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Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease. Global Burden of Disease (GBD) data from 1990 to 2019 reported a rise in prevalence (9-13%) in Australia, which also ranked third highest for NAFLD prevalence compared to 14 similar countries. As a result of underdiagnosis, NAFLD burden is underestimated by GBD., (© 2024 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: A Mediterranean diet (MD) appears to be beneficial in non-alcoholic fatty liver disease (NAFLD) patients in Mediterranean countries; however, the acceptability of a MD in non-Mediterranean populations has not been thoroughly explored. The present study aimed to explore the acceptability through understanding the barriers and enablers of the MD and low-fat diet (LFD) interventions as perceived by participating Australian adults from multicultural backgrounds with NAFLD., Methods: Semi-structured telephone interviews were performed with 23 NAFLD trial participants at the end of a 12-week dietary intervention in a multicentre, parallel, randomised clinical trial. Data were analysed using thematic analysis., Results: Participants reported that they enjoyed taking part in the MD and LFD interventions and perceived that they had positive health benefits from their participation. Compared with the LFD, the MD group placed greater emphasis on enjoyment and intention to maintain dietary changes. Novelty, convenience and the ability to swap food/meals were key enablers for the successful implementation for both of the dietary interventions. Flavour and enjoyment of food, expressed more prominently by MD intervention participants, were fundamental components of the diets with regard to reported adherence and intention to maintain dietary change., Conclusions: Participants randomised to the MD reported greater acceptability of the diet than those randomised to the LFD, predominantly related to perceived novelty and palatability of the diet., (© 2022 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Background and Aim: The validity of non-invasive tests (NITs) of liver fibrosis for the prediction of liver and mortality outcomes in an Australian cohort is unknown. We aimed to verify the utility of available NITs to predict overall and cause-specific mortality and major adverse liver outcome (MALO)., Methods: This was an analysis from the Crossroads 1 clinic sub-study of a randomly sampled adult cohort from regional Australia between 2001 and 2003. Baseline variables 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 defined by fatty liver index ≥ 60 and other accepted criteria. Outcomes were defined by the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes for linked hospitalization and death registry data. Available serum-based NITs were analyzed as predictors of overall, cardiovascular disease-related, and cancer-related mortality and MALO in those with fatty liver disease (FLD)., Results: In total, 1324 and 1444 participants were included for NAFLD and MAFLD analysis (prevalence 35.4% and 40.7%, respectively). There were 298 deaths (89 cardiovascular disease-related and 98 cancer-related) and 24 MALO over a median 19.7 years of follow-up time. In both forms of FLD, fibrosis-4 index, Steatosis-Associated Fibrosis Estimator score, and Forns fibrosis score consistently had the highest area under the receiver operating characteristic curve (AUROC) for overall and cause-specific mortality, with AUROC > 0.70 for each outcome. However, all had poor discriminatory ability for determining MALO in each FLD., Conclusions: Several liver fibrosis NITs perform similarly reasonably well in predicting the risk of mortality outcomes in those with FLD but are poorly discriminatory for MALO prediction., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

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., (© 2024. Crown.)

Practice guidelines for non-alcoholic fatty liver disease (NAFLD) recommend promoting the Mediterranean dietary pattern (MDP) which is cardioprotective and may improve hepatic steatosis. This study aimed to explore multidisciplinary clinicians' perspectives on whether the MDP is recommended in routine management of NAFLD and barriers and facilitators to its implementation in a multi-ethnic setting. Semi-structured individual interviews were conducted with fourteen clinicians (seven doctors, three nurses, three dietitians and one exercise physiologist) routinely managing patients with NAFLD in metropolitan hospital outpatient clinics in Australia. Interviews were audio-recorded, transcribed and analysed using thematic content analysis. Clinicians described that lifestyle modification was their primary treatment for NAFLD and promoting diet was recognised as everyone's role, whereby doctors and nurses raise awareness and dietitians provide individualisation. The MDP was regarded as the most evidence-based diet choice currently and was frequently recommended in routine care. Facilitators to MDP implementation in practice were: improvement in diet quality as a parallel goal to weight loss; in-depth knowledge of the dietary pattern; access to patient education and monitoring resources and; service culture, including an interdisciplinary clinic goal, and knowledge sharing from expert dietitians. Barriers included perceived challenges for patients from diverse cultural and socio-economic backgrounds and limited clinician training, time and resourcing to support behaviour change. Integration of MDP in routine management of NAFLD in specialist clinics was facilitated by a focus on diet quality, knowledge sharing, belief in evidence and an interdisciplinary team. Innovations to service delivery could better support and empower patients to change dietary behaviour long-term.

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. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is a global health challenge, with a rising rate in line with other metabolic diseases. We aimed to assess the global prevalence of NAFLD in adult and pediatric populations., Methods: PubMed, Scopus and Web of Science databases were systematically searched up to May 2023. Heterogeneity was assessed using Cochran's Q test and I 2 statistics, and random-effects model was used for meta-analysis. Analyses were performed using STATA version 18., Results: A total of 479 studies with 78,001,755 participants from 38 countries were finally included. The global prevalence of NAFLD was estimated to be 30.2% (95% CI: 28.7-31.7%). Regionally, the prevalence of NAFLD was as follows: Asia 30.9% (95% CI: 29.2-32.6%), Australia 16.1% (95% CI: 9.0-24.8%), Europe 30.2% (95% CI: 25.6-35.0%), North America 29% (95% CI: 25.8-32.3%), and South America 34% (95% CI: 16.9-53.5%). Countries with a higher human development index (HDI) had significantly lower prevalence of NAFLD (coefficient = -0.523, p = 0.005). Globally, the prevalence of NAFLD in men and women was 36.6% (95% CI: 34.7-38.4%) and 25.5% (95% CI: 23.9-27.1%), respectively. The prevalence of NAFLD in adults, adults with obesity, children, and children with obesity was 30.2% (95% CI: 28.8-31.7%), 57.5% (95% CI: 43.6-70.9%), 14.3% (95% CI: 10.3-18.8%), and 38.0% (95% CI: 31.5-44.7%), respectively., Conclusion: The prevalence of NAFLD is remarkably high, particularly in countries with lower HDI. This substantial prevalence in both adults and children underscores the need for disease management protocols to reduce the burden., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) cirrhosis is often underestimated in healthcare and administrative databases that define disease burden using International Classification of Diseases (ICD) codes. This retrospective audit was conducted to explore the accuracy and limitations of the ICD, Tenth Revision, Australian Modification (ICD-10-AM) to detect NAFLD, metabolic risk factors (obesity and diabetes) and other aetiologies of chronic liver disease., Design/method: ICD-10-AM codes in 308 admitted patient encounters at two major Australian tertiary hospitals were compared with data abstracted from patients' electronic medical records. Accuracy of individual codes and grouped combinations was determined by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa coefficient (κ)., Results: The presence of an ICD-10-AM code accurately predicted the presence of NAFLD/NASH (PPV 91.2%) and obesity (PPV 91.6%) in most instances. However, codes underestimated the prevalence of NAFLD/NASH and obesity by 42.9% and 45.3%, respectively. Overall concordance between clinical documentation and 'grouped alcohol' codes (κ 0.75) and hepatitis C codes (κ 0.88) was high. Hepatitis B codes detected false-positive cases in patients with previous exposure (PPV 55.6%). Accuracy of codes to detect diabetes was excellent (sensitivity 95.8%; specificity 97.6%; PPV 94.9%; NPV 98.1%) with almost perfect concordance between codes and documentation in medical records (κ 0.93)., Conclusion: Recognition of the utility and limitations of ICD-10-AM codes to study the burden of NAFLD/NASH cirrhosis is imperative to inform public health strategies and appropriate investment of resources to manage this burgeoning chronic disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Conflicts of interest The authors have no competing interests to declare.

