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.

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.

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 Hidden Epidemic: The Prevalence and Impact of Concurrent Liver Diseases in Patients Undergoing Liver Transplantation in Australia and New Zealand.

Prevalence of concurrent liver diseases among liver transplant recipients and impact on posttransplant outcomes are unknown. Methods: This retrospective study included adult liver transplants between January 1' 1985' and December 31' 2019' from the Australian and New Zealand Liver and Intestinal Transplant Registry. Up to 4 liver disease causes were recorded for each transplant; concurrent liver diseases were defined as >1 liver disease indication for transplantation, excluding hepatocellular carcinoma. Impact on posttransplant survival was determined using Cox regression. Results: A total of 840 (15%) of 5101 adult liver transplant recipients had concurrent liver diseases. Recipients with concurrent liver diseases were more likely male (78% versus 64%) and older (mean age 52 versus 50 y). A higher proportion of liver transplants for hepatitis B (12% versus 6%), hepatitis C (33% versus 20%), alcohol liver disease (23% versus 13%), and metabolic-associated fatty liver disease (11% versus 8%, all P < 0.001) were identified when all indications were included than with primary diagnosis only. The number and proportion of liver transplants performed for concurrent liver diseases have increased from 8 (6%) during Era 1 (1985-1989) to 302 (20%) during Era 7 (2015-2019; P < 0.001). Concurrent liver diseases were not associated with increased posttransplant mortality (adjusted hazard ratio, 0.98, 95% confidence interval, 0.84-1.14). Conclusions: Concurrent liver diseases are increasing among adult liver transplant recipients in Australia and New Zealand; however, they do not appear to impact posttransplant survival. Reporting all liver disease causes in the transplant registry reports provides more accurate estimates of liver disease burden.

Turning the Tide on Hepatitis C Virus-Related Liver Transplantation: The Return on Investment in Hepatitis C Virus Treatment in Australia and New Zealand.

Introduction of universal access to direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in Australia and New Zealand on March 1st , 2016, has had a major impact on the number of people with chronic HCV infection, but the impact on liver transplantation rates is unknown. We conducted a retrospective registry study including all adult liver transplantations from the Australia and New Zealand Liver and Intestinal Liver Transplant Registry (ANZLITR) data set. Interrupted time series analysis determined the impact of DAAs in 2016 on the number of HCV liver transplantations per year. Cox regression analysis was used to determine the impact of DAAs on post-liver transplantation survival. Between January 1, 1990, and December 31, 2019 5318 adult liver transplantations were performed, and 29% (1531) were for HCV infection. Prior to the introduction of DAAs, there was a mean increase of 3.5 adult liver transplantations performed for HCV per annum, but between 2016 and 2019 there was a mean decrease of 7.9 adult liver transplantations per annum (P < 0.001). Similarly, the proportion of liver transplantations performed for HCV increased from 9% (1990) to 33% in 2016 and then fell to 23% in 2019 (P < 0.001). The number and proportion of patients with HCV added to the liver transplantation waiting list also fell in 2016 (P < 0.001) when compared with other indications. The introduction of DAAs was associated with a 31% reduction in death after liver transplantation, adjusted for age at transplant and hepatocellular carcinoma (HCC; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.48-0.99; P = 0.047). The number of adult liver transplantations performed for HCV-related liver cirrhosis and HCC has reduced since the introduction of universal access to DAAs in 2016 in Australia and New Zealand.

Predicting Liver-Related Outcomes in People With Nonalcoholic Fatty Liver Disease: The Prognostic Value of Noninvasive Fibrosis Tests.

It remains unclear whether screening for advanced fibrosis in the community can identify the subgroup of people with nonalcoholic fatty liver disease (NAFLD) at higher risk for development of liver-related complications. We aimed to determine the prognostic value of baseline noninvasive fibrosis tests for predicting liver-related outcomes and mortality in patients with NAFLD from type 2 diabetes (T2D) clinics or primary care. Patients (n = 243) who were screened for NAFLD with advanced fibrosis by using NAFLD fibrosis score (NFS), fibrosis 4 score (FIB-4), enhanced liver fibrosis (ELF) test, and liver stiffness measurements (LSMs) were followed up for clinical outcomes by review of electronic medical records. During a median follow-up of 50 months, decompensated liver disease or primary liver cancer occurred in 6 of 35 (17.1%) patients with baseline LSM > 13 kPa, 1 of 17 (5.9%) patients with LSM 9.5-13 kPa, and in no patients with LSM < 9.5 kPa. No patient with low-risk NFS developed liver decompensation or liver-related mortality. Following repeat NFSs at the end of follow-up, all patients with a liver-related complication were in the high-risk NFS category. Patients who developed liver-related complications were also more likely to have baseline high-risk FIB-4 scores or ELF test ≥9.8 compared to patients who did not develop liver outcomes. Conclusion: Liver fibrosis risk stratification in non-hepatology settings can identify the subset of patients at risk of liver-related complications. Although the rate of development of a decompensation event or hepatocellular carcinoma was low (2.1% per year) in our patients with compensated cirrhosis (LSM > 13 kPa), these events are projected to lead to a substantial increase in NAFLD-related disease burden over the next decade due to the high prevalence of NAFLD in people with obesity and T2D.

