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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, β = 4.8, p

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, In a cohort study of 1651 patients with hepatocellular carcinoma, we found patients living in rural and remote areas were more likely to present with late stage of tumor, less likely to receive curative treatment such as surgical resection, and experience 25% shorter survival time. In a multivariate analysis, remote residence, preferred language, older age at presentation, poorly differentiated tumor, and presence of medical comorbidity were associated with poorer HCC survival, possibly because of limited access to surveillance and curative treatment.

Background and aim End-stage liver disease is a leading cause of mortality. Fewer than 60% of patients with decompensated cirrhosis survive after two years, with patients often experiencing distressing symptoms impairing quality of life. Early advanced care planning and timely palliative care referral can improve quality of life and the end of life experience. We aimed to determine palliative care referral rates and patterns for patients admitted with decompensated cirrhosis, and to identify the factors associated with referral. Methods This was a retrospective, single-centre study undertaken at a metropolitan tertiary referral hospital. Patients admitted between the 1st June 2016 to 31st January 2019 with a Child-Pugh score of B or C, and a Model for End-Stage Liver Disease score ≥15 were included. We assessed survival and compared those referred and not referred to palliative care, adjusting for lag-time to referral (Kaplan-Meier analysis). Results One-hundred-and-sixteen admissions met eligibility criteria for referral. The median age at admission was 59 years, with 76% male. Only a fifth of eligible patients (25/116) were referred to palliative care. The median survival (from referral) for those referred to palliative care was 20 days, versus 148 days for those not referred. Conclusions Despite benefits from timely referral, less than one-quarter of palliative care eligible patients were referred. Referral appears reserved for those facing imminent death - surviving just under three weeks post-referral, yet mortality in non-referred patients remained high (148-day median). Low rates and late referral are a missed opportunity to improve the end of life care for patients with end-stage liver disease.

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

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, Measuring health‐related quality of life is important for understanding patients' experiences living with cirrhosis. Multiattribute utility is a summary measure commonly derived from health‐related quality‐of‐life questionnaires by applying population‐based preference weights with anchors of death (0.00) and perfect health (1.00) and is used in health state modelling, including economic evaluations that incorporate quality‐adjusted life years (known as QALYs). Here, we report health‐related quality‐of‐life and multiattribute utility values for a range of cirrhosis disease stages. These values will inform both clinical and economic research, including cost‐effectiveness modelling that captures benefits to both the quantity and quality of people's lives through the better prevention and management of cirrhosis.

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

Christina M Bernardes,1 Paul J Clark,2 Cath Brown,1 Katherine Stuart,3 Gregory Pratt,1 Maree Toombs,4 Gunter Hartel,1 Elizabeth E Powell,3,5,&ast; Patricia C Valery1,&ast; 1QIMR Berghofer Medical Research Institute, Herston, QLD, Australia; 2Department of Gastroenterology and Hepatology, Mater Hospitals, Brisbane, QLD, Australia; 3Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia; 4Rural Clinical School, Faculty of Medicine, University of Queensland, Toowoomba, QLD, Australia; 5Centre for Liver Disease Research, Translational Research Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia&ast;These authors contributed equally to this workCorrespondence: Patricia C Valery Tel +61 07 3362 0376Email Patricia.Valery@qimrberghofer.edu.auPurpose: 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.Keywords: chronic liver disease, patient reported outcomes, perceived needs, unmet needs, Indigenous Australians

Background Culturally and linguistically diverse communities face several challenges to receiving screening and curative treatment of hepatocellular carcinoma (HCC). We reported the predictors of receipt of treatment and survival in a cohort of patients diagnosed with HCC in Southeast Queensland. Methods Data from 1651 HCC patients (147 migrants) followed between January 1, 2007, and December 31, 2016 were analyzed using chi-square statistic to test for the association between socio-economic variables and receipt of treatment. Bayesian Weibull Accelerated Failure Time regression was used to identify predictors of time to death, and we reported time ratios. Results Receipt of surgical resection for HCC was associated with non-metropolitan residence (P=0.02), non-English language (P Conclusions Improving access to HCC surveillance and uptake of timely curative treatment for persons living in remote areas and having socioeconomic disadvantage may help patients present to clinic with early stage tumor and provide better survival. Key messages Remoteness of residence is associated with late presentation, low rate of receipt of treatment and predicts survival of patients with HCC.