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., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Viral hepatitis, alcohol-related liver disease (ARLD) and nonalcoholic fatty liver disease (NAFLD) are the main risk factors for hepatocellular carcinoma (HCC) in many countries. In Australia, given the access to hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy since 2016, a temporal change in HCC aetiology was hypothesized. This study evaluated the temporal change in the aetiology and characteristics of HCC in New South Wales (NSW)., Methods: Patients diagnosed with HCC, admitted to three public hospitals in NSW between 2008 and 2021, were included in the analyses. We assessed the annual frequency of each HCC aetiology and the distribution of HCC characteristics in participants., Results: Among 1370 patients, the most common HCC etiologies were HCV (n = 483, 35%), ARLD (n = 452, 33%), NAFLD (n = 347, 25%) and hepatitis B virus (n = 301, 22%). The proportion of HCV-related HCC was the highest in 2011-2016 (41%) and significantly declined to 30% in 2017-2021 (odds ratio [OR], 0.53 [95% confidence interval (CI), 0.35-0.79]; P = 0.002). The proportion of HCC diagnosed at an early stage (Barcelona Clinic Liver Cancer stage O/A) increased from 41% in 2008-2009 to 56% in 2020-2021 (OR per annum, 1.05 [95% CI, 1.02-1.08]; P = 0.002), and the proportion of patients receiving potentially curative HCC management increased from 29% in 2008-2009 to 41% in 2020-2021 (OR per annum, 1.06 [95% CI, 1.03-1.10]; P < 0.001)., Conclusion: The contribution of HCV to HCC burden has been decreasing in the DAA era, suggesting the role of HCV elimination in decreasing HCC risk. Increasing frequency of less advanced HCC at diagnosis over time suggests improved HCC surveillance., (© 2023 Royal Australasian College of Physicians.)

Background: Non‐alcoholic fatty liver disease (NAFLD) is a major healthcare burden. Real‐world outcomes in dedicated tertiary care settings in Australia remain unknown. Aim: To evaluate the initial outcomes of patients referred to a dedicated multidisciplinary tertiary care NAFLD clinic. Methods: Retrospective review of all adult patients with NAFLD who attended a dedicated tertiary care NAFLD clinic between January 2018 and February 2020 and who had two clinic visits and FibroScans at least 12 months apart. Demographic and health‐related clinical and laboratory data were extracted from electronic medical records. Key outcome measures were serum liver chemistries, liver stiffness measurement (LSM) and weight control at 12 months. Results: A total of 137 patients with NAFLD were included. Median (interquartile range (IQR)) follow‐up time was 392 days (343–497 days). One hundred and eleven patients (81%) achieved weight control (i.e. weight loss or stability). Markers of liver disease activity were significantly improved, including median (IQR) serum alanine aminotransferase (48 (33–76) vs 41 (26–60) U/L, P = 0.009) and aspartate aminotransferase (35 (26–54) vs 32 (25–53) U/L, P = 0.020). Median (IQR) LSM across the whole cohort was significantly improved (8.4 (5.3–11.8) vs 7.0 (4.9–10.1) kPa, P = 0.001). No significant reduction was observed in mean body weight or the frequency of metabolic risk factors. Conclusions: This study highlights a new model of care for patients with NAFLD and demonstrates promising initial outcomes in relation to significant reductions in markers of liver disease severity. Although most patients achieved weight control, further refinements are needed to achieve significant weight reduction including more frequent and structured dietetic and/or pharmacotherapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is a well-established risk factor for cardiovascular disease, with ethnic and regional differences noted. With the recent surge of research within this field, we re-examine the evidence associating NAFLD with subclinical atherosclerosis, and investigate potential regional differences., Methods: This is a systematic review and meta-analysis. PubMed and EMBASE were systematically searched for publications from January 1967 to July 2020 using standardised criteria. Original, observational studies investigating the association between NAFLD and either carotid intima-media thickness (CIMT) and/or coronary artery calcification (CAC) were included. Key outcomes included differences in mean CIMT, the presence of increased CIMT, the presence of CAC and the development/progression of CAC. Pooled ORs and pooled standard differences in means were calculated using random-effects models. Between-study heterogeneity was quantified using the Q statistic and I². Subgroup analyses stratified by region of study (Asian vs Western) were also conducted., Results: 64 studies involving a total of 172 385 participants (67 404 with NAFLD) were included. 44 studies assessed the effect of NAFLD on CIMT, with the presence of NAFLD associated with increased CIMT (OR 2.00, 95% CI 1.56 to 2.56). 22 studies assessed the effects of NAFLD on CAC score, with the presence of NAFLD associated with the presence of any coronary calcification (OR 1.21, 95% CI 1.12 to 1.32), and the development/progression of CAC (OR 1.26, 95% CI 1.04 to 1.52). When stratified by region, these associations remained consistent across both Asian and Western populations (p>0.05). The majority (n=39) of studies were classified as 'high quality', with the remaining 25 of 'moderate quality'., Conclusions: There is a significant positive association between various measures of subclinical atherosclerosis and NAFLD, seen across both Western and Asian populations. These results re-emphasise the importance of early risk evaluation and prophylactic intervention measures to preclude progression to clinical cardiovascular disease in patients with NAFLD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) patients with diabetes are at increased risk of cirrhosis and liver-related death, and thus accurate fibrosis assessment in these patients is important. We examined the ability of non-invasive fibrosis models to determine cirrhosis and outcomes in NAFLD patients with and without diabetes., Methods: Non-alcoholic fatty liver disease patients diagnosed between 2006 and 2015 had Hepascore, NAFLD fibrosis score (NFS), APRI and FIB-4 scores calculated at baseline and were followed up for outcomes of overall and liver-related mortality/liver transplantation, hepatic decompensation and hepatocellular carcinoma (HCC). Model accuracy was determined by Harrell's C-index and by Kaplan-Meier analysis., Results: A total of 284 patients (53% diabetic, 15% cirrhotic) were followed up for a median of 51.4 months, (range 6.1-146). During follow-up, diabetic patients had a greater risk of liver-related death/transplantation, HR 3.4 (95% CI 1.2-9.1) decompensation, HR 4.7 (95% CI 2.0-11.3) and HCC, HR 2.9 (95% CI 1.2-7.3). Among 241 subjects with a baseline liver biopsy, the accuracy of Hepascore, APRI and FIB-4 for predicting cirrhosis was lower amongst diabetics compared to non-diabetics (P < .005 for all). Model accuracy apart from Hepascore, was also significantly lower for predicting liver death/transplantation in patients with diabetes. No patient with a low fibrosis score and without diabetes developed liver decompensation or HCC, whereas up to 21% of diabetic patients with a low fibrosis score developed liver decompensation and up to 27% developed HCC at 5 years., Conclusions: Non-invasive scoring systems are less accurate at predicting cirrhosis and liver-related outcomes in patients with NAFLD and diabetes., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Metabolic-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide, affecting 25% of people globally and up to 80% of people with obesity. MAFLD is characterised by fat accumulation in the liver (hepatic steatosis) with varying degrees of inflammation and fibrosis. MAFLD is strongly linked with cardiometabolic disease and lifestyle-related cancers, in addition to heightened liver-related morbidity and mortality. This position statement examines evidence for exercise in the management of MAFLD and describes the role of the exercise professional in the context of the multi-disciplinary care team. The purpose of these guidelines is to equip the exercise professional with a broad understanding of the pathophysiological underpinnings of MAFLD, how it is diagnosed and managed in clinical practice, and to provide evidence- and consensus-based recommendations for exercise therapy in MAFLD management. The majority of research evidence indicates that 150-240 min per week of at least moderate-intensity aerobic exercise can reduce hepatic steatosis by ~ 2-4% (absolute reduction), but as little as 135 min/week has been shown to be effective. While emerging evidence shows that high-intensity interval training (HIIT) approaches may provide comparable benefit on hepatic steatosis, there does not appear to be an intensity-dependent benefit, as long as the recommended exercise volume is achieved. This dose of exercise is likely to also reduce central adiposity, increase cardiorespiratory fitness and improve cardiometabolic health, irrespective of weight loss. Resistance training should be considered in addition to, and not instead of, aerobic exercise targets. The information in this statement is relevant and appropriate for people living with the condition historically termed non-alcoholic fatty liver disease (NAFLD), regardless of terminology., (© 2023. The Author(s).)