Medication Discrepancies and Regimen Complexity in Decompensated Cirrhosis: Implications for Medication Safety.

Discrepancies between the medicines consumed by patients and those documented in the medical record can affect medication safety. We aimed to characterize medication discrepancies and medication regimen complexity over time in a cohort of outpatients with decompensated cirrhosis, and evaluate the impact of pharmacist-led intervention on discrepancies and patient outcomes. In a randomized-controlled trial (n = 57 intervention and n = 57 usual care participants), medication reconciliation and patient-oriented education delivered over a six-month period was associated with a 45% reduction in the incidence rate of 'high' risk discrepancies (IRR = 0.55, 95%CI = 0.31-0.96) compared to usual care. For each additional 'high' risk discrepancy at baseline, the odds of having ≥ 1 unplanned medication-related admission during a 12-month follow-up period increased by 25% (adj-OR = 1.25, 95%CI = 0.97-1.63) independently of the Child-Pugh score and a history of variceal bleeding. Among participants with complete follow-up, intervention patients were 3-fold less likely to have an unplanned medication-related admission (adj-OR = 0.27, 95%CI = 0.07-0.97) compared to usual care. There was no association between medication discrepancies and mortality. Medication regimen complexity, frequent changes to the regimen and hepatic encephalopathy were associated with discrepancies. Medication reconciliation may improve medication safety by facilitating communication between patients and clinicians about 'current' therapies and identifying potentially inappropriate medicines that may lead to harm.

The Patient's Perspective in Cirrhosis: Unmet Supportive Care Needs Differ by Disease Severity, Etiology, and Age.

Patients with cirrhosis have significant physical, psychological, and practical needs. We documented patients' perceived need for support with these issues and the differences with increasing liver disease severity, etiology, and age. Using the supportive needs assessment tool for cirrhosis (SNAC), we examined the rate of moderate-to-high unmet needs (Poisson regression; incidence rate ratio [IRR]) and the correlation between needs and sociodemographic/clinical characteristics (multivariable linear regression) in 458 Australians adults with cirrhosis. Primary liver disease etiology was alcohol in 37.6% of patients, chronic viral hepatitis C in 25.5%, and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in 23.8%. A total of 64.6% of patients had Child-Pugh class A cirrhosis. Most patients (81.2%) had at least one moderate-to-high unmet need item; more than 25% reported a moderate-to-high need for help with "lack of energy," "sleep poorly," "feel unwell," "worry about … illness getting worse (liver cancer)," "have anxiety/stress," and "difficulty with daily tasks." Adjusting for key sociodemographic/clinical factors, patients with Child-Pugh C had a greater rate of "practical and physical needs" (vs. Child-Pugh A; IRR = 2.94, 95% confidence interval [CI] 2.57-3.37), patients with NAFLD/NASH had a greater rate of needs with "lifestyle changes" (vs. alcohol; IRR = 1.81, 95% CI 1.18-2.77) and "practical and physical needs" (IRR = 1.43, 95% CI 1.23-1.65), and patients aged ≥65 years had fewer needs overall (vs. 18-64 years; IRR = 0.70, 95% CI 0.64-0.76). Higher overall SNAC scores were associated with Child-Pugh B and C (both P < 0.001), NAFLD/NASH (P = 0.028), patients with "no partner, do not live alone" (P = 0.004), unemployment (P = 0.039), ascites (P = 0.022), and dyslipidemia (P = 0.024) compared with their counterparts. Conclusion: Very high levels of needs were reported by patients with cirrhosis. This information is important to tailor patient-centered care and facilitate timely interventions or referral to support services.

Assessment of health-related quality of life and health utilities in Australian patients with cirrhosis.

