High prevalence of diabetes among young First Nations Peoples with metabolic dysfunction-associated steatotic liver disease: a population-based study in Australia.

BACKGROUND: Liver disease is an important contributor to the mortality gap between First Nations Peoples and non-Indigenous Australian adults. Despite a high burden of metabolic comorbidities among First Nations Peoples, data about the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) in this population is scarce. METHODS: A retrospective analysis of all adults hospitalized with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) with/without cirrhosis during 2007-2019 in the state of Queensland was performed. Patients were followed from the first admission with MASLD/MASH (identified based on validated algorithms) to decompensated cirrhosis and overall mortality. We explored differences according to Indigenous status using Multivariable Cox regression. FINDINGS: 439 First Nations Peoples and 7,547 non-Indigenous Australians were followed for a median of 4.6 years (interquartile range 2.7-7.2). Overall, women were overrepresented, but more so in the First Nations cohort (72.7% vs. 57.0%, p < 0.001). First Nations patients were younger, a higher proportion lived in remote and socioeconomic disadvantaged areas, and had higher comorbidity compared to non-Indigenous Australians (all p < 0.001). Diabetes, the most common comorbidity affecting both groups, was overrepresented in First Nations Peoples versus non-Indigenous Australians (43.5% vs. 30.8%, p < 0.001, respectively). Nineteen (4.3%) First Nations Peoples and 332 (4.4%) of non-Indigenous patients progressed to cirrhosis decompensation (9.0% [95%CI 4.5-17.7] vs. 7.7% [95%CI 6.6-8.9; p = 0.956] respectively within 10 years). In multivariable analysis, there was no association between Indigenous status and progression to decompensated cirrhosis (p = 0.759) and survival (p = 0.437). CONCLUSIONS: This study provides the first population-based epidemiological data on MASLD in First Nations Australians. The high prevalence of diabetes (that is associated with advanced fibrosis and liver disease mortality) among young First Nations Peoples with MASLD raises concern about future risk of progressive liver disease in this patient population. These data highlight the importance of early identification of MASLD, and providing culturally appropriate intervention to reduce disease progression in parallel with the management of cardiometabolic comorbidities.

Changing Prevalence of Medication Use in People with Cirrhosis: A Retrospective Cohort Study Using Pharmaceutical Benefits Scheme Data.

BACKGROUND: Safe and appropriate use of medicines is essential to improve health outcomes in cirrhosis. However, little is known about the number and type of medicines dispensed to people with cirrhosis in Australia, as this predominantly occurs in the community. We aimed to characterise the prescriptions dispensed to people with cirrhosis and explore changes in the use of medication groups over time. METHODS: Pharmaceutical Benefits Scheme data between 1 January 2016 and 30 June 2020 was extracted for consenting CirCare participants (multi-site, prospective, observational study). Prescriptions dispensed from cirrhosis diagnosis until liver transplant or death were included. Safety classifications for dispensed medicines were defined using published evidence-based recommendations. The pattern of medication use was analysed in 6-monthly time intervals. Generalised estimating equations models were used to estimate the change in consumption of medicines over time. RESULTS: Five hundred twenty-two patients (mean age 60 years, 70% male, 34% decompensated at recruitment) were dispensed 89,615 prescriptions during the follow-up period, representing a median of 136 [interquartile range (IQR) 62-237] prescriptions and a median of 16 (IQR 11-23) unique medicines per patient (total n = 9306 medicines). The most commonly used medicines were proton pump inhibitors (PPIs) (dispensed at least once to 73% of patients), opioids (68%) and antibiotics (89%). Polypharmacy was prevalent, with 59-69% of observed participants in each time period dispensed five or more unique medicines. Prescription medication use increased over time (p < 0.001) independently of age, comorbidity burden and liver disease aetiology. The likelihood of taking PPIs, opioids, antidepressants and inhaled medicines also increased with each successive time period. Use of angiotensin therapies, metformin and statins differed over time between patients with compensated versus decompensated cirrhosis. General practitioners prescribed 69% of dispensed medicines, including a higher proportion of 'unsafe' and 'safety unknown' medicines compared with consultants/specialists (p < 0.001). CONCLUSIONS: Polypharmacy is common in people with cirrhosis and some medication groups may be overused. Pharmacovigilance is required and future medication safety efforts should target high-risk prescribing practices and promote medication rationalisation in the community.

