use of a general practitioner for support with cirrhosis, and a dietician was the allied health clinician most accessed by patients (45.9%). Despite the high prevalence of psychosocial needs, there was relatively limited use of mental health and social work services (14.1% of patients reported the use of a psychologist), confirmed by a low prevalence of use of mental health services (17.7%) in the linked data.Conclusion:Patients with cirrhosis who have unmet complex physical and psychosocial needs require better strategies to increase their engagement with allied health and community services.

BACKGROUND:Stereotactic body radiotherapy (SBRT) has been established as a safe and effective treatment for hepatocellular carcinoma (HCC). Currently, there are no consensus guidelines to advise optimal patient selection and radiotherapy planning parameters to minimise the risk of surgical and medical complications after liver transplant (LT) in patients who have had prior SBRT for HCC, whilst optimising treatment benefit.METHODS:We performed a retrospective analysis of all adult patients who received liver SBRT as a bridge to LT at a tertiary institution between 2017 and 2019.RESULTS:Nine patients received SBRT as bridging therapy to LT. HCC location varied from peripheral to central/hilar regions and HCC diameter was 13-54 mm. Median time between SBRT and LT was 141 days (range 27-461 days). Median operating time was 360 min (range 270-480 min). Four patients (44%) had visible SBRT reaction or fibrosis at the time of LT. SBRT reaction resulted in clinical impact in one patient (11%) only, where vascular clamping of the IVC was required for 10 min.CONCLUSION:SBRT is a safe and effective treatment for HCC enabling patients to remain within LT criteria, even for lesions not amenable to other more conventional bridging therapies. We describe a preliminary decision pathway to guide the optimal use of SBRT as a bridge to LT developed in our institution.

Aims: Standard curative options for early-stage, solitary hepatocellular carcinoma (HCC) are often unsuitable due to liver dysfunction, comorbidities and/or tumour location. Stereotactic body radiation therapy (SBRT) has shown high rates of local control in HCC; however, limited data exist in the treatment-naive, curative-intent setting. We report the outcomes of patients with solitary early-stage HCC treated with SBRT as first-line curative-intent therapy.Materials and methods: A multi-institutional retrospective study of treatment-naive patients with Barcelona Clinic Liver Cancer stage 0/A, solitary <= 5 cm HCC, Child-Pugh score (CPS) A liver function who underwent SBRT between 2010 and 2019 as definitive therapy. The primary end point was freedom from local progression. Secondary end points were progression-free survival, overall survival, rate of treatment-related clinical toxicities and change in CPS >1.Results: In total, 68 patients were evaluated, with a median follow-up of 20 months (range 3-58). The median age was 68 years (range 50-86); 54 (79%) were men, 62 (91%) had cirrhosis and 50 (74%) were Eastern Cooperative Oncology Group 0. The median HCC diameter was 2.5 cm (range 1.3-5) and the median prescription biologically effective dose with a tumour a/b ratio of 10 Gy (BED10) was 93 Gy (interquartile range 72-100 Gy). Two-year freedom from local progression, progression-free survival and overall survival were 94.3% (95% confidence interval 86.6-100%), 59.5% (95% confidence interval 46.3-76.4%) and 88% (95% confidence interval 79.2-97.6%), respectively. Nine patients (13.2%) experienced grade >= 2 treatment-related clinical toxicities. A rise >1 in CPS was observed in six cirrhotic patients (9.6%).Conclusion: SBRT is an effective and well-tolerated option to consider in patients with solitary, early-stage HCC. Prospective, randomised comparative studies are warranted to further refine its role as a first-line curative-intent therapy.(c) 2023 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