BACKGROUND AND AIM: Health-related quality-of-life measurements are important to understand lived experiences of patients who have cirrhosis. These measures also inform economic evaluations by modelling quality-adjusted life years (QALYs). We aimed to describe health-related quality of life, specifically multiattribute utility (scale anchors of death = 0.00 and full health = 1.00), across various stages and etiologies of cirrhosis. METHODS: Face-to-face interviews were used to collect Short Form 36 (SF-36) questionnaire responses from CirCare study participants with cirrhosis (June 2017 to December 2018). The severity of cirrhosis was assessed using the Child-Pugh score classified as class A (5-6 points), B (7-9), or C (10-15) and by the absence ("compensated") versus presence ("decompensated") of cirrhosis-related complications. RESULTS: Patients (n = 562, average 59.8 years [SD = 11.0], male 69.9%) had a range of primary etiologies (alcohol-related 35.2%, chronic hepatitis C 25.4%, non-alcoholic fatty liver disease (NAFLD) 25.1%, chronic hepatitis B 5.9%, "other" 8.4%). Significantly lower (all P < 0.001) mean multiattribute utility was observed in the health states of patients with decompensated (mean = 0.62, SD = 0.15) versus compensated cirrhosis (mean = 0.68, SD = 0.12), Child-Pugh class C (mean = 0.59, SD = 0.15) or B (mean = 0.63, SD = 0.15) versus A (mean = 0.68, SD = 0.16), and between those of working age (18-64 years; mean = 0.64, SD = 0.16) versus those aged 65+ years (mean = 0.70, SD = 0.16). The greatest decrements in health-related quality of life relative to Australian population norms were observed across physical SF-36 domains. CONCLUSIONS: Persons with more advanced cirrhosis report greater life impacts. Estimates from this study are suitable for informing economic evaluations, particularly cost-utility modelling, which captures the benefits of effective prevention, surveillance, and treatments on both the quality and quantity of patients' lives.

Changing prevalence of aetiological factors and comorbidities among Australians hospitalised for cirrhosis.

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.

Efficacy and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus (HCV) NS5A-Inhibitor Experienced Patients With Difficult to Cure Characteristics.

BACKGROUND: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. METHODS: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). FINDINGS: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. CONCLUSIONS: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease.

Stereotactic radiotherapy for hepatocellular carcinoma: Expanding the multidisciplinary armamentarium.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third most common cause of cancer-related death. Long-term prognosis remains poor with treatment options frequently limited by advanced tumor stage, tumor location, or underlying liver dysfunction. Stereotactic ablative body radiotherapy (SABR) utilizes technological advances to deliver highly precise, tumoricidal doses of radiation. There is an emerging body of literature on SABR in HCC demonstrating high rates of local control in the order of 80-90% at 3 years. SABR is associated with a low risk of radiation-induced liver disease or decompensation in appropriately selected HCC patients with compensated liver function and is now being incorporated into guidelines as an additional treatment option. This review outlines the emerging role of SABR in the multidisciplinary management of HCC and summarizes the current evidence for its use as an alternative ablative option for early-stage disease, as a bridge to transplant, and as palliation for advanced-stage disease. We outline specific considerations regarding patient selection, toxicities, and response assessment. Finally, we compare current international guidelines and recommendations for the use of SABR and summarize ongoing studies.

Effectiveness of patient-oriented education and medication management intervention in people with decompensated cirrhosis.

People with chronic disease often have poor comprehension of their disease and medications, which can negatively affect health outcomes. In a randomised-controlled trial, we found that patients with decompensated cirrhosis who received a pharmacist-led, patient-oriented education and medication management intervention (n = 57) had greater knowledge of cirrhosis and key self-care tasks compared with usual care (n = 59). Intervention patients also experienced improved quality of life. Dedicated resources are needed to support implementation of evidence-based measures at local centres to improve outcomes.

Development and Evaluation of the Supportive Needs Assessment Tool for Cirrhosis (SNAC).

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

Increasing Hospitalization Rates for Cirrhosis: Overrepresentation of Disadvantaged Australians.

