Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

Broadening and strengthening the health providers caring for patients with chronic hepatitis C may improve continuity of care.

BACKGROUND: Direct-acting antiviral (DAA) therapies for hepatitis C virus infection (HCV) lead to excellent rates of sustained virological response (SVR). However, loss to follow-up (LTFU) for SVR testing remains a challenge. We examine factors associated with LTFU in a real-world setting. METHODS: Adults who received DAA therapy for HCV in one of 26 centers across Australia during 2016-2021 were followed up for 2 years. Data sources included the patient medical records and the national Pharmaceutical and Medicare Benefits Schemes. Linkage to Medicare provided utilization data of other health-care providers and re-treatment with DAAs. LTFU was defined as no clinic attendance for SVR testing by at least 52 weeks after DAA treatment commencement. Multivariable logistic regression assessed factors associated with LTFU. RESULTS: In 3619 patients included in the study (mean age 52.0 years; SD = 10.5), 33.6% had cirrhosis (69.4% Child-Pugh class B/C), and 19.3% had HCV treatment prior to the DAA era. Five hundred and fifteen patients (14.2%) were LTFU. HCV treatment initiation in 2017 or later (adj-OR = 2.82, 95% confidence interval [CI] 2.25-3.54), younger age (adj-OR = 2.63, 95% CI 1.80-3.84), Indigenous identification (adj-OR = 1.99, 95% CI 1.23-3.21), current injection drug use or opioid replacement therapy (adj-OR = 1.66, 95% CI 1.25-2.20), depression treatment (adj-OR = 1.49, 95% CI 1.17-1.90), and male gender (adj-OR = 1.31, 95% CI 1.04-1.66) were associated with LTFU. CONCLUSIONS: These findings stress the importance of strengthening the network of providers caring for patients with HCV. In particular, services targeting vulnerable groups of patients such as First Nations Peoples, youth health, and those with addiction and mental health disorders should be equipped to treat HCV.

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.

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.

Liver Disease and Poor Adherence Limit Hepatitis C Cure: A Real-World Australian Treatment Cohort.

BACKGROUND AND AIMS: In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment. METHODS: 3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020. Clinical history and sustained viral response (SVR) were obtained from medical records and data linkage to the Australian Pharmaceutical Benefits Scheme. Factors associated with SVR were assessed by multivariable logistic regression (MVR). RESULTS: At recruitment, 32.2% had cirrhosis (72.9% Child Pugh class B/C), and 19.9% were treatment experienced. Of the 2,939 with data, 93.3% confirmed SVR. 137 patients received second-line therapy. Patients with cirrhosis had lower SVR rate (88.4 vs. 95.8%; p < 0.001). On MVR, failure to achieve SVR was associated with Genotype 3 (adj-OR = 0.42, 95%CI 0.29-0.61), male gender (adj-OR = 0.49, 95%CI 0.31-0.77), fair/poor adherence (adj-OR = 0.52, 95%CI 0.28-0.94), cirrhosis (adj-OR = 0.57, 95%CI 0.36-0.88), FIB-4 > 3.25 (adj-OR = 0.52, 95%CI 0.33-0.83) and MELD score ≥ 20 (adj-OR = 0.25, 95%CI 0.08-0.80). Consistent results were seen in cirrhotic sub-analysis. CONCLUSIONS: Excellent SVR rates were achieved with DAAs in this real-world cohort of patients with chronic HCV infection. More advanced liver disease and clinician impression of poor adherence were associated with HCV treatment failure. Supports to improve liver fibrosis assessment skills for non-specialist DAA prescribers in the community and to optimize patient adherence are likely to enable more effective pursuit of HCV elimination in Australia.

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.

Development of the motivational thought frequency scale for alcohol abstinence (MTF-A).

