Mediterranean Diet and Ultra-Processed Food Intake in Older Australian Adults-Associations with Frailty and Cardiometabolic Conditions.

Dietary patterns contribute to overall health and diseases of ageing but are understudied in older adults. As such, we first aimed to develop dietary indices to quantify Mediterranean Diet Score (MDS) utilisation and Ultra-processed Food (UPF) intake in a well-characterised cohort of relatively healthy community-dwelling older Australian adults. Second, we aimed to understand the relationship between these scores and the association of these scores with prevalent cardiometabolic disease and frailty. Our major findings are that in this population of older adults, (a) pre-frailty and frailty are associated with reduced MDS and increased UPF intake; (b) adherence to MDS eating patterns does not preclude relatively high intake of UPF (and vice versa); and (c) high utilisation of an MDS eating pattern does not prevent an increased risk of frailty with higher UPF intakes. As such, the Mediterranean Diet pattern should be encouraged in older adults to potentially reduce the risk of frailty, while the impact of UPF intake should be further explored given the convenience these foods provide to a population whose access to unprocessed food may be limited due to socioeconomic, health, and lifestyle factors.

Initial Trans-Arterial Chemo-Embolisation (TACE) Is Associated with Similar Survival Outcomes as Compared to Upfront Percutaneous Ablation Allowing for Follow-Up Treatment in Those with Single Hepatocellular Carcinoma (HCC) ≤ 3 cm: Results of a Real-World Propensity-Matched Multi-Centre Australian Cohort Study.

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.

Serum Transaminases And Older Adults: Distribution And Associations With All-Cause Mortality.

BACKGROUND: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly ordered tests in general medical practice. However, their distribution and significance in older adults is understudied. As such, we aimed to evaluate sex-stratified distribution of both ALT and AST in older adults (≥ 70 years) and assess for associations with mortality. METHODS: Post-hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised, placebo-controlled trial of daily low-dose aspirin for initially relatively healthy older persons. Univariate analysis and multiple logistic regression were used to explore baseline characteristics. Cox regression and restricted cubic splines were used to examine links between transaminase levels and mortality. RESULTS: Of the 11853 participants with ALT and AST levels, 1054 (8.9%) deaths were recorded over median 6.4 (IQR 5.4-7.6) years. For ALT, the lowest quintiles for males and females were 6-15 U/L and 5-13 U/L respectively; for AST, the lowest quintiles were 8-18 U/L and 7-17 U/L. On both univariate and models adjusted for covariates including age, BMI, frailty, diabetes, and kidney disease, males and females in the lowest quintile of ALT had an increased hazard of mortality (aHR 1.51 [95% CI 1.14-1.99] and aHR 1.39 [95% CI 1.03-1.88] respectively). For the lowest quintile of AST, only males were at increased risk (aHR 1.33 [95% CI 1.04-1.70]). Associations remained significant when removing outliers. CONCLUSION: Low ALT levels independently confer an increased hazard of mortality for older males and females; low AST only impacted older male survival. Further evaluation of mechanisms would be worthwhile, and re-evaluating the lower limit of normal for ALT in older adults should be considered.

NAFLD and MAFLD independently increase the risk of major adverse cardiovascular events (MACE): a 20-year longitudinal follow-up study from regional Australia.

BACKGROUND AND AIMS: The association between fatty liver disease (FLD) and cardiovascular disease (CVD) in an Australian context has yet to be defined. The primary aim of this study was to investigate the association between FLD and 3-point major adverse cardiovascular events (MACE). METHODS: This was a longitudinal follow-up study of a randomly sampled adult cohort from regional Australia between 2001 and 2003. Baseline covariates included demographic details, anthropometry, health and lifestyle data, and laboratory tests. Non-alcoholic fatty liver disease (NAFLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) were diagnosed in participants with fatty liver index (FLI) ≥ 60 and meeting other standard criteria. ICD-10 codes were used to define clinical outcomes linked to hospitalisations. Three-point MACE defined as non-fatal myocardial infarction (MI) and cerebrovascular accident (CVA) and CVD death. RESULTS: In total, 1324 and 1444 participants met inclusion criteria for NAFLD and MAFLD analysis, respectively. Over 23,577 and 25,469 person-years follow-up, NAFLD and MAFLD were independent predictors for 3-point MACE, adjusting for demographic covariates and known cardiometabolic risk factors, whilst considering non-CVD death as a competing event (NAFLD: sub-hazard ratio [sHR] 1.56, 95% confidence interval [CI 1.12-2.19]; MAFLD: sHR 1.51, 95% CI 1.11-2.06). The results held true on several sensitivity analyses. CONCLUSIONS: Both forms of FLD increase the risk for CVD independent of traditional cardiometabolic risk factors.