Gene Variants Implicated in Steatotic Liver Disease: Opportunities for Diagnostics and Therapeutics.

Non-alcoholic fatty liver disease (NAFLD) describes a steatotic (or fatty) liver occurring as a consequence of a combination of metabolic, environmental, and genetic factors, in the absence of significant alcohol consumption and other liver diseases. NAFLD is a spectrum of conditions. Steatosis in the absence of inflammation is relatively benign, but the disease can progress into more severe forms like non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. NAFLD onset and progression are complex, as it is affected by many risk factors. The interaction between genetic predisposition and other factors partially explains the large variability of NAFLD phenotype and natural history. Numerous genes and variants have been identified through large-scale genome-wide association studies (GWAS) that are associated with NAFLD and one or more subtypes of the disease. Among them, the largest effect size and most consistent association have been patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane-bound O-acyltransferase domain containing 7 (MBOAT7) genes. Extensive in vitro and in vivo studies have been conducted on these variants to validate these associations. The focus of this review is to highlight the genetics underpinning the molecular mechanisms driving the onset and progression of NAFLD and how they could potentially be used to improve genetic-based diagnostic testing of the disease and develop personalized, targeted therapeutics.

A discrete choice experiment to elicit preferences for a liver screening programme in Queensland, Australia: a mixed methods study to select attributes and levels.

BACKGROUND: In Australia, the overall prevalence of liver disease is increasing. Maximising uptake of community screening programmes by understanding patient preferences is integral to developing consumer-centred care models for liver disease. Discrete choice experiments (DCEs) are widely used to elicit preferences for various healthcare services. Attribute development is a vital component of a well-designed DCE and should be described in sufficient detail for others to assess the validity of outcomes. Hence, this study aimed to create a list of potential attributes and levels which can be used in a DCE study to elicit preferences for chronic liver disease screening programmes. METHODS: Key attributes were developed through a multi-stage, mixed methods design. Focus groups were held with consumers and health care providers on attributes of community screening programmes for liver disease. Stakeholders then prioritised attributes generated from the focus group in order of importance via an online prioritisation survey. The outcomes of the prioritisation exercise were then reviewed and refined by an expert panel to ensure clinically meaningful levels and relevance for a DCE survey. RESULTS: Fifteen attributes were generated during the focus group sessions deemed necessary to design liver disease screening services. Outcomes of the prioritisation exercise and expert panel stages recognised five attributes, with three levels each, for inclusion in a DCE survey to elicit consumer preferences for community screening for liver disease. This study also highlights broader social issues such as the stigma around liver disease that require careful consideration by policy makers when designing or implementing a liver screening programme. CONCLUSIONS: The attributes and levels identified will inform future DCE surveys to understand consumer preferences for community screening programmes for liver disease. In addition, the outcomes will help inform the implementation of the LOCATE-NAFLD programme in real-world practice, and could be relevant for other liver and non-liver related chronic disease screening programmes.

Diabetes mellitus and the progression of non-alcoholic fatty liver disease to decompensated cirrhosis: a retrospective cohort study.

