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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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: Five hundred twenty-two patients (mean age 60 years, 70% male, 34% decompensated at recruitment) were dispensed 89,615 prescriptions during the follow-up period, representing a median of 136 [interquartile range (IQR) 62–237] prescriptions and a median of 16 (IQR 11–23) unique medicines per patient (total n = 9306 medicines). The most commonly used medicines were proton pump inhibitors (PPIs) (dispensed at least once to 73% of patients), opioids (68%) and antibiotics (89%). Polypharmacy was prevalent, with 59–69% of observed participants in each time period dispensed five or more unique medicines. Prescription medication use increased over time (p < 0.001) independently of age, comorbidity burden and liver disease aetiology. The likelihood of taking PPIs, opioids, antidepressants and inhaled medicines also increased with each successive time period. Use of angiotensin therapies, metformin and statins differed over time between patients with compensated versus decompensated cirrhosis. General practitioners prescribed 69% of dispensed medicines, including a higher proportion of 'unsafe' and 'safety unknown' medicines compared with consultants/specialists (p < 0.001). Conclusions: Polypharmacy is common in people with cirrhosis and some medication groups may be overused. Pharmacovigilance is required and future medication safety efforts should target high-risk prescribing practices and promote medication rationalisation in the community. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic body radiotherapy (SBRT) is an emerging, therapeutic option in the management of hepatocellular carcinoma (HCC). A multicentre Liver Ablative Stereotactic Radiation (LASR) database was established to provide a collaborative platform for Australian institutions to define the practice of liver SBRT for HCC. This study explores the patterns of SBRT practice amongst Australian institutions.Methods: This was a multi-institutional retrospective study of patients treated with SBRT for HCC at 10 institutions between January 2013 and December 2019. Patients' demographics, disease characteristics and SBRT details were evaluated.Results: Three hundred and seventeen patients were evaluated with a median age of 67 years (range, 32-90). Liver cirrhosis was present in 88.6%, baseline Child-Pugh score was A5/6 in 85.1% and B7/8 in 13.2%. Median size of HCC treated was 30 mm (range, 10-280). 63.1% had early-stage disease (Barcelona clinic liver cancer (BCLC) stage 0/A) and 36% had intermediate/advanced-stage disease (BCLC B/C). In 2013/2014, six courses of SBRT were delivered, increasing to 108 in 2019. SBRT was prescribed in five fractions for 71.3% of the cohort. The most common dose fractionation schedule was 40 Gy in five fractions (24.3%). Median biologically effective dose (BED10 ) delivered was 85.5 Gy for early-stage and 60 Gy for intermediate/advanced disease, respectively. The most common prescription range was 100-120 Gy BED10 (32.8%).Conclusion: SBRT utilisation for HCC is increasing in Australia. There was wide variation in size of tumours and disease stages treated, and prescription patterns. Uniform reporting of clinical and dosimetric details are important in refining the role of liver SBRT. [ABSTRACT FROM AUTHOR]

Background: The rate of hospital admissions for cirrhosis increased 1.3‐fold during 2008–2016 in Queensland. Alcohol misuse was a contributing factor for cirrhosis in 55% of admissions and 40% of patients had at least one comorbidity. Aims: To examine the temporal change in aetiology of liver disease and presence of comorbidity in patients admitted with cirrhosis. Methods: Population‐based retrospective cohort study of all people treated in hospital for cirrhosis (10 254 patients) in Queensland during 2008–2016. Data were sourced from Queensland Hospital Admitted Patient Data Collection. Results: The commonest aetiology was alcohol (49.5%), followed by cryptogenic (unspecified cirrhosis; 28.5%), hepatitis C virus (19.3%), non‐alcoholic fatty liver disease (NAFLD)/non‐alcoholic steatohepatitis (NASH) (4.8%) and hepatitis B virus (HBV) (4.3%). The prevalence of alcohol‐related (P = 0.41) and hepatitis C virus (P = 0.08) remained stable between 2008–2010 and 2014–2016, that of NAFLD/NASH, cryptogenic and HBV‐cirrhosis increased by 67% (P < 0.00001), 27% (P < 0.00001) and 20% (P = 0.00019), respectively; 