Background: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH)., Aims: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH., Methods: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m 2 , 64% male), NAFLD Activity Score 5 (range 3-7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85-95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined as ≥ 70% program completion and ≥ 70% global adherence (including session attendance, interval intensity adherence, and duration adherence) were assessed. Changes in cardiorespiratory fitness (V̇O 2 peak), exercise capacity (time-on-test) and peripheral insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed. Data were analysed using ANCOVA with baseline value as the covariate., Results: There were no HIIT-related adverse events and HIIT was globally feasible [program completion 75%, global adherence 100% (including adherence to session 95.4 ± 7.3%, interval intensity 95.3 ± 6.0% and duration 96.8 ± 2.4%)]. A large between-group effect was observed for exercise capacity [mean difference 134.2 s (95% CI 19.8, 248.6 s), ƞ 2 0.44, p = 0.03], improving in HIIT (106.2 ± 97.5 s) but not CON (- 33.4 ± 43.3 s), and for peripheral insulin sensitivity [mean difference 3.4 mg/KgLegFFM/min (95% CI 0.9,6.8 mg/KgLegFFM/min), ƞ 2 0.32, p = 0.046], improving in HIIT (1.0 ± 0.8 mg/KgLegFFM/min) but not CON (- 3.1 ± 1.2 mg/KgLegFFM/min)., Conclusions: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH., Clinical Trial Registration Number: Australian New Zealand Clinical Trial Registry (anzctr.org.au) identifier ACTRN12616000305426 (09/03/2016)., (© 2022. The Author(s).)

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in Australia and its recent increase mirrors the obesity and type 2 diabetes epidemics. Currently, many patients who present to primary care with abnormal liver function tests or steatosis on liver ultrasound are referred for assessment in secondary care. Due to the large number of patients with NAFLD, this results in long waits for clinical and fibrosis assessment, placing unnecessary burden on the public hospital system., Methods: We will conduct a 1:1 parallel randomised trial to compare two alternative models of care for NAFLD. Participants will be randomised to usual care or the LOCal Assessment and Triage Evaluation (LOCATE) model of care and followed for 1 year. We will recruit patients from the non-neighbouring Sunshine Coast and Metro South Hospital and Health Services (HHSs) in Queensland, Australia. Our primary outcome of interest is time to diagnosis of high-risk NAFLD, based on the number of participants in each arm of the study who receive a diagnosis of clinically significant fibrosis. Two hundred and 34 participants will give us a 95% power to detect a 50% reduction in the primary outcome of time to diagnosis of high-risk disease. We will also conduct an economic evaluation, evaluating the cost-effectiveness of the new model of care. We will also evaluate the implementation of the new model of care., Discussion: It is anticipated that the results of this study will provide valuable new information regarding the management of NAFLD in the Australian setting. A relatively simple change to care could result in earlier identification of patients with significant liver disease and lower overall costs for the health system. Results will be directly disseminated to key staff for further distribution to consumers, policy- and decision-makers in the form of evidence briefs, plain language summaries and policy recommendations., Trial Registration: The trial was registered on 30 January, 2020 and can be found via ANZCTR - number ACTRN12620000158965.

We aimed to compare the dietary intakes of Australian patients with non-alcoholic fatty liver disease (NAFLD) to general Australian population intake data and determine whether the intake of any nutrient or food group was able to predict the degree of steatosis. Dietary data from fifty adult patients with NAFLD were compared to intake data from the Australian Health Survey for energy, macronutrients, fat sub-types, alcohol, iron, folate, sugar, fibre, sodium and caffeine. Linear regression models adjusting for potential confounders (age, sex, physical activity and body mass index) were used to examine predictive relationships between hepatic steatosis (quantified via magnetic resonance spectroscopy) and dietary components. The mean percentage differences between NAFLD and Australian usual intakes were significant for energy, protein, total fat, saturated fat, monounsaturated and polyunsaturated fats (all p < 0.001). The contribution of fat and protein to total energy intake was significantly higher in the NAFLD cohort ( p < 0.05). No individual nutrients or food groups were strongly related to hepatic fat in the adjusted models. Higher overall consumption appears to be a major feature of dietary intake in NAFLD when compared to the general population. A whole-diet approach to NAFLD treatment and prevention is likely to be more effective than focusing on single food components.