OBJECTIVE: To determine the incidence of decompensated cirrhosis and associated risk factors in people hospitalised with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) with or without cirrhosis. DESIGN: Retrospective cohort study; analysis of linked Queensland Hospital Admitted Patient Data Collection, Queensland Registry of Births, Deaths and Marriages, and Queensland Cancer Register data. SETTING, PARTICIPANTS: Queensland residents aged 20 years or older admitted to Queensland hospitals with NAFLD/NASH during 1 July 2009 - 31 December 2018. MAIN OUTCOME MEASURES: Progression to decompensated cirrhosis (ascites, hepatic encephalopathy, or oesophageal variceal bleeding). RESULTS: We included data for 8006 patients in our analysis (10 082 admissions), including 4632 women (58%) and 2514 people with diabetes mellitus (31%); median follow-up time was 4.6 years (interquartile range, 2.7-7.2 years). Three hundred and fifty-one people (4.4%) experienced decompensated cirrhosis during the follow-up period. Of the 6900 people without cirrhosis, 4.5% (95% confidence interval [CI], 3.6-5.7%) experienced decompensated cirrhosis within ten years (mean, 0.5% per year; 95% CI, 0.4-0.6% per year); risk of progression was greater for people aged 70 years or older (v 20-39 years: adjusted hazard ratio [aHR], 4.7; 95% CI, 2.0-11.0) and those who had extrahepatic cancers (aHR, 5.0; 95% CI, 3.0-8.2), history of major cardiovascular events (aHR, 1.9; 95% CI, 1.2-3.1), or diabetes mellitus (aHR, 2.8; 95% CI, 2.0-3.9). Of the 1106 people with cirrhosis, 32.4% (95% CI, 27.2-38.3%) experienced decompensated cirrhosis within ten years (mean, 5.5% per year; 95% CI, 4.8-6.3% per year); risk of progression was greater for those with portal hypertension (aHR, 1.8; 95% CI, 1.3-2.7), extrahepatic cancer (aHR, 1.8; 95% CI, 1.1-2.9), or diabetes mellitus (aHR, 1.5; 95% CI, 1.1-2.0). Compared with people who had neither cirrhosis nor diabetes mellitus, the risk of decompensation was greater for people with cirrhosis (aHR, 10.7; 95% CI, 7.6-15.0) or cirrhosis and diabetes mellitus (aHR, 14.4; 95% CI, 10.1-20.6). CONCLUSIONS: Given the greater risk of progression to cirrhosis decompensation in people with diabetes mellitus, a disorder common in people with NAFLD/NASH, identifying advanced fibrosis and providing appropriate treatment for averting disease progression is vital.

Lower prevalence of elevated liver stiffness measurements in people with type 2 diabetes taking sodium-glucose co-transporter 2 inhibitors or glucagon-like peptide-1 receptor agonists.

INTRODUCTION AND OBJECTIVES: Among people with type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) is very common and has an increased risk of clinically significant liver disease. The use of sodium-glucose co-transporter 2 (SGLT2i) inhibitors and glucagon-like peptide-1 (GLP-1a) receptor agonists is endorsed to reduce major cardiovascular events and/or progression of chronic kidney disease. Their prevalence of use in people with T2D and co-existent NAFLD remains unclear. We sought to determine the prevalence of use of these medications at two different time periods, and their association with prevalence of clinically significant liver disease. MATERIALS AND METHODS: Consecutive people with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) were recruited from diabetes clinics between Jun-2021 and Jun-2022 ('current' cohort). Liver stiffness measurements (LSM) using FibroScan were performed. Medication data were collected prospectively at recruitment and verified with the dispensing pharmacy or general practitioner medical records. Data for a historical cohort with NAFLD and T2D recruited from the same clinics during 2015-2017 ('historical' cohort) were available. Logistic regression was used to evaluate factors associated with LSM <8.0 or ≥8 kPa (clinically significant fibrosis). RESULTS: There were 292 participants, 177 in the historical cohort and 115 in the current cohort. In the current cohort, 57.4% of patients with T2D and NAFLD were taking a GLP-1a and 42.6% were taking a SGLT2i; a 2.6 to 3.4-fold higher prevalence than in 2015-2017. A lower proportion of the current cohort (23.9% compared to 38.4%) had clinically significant fibrosis (LSM ≥8 kPa; p = 0.012). When the cohorts were pooled and differences adjusted for in multivariable logistic regression analysis, patients taking a GLP-1a or a SGLT2i were 2 times more likely to have a lower LSM (<8 kPa) compared to patients not taking these drugs (OR=2.05, 95%CI 1.07-3.94, p = 0.03 and OR 2.07 95%CI 1.04-4.11, p = 0.04, respectively). CONCLUSIONS: The observation of a lower LSM in people taking SGLT2i and/or GLP-1a following adjustment for other relevant clinico-demographic variables provides support for clinical trials to assess their efficacy in reducing the progression of NAFLD.