41.1% of patients had at least one comorbidity. The prevalence of type 2 diabetes nearly doubled (from 13.7% to 25.4%; P < 0.00001) between 2008–2010 and 2014–2016. Conclusions: Alcohol misuse was the most important aetiology. The importance of NAFLD/NASH, cryptogenic and HBV‐cirrhosis and the burden of comorbidity increased during 2008–2016. Ongoing alcohol misuse and the increasing prevalence of NAFLD/NASH, cryptogenic cirrhosis and comorbid type 2 diabetes among admissions for cirrhosis has implications for public health interventions to reduce the burden of unhealthy lifestyle and metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: We report the development and psychometric testing of a Supportive Needs Assessment tool for Cirrhosis (SNAC). Methods: The 50-item SNAC was administered to patients (n=465) diagnosed with cirrhosis recruited from five metropolitan hospitals in Queensland, Australia. Items were assessed for ceiling and floor effects, and exploratory factor analysis was used to assess the factor structure. Identified factors were assessed for internal consistency and convergent validity to validated psychosocial tools. Results: Exploratory factor analysis identified 4 factors (39 items), which together accounted for 49.2% of the total variance. The 39-item SNAC met the requirements of a needs assessment tool and identified a range of needs important to patients with cirrhosis that were grouped in four subscales: "Psychosocial issues", "Practical and physical needs", "Information needs", and "Lifestyle changes". Cronbach's alpha values for the four subscales ranged from 0.64 to 0.92. Convergent validity was supported by a strong correlation between the total SNAC score and that of the Chronic Liver Disease Questionnaire (CLDQ; Spearman rho − 0.68; p< 0.001), and moderate correlations with the Distress Thermometer (Spearman rho 0.53; p< 0.001) and seven subscales of a generic health-related quality of life instrument (Short Form 36; Spearman rho ranged from − 0.48 to − 0.57; p< 0.001). The SNAC discriminated patient groups with respect to sex (p=0.013), age group (p< 0.001), and hospital admission status (admitted vs not; p< 0.001). Conclusion: These data provide initial evidence for the validity and reliability of the SNAC, an instrument designed to measure type and amount of perceived unmet practical and psychological needs of people diagnosed with cirrhosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Non‐alcoholic fatty liver disease (NAFLD) is a common cause of incidental liver test abnormalities. General practitioners (GP) have a key role in identifying people with NAFLD at risk of significant liver disease. Recent specialist guidelines emphasise the use of fibrosis algorithms or serum biomarkers rather than routine liver tests, to assess advanced fibrosis. Aim: To evaluate primary care clinicians’ current approach to diagnosis, management and referral of NAFLD. Methods: A cross‐sectional survey of primary care clinicians was undertaken through a structured questionnaire about NAFLD. A convenience sample of general practice clinics and general practice conferences in Metropolitan Brisbane and regional south east Queensland was selected. Results: A total of 108 primary care clinicians completed the survey (participation rate 100%). Fifty‐one percent of respondents considered the prevalence of NAFLD in the general population to be ≤10%. Twenty‐four percent of respondents felt that liver enzymes were sufficiently sensitive to detect underlying NAFLD. Most respondents were unsure whether the Fibrosis 4 score (62.7% unsure) or Enhanced Liver Fibrosis score (63.7% unsure) could help to identify advanced fibrosis or cirrhosis. Although 47% of respondents said they would refer a patient to a Gastroenterologist/Hepatologist if they suspect the patient has NAFLD, 44.1% do not make any referrals. Of concern, 70.6% of clinicians said they were unlikely to refer a patient to Hepatology unless liver function tests are abnormal. Conclusion: Our findings demonstrate that many primary care clinicians underestimate the prevalence of NAFLD and under‐recognise the clinical spectrum of NAFLD and how this is assessed. [ABSTRACT FROM AUTHOR]