The epidemiologic and demographical features of nonalcoholic fatty liver disease (NAFLD) vary significantly across countries and continents. In this review, we analyze current data regarding prevalence of NAFLD in Latin America and Caribbean and Australia and review some peculiarities found in these regions. We stress the need of greater awareness of NAFLD and the development of cost-effective risk stratification strategies and clinical care pathways of the disease. Finally, we highlight the need of effective public health policies to control the main risk factors for NAFLD., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aim: The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population., Method: Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period., Results: Three hundred and thirteen (313) newly diagnosed HCC patients with MAFLD (n = 77), MAFLD plus other liver disease (n = 57) (the "mixed" group), and non-MAFLD (n = 179) were included in the study. Alcohol-associated liver disease (ALD) (43%) and MAFLD (43%) were the most common underlying liver diseases. MAFLD-HCC patients were older (73 years vs 67 years vs 63 years), more likely to be female (40% vs 14% vs 20%), less likely to have cirrhosis (69% vs 88% vs 85%), showed higher ECOG, and were less likely to be identified by screening (29% vs 53% vs 45%). Metabolic syndrome was more prevalent in the MAFLD and mixed groups. The severity of underlying liver disease and HCC characteristics were the same across groups. While the MAFLD population self-reported more sedentary lifestyles, reported dietary patterns were no different across the groups. Dyslipidemia was associated with tumor size, and those taking statins had a lower recurrence rate., Conclusion: Equal to ALD, MAFLD is now the most common underlying liver disease seen in HCC patients in Australia. Future HCC prevention screening and treatment strategies need to take this important group of patients into consideration., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Low-level alcohol consumption is associated with reduced cardiovascular disease (CVD) in the general population. It is unclear whether this association is seen in patients with nonalcoholic fatty liver disease (NAFLD) who have an increased risk of CVD. We examined the association between alcohol consumption and CVD-related outcomes in subjects with NAFLD from a general population cohort. Subjects participating in the 1994-1995 Busselton Health survey underwent clinical and biochemical assessment. NAFLD was identified using the Fatty Liver Index of >60, and alcohol consumption quantified using a validated questionnaire. CVD hospitalizations and death during the ensuing 20 years were ascertained using the Western Australian data linkage system. A total of 659 of 4,843 patients were diagnosed with NAFLD. The average standard drinks per week was 8.0 for men and 4.0 for women. Men consuming 8-21 drinks per week had a 38% (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.43-0.90) lower risk of CVD hospitalization as compared with men consuming 1-7 drinks per week. With both men and women combined, consumption of 8-21 drinks per week was associated with a 32% (HR 0.68, 95% CI 0.49-0.93) reduction in CVD hospitalization in minimally adjusted and 29% (HR 0.71, 95% CI 0.51-0.99) in fully adjusted models. No protective association was observed with binge drinking. There was no association between alcohol consumption and CVD death. Conclusion: Low to moderate alcohol consumption is associated with fewer CVD hospitalizations but not CVD death in subjects with NAFLD., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Metabolic Associated Fatty Liver Disease (MAFLD) is the most common cause of liver disease in Australia, but prevalence data are limited. We aimed to describe the frequency of alanine aminotransferase (ALT) elevation, and MAFLD within a large prospective Australian cohort. Cross-sectional analysis of the 2012 survey of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study which included 4747 Australian adults (aged 34-97 yrs) was performed. Frequency of ALT elevation (men ≥ 40 IU/L, women ≥ 30 IU/L) and MAFLD (Fatty Liver Index (FLI) > 60 alongside metabolic risk factors) was determined and risk of advanced fibrosis stratified using the BARD score. Elevated ALT was found in 13% of the cohort, including 22% of people with diabetes, 18% with obesity, and 17% with the metabolic syndrome. 37% of the cohort had MAFLD, and those with MAFLD were more likely to be older (OR 1.01 per 1 year (95% CI 1.00-1.02)), male (OR 1.37 (95% CI 1.17-1.59)), have ALT elevation (OR 3.21 (95% CI 2.59-3.99)), diabetes (OR 3.39 (95% CI 2.61-4.39)), lower HDL-C (OR 0.15 per 1 mmol/L (95% CI 0.12-0.19)), higher diastolic blood pressure (OR 1.05 per 10 mmHg (95% CI 1.05-1.06)), a sedentary lifestyle (OR 1.99 (95% CI 1.59-2.50)) and less likely to have tertiary education (OR 0.81 (95% CI 0.7-0.94) compared to those without MAFLD. Of those with MAFLD, 61% had a BARD score suggesting risk of advanced fibrosis and 22% had an elevated ALT. Over 10% of this Australian cohort had elevated ALT, and 37% had MAFLD, with many at risk for advanced fibrosis., (© 2022. The Author(s).)

Background and Aims: Clinical and public health implications of the recent redefining of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD) remain unclear. We sought to determine the prevalence and compare MAFLD with NAFLD in a well-defined cohort., Methods: A cross-sectional study was conducted in regional Victoria with participants from randomly selected households. Demographic and health-related clinical and laboratory data were obtained. Fatty liver was defined as a fatty liver index ≥ 60 with MAFLD defined according to recent international expert consensus., Results: A total of 722 participants were included. Mean age was 59.3 ± 16 years, and 55.3% were women with a median body mass index of 27.8 kg/m 2 . Most (75.2%) participants were overweight or obese. MAFLD was present in 341 participants giving an unadjusted prevalence of 47.2% compared with a NAFLD prevalence of 38.7%. Fifty-nine (17.5%) participants met the criteria of MAFLD but not NAFLD. The increased prevalence of MAFLD in this cohort was primarily driven by dual etiology of fatty liver. All participants classified as NAFLD met the new definition of MAFLD. Compared with NAFLD subjects, participants with MAFLD had higher ALT (26.0 [14.0] U/L vs 30.0 [23] U/L, P = 0.024), but there were no differences in non-invasive markers for steatosis or fibrosis., Conclusion: Metabolic-associated fatty liver disease is a highly prevalent condition within this large community cohort. Application of the MAFLD definition increased prevalence of fatty liver disease by including people with dual etiologies of liver disease., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common conditions with a rising burden. Yet there are significant management gaps between clinical guidelines and practice in patients with NAFLD and NASH. Further, there is no single global guiding strategy for the management of NAFLD and NASH. The American Gastroenterological Association, in collaboration with 7 professional associations, convened an international conference comprising 32 experts in gastroenterology, hepatology, endocrinology, and primary care providers from the United States, Europe, Asia, and Australia. Conference content was informed by the results of a national NASH Needs Assessment Survey. The participants reviewed and discussed published literature on global burden, screening, risk stratification, diagnosis, and management of individuals with NAFLD, including those with NASH. Participants identified promising approaches for clinical practice and prepared a comprehensive, unified strategy for primary care providers and relevant specialists encompassing the full spectrum of NAFLD/NASH care. They also identified specific high-yield targets for clinical research and called for a unified, international public health response to NAFLD and NASH., (© 2021 by the AGA Institute, the American Diabetes Association, Elsevier, and The Obesity Society.)