Background Indigenous Australians experience greater health disadvantage and have a higher prevalence of many chronic health conditions. Liver diseases leading to cirrhosis are among the most common contributor to the mortality gap between Indigenous and other Australian adults. However, no comparative data exist assessing differences in presentation and patient outcomes between Indigenous and non-Indigenous Australians hospitalised with cirrhosis. Methods Using data from the Hospital Admitted Patient Data Collection and the Death Registry, this retrospective, population-based, cohort study including all people hospitalised for cirrhosis in the state of Queensland during 2008–2017 examined rate of readmission (Poisson regression), cumulative survival (Kaplan–Meier), and assessed the differences in survival (Multivariable Cox regression) by Indigenous status. Predictor variables included demographic, health service characteristics and clinical data. Results We studied 779 Indigenous and 10,642 non-Indigenous patients with cirrhosis. A higher proportion of Indigenous patients were younger than 50 years (346 [44%] vs. 2063 [19%] non-Indigenous patients), lived in most disadvantaged areas (395 [51%) vs. 2728 [26%]), had alcohol-related cirrhosis (547 [70%] vs. 5041 [47%]), had ascites (314 [40%] vs. 3555 [33%), and presented to hospital via the Emergency Department (510 [68%] vs. 4790 [47%]). Indigenous patients had 3.04 times the rate of non-cirrhosis readmissions (95%CI 2.98–3.10), 1.35 times the rate of cirrhosis-related readmissions (95%CI 1.29–1.41), and lower overall survival (17% vs. 27%; unadjusted hazard ratio (HR) = 1.16 95%CI 1.06–1.27), compared to non-Indigenous patients. Most of the survival deficit was explained by Emergency Department presentation (adj-HR = 1.03 95%CI 0.93–1.13), and alcohol-related aetiology (adj-HR = 1.08 95%CI 0.99–1.19). The remaining survival deficit was influenced by the other clinico-demographic and health service factors (final adj-HR = 1.08 95%CI 0.96–1.20). Conclusions There was evidence of differential presentation, higher rates of readmissions, and poorer survival for Indigenous Australians with cirrhosis, compared to other Australians. The increased prevalence of Emergency Department presentation among Indigenous patients suggests missed opportunities for early intervention to prevent progressive cirrhosis complications and hospital readmissions.

Objective: Describe the sociodemographic and clinical characteristics of patients with Hepatitis C Virus (HCV) attending an urban Indigenous primary health clinic (IPHC) in Brisbane, Australia. Methods: A retrospective chart review of sociodemographic characteristics, presence of liver disease and treatments, lifestyle behaviours and comorbidities in patients with a HCV infection was conducted between October 2015 and March 2016. Results: One hundred and thirteen patients with confirmed HCV infection were aged between seven and 63 years; 66% were male, and 84% were Indigenous. Sixty‐nine per cent had been incarcerated; 41% had experienced conflict or domestic violence; 47% were injecting drugs; 72% had depression; and 61% had anxiety. Cirrhosis was present in 7/95 patients with adequate data and associated with age (p=0.02). Eleven patients had commenced direct acting antiviral (DAA) therapy in the 18 months that it had been available. Conclusions: The study highlights the opportunities for enhancing treatment of patients with HCV infection. Opportunities to improve treatment rates in an Indigenous primary healthcare include optimising diagnostic pathways, improving patient engagement, and general practitioner and peer worker participation. Implications for public health: HCV poses a serious threat to public health in Australia and IPHCs are key sites to addressing this for Indigenous people. Optimising care of patients with HCV attending IPHC requires recognition of the complex health needs and social context, to reduce the incidence and consequences of HCV infection.

Background Treatment seeking for people with alcohol use disorders (AUD), injecting drug use and viral hepatitis is low, and has worsened during the coronavirus disease 2019 (COVID-19) pandemic. Deferring clinical care and increasing drug and alcohol use exacerbate the risks of progression for individuals with chronic liver disease from viral hepatitis and/or alcohol-related liver disease (ALD). We explored the impact COVID-19 epidemic may have on patients with chronic liver disease and suggested mechanisms to protect this at-risk population during and after the pandemic. # Methods We searched PubMed, EMBASE, and Google Scholar for published articles and grey literature and synthesized information about the impact COVID-19 has on patients with chronic liver disease, specifically related to impacts and opportunities to prevent viral hepatitis and ALD. # Results The COVID-19 pandemic has caused significant disruption of clinical management of patients with liver disease, but also to alcohol and drug services, needle and syringe programs (NSP), hepatitis B (HBV) screening, and treatment efforts. Social isolation and pandemic-related anxiety have caused an increase in alcohol and drug use. COVID-19 pandemic disruptions may lead to an increase in the incidence of viral hepatitis and ALD, but also cause patients to undertake risky behaviours. The pandemic impacts people with chronic conditions such as HBV to defer medical visits or undertake screening tests. These factors may worsen rates of decompensation for patients with cirrhosis, for whom these deleterious impacts are believed to stay for some time after the pandemic. Interruption in screening, treatment, and monitoring services during the period disrupts chronic disease management of viral hepatitis and ALD and increases the risk of worsening the clinical course of liver disease and delayed diagnosis of hepatocellular carcinoma. # Conclusions Successful mitigation of the impact of COVID-19 on the incidence of viral hepatitis and alcoholic liver disease requires adaptive approaches to reach people with injecting drug use and AUD including community-based networks, fixed site and mobile NSP, mail delivery systems, the use of telehealth, and other digital media for promoting and implementing alcohol harm reduction during and after the COVID-19 pandemic.