Low Prevalence of Use of Allied Health and Community Services for Patients with Cirrhosis in Australia: A Need for Greater Engagement.

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

Higher levels of supportive care needs are linked to higher health service use and cost, poor quality of life, and high distress in patients with cirrhosis in Queensland, Australia.

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

Partnering with support persons and clinicians to improve the health care experiences of patients with cirrhosis.

AIM: To explore the care experiences of Aboriginal and Torres Strait Islander Australians diagnosed with cirrhosis with a focus on support needed. BACKGROUND: Cirrhosis disproportionately affects Indigenous Australians, and liver diseases contribute to the mortality gap between Indigenous and other Australian adults. DESIGN: A qualitative study. METHODS: Using yarning methods, Indigenous patients (n = 13) and support persons (n = 3) were interviewed by an Aboriginal researcher during April-July, 2020. Thematic analysis was used to identify common themes using an inductive approach. RESULTS: Six themes emerged. (1) Experience of diagnosis. This theme included stories of delays in the system, self-awareness of signs and symptoms and relief of being diagnosed. (2) 'Shame, shame, shame'. Experiences of prejudices and discrimination from health professionals, the lack of understanding of cirrhosis among health professionals, and stories about alcohol cessation and counselling around alcohol cessation. (3) Health literacy. Participants' understanding of cirrhosis was variable. While the importance of knowledge was recognised, 'what works for someone might not work for others'. Several patients partnered with their support persons and clinicians to bridge the health literacy gap. (4) Sources of support included family and friends, transport facilities, health professionals and peers. (5) Positive and negative aspects of communication and patient consultation were discussed. (6) Psychosocial counselling to 'look after the caring side'. The need for more mental health care services was raised. CONCLUSION: Barriers related to poor health literacy, stigma and lack of practical and emotional support, and issues with communication and patient consultation, may lead to inequitable access to cirrhosis care and treatment for Indigenous Australians. RELEVANCE TO CLINICAL PRACTICE: Gaining knowledge of the experiences of Indigenous Australians with cirrhosis is important for providing patient-centred and culturally appropriate care. Liver specialist nurses have an important role in bridging the health literacy gap and in supporting Indigenous patients and families.

Validation of the new 2021 EASL algorithm for the noninvasive diagnosis of advanced fibrosis in NAFLD.

BACKGROUND AND AIMS: The European Association for the Study of the Liver (EASL) has recently proposed an algorithm for the diagnosis of advanced liver fibrosis. We aimed to evaluate the diagnostic accuracy of this algorithm in nonalcoholic fatty liver disease (NAFLD). APPROACH AND RESULTS: One thousand fifty-one patients with NAFLD, liver biopsy, and four noninvasive tests (NITs; Fibrosis-4 [FIB4], vibration controlled transient elastography [VCTE], FibroMeter, Fibrotest) were included. The enhanced liver fibrosis (ELF) score was available in 396 patients. A cohort of 230 patients from primary care/diabetes clinics had FIB4, VCTE, and ELF. Compared with the performance of single NITs, agreement between two NITs (FIB4 and VCTE, VCTE and patented serum tests) increased specificity and positive predictive value by 20%, thus justifying the sequential use proposed in the EASL algorithm. The FIB4/VCTE/FibroMeter and FIB4/VCTE/Fibrotest algorithms performed similarly, providing 85% diagnostic accuracy and a liver biopsy requirement rate of only 10%. The FIB4/VCTE/ELF algorithm performed similarly in the subgroup where ELF was available. Simulations of algorithm accuracies at different prevalence showed that positive predictive values rapidly increased, reaching a plateau above 75% starting at 15% prevalence. Negative predictive values remained higher than 90% up to 25% prevalence. The rate of liver biopsy requirement remained stable, increasing by only 5% between low and high prevalence settings. When the EASL algorithm was applied in the primary care/diabetes clinic cohort, liver biopsy requirement was only 3%, and the agreement among the three steps provided 75% positive predictive value. CONCLUSIONS: Our study validates the algorithm proposed by the EASL in its latest 2021 guidelines for the diagnosis of advanced fibrosis in the setting of NAFLD.

