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 of cirrhotic patients with infections in Australian and New Zealand ICUs between 2005 and 2017.

BACKGROUND & AIMS: Changes in outcomes of cirrhotic patients admitted to intensive care units (ICUs) with infections are poorly understood. We aimed to describe changes over time in outcomes for such patients and to compare them to other ICU admissions. METHODS: Analysis of consecutive admissions to 188 ICUs between 2005 and 2017 as recorded in the Australian and New Zealand Intensive Care Society Centre for Outcome and Research Evaluation Adult Patient Database. RESULTS: Admissions for cirrhotic patients with infections accounted for 4645 (0.6%) of 813 189 non-elective ICU admissions. Hospital mortality rate (35.5%) was significantly higher compared with other cirrhotic patients' admissions (28.5%), and other ICU admissions for infection (17.1%, p < .0001), and increased to 52.2% in the presence of acute-on-chronic liver failure (ACLF). Hospital mortality in cirrhotic patients' ICU admissions for infection decreased significantly over time (annual decline odds ratio, 0.97; 95% CI, 0.95-0.99, p = .002). There was a comparable reduction in-hospital mortality rates over time in other ICU admissions for infections and other cirrhotic patients' ICU admissions. However, mortality rates did not change over time in the ACLF subgroup. Median hospital and ICU length of stays for cirrhotic patients' ICU admissions for infections were 12.1 and 3.5 days, respectively, and decreased significantly by 1 day every 4 years in-hospital survivors(p < .0001). CONCLUSION: Hospital mortality in ICU admissions for cirrhotic patients with infection is double that of non-cirrhotic patients with infection but has declined significantly over time. Outcomes in the subgroup with ACLF remained poor without significant improvement over the study period.

Liver stiffness (Fibroscan®) is a predictor of all-cause mortality in people with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Progressive liver fibrosis related to non-alcoholic fatty liver disease (NAFLD) is associated with all-cause and liver-related mortality. We assessed vibration-controlled transient elastography (VCTE) as a predictor of mortality. METHOD: Data from patients who underwent VCTE for NAFLD at four large health services in Victoria, Australia between the years 2008 and 2019 were linked to state-wide data registries. Cause of death (COD) and predictors of all-cause mortality were subsequently analysed using descriptive statistics and Cox-proportional regression analysis. RESULTS: Of 7079 VCTE records submitted for data linkage, 6341 were matched via data registry linkage. There were 217 deaths over a 22 653 person-year follow-up. COD included malignancies other than hepatocellular carcinoma (HCC) (18.0%, n = 39), sepsis (16.1%, n = 35), decompensated liver disease (15.2%, n = 33), cardiac disease (15.2%, n = 33) and HCC 6.0% (n = 13). Controlled attenuation parameter (CAP) was not associated with mortality in univariable analysis (HR = 1.00, CI 1.0-1.0, p = .488). Increased liver stiffness measurement (LSM) (HR 1.02 per kiloPascal, CI 1.01-1.03, p < .001), Charlson comorbidity index (CCI) (HR 1.32 for each point, CI 1.27-1.38, p < .001) and age (HR 1.05 per annum, CI 1.03-1.07, p < .001) were each associated with higher rates of all-cause mortality in multivariable analysis. LSM ≥10 kPa suggestive of compensated advanced chronic liver disease (cACLD) was associated with mortality in multivariable analysis (HR 2.31, CI 1.73-3.09, p < .001). CONCLUSION: VCTE LSM, in addition to age and CCI, is independently associated with increased all-cause mortality in a large cohort with NAFLD.

Validation of a novel point-of-care test for alanine aminotransferase measurement: A pilot cohort study.