Summary of recommendations and levels of evidence Chapter 2: Screening and assessment for unhealthy alcohol use Screening Screening for unhealthy alcohol use and appropriate interventions should be implemented in general practice (Level A), hospitals (Level B), emergency departments and community health and welfare settings (Level C). Quantity–frequency measures can detect consumption that exceeds levels in the current Australian guidelines (Level B). The Alcohol Use Disorders Identification Test (AUDIT) is the most effective screening tool and is recommended for use in primary care and hospital settings. For screening in the general community, the AUDIT-C is a suitable alternative (Level A). Indirect biological markers should be used as an adjunct to screening (Level A), and direct measures of alcohol in breath and/or blood can be useful markers of recent use (Level B). Assessment Assessment should include evaluation of alcohol use and its effects, physical examination, clinical investigations and collateral history taking (Level C). Assessment for alcohol-related physical problems, mental health problems and social support should be undertaken routinely (GPP). Where there are concerns regarding the safety of the patient or others, specialist consultation is recommended (Level C). Assessment should lead to a clear, mutually acceptable treatment plan which specifies interventions to meet the patient’s needs (Level D). Sustained abstinence is the optimal outcome for most patients with alcohol dependence (Level C). Chapter 3: Caring for and managing patients with alcohol problems: interventions, treatments, relapse prevention, aftercare, and long term follow-up Brief interventions Brief motivational interviewing interventions are more effective than no treatment for people who consume alcohol at risky levels (Level A). Their effectiveness compared with standard care or alternative psychosocial interventions varies by treatment setting. They are most effective in primary care settings (Level A). Psychosocial interventions Cognitive behaviour therapy should be a first-line psychosocial intervention for alcohol dependence. Its clinical benefit is enhanced when it is combined with pharmacotherapy for alcohol dependence or an additional psychosocial intervention (eg, motivational interviewing) (Level A). Motivational interviewing is effective in the short term and in patients with less severe alcohol dependence (Level A). Residential rehabilitation may be of benefit to patients who have moderate-to-severe alcohol dependence and require a structured residential treatment setting (Level D). Alcohol withdrawal management Most cases of withdrawal can be managed in an ambulatory setting with appropriate support (Level B). Tapering diazepam regimens (Level A) with daily staged supply from a pharmacy or clinic are recommended (GPP). Pharmacotherapies for alcohol dependence Acamprosate is recommended to help maintain abstinence from alcohol (Level A). Naltrexone is recommended for prevention of relapse to heavy drinking (Level A). Disulfiram is only recommended in close supervision settings where patients are motivated for abstinence (Level A). Some evidence for off-label therapies baclofen and topiramate exists, but their side effect profiles are complex and neither should be a first-line medication (Level B). Peer support programs Peer-led support programs such as Alcoholics Anonymous and SMART Recovery are effective at maintaining abstinence or reductions in drinking (Level A). Relapse prevention, aftercare and long-term follow-up Return to problematic drinking is common and aftercare should focus on addressing factors that contribute to relapse (GPP). A harm-minimisation approach should be considered for patients who are unable to reduce their drinking (GPP). Chapter 4: Providing appropriate treatment and care to people with alcohol problems: a summary for key specific populations Gender-specific issues Screen women and men for domestic abuse (Level C). Consider child protection assessments for caregivers with alcohol use disorder (GPP). Explore contraceptive options with women of reproductive age who regularly consume alcohol (Level B). Pregnant and breastfeeding women Advise pregnant and breastfeeding women that there is no safe level of alcohol consumption (Level B). Pregnant women who are alcohol dependent should be admitted to hospital for treatment in an appropriate maternity unit that has an addiction specialist (GPP). Young people Perform a comprehensive HEEADSSS assessment for young people with alcohol problems (Level B). Treatment should focus on tangible benefits of reducing drinking through psychotherapy and engagement of family and peer networks (Level B). Aboriginal and Torres Strait Islander peoples Collaborate with Aboriginal or Torres Strait Islander health workers, organisations and communities, and seek guidance on patient engagement approaches (GPP). Use validated screening tools and consider integrated mainstream and Aboriginal or Torres Strait Islander-specific approaches to care (Level B). Culturally and linguistically diverse groups Use an appropriate method, such as the “teach-back” technique, to assess the need for language and health literacy support (Level C). Engage with culture-specific agencies as this can improve treatment access and success (Level C). Sexually diverse and gender diverse populations Be mindful that sexually diverse and gender diverse populations experience lower levels of satisfaction, connection and treatment completion (Level C). Seek to incorporate LGBTQ-specific treatment and agencies (Level C). Older people All new patients aged over 50 years should be screened for harmful alcohol use (Level D). Consider alcohol as a possible cause for older patients presenting with unexplained physical or psychological symptoms (Level D). Consider shorter acting benzodiazepines for withdrawal management (Level D). Cognitive impairment Cognitive impairment may impair engagement with treatment (Level A). Perform cognitive screening for patients who have alcohol problems and refer them for neuropsychological assessment if significant impairment is suspected (Level A). Summary of key recommendations and levels of evidence Chapter 5: Understanding and managing comorbidities for people with alcohol problems: polydrug use and dependence, co-occurring mental disorders, and physical comorbidities Polydrug use and dependence Active alcohol use disorder, including dependence, significantly increases the risk of overdose associated with the administration of opioid drugs. Specialist advice is recommended before treatment of people dependent on both alcohol and opioid drugs (GPP). Older patients requiring management of alcohol withdrawal should have their use of pharmaceutical medications reviewed, given the prevalence of polypharmacy in this age group (GPP). Smoking cessation can be undertaken in patients with alcohol dependence and/or polydrug use problems; some evidence suggests varenicline may help support reduction of both tobacco and alcohol consumption (Level C). Co-occurring mental disorders More intensive interventions are needed for people with comorbid conditions, as this population tends to have more severe problems and carries a worse prognosis than those with single pathology (GPP). The Kessler Psychological Distress Scale (K10 or K6) is recommended for screening for comorbid mental disorders in people presenting for alcohol use disorders (Level A). People with alcohol use disorder and comorbid mental disorders should be offered treatment for both disorders; care should be taken to coordinate intervention (Level C). Physical comorbidities Patients should be advised that alcohol use has no beneficial health effects. There is no clear risk-free threshold for alcohol intake. The safe dose for alcohol intake is dependent on many factors such as underlying liver disease, comorbidities, age and sex (Level A). In patients with alcohol use disorder, early recognition of the risk for liver cirrhosis is critical. Patients with cirrhosis should abstain from alcohol and should be offered referral to a hepatologist for liver disease management and to an addiction physician for management of alcohol use disorder (Level A). Alcohol abstinence reduces the risk of cancer and improves outcomes after a diagnosis of cancer (Level A).