Differences in the pattern and cost of hospital care between Indigenous and non-Indigenous Australians with cirrhosis: an exploratory study.

BACKGROUND: Liver diseases are important contributors to the mortality gap between Indigenous and non-Indigenous Australians. AIMS: This cohort study examined factors associated with hospital admissions and healthcare outcomes among Indigenous Australians with cirrhosis. METHODS: Patient-reported outcomes were obtained by face-to-face interview (Chronic Liver Disease Questionnaire and Short Form 36 (SF-36)). Clinical data were extracted from medical records and through data linkage for 534 patients (25 indigenous). Cumulative overall survival (Kaplan-Meier), rates of hospital admissions and emergency presentations, and costs were assessed by indigenous status. Incidence rate ratios (IRR; Poisson regression) were reported. RESULTS: Indigenous Australians admitted to hospital with cirrhosis had lower educational status compared with non-indigenous patients (79.2% vs 43.4%; P < 0.001). The two groups had, in general, similar clinical characteristics including disease severity (P = 0.78), presence of cirrhosis complications (P = 0.67), comorbidities (P = 0.62), rates of cirrhosis-related admissions (P = 0.86) and 5-year survival (P = 0.30). However, indigenous patients had a lower score in the SF-36 domain related to bodily pain (P = 0.037), more cirrhosis admissions via the emergency department (IRR = 1.42, 95% confidence interval (CI) 1.10-1.83) and fewer planned cirrhosis admissions (IRR = 0.32, 95% CI 0.14-0.72). The total cost for cirrhosis-related hospital admissions for 534 patients over 6 years (July 2012 to June 2018) was A$13.7 million. The cost of cirrhosis-related hospital admissions was double for indigenous patients (cost ratio = 2.04, 95% CI 2.04-2.05). CONCLUSIONS: Our data highlight the disparities in health service use and patient-reported outcomes, despite having similar clinical profiles. Integration between primary care, Aboriginal Community Controlled Health Organisations and liver specialists is critical for appropriate health service delivery and effective use of resources. Chronic liver disease costs the community dearly.

Serum CC-Chemokine Ligand 2 Is Associated with Visceral Adiposity but Not Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver as a consequence of metabolic perturbations associated with obesity, type 2 diabetes, dyslipidemia, and insulin resistance. People with NAFLD may develop metabolic and cardiovascular complications and/or liver-related complications, especially fibrosis and hepatocellular carcinoma, associated with high morbidity and mortality. Due to the high and increasing prevalence of NAFLD, there is an urgent need to identify people at risk of developing liver fibrosis and complications. CC-chemokine ligand 2 (CCL2) is chemokine that attracts inflammatory monocytes to stressed or injured tissues. Infiltrating inflammatory monocytes and CCL2 are strongly implicated in the pathogenesis of liver disease in animal models; however, evidence in patient cohorts is conflicting. METHODS: We investigated associations between circulating CCL2 and clinical parameters, including fibrosis assessed by liver stiffness measurement, in a cohort of 250 NAFLD patients. We also measured fatty acid binding protein 2 (FABP2), a putative biomarker of intestinal permeability in patients with liver disease, since pro-inflammatory gut-derived microbial products may induce inflammatory chemokines such as CCL2. RESULTS: Serum CCL2 levels were weakly associated with liver stiffness, but the association was no longer significant after accounting for age, diabetes, and BMI in a multivariable model. Consistent with this, girth and BMI were the strongest predictors of elevated circulating CCL2. Serum FABP2 was weakly, but significantly, correlated with CCL2, and negatively correlated with estimated glomerular filtration rate. CONCLUSION: Circulating CCL2 and FABP2 are associated with NAFLD comorbidities but not liver disease progression in patients with NAFLD.