Rotational thromboelastometry predicts future bleeding events in patients with cirrhosis.

BACKGROUND AND AIMS: Patients with cirrhosis of the liver are in a delicate state of rebalanced haemostasis and are at risk of developing both bleeding and thrombotic complications. Conventional haemostatic tests are unable to predict bleeding and thrombosis in these patients. We aimed to explore the role of Rotational Thromboelastometry (ROTEM) in predicting bleeding and thrombotic events in patients with cirrhosis. METHODS: We conducted a prospective cohort study of patients with cirrhosis at two metropolitan hospitals. All patients underwent ROTEM analysis and were then followed to record any bleeding and thrombotic events. Univariate and multivariate logistic regression analyses were performed to explore associations with bleeding and thrombotic events. RESULTS: Nineteen of the 162 patients recruited experienced a bleeding event within one year of ROTEM analysis. On univariate analysis, maximum clot firmness (MCF) using both EXTEM and INTEM tests was significantly reduced in patients who had a bleeding event, compared to those who did not (50 mm vs. 57 mm, p < 0.01 and 48 mm vs. 54 mm, p < 0.01, respectively). In addition, on univariate analysis, clotting time (CT) in the INTEM test was prolonged in the bleeding group (214 s vs. 198 s, p = 0.01). On multivariate analysis, only MCFEX was a significant predictor of bleeding events. In contrast, there was no association found between ROTEM parameters and development of thrombosis within a one-year period. CONCLUSIONS: ROTEM may provide a useful tool in predicting future bleeding events in patients with cirrhosis. Larger studies are required to further validate this finding and explore its application in clinical practice.

AI-powered prediction of HCC recurrence after surgical resection: Personalised intervention opportunities using patient-specific risk factors.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence following surgical resection remains a significant clinical challenge, necessitating reliable predictive models to guide personalised interventions. In this study, we sought to harness the power of artificial intelligence (AI) to develop a robust predictive model for HCC recurrence using comprehensive clinical datasets. METHODS: Leveraging data from 958 patients across multiple centres in Australia and Hong Kong, we employed a multilayer perceptron (MLP) as the optimal classifier for model generation. RESULTS: Through rigorous internal cross-validation, including a cohort from the Chinese University of Hong Kong (CUHK), our AI model successfully identified specific pre-surgical risk factors associated with HCC recurrence. These factors encompassed hepatic synthetic function, liver disease aetiology, ethnicity and modifiable metabolic risk factors, collectively contributing to the predictive synergy of our model. Notably, our model exhibited high accuracy during cross-validation (.857 ± .023) and testing on the CUHK cohort (.835), with a notable degree of confidence in predicting HCC recurrence within accurately classified patient cohorts. To facilitate clinical application, we developed an online AI digital tool capable of real-time prediction of HCC recurrence risk, demonstrating acceptable accuracy at the individual patient level. CONCLUSION: Our findings underscore the potential of AI-driven predictive models in facilitating personalised risk stratification and targeted interventions to mitigate HCC recurrence by identifying modifiable risk factors unique to each patient. This model aims to aid clinicians in devising strategies to disrupt the underlying carcinogenic network driving recurrence.

Different Patterns of Care and Survival Outcomes in Transplant-Centre Managed Patients with Early-Stage HCC: Real-World Data from an Australian Multi-Centre Cohort Study.

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.

WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.

Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis.

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.

WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.

Late-Life Metabolic Dysfunction-Associated Steatotic Liver Disease and its Association With Physical Disability and Dementia.

BACKGROUND: The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing rapidly, including among older adults. The number of older adults is also rising with concomitantly increasing rates of age-related physical and cognitive dysfunction. However, data on whether MASLD affects physical and cognitive function in older adults is limited. As such, we aimed to identify whether prevalent MASLD influences the risk of incident physical disability or dementia in initially healthy older adults. METHODS: A post-hoc analysis of participants from the ASPREE-XT cohort study, which recruited community-dwelling older adults without a history of cardiovascular disease, dementia, or independence-limiting functional impairment. The Fatty Liver Index (to identify MASLD) was calculated in those with complete data. Cox proportional-hazards models were used to investigate the outcomes of dementia and persistent physical disability in participants with MASLD vs those without. RESULTS: Of the 9 097 individuals included (mean age 75.1 ±â€…4.2 years; 45.0% men), 341 (3.7%) developed persistent physical disability and 370 (4.1%) developed dementia over a median follow-up of 6.4 years (IQR 5.3-7.5 years). When adjusting for known contributors including age, gender, education, comorbidity, and functional measures, MASLD was associated with an increased risk of persistent physical disability (HR 1.41 [95% CI: 1.07-1.87]) and reduced risk of incident dementia (HR 0.63 [95% CI: 0.48-0.83]). CONCLUSIONS: Prevalent MASLD is associated with reduced rates of incident dementia but increased risk of persistent physical disability in initially relatively healthy older adults. Understanding the mechanisms underlying these divergent results to allow appropriate risk stratification and counseling is important.