Background: Liver disease and hepatocellular carcinoma (HCC) are important contributors to the mortality gap between Indigenous and non-Indigenous Australians. However, there is a lack of population based high quality data assessing the differences in HCC epidemiology and outcomes according to Indigenous status. The aim of this study was therefore to perform a large epidemiological study of HCC investigating differences between Indigenous and non-Indigenous Australians with HCC. Methods: Study design was a retrospective cohort study. Data linkage methodology was used to link data from cancer registries with hospital separation summaries across three Australian jurisdictions during 2000–2017. Cumulative survival (Kaplan-Meier) and the differences in survival (Multivariable Cox-regression) by Indigenous status were assessed. Findings: A total of 229 Indigenous and 3587 non-Indigenous HCC cases were included in the analyses. Significant epidemiological differences identified for Indigenous HCC cases included younger age at onset, higher proportion of females, higher rurality, lower socioeconomic status, and higher comorbidity burden (all p < 0.001). The distribution of cofactors was also significantly different for Indigenous Australians including higher prevalence of alcohol misuse, hepatitis B, and diabetes and more frequent presence of multiple HCC cofactors (all p < 0.001). Indigenous Australians received curative HCC therapies less frequently (6.6% vs. 14.5%, p < 0.001) and had poorer 5-year survival (10.0% vs. 17.3%, p < 0.001; unadjusted hazard ratio (HR) =1.42 96%CI 1.21–1.65) compared to non-Indigenous Australians. The strength of the association between indigenous status and survival was weaker and statistically non-significant after adjusting for rurality, comorbidity burden and lack of curative therapy (adjusted-HR=1.20 95%CI 0.97–1.47) Interpretation: Such data provide a call to action to help design and implement health literacy, liver management and HCC surveillance programs for Indigenous people to help close the liver cancer mortality gap.

Aim: To better understand the hepatocellular carcinoma (HCC) patient journey, we conducted a patient survey across 13 countries. Methods: The survey included closed- and open-ended questions developed using an iterative process to gather information on demographics, diagnosis and treatment. Patients self-selected or were directed to the online survey by their doctor. Results: A total of 256 patients completed the survey. More than two-thirds (68%) felt they did not receive enough information about HCC at diagnosis. Treatments included oral anticancer therapy, transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT). A total of 81% receiving sorafenib, 45% receiving SIRT and 32% receiving TACE reported impaired quality-of-life (QoL). A total of 42, 19 and 0% of patients using sorafenib rated their current QoL as ‘poor’, ‘good’ and ‘excellent’, respectively; compared with SIRT (22, 33 and 6%) or TACE (11, 37 and 13%). Conclusion: Most patients with HCC require additional accessible information. People with incurable HCC require treatments that preserve QoL.