Study Question: Is the cardiometabolic health of adolescents conceived through ART worse than that of their counterparts conceived without ART?, Summary Answer: The majority of cardiometabolic and vascular health parameters of adolescents conceived through ART are similar or more favourable, than those of their counterparts of similar age and conceived without ART., What Is Known Already: It has been proposed that the cardiometabolic health of offspring conceived with ART may be unfavourable compared to that of their counterparts conceived without ART. The literature pertaining to cardiometabolic health of offspring conceived after ART is contradictory, but generally suggests unfavourable cardiometabolic health parameters, such as an increase in blood pressure (BP), vascular dysfunction and adiposity, as well as unfavourable glucose and lipid profiles. With over 8 million children and adults born through ART worldwide, it is important to investigate whether these early signs of adverse cardiometabolic differences persist into adolescence and beyond., Study Design, Size, Duration: The Growing Up Healthy Study (GUHS) is a prospective cohort study that recruited 303 adolescents and young adults conceived after ART (aged 13-21 years) and born between 1991 and 2001 in Western Australia. Their health parameters, including cardiometabolic factors, were assessed and compared with counterparts from the Raine Study Generation 2 (Gen2). The 2868 Gen2 participants were born 1989-1992 and are representative of the Western Australian adolescent population. At ∼17 years of age (2013-2017), 163 GUHS participants replicated assessments previously completed by Gen2 at a similar age., Participants/materials, Setting, Methods: Cardiometabolic parameters were compared between a total of 163 GUHS and 1457 Gen2 adolescents. Separate male (GUHS n = 81, Gen2 n = 735) and female (GUHS n = 82, Gen2 n = 722) analyses were conducted. Assessments consisted of a detailed questionnaire including health, lifestyle and demographic parameters, anthropometric assessments (height, weight, BMI, waist circumference and skinfold thickness), fasting serum biochemistry, arterial stiffness and BP (assessed using applanation tonometry). Abdominal ultrasonography was used to assess the presence and severity of hepatic steatosis, and thickness of abdominal fat compartments. Non-alcoholic fatty liver disease (NAFLD) was diagnosed if there was sonographic fatty liver in the absence of significant alcohol consumption. Chi2, Fisher's exact and Mann-Whitney U tests, performed in SPSS V25, examined cohort differences and generalized estimating equations adjusted for the following covariates: singleton vs non-singleton pregnancy, birthweight (z-score), gestational age, BMI, smoking, alcohol consumption in the past 6 months and parent cardiovascular status. Arterial stiffness measures and waist circumference were additionally adjusted for height, and female analyses were additionally adjusted for use of oral contraceptives in the preceding 6 months., Main Results and the Role of Chance: In adjusted analyses, GUHS females had a lower BMI (22.1 vs 23.3 kg/m2, P = 0.014), and thinner skinfolds (triceps, subscapular, mid-abdominal; 16.9 vs 18.7 mm, P = 0.021, 13.4 vs 15.0 mm, P = 0.027, 19.7 vs 23.2 mm, P < 0.001, respectively), whereas males were not significantly different. Waist circumference was lower in GUHS adolescents (males: 78.1 vs 81.3 cm, P = 0.008, females: 76.7 vs 83.3 cm, P = 0.007). There were no significant differences between the two groups in glucose, insulin, homeostatic model assessment for insulin resistance, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), alanine aminotransferase and high-sensitivity C-reactive protein in both sexes. In females, serum triglycerides were lower in GUHS adolescents (1.0 vs 1.2 mmol/l, P = 0.029). GUHS males had higher serum HDL-C (1.1 vs 1.0 mmol/l, P = 0.004) and a lower TC/HDL-C ratio (3.2 vs 3.6, P = 0.036). There were no significant differences in the prevalence of NAFLD or steatosis severity scores between the cohorts in males and females. GUHS females had less subcutaneous adipose tissue (9.4 vs 17.9 mm, P < 0.001), whereas GUHS males had greater visceral adipose thickness (44.7 vs 36.3 mm, P < 0.001). There was no significant difference in pre-peritoneal adipose thickness. Pulse wave velocity was lower in GUHS males (5.8 vs 6.3 m/s, P < 0.001) and heart rate corrected augmentation index was lower in GUHS females (-8.4 vs -2.7%, P = 0.048). There were no significant differences in BP or heart rate in males or females between the two groups., Limitations, Reasons for Caution: Despite the substantial study size and the unique study design of the ART cohort, we were unable to differentiate between different types of ART, due to the low number of ICSI cycles (e.g. IVF vs ICSI), draw definite conclusions, or relate the outcomes to the cause of infertility. Considering the differences in time points when both cohorts were studied, external factors could have changed, which could not be accounted for. Given the observational nature of this study, causation cannot be proven., Wider Implications of the Findings: Contrary to our hypothesis and previous findings focussing mainly on childhood, this study reports mostly similar or favourable cardiometabolic markers in adolescents conceived with ART compared to those conceived without ART. The greater visceral adipose thickness, particularly present in males, requires further investigation. While these findings are generally reassuring, future well-designed and appropriately powered studies are required to definitively address the issue of cardiometabolic health in ART adults., Study Funding/competing Interest(s): This project was supported by NHMRC project grant number 1042269 and R.J.H. received education grant funding support from Ferring Pharmaceuticals. R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director of PIVET Medical Centre, Perth, Western Australia., Trial Registration Number: N/A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Metabolic (dysfunction) associated fatty liver disease (MAFLD; previously non-alcoholic fatty liver disease [NAFLD]) affects one in four Australian adults and many children. The disease is a consequence of poor metabolic health resulting from lifestyle choices., Objective: The aim of this article is to outline recent advances in MAFLD pathophysiology, diagnosis and management., Discussion: All patients with evidence of metabolic dysregulation are at risk of MAFLD. Diagnosis requires fulfillment of the new diagnostic criteria for MAFLD. Most patients with MAFLD die as a result of cardiovascular disease or extrahepatic cancer, but liver-related outcomes including cancer can develop, especially in those with more advanced stages of fibrosis. There is no approved medication therapy for MAFLD, and so management focuses on lifestyle intervention, diabetes control, treatment to target of risk factors such as dyslipidaemia, and avoidance of smoking and alcohol. Most patients with MAFLD are best managed in primary care.

Background: Liver biopsy remains the gold standard for characterizing and evaluating treatment response in nonalcoholic fatty liver disease (NAFLD). Liver heterogeneity and sampling variability can affect the reliability of results. This study aimed to compare histological variability of intraoperative wedge and core liver biopsies from different lobes in bariatric patients, to better inform surgeons on biopsy method and guide interpretation of results., Methods: We prospectively recruited bariatric surgical patients. Intraoperative core biopsies were taken from the left and right lobe, with a wedge biopsy taken from the left. All biopsies were graded by a specialist liver pathologist, blinded to clinical details and biopsy site. Concordance of histological findings between sites was evaluated., Results: There were 91 participants (72.2% female), mean age 46.8 ± 12.0 years, body mass index 45.9 ± 9.4 kg/m 2 . There was no significant pattern for up- or down-grading disease dependent on biopsy technique. Moderate to strong agreement was seen in the presence of NAFLD and nonalcoholic steatohepatitis (NASH, κ = 0.609-0.865, p < 0.001) between biopsy sites. Individual components (steatosis, inflammation, ballooning) showed weaker agreement (κ = 0.386-0.656, p < 0.01). Fibrosis showed particularly poor agreement (κ = 0.223-0.496, p < 0.01). Detection of pathology improved with a combination of biopsy techniques, compared to a single biopsy method., Conclusion: Overall diagnosis of NAFLD or NASH shows good agreement between biopsy sites, but individual components, particularly fibrosis stage, vary significantly. Clinicians should consider biopsies from varied sites, to better assess liver disease severity. These data have important implications in fibrosis assessment of NAFLD and are relevant in the interpretation of histological efficacy of investigational pharmacotherapies., Trial Registration: ACTRN12615000875505 (Australian Clinical Trials Register).

Aims: Metabolic associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease and has been increasingly associated with gestational diabetes (GDM). This study aimed to assess the prevalence of MAFLD in women with GDM in the antenatal period., Methods: 108 pregnant women with GDM diagnosed on a 75-gram oral glucose tolerance test were enrolled from a multiethnic cohort attending a large obstetrics clinic in Sydney, Australia and had a single FibroScan® assessment after 24 weeks gestation to assess for hepatic steatosis and fibrosis. A control attenuated parameter (CAP) cut-off score of ≥ 233.5 dB/m was chosen to signify presence of hepatic steatosis which indicates MAFLD. Obstetric, anthropometric and metabolic measures were analysed., Results: 29 (26.9%) women had evidence of FibroScan®-detected MAFLD, whilst none had evidence of hepatic fibrosis. Increased maternal BMI (aOR 1.12, 95% CI: 1.04-1.20) was associated with the finding of MAFLD in this cohort., Conclusions: We found a significant antenatal prevalence of FibroScan®-detected MAFLD in this cohort of multiethnic women with GDM. FibroScan® is a safe and rapid assessment tool which may have a role in screening for MAFLD in pregnancy in appropriate at-risk women., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (© 2020 Royal Australasian College of Physicians.)