BACKGROUND: Alanine aminotransferase (ALT) measurement is essential for evaluation of liver disease. We validated a novel rapid point-of-care (POC) test for ALT1 against laboratory ALT. METHODS: Stored plasma samples from adults with chronic liver disease (Test cohort n = 240; Validation cohort n = 491) were analysed using the BioPoint® antigen immunoassay POC ALT1 lateral flow test, which provides quantitative ALT results (Axxin handheld reader) or semi-quantitative results (visual read, cut off 40 IU/ml). The accuracy of POC ALT1 to detect ALT > 40 IU/L was determined by ROC analysis. In patients with chronic hepatitis B, treatment eligibility (EASL criteria) was determined using POC ALT1 and compared to laboratory ALT. RESULTS: POC ALT1 test had good accuracy for laboratory ALT > 40 IU/L: AUROC 0.93 (95% CI: 0.89-0.96) in the Test cohort and AUROC 0.92 (95% CI: 0.88-0.95) in the Validation cohort. POC ALT1 cut off of 0.8 for ALT > 40 IU/L maximised sensitivity (97%) and specificity (71%) in the Test cohort (42% laboratory ALT > 40 IU/L) and yielded PPV 84% and NPV 91% in the Validation cohort (19% laboratory ALT > 40 IU/L). Semi-quantitative POC ALT1 had good accuracy for laboratory ALT in the Validation cohort (AUROC 0.85, 95% CI: 0.81-0.99; sensitivity 77% and specificity 93%). Combined with HBV DNA and transient elastography, both quantitative and semi-quantitative POC ALT1 tests had good accuracy for excluding hepatitis B treatment needs (sensitivity 96%, specificity 78% and NPV 99%). CONCLUSION: The POC ALT1 test had good accuracy for elevated ALT levels and for determining treatment eligibility among people with chronic hepatitis B.

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.

Initial outcomes of a dedicated multidisciplinary non-alcoholic fatty liver disease clinic: a retrospective cohort study.

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.

A multi-site, nurse-coordinated hepatitis C model of care in primary care and community services in Melbourne, Australia.

BACKGROUND: Hepatitis C virus (HCV) treatment through primary care and community-based services will be a critical component of HCV elimination. We evaluated a nurse-coordinated programme providing care across eight sites and analysed progression through the HCV care cascade. METHODS: People-accessing services from six primary care clinics, a homeless crisis accommodation provider and a mental health service were directly referred to nurses or engaged by nurses during regular clinic visits. Nurses supported HCV testing, treatment and follow-up. The prescription was provided by affiliated clinicians. Logistic regression was used to examine factors associated with treatment commencement and sustained virological response (SVR) testing. RESULTS: Of 640 people referred to and/or engaged by the nurses from January 2017 to July 2019, 518 had an HCV RNA test of whom 381 (74%) were HCV RNA positive. Treatment was commenced by 281 (74%) people of whom 161 had an SVR test, 157 (97.5%) were cured. Opioid agonist therapy was associated with treatment commencement (aOR 2.68, 95% CI 1.48-4.88). People who were homeless/unstably housed were less likely to commence treatment (aOR 0.45, 95% CI 0.23-0.87). Treatment prescription from a specialist (aOR 2.39, 95% CI 1.20-4.74) and recent injection drug use (<6 months) (aOR 2.15, 95% CI 1.07-4.31) was associated with SVR testing. CONCLUSION: A nurse-coordinated model of care led to high levels of HCV treatment uptake and cure amongst people attending primary care and community services. More tailored models of care may be beneficial for people who are homeless or have unstable housing. These results support primary care and community-based hepatitis C treatment.

Australian consensus recommendations for the management of hepatitis B.