Objective: Management of coagulopathy in chronic liver disease (CLD) poses a challenge for critical care physicians. Prothrombinex (R)-VF is a low-volume product with rapid onset of action. Evidence for its efficacy and safety in CLD is limited and cases of acute intravascular coagulation and fibrinolysis (AICF) and/or disseminated intravascular coagulation (DIC) have been reported. Our objective was to evaluate the role of Prothrombinex (R) VF in reversal of coagulopathy and the incidence AICF/DIC, thromboembolic events and mortality. Methods: This was a retrospective, multi-centre study of Prothrombinex (R) VF use in CLD across 11 hospitals over a 2-year period, excluding those on therapeutic anticoagulation. Patients were subclassified into acute on chronic liver failure (ACLF), acute decompensation (ADC) and compensated cirrhosis. Reversal of coagulopathy was defined as international normalised ratio (INR) < 1.5 x upper limit normal (ULN), prothrombin time < 1.5x ULN, activated partial thromboplastin time < 1.5 x ULN and fibrinogen > 1 g/L. Markers of AICF/ DIC were recorded. Results: Thirty CLD patients were included, and the median model for end-stage liver disease score was 23.5. Acute bleeding was the most common indication for Prothrombinex((R))-VF (60%). All had baseline coagulopathy and the majority did not achieve reversal. Key indicators of AICF/DIC were mainly observed in those with ACLF; bleeding from mucosa or lines (53%), worsening hypofibrinogenaemia (60%), worsening thrombocytopaenia (60%). The ADC and compensated cirrhosis groups were relatively unaffected. Incidence of venous thromboembolism was 6%. Overall mortality was 43% and 70% in ACLF. Conclusion: Prothrombinex((R))-VF did not lead to meaningful reversal of coagulopathy and should be used with caution in CLD. Patients with ACLF were more likely to develop AICF/ DIC following Prothrombinex((R))-VF,although the association is uncertain. Further studies are needed to evaluate the safety and efficacy of Prothrombinex((R))-VF use in CLD.

Safe and appropriate use of medicines is essential to improve health outcomes in cirrhosis. However, little is known about the number and type of medicines dispensed to people with cirrhosis in Australia, as this predominantly occurs in the community. We aimed to characterise the prescriptions dispensed to people with cirrhosis and explore changes in the use of medication groups over time. Pharmaceutical Benefits Scheme data between 1 January 2016 and 30 June 2020 was extracted for consenting CirCare participants (multi-site, prospective, observational study). Prescriptions dispensed from cirrhosis diagnosis until liver transplant or death were included. Safety classifications for dispensed medicines were defined using published evidence-based recommendations. The pattern of medication use was analysed in 6-monthly time intervals. Generalised estimating equations models were used to estimate the change in consumption of medicines over time. Five hundred twenty-two patients (mean age 60 years, 70

Background: Australians with cirrhosis have significant practical and psychosocial needs. This longitudinal study examined the association between supportive care needs and health service use and costs, and patient outcomes from June 2017 to December 2018. Methods: The Supportive Needs Assessment tool for Cirrhosis (SNAC), quality of life (Chronic Liver Disease Questionnaire and Short Form 36), and distress (distress thermometer) were self-reported through an interview at recruitment (n=433). Clinical data were obtained from medical records and through linkage, and health service use and costs through linkage. Patients were grouped as by needs status. Rates of hospital admissions (per person days at risk) and costs were assessed by needs status [incidence rate ratios (IRR), Poisson regression]. Multivariable linear regression was used to assess the differences in SNAC scores by quality of life and distress. Multivariable models included Child-Pugh class, age, sex, recruitment hospital, living arrangements, place of residence, comorbidity burden, and primary liver disease etiology. Results: In adjusted analyses, compared with patients with low/no needs, patients with unmet needs had more cirrhosis-related admissions (adjusted IRR=2.11, 95% CI=1.48–3.13; p <0.001), admissions through the emergency department (IRR=2.99, 95% CI=1.80–4.97, p <0.001), and emergency presentations (IRR=3.57, 95% CI=1.41–9.02; p <0.001). Total hospitalization costs for cirrhosis admissions were higher for those with unmet needs ($431,242 per person days at risk) compared with those with met needs ($87,363 per person days at risk, adjusted cost ratio=3.52, 95%CI=3.49–3.54; p <0.001). In multivariable analysis, increasing overall mean SNAC scores (higher needs) were correlated with poorer quality of life and higher level of distress ( p <0.001 for all comparisons). Conclusions: Patients with cirrhosis and high unmet psychosocial needs and practical and physical needs have poor quality of life, high distress, and very high service use and costs, highlighting the importance of urgently addressing unmet needs.