Metabolic and transcriptomic characterization of summer and winter dormancy in the solitary bee, Osmia lignaria.

The solitary bee Osmia lignaria is a native pollinator in North America with growing economic importance. The life cycle of O. lignaria provides a unique opportunity to compare the physiological and molecular mechanisms underlying two ecologically contrasting dormancies within the same species. O. lignaria prepupae become dormant during the summer to avoid high temperatures. Shortly after adult eclosion, they enter a second dormancy and overwinter as diapausing adults. To compare these two dormancies, we measured metabolic rates and gene expression across development as bees initiate, maintain, and terminate both prepupal (summer) and adult (overwintering) dormancies. We observed a moderate temperature-independent decrease in gas exchange during both the prepupal dormancy after cocoon spinning (45 %) and during adult diapause after eclosion (60 %). We sequenced and assembled a high-quality reference genome from a single haploid male bee with a contiguous n50 of 5.5 Mbp to facilitate our transcriptomic analysis. The transcriptomes of dormant prepupae and diapausing adults clustered into distinct groups more closely associated with life stage than dormancy status. Membrane transport, membrane-bound cellular components, oxidoreductase activity, glutathione metabolism, and transcription factor activity increased during adult diapause, relative to prepupal dormancy. Further, the transcriptomes of adults in diapause clustered into two groups, supporting multiple phases of diapause during winter. Late adult diapause was associated with gene expression profiles supporting increased insulin/IGF, juvenile hormone, and ecdysone signaling.

Metabolic dysfunction-associated steatotic liver disease in older adults is associated with frailty and social disadvantage.

BACKGROUND & AIMS: The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing rapidly, as is the number of older adults globally. However, relatively few studies have been performed evaluating the prevalence and risk factors for MASLD in older adults. As such, we aimed to identify the prevalence of MASLD in older adults, as well as sociodemographic, clinical, functional and biochemical associations. METHODS: The study population included older adults without a history of cardiovascular disease, dementia or independence-limiting functional impairment who had participated in the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. MASLD was defined using the Fatty Liver Index (FLI). Associations were identified using Poisson regression with robust variance for FLI ≥ 60 vs FLI < 30. RESULTS: 9097 Australian participants aged ≥70 years had complete biochemical and anthropometric data to identify MASLD. The study population had a mean age of 75.1 ± 4.3 years and was 45.0% male. Almost one-third (33.0%) had prevalent MASLD, and the prevalence decreased with increasing age (adjusted RR [aRR] 0.96, 95% CI: 0.96-0.97). MASLD was also negatively associated with social advantage (aRR 0.94, 95% CI: 0.90-0.99) and exercise tolerance and was positively associated with diabetes mellitus (aRR: 1.22, 95% CI: 1.16-1.29), hypertension (aRR: 1.31, 95% CI: 1.22-1.41), male sex (aRR: 1.66, 95% CI: 1.57-1.74), pre-frailty (aRR: 1.99, 95% CI: 1.82-2.12) and frailty (aRR: 2.36, 95% CI: 2.16-2.56). MASLD and nonalcoholic fatty liver disease (NAFLD) results were 100% concordant. CONCLUSION: This study in a large cohort of relatively healthy community-dwelling older adults shows that MASLD is common, decreases with age and is associated with poorer metabolic health, social disadvantage and frailty.

Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study.

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.

Current Therapeutics in Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is an orphan, cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease. Its pathophysiology is poorly understood. Chronic biliary inflammation is likely driven by immune dysregulation, gut dysbiosis, and environmental exposures resulting in gut-liver crosstalk and bile acid metabolism disturbances. There is no proven medical therapy that alters disease progression in PSC, with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses (15-23 mg/kg/day) but not alter transplant-free survival or liver-related outcomes. Liver transplantation is the only option for patients who develop end-stage liver disease or refractory complications of PSC. Immunosuppressive and antifibrotic agents have not proven to be effective, but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and antibiotics. Bile acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid, or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III trials. In view of the enhanced malignancy risk, statins, and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC patients. For patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function, balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.

Rotational ThromboElastometry-guided blood component administration versus standard of care in patients with Cirrhosis and coagulopathy undergoing Invasive ProcEdures (RECIPE): study protocol for a randomised controlled trial.