INTRODUCTION: The prevalence of hepatitis B virus (HBV) infection in Australia is nearly 1%. In certain well defined groups the prevalence is far greater, yet an estimated 27% of people living with HBV infection remain undiagnosed. Appropriate screening improves detection, increases opportunity for treatment, and ultimately reduces the significant morbidity and mortality associated with the development of liver fibrosis and hepatocellular carcinoma (HCC). MAIN RECOMMENDATIONS: This statement highlights important aspects of HBV infection management in Australia. There have been recent changes in nomenclature and understanding of natural history, as well as a newly defined upper limit of normal for liver tests that determine phase classification and threshold for antiviral treatment. As the main burden of hepatitis B in Australia is within migrant and Indigenous communities, early identification and management of people living with hepatitis B is essential to prevent adverse outcomes including liver cancer and cirrhosis. CHANGE IN MANAGEMENT AS A RESULT OF THIS GUIDELINE: These recommendations aim to raise awareness of the current management of hepatitis B in Australia. Critically, the timely identification of individuals living with hepatitis B, and where appropriate, commencement of antiviral therapy, can prevent the development of cirrhosis, HCC and mother-to-child transmission as well as hepatitis B reactivation in immunocompromised individuals. Recognising patient and viral factors that predispose to the development of cirrhosis and HCC will enable clinicians to risk-stratify and appropriately implement surveillance strategies to prevent these complications of hepatitis B.

Impact of renaming NAFLD to MAFLD in an Australian regional cohort: Results from a prospective population-based study.

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/m2 . 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.

Determinants of Short- and Long-Term Outcomes of an Australian Cohort of Patients Admitted with Alcoholic Hepatitis.

BACKGROUND AND AIMS: Alcoholic hepatitis is a common condition with high mortality. This study aimed to firstly describe the presentation, treatment, and short- and long-term outcomes of an Australian cohort of patients admitted to hospital with alcoholic hepatitis and secondly to validate existing prognostic models. METHODS: This is a retrospective study of consecutive patients admitted with alcoholic hepatitis to a major academic liver center in Melbourne, Australia, between January 1, 2010, and December 31, 2019. Cases were identified through appropriate International Classification of Diseases version 10 coding as well as review of non-coded patients with compatible biochemistry. Baseline demographic data, alcohol consumption, laboratory values, treatment, and outcomes at 30 days, 90 days, and 12 months post-diagnosis were collected from electronic medical records. Mortality data were extracted from an independent state government death registry. RESULTS: In total, 126 patients (72 males [57%], median age 51 years) were included in the final analysis. Ninety-five (75%) were cirrhotic at diagnosis, 81 (64%) met criteria for severe alcoholic hepatitis, and 41 (33%) had an infection during their index admission. 54% of eligible patients were treated with corticosteroids. 30-day and 12-month mortality rates were 8.7% and 27.1%, respectively, with hepatic encephalopathy (hazard ratio 5.45) and neutrophil-to-lymphocyte ratio (hazard ratio 1.09) independent markers for 12-month mortality on Cox regression analysis. Glasgow alcoholic hepatitis score outperformed other major prognostic models for short-term mortality. CONCLUSIONS: The 12-month mortality rate of 27% following alcoholic hepatitis is lower than previously reported studies, with hepatic encephalopathy and neutrophil-to-lymphocyte ratio predictive of long-term outcome.

Artificial Intelligence in Hepatology: A Narrative Review.

There has been a tremendous growth in data collection in hepatology over the last decade. This wealth of "big data" lends itself to the application of artificial intelligence in the development of predictive and diagnostic models with potentially greater accuracy than standard biostatistics. As processing power of computing systems has improved and data are made more accessible through the large databases and electronic health record, these more contemporary techniques for analyzing and interpreting data have garnered much interest in the field of medicine. This review highlights the current evidence base for the use of artificial intelligence in hepatology, focusing particularly on the areas of diagnosis and prognosis of advanced chronic liver disease and hepatic neoplasia.

Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis.