Background: Many patients with cirrhosis follow complex medication and dietary regimens, and those with decompensated cirrhosis suffer debilitating complications. These factors impact activities of daily living and quality of life. Aims: To explore the concerns and challenges of people with cirrhosis and their use of support services and to also describe health professionals’ (HP) perspectives of patients’ concerns. Methods: This is a cross-sectional study at a tertiary liver clinic involving 50 patients and 54 HP. Data were collected using structured questionnaires. The study includes patients’ report of their challenges/problems now that they have cirrhosis (‘patient-volunteered concerns’) and HP’ report of patients’ concerns. Both also ranked a list of 10 potential concerns. Results: Patients were, on average, 58 years old (SD = 10.2), mostly male (78%), Caucasian (86%) and with compensated cirrhosis (60%). The patients’ most common volunteered concerns related to managing symptoms, emotional issues and disease. Most ranked ‘developing liver cancer’ (79%), ‘losing ability to do daily tasks for yourself’ (76%), ‘fear of dying’ (64%) and ‘fear of the unknown’ (64%) as priority concerns. Regarding the use of support services, 24% of patients had accessed a dietician, 20% a pharmacist and 18% a psychologist. From the HP’ perspective, the patients’ most significant challenges related to managing disease (65%) and symptoms (48%), access to healthcare (56%) and information/knowledge (48%). Conclusions: Our findings demonstrate that cirrhosis (its symptoms, complications and treatment) is associated with significant concerns for patients. The discrepancies between the views of HP and patients suggest that we may not be measuring or addressing patients’ needs appropriately.

Background: Primary liver cancer is a leading cause of cancer deaths worldwide. Global burden varies, reflecting geographical distribution of viral hepatitis. Our objective was to perform a systematic review and meta-analysis of published current trends in incidence of adult liver cancers and histological types worldwide. Methods: This study used systematic searches of PubMed, Embase, CINAHL, and Web of Science databases for English-language peer-reviewed articles published from 1 January 2008 to 01 September 2019. Inclusion criteria were population-based studies of adult liver cancer patients with quantitative estimates of temporal trends in incidence for liver cancers and/or histological types. For multiple studies from the same geographical area, only the publication that reported the most recent trends for the same cancer type and population subgroup was included. Review was conducted per PRISMA guidelines. Two authors independently extracted data and critically assessed studies. Proposed contributors to observed trends were extracted from included articles. Study-specific estimates of the annual percentage change (APC) in incidence rates with 95% confidence intervals (CIs) were pooled using random-effects meta-analysis models. Heterogeneity was measured using the I2 statistics and publication bias evaluated using funnel plots and Egger's tests. Results: Overall, 53 studies met the inclusion criteria, of which 31 were included in the meta-analysis. Overall, pooled APC estimates were +0.8 (95% CI −0.3, +2.0) for liver cancers combined, +2.6 (95% CI +1.2, +4.0) for hepatocellular carcinoma (HCC), and +4.3 (95% CI +2.5, +6.1) for intrahepatic cholangiocarcinoma. Subgroup analyses indicated increasing trends for liver cancers (APC +3.2, 95% CI +2.5, +3.9) and HCC (APC +3.6, 95% CI +2.9, +4.4) in the region of North America/Europe/Australia, whereas corresponding trends were decreasing (APC −1.7, 95% CI −2.2, −1.1) and stable (APC −0.7, 95% CI −1.9, +0.5) in Asia, respectively. Conclusions: Incidence is increasing for adult liver cancers and HCC in Western countries, whereas trends are decreasing in the Asian region, although still remaining high. Our findings highlight the importance of viral hepatitis control and lifestyle interventions to reduce global liver cancer burden. Ongoing surveillance is also vital to detect early shifts in incidence trends.

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

Rash impulsiveness, the propensity for approach behaviour despite potential negative consequences, is associated with stronger alcohol craving in patients with Alcohol Use Disorder (AUD). This relationship is poorly understood and implications for treatment response are unexamined. This study explored the relationship between rash impulsiveness, craving, and treatment response among 304 outpatients enrolled in a 12-week abstinence-based Cognitive-Behavioural Therapy (CBT) program for AUD. Assessments were completed pre-and-post treatment, with craving and alcohol consumption monitored at each treatment session. Higher rash impulsiveness predicted more frequent craving over treatment (b = 0.95, 95% CI = 0.40, 1.50). Higher craving was associated with greater lapse-risk (b = 0.04, 95% CI = 0.03, 0.05), with the association between craving and lapse-risk increasing as treatment progressed (b = 0.01, 95% CI = 0.01, 0.02). Craving positively mediated the relationship between rash impulsiveness and lapse-risk (µ = 0.38, 95% CI = 0.10, 0.70). Contrary to hypotheses, the risk of lapse in response to craving was not moderated by rash-impulsiveness. These results suggest that AUD patients with a predisposition for rash impulsiveness are more vulnerable to alcohol craving, and subsequently, poorer treatment outcomes.