BACKGROUND: Patients with cirrhosis often undergo invasive procedures both for management of complications of their advanced liver disease, including treatment for hepatocellular carcinoma, as well as underlying comorbidities. Despite a current understanding that most patients with cirrhosis are in a rebalanced haemostatic state (despite abnormalities in conventional coagulation tests, namely INR and platelet count), patients with cirrhosis are still often given prophylactic blood components based on these conventional parameters, in an effort to reduce procedure-related bleeding. Viscoelastic tests such as Rotational Thromboelastometry (ROTEM) provide a global measurement of haemostasis and have been shown to predict bleeding risk more accurately than conventional coagulation tests, and better guide blood product transfusion in a number of surgical and trauma-related settings. The aim of this study is to assess the utility of a ROTEM-based algorithm to guide prophylactic blood component delivery in patients with cirrhosis undergoing invasive procedures. We hypothesise that ROTEM-based decision-making will lead to a reduction in pre-procedural blood component usage, particularly fresh frozen plasma (FFP), compared with standard of care, whilst maintaining optimal clinical outcomes. METHODS: This is a multi-centre randomised controlled trial comparing ROTEM-guided prophylactic blood component administration to standard of care in patients with cirrhosis and coagulopathy undergoing invasive procedures. The primary efficacy outcome of the trial is the proportion of procedures requiring prophylactic transfusion, with the primary safety outcome being procedure-related bleeding complications. Secondary outcomes include the amount of blood products (FFP, platelets, cryoprecipitate) transfused, transfusion-related side effects, procedure-related complications other than bleeding, hospital length of stay and survival. DISCUSSION: We anticipate that this project will lead to improved prognostication of patients with cirrhosis, in terms of their peri-procedural bleeding risk. We hope to show that a significant proportion of cirrhotic patients, deemed coagulopathic on the basis of standard coagulation tests such as INR and platelet count, are actually in a haemostatic balance and thus do not require prophylactic blood product, leading to decreased and more efficient blood component use. TRIAL REGISTRATION: RECIPE has been prospectively registered with the Australia and New Zealand Clinical Trials Registry on the 30th April 2019 ( ACTRN12619000644167 ).

Non-alcoholic fatty liver disease prevalence in Australia has risen over 15 years in conjunction with increased prevalence of obesity and reduction in healthy lifestyle.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver condition globally. The aim of this study was to evaluate the change in age- and sex-standardized prevalence of NAFLD in regional Victoria over a 15-year period and explore the underlying factors associated with differences over time. METHODS: Repeated comparative cross-sectional studies in four towns in regional Victoria, Australia. Individuals randomly selected from households from residential address lists from local government organizations in 2001-2003 (CrossRoads I [CR1]) and 2016-2018 (CrossRoads II [CR2]) with 1040 (99%) and 704 (94%) participants from CR1 and CR2 having complete data for analysis. Primary outcome was change in prevalence estimates of NAFLD (defined by a fatty liver index ≥ 60 in the absence of excess alcohol and viral hepatitis) between 2003 and 2018. RESULTS: Crude prevalence of NAFLD increased from 32.7% to 38.8% (P < 0.01), while age-standardized/sex-standardized prevalence increased from 32.4% to 35.4% (P < 0.01). Concurrently, prevalence of obesity defined by BMI and elevated waist circumference increased 28% and 25%, respectively. Women had a greater increase in the prevalence of NAFLD than men, in parallel with increasing prevalence of obesity. Proportion of participants consuming takeaway food greater than once weekly increased significantly over time. Up to 60% of NAFLD patients require additional tests for assessment of significant fibrosis. CONCLUSIONS: Crude and age-standardized/sex-standardized prevalence of NAFLD have both increased significantly over the last 15 years, particularly among women, in association with a parallel rise in the prevalence of obesity.

Current understanding and future perspectives on the impact of changing NAFLD to MAFLD on global epidemiology and clinical outcomes.

INTRODUCTION: For the first time in nearly half a century, fatty liver disease has undergone a change in name and definition, from the exclusive term, non-alcoholic fatty liver disease (NAFLD), to the inclusion-based, metabolic-associated fatty liver disease (MAFLD). This has led investigators across the globe to evaluate the impact the nomenclature change has had on the epidemiology and natural history of the disease. METHODS: This systematic review provides a comprehensive overview on how the shift in name and diagnostic criteria has influenced point prevalence in different geographic regions, as well as morbidity and mortality risk, whilst highlighting gaps in the literature that need to be addressed. CONCLUSIONS: MAFLD prevalence is higher than NAFLD prevalence, carries a higher risk of overall mortality, with greater granularity in risk-stratification amongst MAFLD subtypes.

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