BACKGROUNDS & AIMS: Obesity often leads to non-alcoholic fatty liver disease (NAFLD), which can progress from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH). The accumulation of certain lipid subtypes is linked with worsening metabolic and liver disease, however, specific changes during progression from No-NAFL to NAFL then NASH are unresolved. Herein, we characterise the liver, adipose tissue and plasma lipidome of worsening NAFLD in obesity, and evaluate the utility of plasma lipids as biomarkers of NAFLD. METHODS: Venous blood, liver, visceral and subcutaneous adipose tissue samples were obtained from 181 patients undergoing bariatric surgery. NAFLD severity was assessed histologically. Lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry. RESULTS: The liver lipidome showed substantial changes with increasing steatosis, with increased triacylglycerols, diacylglycerols and sphingolipids including ceramide, dihydroceramide, hexosyl-ceramide and GM3 ganglioside species. These lipid species were also increased in plasma with increasing hepatic steatosis and showed strong correlations with liver lipids. Adipose tissue lipidomes showed no correlation with NAFLD. There were no significant changes in liver lipids with NASH compared to NAFL. The addition of plasma lipid variables to routine markers yielded significant improvements in diagnostic accuracy for NASH (AUROC 0.667 vs. 0.785, p = 0.025). CONCLUSION: Overall, these data provide a detailed description of the lipidomic changes with worsening NAFLD, showing significant changes with steatosis but no additional changes with NASH. Alterations in the liver lipidome are paralleled by similar changes in plasma. Further investigation is warranted into the potential utility of plasma lipids as non-invasive biomarkers of NAFLD in obesity. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) is characterised by distinct changes in the liver lipidome with steatosis. The development of non-alcoholic steatohepatitis (NASH) does not result in further changes in the lipidome. Lipids within body fat do not appear to influence the lipid profile of the liver or blood. Changes in liver lipids are paralleled by changes in blood lipids. This has potential to be developed into a non-invasive biomarker for NAFLD. CLINICAL TRIAL NUMBER: ACTRN12615000875505.

Comparison of 48-week efficacy of tenofovir vs entecavir for patients with chronic hepatitis B: A network meta-analysis.

Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are accepted as first-line treatments for chronic hepatitis B (CHB). However, there are few randomized studies comparing their efficacy. The primary aim of this study was to compare the efficacy of TDF and ETV using a network meta-analysis of randomized trials. The secondary aim was to additionally include propensity-matched cohort studies in a conventional meta-analysis. We systematically searched PubMed, EMBASE, Cochrane Library and Web of Science for published English-language randomized and propensity-matched studies between 1/1/2000 and 4/2/2020. Outcomes included undetectable HBV DNA, ALT normalization and HBeAg seroconversion at 48 weeks. We excluded patients who had co-infection or significant prior treatment with antivirals. 13 517 participants from 16 studies (11 RCTs, n = 2675; five propensity-matched cohort studies, n = 10 842) were included. Virological response at 48 weeks was higher in patients receiving TDF compared to ETV using both the network meta-analytic approach (OR 1.69, P < .001) and the conventional meta-analysis including propensity-matched cohort studies (OR 1.40, P < .001). On subgroup analysis, this difference was only significant in HBeAg-positive patients (OR 1.81, P = .037). There was limited evidence to suggest a higher rate of ALT normalization with ETV (OR 0.74, P = .07). There was no difference in rates of HBeAg seroconversion between the two antivirals. TDF is more likely than ETV to induce virological response at 48 weeks in treatment-naïve CHB patients. Future studies should focus on elucidating associations between early and sustained virological response with adverse patient outcomes including development of HCC or cirrhosis.

Management, outcomes and survival of an Australian IgG4-SC cohort: The MOSAIC study.

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

Irreversible electroporation versus radiofrequency ablation for hepatocellular carcinoma: a single centre propensity-matched comparison.