Poor disease knowledge is associated with higher healthcare service use and costs among patients with cirrhosis: an exploratory study.

BACKGROUND: Optimal management of cirrhosis is complex, and patients often lack knowledge and skills, which can affect self-management. We assessed patient knowledge about cirrhosis and examined whether knowledge was associated with clinical outcomes, healthcare service use, and healthcare costs. A cross-sectional 'knowledge survey' was conducted during 2018-2020. We assessed patient knowledge about cirrhosis and explore whether knowledge was associated with clinical outcomes, healthcare service use, and costs. METHODS: Patients with cirrhosis (n = 123) completed a 'knowledge survey'. We calculated the proportion of correct answers to eight questions deemed to be "key knowledge" about cirrhosis by an expert panel, and dichotomized patients as 'good knowledge'/'poor knowledge'. Clinical data, healthcare costs, and health-related quality of life (SF-36) were available. RESULTS: 58.5% of patients had 'good knowledge' about cirrhosis. Higher education level was associated with higher odds of having 'good knowledge' about cirrhosis (adjusted-OR = 5.55, 95%CI 2.40-12.84). Compared to patients with 'poor knowledge', those with 'good knowledge' had a higher health status in the SF-36 physical functioning domain (p = 0.011), fewer cirrhosis-related admissions (adjusted incidence rate ratio [IRR] = 0.59, 95%CI 0.35-0.99) and emergency presentations (adj-IRR = 0.34, 95%CI 0.16-0.72), and more planned 1-day cirrhosis admissions (adj-IRR = 3.96, 95%CI 1.46-10.74). The total cost of cirrhosis admissions was lower for patients with 'good knowledge' (adj-IRR = 0.30, 95%CI 0.29-0.30). CONCLUSION: Poor disease knowledge is associated with increased use and total cost of healthcare services. Targeted educational interventions to improve patient knowledge may be an effective strategy to promote a more cost-effective use of healthcare services.

The Impact of Social Workers in Cirrhosis Care: a Systematic Review.

Purpose of review: To report social workers' involvement in supporting patients with cirrhosis. Recent findings: Six intervention studies (three published in the past 3 years) highlighed the potential role of social worker-led interventions to improve the outcomes of patients with cirrhosis. In studies of patients with alcohol-related liver disease (n = 4), social workers conducted psychosocial assessments, screened for substance use disorder and psychological distress, coordinated referrals to addiction services, and provided relapse prevention therapy. In studies including transplant recipients or candidates (n = 2), social workers focused on psychosocial interventions. In two studies (n = 1 patient with alcohol-related liver disease; n = 1 transplant recipients), social workers provided practical support (e.g., housing, transportation). Most articles provided limited information about the intervention and the role of the social worker, making comparisons of the studies difficult. Summary: More high-quality evidence is needed to formally assess the impact of social workers in improving the outcomes of patients with cirrhosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s11938-022-00381-2.

Epidemiology of ascites fluid infections in patients with cirrhosis in Queensland, Australia from 2008 to 2017: A population-based study.