Background and Aims: IgG4 sclerosing cholangitis (IgG4-SC) is the biliary component of the multisystem IgG4-related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4-SC in a large Australian cohort., Methods: We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA-CRN). 39 sites were invited to participate. IgG4-SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes., Results: 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09-67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas., Conclusions: Our study confirms the preponderance of IgG4-SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine., Methods: We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment., Results: The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P = .07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events., Conclusion: In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

An increased liver disease burden has been reported for Aboriginal and Torres Strait Islanders (ATSIs) in Australia; however, few proceed to liver transplantation (LT). We aimed to compare overall survival and graft survival after LT between ATSI and non-ATSI populations, assess the factors influencing survival within ATSIs, and finally examine the proportion of ATSIs undergoing LT. This study was a retrospective review of the Australia and New Zealand Liver Transplant Registry from 1985 to 2012 and examined consecutive primary LT performed in Australia. Overall and graft survival were compared between ATSI and non-ATSI groups. The Accessibility/Remoteness Index of Australia (ARIA) was used to calculate the remoteness of individuals. There were 3493 primary LT performed, and 45 patients (1.3%; 14 children and 31 adults) were ATSIs. The median (range) ages of the ATSI children and adults at the time of LT were 9.6 (0.2-15.3) years and 44.5 (19.5-65.5) years, respectively. There were 10 deaths in the ATSI cohort. The median (range) overall survival was similar for ATSI and non-ATSI children [6.5 (0.1-23.5) years versus 9.0 (0-28.2) years, P = 0.9] and adults [7.1 (0.1-15.7) years versus 6.3 0-26.7) years, P = 0.8]. The cumulative graft survival was similar for ATSI and non-ATSI children (P = 0.8) and adults (P = 0.8). High ARIA scores [hazard ratio (HR) = 1.2, 95% confidence interval (CI) = 1.01-1.53, P = 0.03] in children and blood group O (HR = 3.8, 95% CI = 1.1-12.7, P = 0.03) in adults predicted worse outcomes for ATSIs. Although ATSIs accounted for 4.7% and 1.8% of the Australian pediatric and adult populations, respectively, they represented only 2.2% of pediatric LT recipients (χ(2)  = 8.2, P = 0.004) and 1.1% of adult LT recipients (χ(2)  = 7.9, P = 0.005). In conclusion, overall survival and graft survival after LT are comparable in ATSIs and non-ATSIs. There is a trend toward increased death/retransplantation in ATSIs from remote areas. ATSI children and adults appear to be underrepresented in the Australian LT population., (© 2014 American Association for the Study of Liver Diseases.)

Unlabelled: Additional markers are required to identify patients on the orthotopic liver transplant (OLT) waiting list at increased risk of death and adverse clinical events. Serum ferritin concentration is a marker of varied pathophysiological events and is elevated with increased liver iron concentration, hepatic necroinflammation, and systemic illness, all of which may cause a deterioration in liver function and clinical status. The aim of this study was to determine whether serum ferritin concentration is an independent prognostic factor in subjects awaiting OLT. This is a dual-center retrospective study. The study cohort consisted of 191 consecutive adults with cirrhosis accepted by the Queensland (Australia) Liver Transplant Service between January 2000 and June 2006 and a validation cohort of 131 patients from University of California Los Angeles (UCLA) Transplant Center. In the study cohort, baseline serum ferritin greater than 200 microg/L was an independent factor predicting increased 180-day and 1-year waiting list mortality. This effect was independent of model for end-stage liver disease (MELD), hepatocellular carcinoma, age, and sex. Subjects with higher serum ferritin had increased frequency of liver-related clinical events. The relationship between serum ferritin and waiting list mortality was confirmed in the UCLA cohort; all deceased patients had serum ferritin greater than 400 microg/L. Serum ferritin greater than 500 microg/L and MELD were independent risk factors for death., Conclusion: Serum ferritin concentration is an independent predictor of mortality-related and liver-related clinical events. Baseline serum ferritin identifies a group of "higher-risk" patients awaiting OLT and should be investigated as an adjunct to MELD in organ allocation.