Introduction A BSG-endorsed care bundle for the management of decompensated cirrhosis in the first 24 hours of admission has been implemented in the North East of England resulting in improved management of these patients; however in this study patient outcomes were not followed up and there have been no subsequent published studies of its use.1,2 In our expanding hepatology unit of a small tertiary hospital in Brisbane, Australia we reviewed inpatient management of decompensated cirrhotic patients to assess morbidity, mortality and if adherence to the care bundle improves patient outcomes. Methods We retrospectively reviewed patient notes for hospital admissions due to decompensated cirrhosis between 1/6/16 – 1/6/17. Admissions were scored according to care bundle adherence and divided into tertiles. Mortality, rates of readmission and inpatient length of stay (LOS) were compared between the most adherent and least adherent groups using Fisher’s exact test with p values Results 59 admissions were reviewed consisting of 39 patients (69% male, median age 60 years) with a median MELD 19. Only Child-Pugh B (33/59, 56%) and C (26/59, 44%) patients were included. The most adherent group had numerically lower 1-year mortality (5/16, 31%) than the least adherent group (7/15, 47%, p=0.4725). Readmission rates within 1 year were reduced in the most adherent group (6/17, 35%) compared to the least adherent group (8/16, 50%), though not statistically significant (p=0.4905). Readmission rates at 30 days and 6 months were also reduced with care bundle adherence however again were not statistically significant. There was no effect on the length of hospital stay between groups. Conclusions Our results suggest reduced mortality and hospital readmission in patients more closely adherent to the BSG care bundle, however this difference did not reach statistical significance. Reasons for this include a small sample size which limited statistical power and that overall adherence to the care bundle was poor. Following this study, we plan to implement a care bundle systematically to further evaluate patient outcomes. References McPherson, S., Dyson, J., Austin, A. & Hudson, M. Response to the NCEPOD report: development of a care bundle for patients admitted with decompensated cirrhosis—the first 24|h. Frontline Gastroenterol. 7, 16–23 ( 2016). Dyson, J. K. et al. Implementation of a ‘care bundle’ improves the management of patients admitted to hospital with decompensated cirrhosis. Aliment. Pharmacol. Ther. 44, 1030–1038 ( 2016).

Summary Background Liver-related mortality varies across developed nations. Aim To assess the relative role of various risk factors in relation to liver-related mortality in an ecological study approach. Methods Data for liver-related mortality, prevalence data for hepatitis B and C, human immunodeficiency virus (HIV), alcohol consumption per capita, Type 2 Diabetes mellitus (T2DM), overweight and obesity were extracted from peer-reviewed publications or WHO databases for different developed countries. As potential other risk-modifying factors, purchase power parity (PPP)-adjusted gross domestic product (GDP) per capita and health expenditure per capita were assessed. As an environmental ‘hygiene factor’, we also assessed the effect of the prevalence of Helicobacter pylori. Only countries with a PPP-adjusted GDP greater than $20 000 and valid information for at least 8 risk modifiers were included. Univariate and multivariate analyses were utilised to quantify the contribution to the variability in liver-related mortality. Results The proportion of chronic liver diseases (CLD)-related mortality ranged from 0.73–2.40% [mean 1.56%, 95% CI (1.43–1.69)] of all deaths. Univariately, CLD-related mortality was significantly associated with Hepatitis B prevalence, alcohol consumption, PPP-adjusted GDP (all P < 0.05) and potentially H. pylori prevalence (P = 0.055). Other investigated factors, including hepatitis C, did not yield significance. Backward elimination suggested hepatitis B, alcohol consumption and PPP-adjusted GDP as risk factors (explaining 66.3% of the variability). Conclusion Hepatitis B infection, alcohol consumption and GDP, but not hepatitis C or other factors, explain most of the variance of liver-related mortality.

Purpose In the interferon era of hepatitis C virus (HCV) therapies, genotype/subtype, cirrhosis, prior treatment failure, sex, and race predicted relapse. Our objective is to validate a targeted proteomics platform of 17 peptides to predict sustained virologic response (SVR). Experimental design Stored plasma from three, open-label, trials of HIV/HCV-coinfected subjects receiving interferon-containing regimens is identified. LC-MS/MS is used to quantitate the peptides directly from plasma, and IL28B genotyping is completed using stored peripheral blood mononuclear cells (PBMC). A logistic regression model is built to analyze the probability of SVR using responders and nonresponders to interferon-based regimens. Results The cohort (N = 35) is predominantly black (51.4%), male (86%), and with median age 48 years. Most patients achieve SVR (54%). Using multivariable models, it is verified that three human corticosteroid binding globulin (CBG) peptides are predictive of SVR in patients with the unfavorable IL28B genotypes (CT/TT). The model performs better than IL28B alone, with an area under the curve of 0.870. Conclusions and clinical relevance In HIV/HCV-coinfected patients, three human CBG peptides that accurately predict treatment response with interferon-based therapy are identified. This study suggests that a stepwise approach combining a genetic predictor followed by targeted proteomics can improve the accuracy of clinical decision-making.