ABSTRACT: Spontaneous bacterial peritonitis (SBP), a common infection in patients with cirrhosis and ascites, is associated with high morbidity and mortality. The aim of this study was to investigate changes in the epidemiology of ascites fluid infections over time in an Australian population, including patient demographics, trends in mortality, length of hospital stay and the nature and antibiotic resistance profile of causative organisms.An observational descriptive population-based epidemiological study of patients with cirrhosis admitted to public hospitals in Queensland during 2008-2017 was performed, linking demographic/clinical and microbiology data.Among 103,165 hospital admissions of patients with cirrhosis, ascites was present in 16,550 and in 60% (9977) a sample of ascitic fluid was tested. SBP was diagnosed in 770 admissions (neutrophil count >250/ml) and bacterascites in 552 (neutrophil count <250/ml with positive culture). The number of admissions with an ascites fluid infection increased by 76% from 2008 to 2017, paralleling an 84% increase in cirrhosis admissions over the same timeframe. Patients with SBP had a longer hospital stay (median 15.7 vs 8.3 days for patients without SBP, P < .001) and higher in-hospital mortality, although this decreased from 39.5% in 2008 to 2010 to 24.8% in 2015 to 2017 (P < .001). Common Gram-positive isolates included coagulase negative staphylococci (37.9%), viridans group streptococci (12.1%), and Staphylococcus aureus (7.2%). Common Gram-negative isolates included Escherichia coli (13.0%), Klebsiella pneumoniae (3.1%) and Enterobacter cloacae (2.6%). The prevalence of resistance to any tested antibiotic was <10%.SBP remains associated with high in-hospital mortality and long hospital stay. Typical skin and bowel pathogens were common, therefore, empirical antibiotic therapy should target these pathogens. This study provides valuable evidence informing infection management strategies in this vulnerable patient population.

Implementing the right care in the right place at the right time for non-alcoholic fatty liver disease (NAFLD-RRR study): a study protocol for a community care pathway for people with type 2 diabetes.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic that affects approximately half of all people with type 2 diabetes. Those with type 2 diabetes are a high-risk NAFLD subgroup because of their increased risk of clinically significant liver-related outcomes from NAFLD which include hepatocellular carcinoma, cirrhosis-related complications and liver disease mortality. They may benefit from early detection of disease as this would allow at risk patients to access hepatocellular carcinoma surveillance, emerging drug trials for NAFLD and specialist hepatology care prior to emergence of liver-related complications. METHODS: This is a prospective cohort study aimed at incorporating and assessing a community care pathway for liver fibrosis screening into routine care for type 2 diabetes. Patients undergo a point of care assessment of hepatic steatosis and stiffness using FibroScan at the time of the routine diabetes appointment or when attending the clinic for blood tests in preparation for this appointment. DISCUSSION: We propose that implementation of a community-based NAFLD diagnosis, risk-stratification, and referral pathway for people with type 2 diabetes is feasible, will provide earlier, targeted detection of advanced fibrosis, and reduce unnecessary referrals to hepatology outpatients for fibrosis risk assessment. Our study will provide important information about the feasibility of establishing a NAFLD pathway for people with type 2 diabetes in primary care. Ultimately, our findings will help direct spending and resource allocation for NAFLD in a high-risk population. Regular evaluation by stakeholders during implementation will help to create a reliable and sustainable community care pathway and establish a perpetual cycle of learning in primary care. TRIAL REGISTRATION: ANZCTR, ACTRN12621000330842 . Registered 23 March 2021.

Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease.

SignificanceWhile increasing evidence associates the disruption of circadian rhythms with pathologic conditions, including obesity, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD), the involved mechanisms are still poorly described. Here, we show that, in both humans and mice, the pathogenesis of NAFLD is associated with the disruption of the circadian clock combined with perturbations of the growth hormone and sex hormone pathways. However, while this condition protects mice from the development of fibrosis and insulin resistance, it correlates with increased fibrosis in humans. This suggests that the perturbation of the circadian clock and its associated disruption of the growth hormone and sex hormone pathways are critical for the pathogenesis of metabolic and liver diseases.