BACKGROUND AND AIMS: For most treatment-seeking patients with severe Alcohol Use Disorder (AUD), abstinence is the clinically indicated goal. Existing AUD motivation scales are non-specific about treatment consumption goals, which limit their effectiveness. Desires and mental imagery are relevant in the motivation for AUD treatment engagement. The Motivational Thought Frequency Scale for an abstinence goal (MTF-A) was adapted from the MTF for controlled drinking (MTF-CD). This study psychometrically evaluated the MTF-A in an alcohol-dependent sample engaged in treatment with a goal of abstinence. To enhance the clinical utility of the scale, a secondary aim was to evaluate a psychometrically equivalent short version of the MTF-A. METHOD: A sample N of 329 treatment-seeking patients with AUD (mean age of 44.44 years, SD = 11.89 years, 72% male) who were undertaking a cognitive behavioral treatment (CBT) program for abstinence completed the Motivational Thought Frequency Scale for Abstinence (MTF-A) and the Severity of Alcohol Dependence Questionnaire (SADQ). The MTF-A measured motivation for abstinence through four factors: intensity, self-efficacy imagery, incentives imagery, and availability. Confirmatory factor analyses (CFAs) were conducted to examine factor structure and model fit. Cronbach's alpha assessed internal consistency. Predictive validity was determined by logistic regression predicting first-session treatment non-attendance and alcohol consumption between baseline assessment and commencement of treatment, controlling for potential confounds. RESULTS: A four-factor structure provided the best fit for the MTF-A, compared with one- and three-factor models. A shortened 9-item MTF-A scale (S-MTF-A) provided better fit than the 13-item MTF-A scale. Both MTF-A and S-MTF-A displayed good internal consistency. Although both MTF-A and S-MTF-A successfully predicted first-session treatment non-attendance, neither predicted alcohol consumption between the baseline assessment and commencement of treatment. CONCLUSIONS: The model fit of the four-factor, 9-item S-MTF-A was superior to the original 13-item MTF-A. Both scales were predictive of participation of AUD treatment. Desires and mental imagery play an important role in AUD treatment motivation.

Monitoring quality of care in hepatocellular carcinoma: A modified Delphi consensus.

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system-level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival.

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

BACKGROUND: First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection. METHODS: Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016-2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU. RESULTS: Compared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p < 0.001), morel likely to reside in most disadvantaged (p = 0.002) and in regional/remote areas (p < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%; p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p = 0.51) and 'good' adherence (90.0% vs. 86.9%, respectively; p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87-0.99) and treatment initiation in 2018-2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23-21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50-0.99). CONCLUSIONS: Our data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.

Targeted antiviral treatment of hepatitis B virus in culturally and linguistically diverse populations to achieve elimination targets in Australia.

The majority of Australia's hepatitis B virus (HBV) burden is borne by culturally and linguistically diverse (CALD) populations, and antiviral treatment is the mainstay of intervention. Using modelling, we estimated the impact of targeted antiviral treatment scale-up and changes in migration on HBV-related mortality and HBV elimination in CALD populations in Australia. We fitted a deterministic mathematical model based on the natural history of HBV and the Australian migration effect in four CALD population groups according to country of birth. We used three antiviral treatment scale-up scenarios: baseline (9.3% coverage); intermediate (coverage of 80% of patients eligible for antiviral therapy by 2030); and optimistic (coverage of 20% of all patients living with HBV by 2022). Our model predicted that if the baseline treatment is followed between 2015 and 2030, the number of chronic HBV cases and HBV-related mortality will increase. Following the optimistic scale-up, the number of new HBV cases could be reduced by 78%, 73%, 74% and 83% in people born in Asia-Pacific, Europe, Africa and the Middle East, and Americas, respectively, between 2015 and 2030. An optimistic treatment scale-up could result in a 19.2%-24.5% reduction in HBV-related mortality and a 15%-25% reduction in HCC-related mortality in CALD populations between 2015 and 2030. In conclusion, our findings highlight that targeted antiviral treatment for CALD populations provides significant health system benefits by reducing HBV-related complications from cirrhosis and HCC. Expanded antiviral treatment programmes focusing on high-prevalence CALD populations may be an effective strategy to reduce HBV-related morbidity and mortality.

Near-Fatal Hepatic Complication After Cardiac Catheter Ablation.

Radiofrequency cardiac ablation is increasingly performed for the management of dysrhythmias. Bleeding is a well-known complication of this procedure. We present a rare case of a near-fatal iatrogenic hepatic hemorrhage after cardiac catheter ablation. (Level of Difficulty: Advanced.).

Fitting Health Care to People: Understanding and Adapting to the Epidemiology and Health Literacy of People Affected by Viral Hepatitis from Culturally and Linguistically Diverse Migrant Backgrounds.