Background and aims:While chronic liver disease is a major global public health problem, it has not been recognized as a National Health Priority Area in Australia. A population-based study using hospital admission data for cirrhosis in the large state of Queensland, Australia during 2008-2016 was performed. Method:Hospital data on all patient admissions (public and private)and deaths during 2008-2016 in the state of Queensland were obtained. Queensland is a large state in the north-east of Australia with a population of 4.9 million. We identified all hospital admissions for cirrhosis for patients aged 20 years or older. We reported age-standardized hospitalization rates/10, 000 person-years by gender and per calendar year, in-hospital case fatality rate among these admissions (n = 30, 327) and examined the factors associated with hospital deaths. Results:Age-adjusted hospitalization rates increased by 32%between 2008 and 2016, from 8.50/10, 000 (95%CI 8.18-8.82) to11.21/10, 000 (95%CI 10.87-11.54). Admission rates peaked in men at34.03/10, 000 in 55-59 year-olds. The age-standardized admission rate for Indigenous Australians was 32.79/10, 000 (95%CI 31.28-34.31). Alcohol misuse was a contributing factor in over half (55.1%) of all admissions, and in 26.8% of admissions patients resided in most socio-economically disadvantaged areas. The overall in-hospital case fatality rate was 9.7% for males and 9.3% for females, and decreased significantly in males from 10.25% in 2008 to 8.32% in 2016 (p Conclusion:Our data highlights the increasing healthcare use by Australians with cirrhosis and this has major resource and economic implications. Greater awareness and emphasis on preventive care is needed to reduce the increasing prevalence of cirrhosis and the personal, social and economic burden of its complications.

Primary liver cancer (PLC) is the sixth most common cancer worldwide and the second most common cause of cancer death. Future predictions can inform health planners and raise awareness of the need for cancer control action. We predicted the future burden of PLC in 30 countries around 2030. Incident cases of PLC (International Classification of Diseases, Tenth Revision, C22) were obtained from 30 countries for 1993-2007. We projected new PLC cases to 2030 using age-period-cohort models (NORDPRED software). Age-standardized incidence rates per 100,000 person-years were calculated by country and sex. Increases in new cases and rates of PLC are projected in both sexes. The largest increases in rates are, among men, in Norway (2.9% per annum), US whites (2.6%), and Canada (2.4%) and, among women, in the United States (blacks 4.0%), Switzerland (3.4%), and Germany (3.0%). The projected declines are in China, Japan, Singapore, and parts of Europe (e.g., Estonia, Czech Republic, Slovakia). A 35% increase in the number of new cases annually is expected compared to 2005. This increasing burden reflects both increasing rates (and the underlying prevalence of risk factors) and demographic changes. Japan is the only country with a predicted decline in the net number of cases and annual rates by 2030. Conclusion: Our reporting of a projected increase in PLC incidence to 2030 in 30 countries serves as a baseline for anticipated declines in the longer term through the control of hepatitis B virus and hepatitis C virus infections by vaccination and treatment; however, the prospect that rising levels of obesity and its metabolic complications may lead to an increased risk of PLC that potentially offsets these gains is a concern. (Hepatology 2018;67:600-611).

Determining risk for recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) is an important clinical need. We assessed consecutive patients who underwent LT for HCC following sequential transarterial chemoembolization (TACE). Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) categories: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Cox proportional hazard models were used to predict HCC recurrence. One hundred seventy-three patients underwent TACE and imaging to assess response prior to LT. TACE responses were: CR = 23.7%, PR = 24.3%, SD = 27.7% and PD = 24.3%. Five-year HCC recurrence rate was 5.3% in patients responding to TACE (CR/PR), versus 17.6%, among patients who did not respond (SD/PD, p = 0.014). In multivariate analysis, independent pre-LT predictors of recurrence were response to TACE and largest radiologic size of tumor (>3 cm vs. ≤3 cm). HCC recurrence rate for patients with tumor size >3 cm and no response to TACE was 35.8%, compared with 1.9% for patients with tumor size ≤3 cm and response to TACE (p = 0.0007). We conclude that mRECIST criteria and tumor size differentiate patients with high or low likelihood of HCC recurrence after LT. These findings raise the possibility of incorporating response to TACE and largest tumor size to identify patients at highest risk for HCC recurrence.

For regional and rural Queenslanders, chronic viral hepatitis treatment is a major unmet health need, with restricted access to specialists outside of tertiary, largely metropolitan hospitals. To increase treatment of chronic viral hepatitis in regional Queensland, a team-based telehealth model was expanded. This expansion embedded an initial nursing consultation prior to specialist telehealth consultation. We conducted a retrospective audit of the introduction and expansion of hepatology telehealth services. Activity from July 2014–June 2015 (pre-expansion) was compared with July 2015– June 2016 (post-expansion). Interviews were conducted with key staff to determine factors contributing to success of the service and identify ongoing challenges to the service model. A greater than four-fold increase in clinical consultation was observed (131 telehealth consultations pre-expansion vs 572 post-expansion; p

Budd-Chiari syndrome (BCS) or hepatic venous outflow obstruction, is a rare and complex clinical entity, with diverse aetiology and a wide range of presentations. Its rarity and heterogeneity create significant challenges for evidence-based clinical decision-making, particularly in the even more infrequent setting of acute BCS presentation. Here we present the case of a young woman with acute, severe BCS, where treatment alternatives were limited due to a significant IVC thrombus burden. A clearly defined acute onset allowed the prompt use of systemic thrombolysis, conducted in consultation with a multi-disciplinary team of clinicians, with close monitoring for both treatment response and complications. Her treatment resulted in resolution of hepatic vein occlusion and prevention of the potentially significant clinical sequelae. We review the literature and discuss current opinion in the management of BCS.