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a large and growing proportion of liver disease burden globally. The burden of NAFLD/NASH manifests in increasing levels of advanced liver disease and primary liver cancer in Australia. A Markov model was used to forecast NAFLD burden in Australia through 2030., Methods: A model was used to estimate fibrosis progression, primary liver cancer, and liver deaths among the Australian NAFLD population, with changes in incident NAFLD cases based on long-term trends for changes in the prevalence of obesity. Published estimates and surveillance data were applied to build and validate the model projections, including surveillance data for the incidence of liver cancer., Results: Prevalent NAFLD cases were projected to increase 25% from the current burden (5 551 000 [4 748 000-6 306 000] cases in 2019) to 7 024 000 [5 838 000-7 886 000] cases in 2030. The projected increase in the number of NASH cases (40%) was greater than that of NAFLD cases. Incident cases of advanced liver disease are projected to increase up to 85% by 2030, and incident NAFLD liver deaths are estimated to increase 85% from 1900 (1100-3300) deaths in 2019 to 3500 (2100-6100) deaths in 2030., Conclusions: Restraining growth of the obese and diabetic populations, along with potential therapeutic options, will be essential for mitigating disease burden., (© 2020 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) reaches up to 30% in the Asian adult population, with a higher prevalence in obese patients. Weight reduction is typically recommended for patients at high risk or diagnosed with NAFLD, but is a challenge to achieve., Objective: We aimed to evaluate the effect of a lifestyle intervention with a mobile app on weight loss in NAFLD patients., Methods: This prospective randomized controlled trial included 108 adults with NAFLD confirmed by steatosis on ultrasound and a body mass index ≥23 kg/m 2 who were recruited from a fatty liver outpatient clinic. The patients were randomly allocated to either a control group (n=53) receiving standard care, consisting of dietary and lifestyle advice by a trained nurse, or an intervention group (n=55) utilizing the Nutritionist Buddy (nBuddy) mobile app in addition to receiving dietary and lifestyle advice by a dietitian. Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST), waist circumference, and blood pressure were measured at baseline, and then at 3 and 6 months. Intention-to-treat and per-protocol analyses were used for statistical comparisons., Results: The intervention group had a 5-fold higher likelihood (relative risk 5.2, P=.003, 95% CI 1.8-15.4) of achieving ≥5% weight loss compared to the control group at 6 months. The intervention group also showed greater reductions in weight (mean 3.2, SD 4.1 kg vs mean 0.5, SD 2.9 kg; P<.001), waist circumference (mean 2.9, SD 5.0 cm vs mean -0.7, SD 4.4 cm; P<.001), systolic blood pressure (mean 12.4, SD 14.8 mmHg vs mean 2.4, SD 12.4 mmHg; P=.003), diastolic blood pressure (mean 6.8, SD 8.9 mmHg vs mean -0.9, SD 10.0 mmHg; P=.001), ALT (mean 33.5, SD 40.4 IU/L vs mean 11.5, SD 35.2 IU/L; P=.004), and AST (mean 17.4, SD 27.5 U/L vs mean 7.4, SD 17.6 IU/L, P=.03) at 6 months., Conclusions: Lifestyle intervention enabled by a mobile app can be effective in improving anthropometric indices and liver enzymes in patients with NAFLD. This treatment modality has the potential to be extended to a larger population scale., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12617001001381; https://tinyurl.com/w9xnfmp., (©Su Lin Lim, Jolyn Johal, Kai Wen Ong, Chad Yixian Han, Yiong Huak Chan, Yin Mei Lee, Wai Mun Loo. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 13.04.2020.)

Background & Aims: Irisin, the cleaved extra-cellular fragment of the Fibronectin type III domain-containing protein 5 (FNDC5) is a myokine that is proposed to have favorable metabolic activity. We aimed to elucidate the currently undefined role of variants in the FNDC5 gene in non-alcoholic fatty liver disease (NAFLD)., Methods: We prioritized single nucleotide polymorphisms in FNDC5 on the basis of their putative biological function and identified rs3480 in the 3' untranslated region (3'UTR). We studied the association of rs3480 with liver disease severity and the metabolic profile of 987 Caucasian patients with NAFLD. Functional investigations were undertaken using luciferase reporter assays of the 3'UTR of human FNDC5, pyrosequencing for allele-specific expression of FNDC5 in liver, measurement of serum irisin, and bioinformatics analysis., Results: The rs3480 (G) allele was associated with advanced steatosis (OR 1.29; 95% CI 1.08-1.55; p = 0.004), but not with other histological features. This effect was independent but additive to PNPLA3 and TM6SF2. The rs3480 polymorphism influenced FNDC5 mRNA stability and the binding of miR-135a-5P. Compared with controls, hepatic expression of this microRNA was upregulated while FNDC5 expression was downregulated. Elevated serum irisin was associated with reduced steatosis, and an improved metabolic profile., Conclusions: Carriage of the FNDC5 rs3480 minor (G) allele is associated with more severe steatosis in NAFLD through a microRNA-mediated mechanism controlling FNDC5 mRNA stability. Irisin is likely to have a favorable metabolic impact on NAFLD., Lay Summary: Irisin is a novel protein produced mainly by muscle, which is known to be released into the circulation, with an unclear role in liver fat deposition. This study demonstrates that genetic variants in the gene encoding the irisin protein modulate the risk of liver fat in patients with fatty liver disease. Interestingly, these effects are independent of, but additive to those of other recently described genetic variants that contribute to liver fat. In functional studies, we have deciphered the detailed molecular mechanisms by which this genetic variant mediates its effects., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Substantial evidence supports the effect of the Mediterranean Diet (MD) for managing chronic diseases, although trials have been primarily conducted in Mediterranean populations. The efficacy and feasibility of the Mediterranean dietary pattern for the management of chronic diseases has not been extensively evaluated in non-Mediterranean settings. This paper aims to describe the development of a MD model that complies with principles of the traditional MD applied in a multiethnic context. Optimal macronutrient and food-based composition was defined, and a two-week menu was devised incorporating traditional ingredients with evidence based on improvements in chronic disease management. Strategies were developed for the implementation of the diet model in a multiethnic population. Consistent with the principles of a traditional MD, the MD model was plant-based and high in dietary fat, predominantly monounsaturated fatty acids from extra virgin olive oil. Fruits, vegetables and wholegrains were a mainstay, and moderate amounts of nuts and seeds, fish, dairy and red wine were recommended. The diet encompassed key features of the MD including cuisine, biodiversity and sustainability. The MD model preserved traditional dietary components likely to elicit health benefits for individuals with chronic diseases, even with the adaptation to an Australian multiethnic population., Competing Interests: The authors declare no conflict of interest.