BACKGROUND AND AIMS: Irreversible electroporation (IRE) is a relatively new non-thermal ablative method for unresectable hepatocellular carcinoma (HCC). We aimed to compare the longer-term efficacy of IRE to the standard thermal technique of radiofrequency ablation (RFA) in HCC. METHODS: All patients who underwent IRE or RFA for HCC in our centre were identified and demographic and clinical data were analysed up until 1st March, 2020. Local recurrence-free survival (LRFS) was compared between groups after propensity score matching for age, gender, Child-Pugh grade, BCLC stage, lesion size and alpha-fetoprotein (AFP) level. RESULTS: A total of 190 HCC ablations (31 IRE and 159 RFA) were identified. After propensity score matching, we compared 25 IRE procedures (76% males, median age 62.4 years, median tumour size 20 mm) to 96 RFA procedures (84.4% males, median age 64.3 years, median tumour size 18.5 mm). LRFS did not differ between groups, with a 1-, 2- and 5-year LRFS of 80.4% (95% CI 55.8-92.2), 69.1% (95% CI 43.3-84.9) and 44.9% (95% CI 18.9-68.1%), respectively for IRE and 84.8% (95% CI 75.2-90.9), 71.3% (95% CI 58.3-81.0) and 52.1% (95% CI 35.4-66.4%), respectively for RFA (p = .63). There were no major procedure-related complications or deaths in either group. CONCLUSIONS: Whilst IRE remains a relatively novel therapy for HCC cases where standard thermal ablation is contraindicated, the LRFS in our centre is comparable to that of RFA. IRE should therefore be considered as a treatment option in such cases when available before stage-migration to non-curative therapies such as transarterial chemoembolization (TACE).

Prevalence of non-alcoholic fatty liver disease in regional Victoria: a prospective population-based study.

OBJECTIVES: To investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) and its risk factors in regional Victoria. DESIGN: Prospective cross-sectional observational study (sub-study to CrossRoads II health study in Shepparton and Mooroopna). SETTING: Four towns (populations, 6300-49 800) in the Goulburn Valley of Victoria. PARTICIPANTS: Randomly selected from households selected from residential address lists provided by local government organisations for participation in the CrossRoads II study. MAIN OUTCOME MEASURES: Age- and sex-adjusted estimates of NAFLD prevalence, defined by a fatty liver index score of 60 or more in people without excessive alcohol intake or viral hepatitis. RESULTS: A total of 705 invited adults completed all required clinical, laboratory and questionnaire evaluations of alcohol use (participation rate, 37%); 392 were women (56%), and their mean age was 59.1 years (SD, 16.1 years). Of the 705 participants, 274 met the fatty liver index criterion for NAFLD (crude prevalence, 38.9%; age- and sex-standardised prevalence, 35.7%). The mean age of participants with NAFLD (61 years; SD, 15 years) was higher than for those without NAFLD (58 years; SD, 16 years); a larger proportion of people with NAFLD were men (50% v 41%). Metabolic risk factors more frequent among participants with NAFLD included obesity (69% v 15%), hypertension (66% v 48%), diabetes (19% v 8%), and dyslipidaemia (63% v 33%). Mean serum alanine aminotransferase levels were higher (29 U/L; SD, 17 U/L v 24 U/L; SD, 14 U/L) and mean median liver stiffness greater (6.5 kPa; SD, 5.6 kPa v 5.3kPa; SD, 2.0 kPa) in participants with NAFLD. CONCLUSION: The prevalence of NAFLD among adults in regional Victoria is high. Metabolic risk factors are more common among people with NAFLD, as are elevated markers of liver injury.

Evaluation of the histological variability of core and wedge biopsies in nonalcoholic fatty liver disease in bariatric surgical patients.

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/m2. 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).

Outcomes of Treatment for Hepatitis C in Primary Care, Compared to Hospital-based Care: A Randomized, Controlled Trial in People Who Inject Drugs.

BACKGROUND: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to direct-acting antivirals (DAAs), especially among people who inject drugs (PWID). We aimed to determine the effectiveness of providing DAAs in primary care, compared with hospital-based specialist care. METHODS: We randomized PWID with HCV attending primary care sites in Australia or New Zealand to receive DAAs at their primary care site or local hospital (standard of care [SOC]). The primary outcome was to determine whether people treated in primary care had a noninferior rate of sustained virologic response at Week 12 (SVR12), compared to historical controls (consistent with DAA trials at the time of the study design); secondary outcomes included comparisons of treatment initiation, SVR12 rates, and the care cascade by study arm. RESULTS: We recruited 140 participants and randomized 136: 70 to the primary care arm and 66 to the SOC arm. The SVR12 rate (100%, 95% confidence interval [CI] 87.7-100) of people treated in primary care was noninferior when compared to historical controls (85% assumed). An intention-to-treat analysis revealed that the proportion of participants commencing treatment in the primary care arm (75%, 43/57) was significantly higher than in the SOC arm (34%, 18/53; P < .001; relative risk [RR] 2.48, 95% CI 1.54-3.95), and the proportion of participants with SVR12 was significantly higher in the primary care arm, compared to in the SOC arm (49% [28/57] and 30% [16/53], respectively; P = .043; RR 1.63, 95% CI 1.0-2.65). CONCLUSIONS: Providing HCV treatment in primary care increases treatment uptake and cure rates. Approaches that increase treatment uptake among PWID will accelerate elimination strategies. CLINICAL TRIALS REGISTRATION: NCT02555475.