This study explored the epidemiology and health literacy of people affected by viral hepatitis (VH) from migrant culturally and linguistically diverse (CALD) backgrounds attending a community-based general practitioner and specialty hepatology shared-care (HEPREACH) clinic in Brisbane, Australia. Patient-reported data on health literacy and clinical information from adult patients (n = 66) of CALD background recruited from the liver clinic were analyzed. Health literacy was assessed using a 5-question, 12-point scale. Variance weighted multiple linear regression was used to identify factors associated with knowledge about VH. About three-quarters of patients (74.2%) were diagnosed with hepatitis B. The median knowledge score was 7.8 (interquartile range [IQR] 6‒9). One in five patients did not understand the infective nature of VH, 30.3% did not understand mother-to-child transmission risk, and 30-40% of patients thought activities such as kissing, sharing food or mosquito bites could spread VH. Only 6% of patients understood the risk of liver cancer and the need for regular screening. Higher educational level (secondary, ß = 4.8, p < 0.0001 or tertiary, ß = 8.1, p < 0.0001 vs. primary) was associated with better knowledge, and transition through a refugee camp (vs. not, ß = - 1.2, p = 0.028) and country of diagnosis (overseas vs. Australia, ß = - 1.9, p = 0.016) were associated with poorer knowledge. Country of origin, refugee status and opportunities for tertiary education impact patients' understanding of VH. Ensuring delivery of culturally appropriate care and education is critical to improve knowledge, reduce misconceptions to improve care and outcomes for VH in CALD migrant communities.

Disparities in Unmet Needs in Indigenous and Non-Indigenous Australians with Cirrhosis: An Exploratory Study.

PURPOSE: Understanding and responding to the supportive care needs of people with cirrhosis is essential to quality care. Indigenous Australians, Aboriginal and Torres Strait Islander people, are overrepresented amongst patients with cirrhosis. This study documented the nature and extent of supportive care needs of Indigenous Australians with cirrhosis, in comparison with non-Indigenous Australians. PATIENTS AND METHODS: The supportive care needs of adult patients diagnosed with cirrhosis attending public hospitals in Queensland were assessed through the Supportive Needs Assessment tool for Cirrhosis (SNAC). Patients indicated how much additional help they needed on four subscales: 1. psychosocial issues; 2. practical and physical needs; 3. information needs; and 4. lifestyle changes. We examined the rate of moderate-to-high unmet needs based on Indigenous status (Poisson regression; incidence rate ratio (IRR)). RESULTS: Indigenous (n=20) and non-Indigenous (n=438) patients included in the study had similar sociodemographic and clinical characteristics except for a lower educational level among Indigenous patients (p<0.01). Most Indigenous patients (85.0%) reported having moderate-to-high unmet needs with at least one item in the SNAC tool. Following adjustment for key sociodemographic and clinical factors, Indigenous patients had a greater rate of moderate-to-high unmet needs overall (IRR=1.5, 95% CI 1.31-1.72; p<0.001), and specifically for psychosocial issues (IRR=1.7, 95% CI 1.39-2.15; p<0.001), and practical and physical needs subscales (IRR=1.5, 95% CI 1.22-1.83; p<0.001), compared to non-Indigenous patients. CONCLUSION: Indigenous Australians with cirrhosis more frequently had moderate-to-high unmet supportive care needs than non-Indigenous patients. Specific targeting of culturally appropriate supportive care for psychosocial, practical and physical needs may optimize cirrhosis care and improve the quality of life for Indigenous Australians with cirrhosis.

Remoteness of residence predicts tumor stage, receipt of treatment, and mortality in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Surveillance and early detection and curative treatment of hepatocellular carcinoma (HCC) are the mainstay of improving survival for patients, but there are several barriers to achieving this goal. We reported the impact of remoteness of residence on receipt of treatment, tumor stage, and survival in patients with HCC in Queensland. METHODS: We conducted a retrospective cohort study of 1651 HCC patients (147 migrants) from 1 January 2007 to 31 December 2016. We used Wilcoxon rank-sum test to compare the median age at the time of diagnosis and Bayesian Weibull accelerated failure time regression to identify independent predictors of time to death. RESULTS: The median survival time after HCC diagnosis was 9.0 months (interquartile range 2.0-24.0). Metropolitan residence (P = 0.02), non-English language (P < 0.001), foreign country of origin (P < 0.001), and HBV etiology (P < 0.001) were significantly associated with receiving surgical resection for HCC treatment. The strongest predictors of time to death were undifferentiated tumor at presentation (time ratio [TR] = 0.30, 95% credible interval (CrI) 0.23-0.39), age ≥70 years (TR = 0.42, 95% CrI 0.34-0.53), living in remote areas (TR = 0.67, 95% CrI 0.55-0.80), and presence of ≥1 comorbidity (TR = 0.69 95% CrI 0.54-0.90). All the other covariates adjusted, including country of birth (TR = 0.76, 95% CrI 0.49-1.06), did not predict survival time. CONCLUSIONS: Patients living in rural and remote areas had late stage clinical presentation and poor survival. Remoteness of residence may limit access to HCC surveillance in at-risk patients such as those with cirrhosis, and timely curative treatment to improve survival in these patients.

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.