Background: Non‐alcoholic fatty liver disease (NAFLD) is the most common liver disease globally, with increased rates in high‐risk populations, including type 2 diabetes and obesity. The condition increases the risk of end‐stage liver disease, hepatocellular carcinoma and all‐cause mortality. NAFLD is asymptomatic and often remains undiagnosed as routine screening in high‐risk groups is not practised. Aims: The aim of this study was to determine the rates and characteristics of NAFLD patients attending liver clinics at two Melbourne metropolitan hospitals. Methods: Liver clinics were prospectively screened for 10 consecutive months and participants with a diagnosis of NAFLD were further evaluated using pathology and imaging results obtained from medical records. Results: Of the 2050 patients screened, 148 (7%) had NAFLD predominantly diagnosed using ultrasound (81%). NAFLD patients were obese (mean body mass index 30.7 ± 5.9 kg/m2), insulin resistant (median HOMA 4.2 (3.2) mmol/L) and had elevated liver enzymes (ALT median, males 47.0 (34.3), females 36.0 (28.0) U/L), and 18% of patients had liver stiffness measuring >12 kPa, suggesting a moderate probability of cirrhosis. Patients with liver stiffness measuring ≥9.6 kPa had significantly higher: glucose (median 5.5 (1.2) vs 6.2 (5.3) mmol/L, P = 0.007), aspartate aminotransferase levels (median 25.5 (26.0) vs 41.0 (62.0) u/L, P = 0.0005) and HOMA (3.1 (3.0) vs 5.4 (5.5) mmol/L, P = 0.040). Conclusions: NAFLD constituted a minority of liver clinic patients, most of who were obese, insulin resistant and hypertensive, and many had an elevated liver stiffness measurement. NAFLD poses added adverse health outcomes to high‐risk patients, and therefore, early detection is warranted. [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 Aim: Liver cirrhosis is the primary risk factor for the development of hepatocellular carcinoma. Most conditions that lead to cirrhosis are treatable, or modifiable. Therefore, a community‐based screening program targeting high‐risk groups was designed for early diagnosis and intervention of liver disease, to offset the rising burden of hepatocellular carcinoma in Australia. Methods: Two nurse consultants from a tertiary liver center performed community screening of pre‐identified cohorts at risk of viral hepatitis and chronic liver disease, with transient elastography and/or serology testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), in addition to standard blood tests. A positive screening result was defined as any of the following: liver stiffness measurement (LSM) ≥ 9.5 kPa, positive HCV RNA, or positive HBV surface antigen. Individuals who screened positive were linked to the liver center for management. Results: Nine hundred and twenty‐six subjects were screened over a 6‐year period, of which 122/926 (13.2%) had evidence of chronic liver disease. Chronic viral hepatitis was diagnosed in 91 participants (HBV = 23, HCV = 67, and co‐infection = 1), while non‐alcoholic fatty liver disease was diagnosed in 14 participants. Advanced fibrosis (LSM ≥ 9.5 kPa) was detected in 42/866 (4.9%) subjects with available LSM. Loss to follow‐up occurred in 36/91 (39.6%) participants with chronic viral hepatitis. Conclusions: Targeting high‐risk populations for community screening and intervention increases early identification of chronic liver disease. This may reduce the incidence of liver cirrhosis and hepatocellular carcinoma. Loss to follow‐up remains an ongoing challenge, requiring better strategies. [ABSTRACT FROM AUTHOR]

The worldwide increase in obesity and diabetes has led to predictions that nonalcoholic steatohepatitis (NASH) will become the leading indication for orthotopic liver transplantation (OLT). Data supporting this prediction from outside the United States are limited. Thus, we aimed to determine trends in the frequency of NASH among adults listed and undergoing OLT in Australia and New Zealand (ANZ) from 1994 to 2017. Data from the ANZ Liver Transplant Registry were analyzed with patients listed for fulminant liver failure, retransplantation, or multivisceral transplants excluded. Nonparametric trend, Spearman rank correlation, and regression analysis were used to assess trends in etiologies of liver disease over time. Of 5016 patient wait-list registrants, a total of 3470 received an OLT. The percentage of patients with NASH activated for OLT increased significantly from 2.0% in 2003 to 10.9% in 2017 (trend analyses; P < 0.001). In 2017, NASH was the third leading cause of chronic liver disease (CLD) among wait-list registrants behind chronic hepatitis C virus (HCV; 29.5%) and alcohol (16.1%). Similarly, significant increases over time in the percentage of patients undergoing OLT were observed for HCV and NASH (all trend analyses; P < 0.001) but with significant reductions in primary sclerosing cholangitis and cryptogenic cirrhosis (both P < 0.05). By 2017, NASH was the third leading cause of liver disease among patients undergoing OLT (12.4%) and behind chronic HCV (30.2%) and alcohol (18.2%). NASH also became the third most frequent etiology of CLD in patients transplanted (13.8%) with concomitant hepatocellular carcinoma by 2017. In conclusion, NASH is increasing as a primary etiology of liver disease requiring listing and liver transplantation in ANZ., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

Aims: Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms., Methods: Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5years., Results: Over 5years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001. Conversely, GGT >70U/L, compared with GGT ≤70U/L, had HR 1.82 (1.48-2.24), p<0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP., Conclusions: As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The epidemiology of chronic liver disease is changing with the introduction of potent antiviral therapies for chronic hepatitis C virus (HCV) and the increasing prevalence of non‐alcoholic steatohepatitis (NASH). Aim: To establish the impact of this change on the rates and clinical patterns of hepatocellular carcinoma (HCC) in South Australia (SA). Methods: Newly diagnosed HCC patients from January 2014 until December 2019 from four tertiary centres in SA were included. The overall age‐standardised incidence rates (ASIR) of HCC were calculated using 2016 SA population as the standard. To assess the trends, Join‐Point regression models were used to calculate the average annual percentage change (AAPC). Forecasting of overall and aetiology‐specific HCC from 2020 to 2024 was performed using linear regression. Results: There were 626 new cases of HCC in SA (males 80%; median age 64 years) during the study period. There was a significant increase in NASH‐related HCC (AAPC: +7.0%; P < 0.05) from 2014 to 2019. However, there were no significant differences in the ASIR for overall HCC (AAPC: −4.1%), HCV‐related HCC (AAPC: −8.0%) and stage of HCC diagnosis (AAPC: +3.0%; P > 0.05). Forecasting analysis projected the decline and increase in the incidence of HCV and NASH‐related HCC, respectively, over the next few years. Conclusion: Overall ASIR of HCC has plateaued in SA. However, NASH‐related HCC has increased significantly and is expected to continue to increase in the near future. Further research and intervention is required to reduce NASH‐related HCC, a major contributor to the current and future burden of HCC. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common conditions with a rising burden. Yet there are significant management gaps between clinical guidelines and practice in patients with NAFLD and NASH. Further, there is no single global guiding strategy for the management of NAFLD and NASH. The American Gastroenterological Association, in collaboration with 7 professional associations, convened an international conference comprising 32 experts in gastroenterology, hepatology, endocrinology, and primary care providers from the United States, Europe, Asia, and Australia. Conference content was informed by the results of a national NASH Needs Assessment Survey. The participants reviewed and discussed published literature on global burden, screening, risk stratification, diagnosis, and management of individuals with NAFLD, including those with NASH. Participants identified promising approaches for clinical practice and prepared a comprehensive, unified strategy for primary care providers and relevant specialists encompassing the full spectrum of NAFLD/NASH care. They also identified specific high-yield targets for clinical research and called for a unified, international public health response to NAFLD and NASH. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Surveillance for HCC in at-risk populations allows diagnosis at an early stage, when potentially curable. However, most Australians diagnosed with HCC die of the cancer or of liver disease. In the changing landscape of HCC management, unique challenges may lead to clinical practice variation. As a result, there is a need to identify best practice management of HCC in an Australian context. This consensus statement has been developed for health professionals involved in the care of adult patients with HCC in Australia. It is applicable to specialists, general medical practitioners, nurses, health coordinators and hospital administrators., Methods and Recommendations: This statement has been developed by specialists in hepatology, radiology, surgery, oncology, palliative care, and primary care, including medical practitioners and nurses. The statement addresses four main areas relevant to HCC management: epidemiology and incidence, diagnosis, treatment, and patient management. A modified Delphi process was used to reach consensus on 31 recommendations. Principal recommendations include the adoption of surveillance strategies, use of multidisciplinary meetings, diagnosis, treatment options and patient management., Changes in Management as a Result of This Statement: This consensus statement will simplify HCC patient management and reduce clinical variation. Ultimately, this should result in better outcomes for patients with HCC., (© 2020 AMPCo Pty Ltd.)