BACKGROUND: Limited information is available about hospitalization rates for cirrhosis in Australia. METHODS: Using information on all hospital episodes of care for patients admitted to Queensland hospitals during 2008-2016, we report age-standardized hospitalization rates/10,000 person-years, in-hospital case-fatality rate among these admissions (n = 30,327), and examine the factors associated with hospital deaths using logistic regression analyses. FINDINGS: Hospitalization rates increased from 8.50/10,000 (95% confidence interval (CI) 8.18-8.82) to 11.21/10,000 (95%CI 10.87-11.54) between 2008 and 2016, and peaked in men aged 55-59 years (34.03/10,000) and in Indigenous Australians (32.79/10,000). The number of admissions increased by 61.7% from 2701 admissions in 2008 to 4367 in 2016. During the same period, the percentage increase varied by socioeconomic disadvantage (3.2%/year in the most affluent vs. 9.4%/year in the most disadvantaged quintile; p < 0.001). Alcohol misuse was a contributing factor for cirrhosis in 55.1% of admissions, and socioeconomic disadvantage in 26.8%. The overall in-hospital case-fatality rate was 9.7% for males and 9.3% for females, and decreased in males (p < 0.001). Predictors of in-hospital mortality included hepatorenal syndrome (adjusted odds ratio (AOR) = 7.24, 95%CI 5.99-8.75), HCC (AOR = 2.53, 95%CI 2.20-2.91), hepatic encephalopathy (AOR = 1.94, 95%CI 1.61-2.34), acute peritonitis (AOR = 1.93, 95%CI 1.61-2.33), jaundice (AOR = 1.82, 95%CI 1.20-2.75), age ≥ 70 years (AOR = 1.63, 95%CI 1.38-1.92), a higher comorbidity index (p = 0.021), and residence outside of a "major city" (p < 0.001). INTERPRETATION: The increasing healthcare use by Australians with cirrhosis has resource and economic implications. Our data highlight the disproportionate impact of cirrhosis on Indigenous Australians and people from the most socioeconomically disadvantaged areas. FUNDING: Brisbane Diamantina Health Partners.

Medication-Related Problems in Outpatients With Decompensated Cirrhosis: Opportunities for Harm Prevention.

People with decompensated cirrhosis are often prescribed a complex regimen of therapeutic and prophylactic medications. In other chronic diseases, polypharmacy increases the risk of medication misadventure and medication-related problems (MRPs), with associated increased morbidity, mortality, and health care costs. This study examined MRPs in a cohort of ambulatory patients with a history of decompensated cirrhosis who were enrolled in a randomized controlled trial of a pharmacist-led, patient-oriented medication education intervention and assessed the association between MRPs and patient outcomes. A total of 375 MRPs were identified among 57 intervention patients (median, 6.0; interquartile range, 3.5-8.0 per patient; maximum 17). Nonadherence (31.5%) and indication issues (29.1%) were the most prevalent MRP types. The risk of potential harm associated with MRPs was low in 18.9% of instances, medium in 33.1%, and high in 48.0%, as categorized by a clinician panel using a risk matrix tool. Patients had a greater incidence rate of high-risk MRPs if they had a higher Child-Pugh score (incidence rate ratio [IRR], 1.31; 95% confidence interval [CI], 1.09-1.56); greater comorbidity burden (IRR, 1.15; 95% CI, 1.02-1.29); and were taking more medications (IRR, 1.12; 95% CI, 1.04-1.22). A total of 221 MRPs (58.9%) were resolved following pharmacist intervention. A greater proportion of high-risk MRPs were resolved compared to those of low and medium risk (68.9% versus 49.7%; P < 0.001). During the 12-month follow-up period, intervention patients had a lower incidence rate of unplanned admissions compared to usual care (IRR, 0.52; 95% CI, 0.30-0.92). Conclusion: High-risk MRPs are prevalent among adults with decompensated cirrhosis. Pharmacist intervention facilitated identification and resolution of high-risk MRPs and was associated with reduced incidence rate of unplanned hospital admissions in this group.

Underappreciation of non-alcoholic fatty liver disease by primary care clinicians: limited awareness of surrogate markers of fibrosis.

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.

Alcohol Consumption in Diabetic Patients with Nonalcoholic Fatty Liver Disease.

AIM: To examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD. METHODS: A cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day), and moderate drinkers (any period with intake >20 g/day). RESULT: Compared with lifetime nondrinkers, light and moderate drinkers were more likely to be male (p = 0.008) and to be Caucasian (p = 0.007) and to have a history of cigarette smoking (p = 0.000), obstructive sleep apnea (p = 0.003), and self-reported depression (p = 0.003). Moderate drinkers required ≥3 hypoglycemic agents to maintain diabetic control (p = 0.041) and fibrate medication to lower blood triglyceride levels (p = 0.044). Compared to lifetime nondrinkers, light drinkers had 1.79 (95% CI: 0.67-4.82; p = 0.247) and moderate drinkers had 0.91 (95% CI: 0.27-3.10; p = 0.881) times the odds of having liver stiffness measurements ≥8.2 kPa (adjusted for age, gender, and body mass index). CONCLUSIONS: In diabetic patients with NAFLD, light or moderate lifetime alcohol consumption was not significantly associated with liver fibrosis. The impact of lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in particular obstructive sleep apnea and hypertriglyceridemia, requires further investigation.