Patient barriers to self-management in cirrhosis are complex.[1] Although several studies have demonstrated improved knowledge or self-care behaviors following education,[1] long-term outcome data are lacking. We previously reported that a multifaceted pharmacist-led intervention for people with decompensated cirrhosis (including patient-oriented education, medication reconciliation, and identification and resolution of "high-risk" medication-related problems) was associated with fewer unplanned admissions at 12 months compared to usual care (adjusted incidence rate ratio [aIRR], 0.52; 95% confidence interval [CI], 0.30–0.92; p = 0.025).[2] Despite the relatively short 6-month intervention delivery period, new outcome data demonstrate unplanned admission rates in the intervention group remained lower than usual care out to 3 years. Participants were followed for a mean of 27.8 (SD, ±11.9) months and censored at death (n = 41; 35.3%), liver transplant (n = 5; 4.3%), or study closeout at 3 years (n = 70; 60.3%). Forty-one patients receiving intervention (41/57, 71.9%) and 50 patients receiving usual care (50/59, 84.7%) had at least one unplanned admission during the follow-up period (unplanned admission rate, 3.72 vs. 4.34; Mann-Whitney U, p = 0.272) (Figure 1). Using a generalized linear model with negative binomial distribution offset by person time to censorship, patients receiving intervention had a significantly lower incidence rate of unplanned admissions at 3 years compared to usual care (aIRR, 0.56; 95% CI, 0.34–0.92; p = 0.023), following adjustment for Child-Pugh score (aIRR, 1.47; 95% CI, 1.28–1.68; p < 0.001), number of medications (aIRR, 1.09; 95% CI, 1.03–1.15; p = 0.005), history of variceal bleeding (aIRR, 2.36; 95% CI, 1.30–4.29; p = 0.005), and alcoholic liver disease (aIRR, 0.63; 95% CI, 0.40–1.00; p = 0.050). We further conducted a subanalysis of unplanned admissions that were considered medication related and potentially preventable.[2] Using a multinomial logistic regression model (due to the large count of zero admissions) adjusted for Child-Pugh score and number of medications, patients receiving usual care were 3.5 times more likely to have three or more "potentially preventable medication-related admissions" compared to zero than patients receiving intervention, although this did not reach statistical significance (adjusted odds ratio, 3.52; 95% CI, 0.69–17.81; p = 0.129). There was no difference in mortality rate (intervention 31.6% vs. usual care 39.0%; p = 0.404) or mean time to censorship (28.5 vs. 27.2 months, respectively; log-rank p = 0.530). These findings suggest that a pharmacist-led intervention, which empowers patients (and their caregivers) with improved knowledge about cirrhosis and medicines,[3] reinforces perceptions of treatment necessity and utility in disease management,[3] provides tools to manage medicines (e.g., a structured list[2]), and builds confidence to actively engage with health care providers, has long-term benefits for patients and the health care system. Despite completion of active pharmacist intervention at 6 months, the benefits persisted over time and translated to fewer hospitalizations independently of liver disease severity. These data support inclusion of a pharmacist in the multidisciplinary team. Nothing to report.

Abstract 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 2018–2020. We 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 1-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.

Background. Prevalence of concurrent liver diseases among liver transplant recipients and impact on posttransplant outcomes are unknown. Methods. This retrospective study included adult liver transplants between January 1‚ 1985‚ and December 31‚ 2019‚ from the Australian and New Zealand Liver and Intestinal Transplant Registry. Up to 4 liver disease causes were recorded for each transplant; concurrent liver diseases were defined as >1 liver disease indication for transplantation, excluding hepatocellular carcinoma. Impact on posttransplant survival was determined using Cox regression. Results. A total of 840 (15%) of 5101 adult liver transplant recipients had concurrent liver diseases. Recipients with concurrent liver diseases were more likely male (78% versus 64%) and older (mean age 52 versus 50 y). A higher proportion of liver transplants for hepatitis B (12% versus 6%), hepatitis C (33% versus 20%), alcohol liver disease (23% versus 13%), and metabolic-associated fatty liver disease (11% versus 8%, all P < 0.001) were identified when all indications were included than with primary diagnosis only. The number and proportion of liver transplants performed for concurrent liver diseases have increased from 8 (6%) during Era 1 (1985–1989) to 302 (20%) during Era 7 (2015–2019; P < 0.001). Concurrent liver diseases were not associated with increased posttransplant mortality (adjusted hazard ratio, 0.98, 95% confidence interval, 0.84-1.14). Conclusions. Concurrent liver diseases are increasing among adult liver transplant recipients in Australia and New Zealand; however, they do not appear to impact posttransplant survival. Reporting all liver disease causes in the transplant registry reports provides more accurate estimates of liver disease burden.