Background: Non-alcoholic fatty liver disease, the most prevalent liver disease in developed countries, remains difficult to manage with no proven safe and effective pharmacotherapy available. While weight reduction is the most commonly practiced treatment strategy, this is difficult to both achieve and/or maintain in the majority. Furthermore evidence-based dietary recommendations to guide the nutritional management of these patients are lacking. Using a randomised controlled trial design, this study compares the effectiveness of the Mediterranean diet to a standard low fat diet in terms of differences in insulin sensitivity, hepatic steatosis and metabolic outcomes in participants with non-alcoholic fatty liver disease.Methods: Ninety four eligible patients who have non-alcoholic fatty liver disease and who are insulin resistant, will be randomised into either a Mediterranean or low fat diet group for a 3 month intervention period. Insulin sensitivity will be measured on peripheral blood using Homeostatic Model Assessment and liver fat content quantified using Magnetic Resonance Spectroscopy. Both arms will consist of three face to face and three telephone call follow up consultations delivered by an Accredited Practicing Dietitian. The intervention arm focuses on recommendations from the traditional Mediterranean diet which have been tailored for use in the Australian population The standard arm uses the Australian Guide to Healthy Eating and the Australian National Heart Foundation dietary guidelines. Study recruitment will take place at four major metropolitan hospitals in Melbourne, Australia. Data collection will occur at all face to face reviews including baseline, 6, and 12 weeks. A follow up assessment to measure sustainability will take place at 6 and 12 months. The primary end point is improved insulin sensitivity scores at the 12 week time point.Discussion: This trial aims to demonstrate in a large cohort of participants with NALFD that a Mediterranean diet independent of weight loss can result in significant benefits in liver fat and insulin sensitivity and that these changes are sustained at 12 months. These metabolic changes would potentially lead to reductions in the risk of chronic liver disease, heart disease, type 2 diabetes and liver cancer.Trial Registration: Australia and New Zealand Clinical Trials RegisterActrn: ACTRN12615001010583 . [ABSTRACT FROM AUTHOR]

Clinical Cases in Hepatitis 2018 was an interactive educational program for Australian physicians (gastroenterologists, hepatologists, and infectious disease specialists) actively involved in the treatment of liver diseases including hepatitis C virus, hepatitis B virus, and non-alcoholic steatohepatitis. This educational program sponsored by Gilead Sciences took place on October 12-13, 2018, and provided timely, informative case-based, and practical education to Australian physicians. This report summarizes keynote lectures from international leaders in the field of hepatitis C virus, hepatitis B virus, and non-alcoholic steatohepatitis and practical clinical case studies designed to inform and educate Australian physicians on managing challenging patients., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: It has recently been shown that neighbourhood socioeconomic disadvantage in childhood is associated with obesity, hypertension, fatty liver, and type 2 diabetes in adulthood. However, it is largely unknown whether neighbourhood socioeconomic circumstances are important predictors of adiposity and associated measures in children, especially in those with severe obesity. Therefore, we evaluated the associations between neighbourhood socioeconomic factors with the severity of obesity, and related cardiometabolic risk factors in a cohort of obese children., Methods: The Childhood Overweight BioRepository of Australia (COBRA) cohort study comprises 444 children (mean age 11.1years, mean BMI z-score 2.5). Neighbourhood socioeconomic advantage/disadvantage was evaluated based on postcode information by the national Australian Socio-Economic Indexes for Areas (SEIFA) scores. Participants/parents also completed self-administered questionnaires on neighbourhood related facilities, family education and family income., Results: In analyses adjusted for age, sex and pubertal status, SEIFA indicating neighbourhood education/occupation was negatively associated with BMI, waist circumference and body fat%. Higher family education was associated with lower BMI. Neighbourhood walkability was related to lower waist circumference. Good shopping facilities in the neighbourhood were associated with increased risk of dyslipidemia and fatty liver, and the existence of parks and playgrounds nearby was related to dyslipidemia., Conclusions: The present data suggest that neighbourhood-related issues are associated with less severe adiposity among children with established obesity. Concerning cardiometabolic risk factors, shopping facilities were related to dyslipidemia and fatty liver. These findings suggest that increased awareness and efforts are needed to diminish socioeconomic inequalities between neighbourhoods., (Copyright © 2019 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD), encompassing both simple steatosis and non-alcoholic steato-hepatitis (NASH), is the most common cause of liver disease in Australia. Non-alcoholic fatty liver disease needs to be considered in the context of the metabolic syndrome, as cardiovascular disease will account for much of the mortality associated with NAFLD., Objective: To provide an approach to the identification of NAFLD in general practice, the distinction between simple steatosis and NASH, and the management of these two conditions., Discussion: Non-alcoholic steato-hepatitis is more common in the presence of diabetes, obesity, older age and increased inflammation, and is more likely to progress to cirrhosis. Cirrhosis may be complicated by hepatocellular carcinoma or liver failure. Hepatocellular carcinoma has also been described in NASH without cirrhosis. Assessment and treatment of features of the metabolic syndrome may reduce associated cardiovascular mortality. Numerous agents have been evaluated, but weight loss remains the only effective treatment for NAFLD.

Unlabelled: Information on the long-term prognosis of nonalcoholic fatty liver disease (NAFLD) is limited. We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis by prospectively studying 247 such patients from four international centers (in Australia, USA, UK and Italy). Their natural history was then compared with 264 patients with HCV infection who were either naïve or non-responders to treatment. Both cohorts were Child-Pugh class A and had advanced fibrosis (stage 3) or cirrhosis (stage 4) confirmed by liver biopsy at enrollment. In the NAFLD cohort, followed up for a mean of 85.6 months (range, 6-297), there were 48 (19.4%) liver-related complications and 33 (13.4%) deaths or liver transplants. In the HCV cohort, followed up for 74.9 months (mean; range, 6-238), there were 47 (16.7%) liver-related complications and 25 (9.4%) deaths or liver transplants. When adjusting for baseline differences in age and gender, the cumulative incidence of liver-related complications was lower in the NAFLD than the HCV cohort (P = 0.03), including incident hepatocellular cancer (6 versus 18; P = 0.03), but that of cardiovascular events (P = 0.17) and overall mortality (P = 0.6) were similar in both groups. In the NAFLD cohort, platelet count, stage 4 fibrosis, lowered platelet count, and lowered serum cholesterol and alanine aminotransferase (ALT) levels were associated with liver-related complications; an aspartate aminotransferase/ALT ratio >1 and older age were associated with overall mortality, and higher serum bilirubin levels and stage 4 fibrosis were associated with liver-related mortality., Conclusions: Patients with NAFLD with advanced fibrosis or cirrhosis have lower rates of liver-related complications and hepatocellular cancer than corresponding patients with HCV infection, but similar overall mortality. Some clinical and laboratory features predict liver-related complications and other outcomes in patients with NAFLD., (Copyright © 2011 American Association for the Study of Liver Diseases.)