Viscoelastic Tests as Point-of-Care Tests in the Assessment and Management of Bleeding and Thrombosis in Liver Disease.

Viscoelastic point-of-care (VET POC) tests provide a global assessment of hemostasis and have an increasing role in the management of bleeding and blood component delivery across several clinical settings. VET POC tests have a rapid turnaround time, provide a better overall picture of hemostasis, predict bleeding more accurately than conventional coagulation tests, and reduce blood component usage and health care costs. Despite commonly having abnormal conventional coagulation tests, most patients with chronic liver disease have a "rebalanced" hemostasis. However, this hemostatic balance is delicate and these patients are predisposed to both bleeding and thromboembolic events. Over recent years, VET POC tests have been increasingly studied for their potential as better functional tests of hemostasis in liver disease patients. This review provides a background on the most common VET POC tests (thromboelastography and rotational thromboelastometry) and discusses the current evidence for these tests in the prediction and management of bleeding and thrombosis in patients with chronic liver disease, and in liver resection and transplant. With the recent publication of several randomized controlled trials, there is growing evidence that VET POC tests may be used to improve bleeding risk assessment and reduce blood product use in liver disease patients outside of the transplant setting. However, consensus is still lacking regarding the VET POC tests' thresholds that should be used to trigger blood product transfusion. VET POC tests also show promise in predicting thrombosis in patients with liver disease, but further research is needed before they can be used to guide anticoagulant therapy.

Prognostic role of alpha-fetoprotein in patients with hepatocellular carcinoma treated with repeat transarterial chemoembolisation.

BACKGROUND: Repeat transarterial chemoembolisation (rTACE) is often required for hepatocellular carcinoma (HCC) to achieve disease control, however, current practice guidelines regarding treatment allocation vary significantly. This study aims to identify key factors associated with patient survival following rTACE to facilitate treatment allocation and prognostic discussion. METHOD: Patients with HCC undergoing rTACE at six Australian tertiary centers from 2009 to 2014 were included. Variables encompassing clinical, tumour, treatment type and response factors were analysed against the primary outcome of overall survival. Univariate analysis and multivariate Cox regression modelling were used to identify factors pre- and post-TACE therapy significantly associated with survival. RESULTS: Total of 292 consecutive patients underwent rTACE with mainly Child Pugh A cirrhosis (61%) and BCLC stage A (57%) disease. Median overall survival (OS) was 30 months (IQR 15.2-50.2) from initial TACE. On multivariate analysis greater tumour number (p = 0.02), higher serum bilirubin (p = 0.007) post initial TACE, and hepatic decompensation (p = 0.001) post second TACE were associated with reduced survival. Patients with serum AFP ≥ 200 ng/ml following initial TACE had lower survival (p = 0.001), compared to patients with serum AFP level that remained < 200 ng/ml post-initial TACE, with an overall survival of 19.4 months versus 34.7 months (p = 0.0001) respectively. CONCLUSION: Serum AFP level following initial treatment in patients undergoing repeat TACE for HCC is a simple and useful clinical prognostic marker. Moreover, it has the potential to facilitate appropriate patient selection for rTACE particularly when used in conjunction with baseline tumour burden and severity of hepatic dysfunction post-initial TACE.