In 2009, an association between the interleukin-28B (IL28B) polymorphism and treatment outcome for genotype 1 (G1) hepatitis C virus (HCV) infection, as well as spontaneous clearance of HCV, was reported. Since the initial publications, over 100 articles have appeared in the peer-reviewed literature, with many more manuscripts in press and abstracts presented at scientific meetings. Despite the proliferation of data concerning the IL28B polymorphism and HCV infection, there remain many critical unanswered questions about clinical implications and the underlying biological mechanisms. In this review, we discuss the basic principles of genome-wide association study methodologies that are important for interpreting the results of genetic association studies. We then review the current literature concerning the association between IL28B variants and interferon (IFN) treatment response in patients with chronic HCV infection, as well as spontaneous HCV clearance. We consider the relevance of the IL28B polymorphism to non-G1 HCV, as well as the special treatment populations of HIV/HCV co-infection and recurrent HCV post-liver transplantation. We review current knowledge of the biological mechanisms underlying this genetic association, including the link to liver IFN-stimulated gene expression, and identify continuing gaps in our knowledge and key research priorities. Finally, pegylated-IFN and ribavirin is no longer the standard of care for the treatment of G1 HCV, and we conclude by considering the relevance of IL28B polymorphisms in the era of direct-acting antivirals.

Cytokeratin-18 (CK-18) is a major intermediate filament protein in liver cells. The M30 fragment of CK-18 has been identified as a useful marker of apoptosis associated with fibrosis and steatosis in nonalcoholic steatohepatitis (NASH). We sought to assess the relationship of this marker and steatosis in a cohort of adult patients with chronic hepatitis C. The study cohort included sera from 267 treatment-naive chronic hepatitis C (CHC) patients and 100 healthy controls with normal alanine aminotransferase (ALT). Biopsies from CHC patients were assessed for METAVIR fibrosis stage, Histology Activity Index (HAI) inflammation score and steatosis grade by expert histopathologists. The M30 fragment of CK-18 was quantified by ELISA. Wilcoxon Rank Sum, Spearman Correlation and Linear Regression tests were performed for statistical analysis. Median CK-18 levels were higher in CHC patients compared to controls (411 vs 196 U/L, P < 0.0001). Fibrosis stage was associated with increasing serum CK-18 levels (P = 0.015) and CK-18 levels were higher for F2-F4 vs F0-F1 (500 vs 344 U/L; P = 0.001). There was no association between CK-18 and increasing steatosis grade 1, 2 or 3 (460.7 vs 416.8 vs 508.3 U/L; P = 0.35) and presence or absence of steatosis (445.3 vs 365.8 U/L; P = 0.075). Fibrosis stage was independently associated with serum M30 in a multivariable linear regression model (P = 0.03). CK-18 levels were higher in CHC compared to healthy controls and associated with hepatic fibrosis. There was no difference in CK-18 M30 levels between CHC patients with and without steatosis. Although apoptosis may still contribute to hepatitis C virus (HCV)-mediated steatosis, our results suggest that serum CK-18 will not be a clinically useful test for identifying significant steatosis in CHC.

Background and Aim: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients.

Purpose of review: To improve understanding of recent developments in the noninvasive assessment of fibrosis and their potential clinical application to a range of chronic liver diseases. Recent findings: Many noninvasive tests have evolved from their primary validation in chronic hepatitis C virus (HCV) infection to integration into clinical management algorithms for chronic liver disease of varying cause. Recent studies consider the use of these techniques in sequence or in combination, and compare the performance of serum and imaging-based noninvasive techniques to identify patients with significant fibrosis, or those at most risk of clinical sequelae from advanced-stage disease. Methods developed in chronic hepatitis C have now been applied in different chronic liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, HIV/HCV co-infection and primary biliary cirrhosis. A number of new management algorithms have been developed to facilitate the integration of noninvasive techniques into clinical practice. Summary: Noninvasive tools to assess liver diseases continue to evolve. New imaging technologies have been developed. Existing biomarkers and imaging modalities have been better integrated into clinical practice algorithms, and applied to different chronic liver diseases. Noninvasive techniques will likely continue to be refined and play an important role in the future management of patients with chronic liver disease.

Recently, single-nucleotide polymorphisms near the IL28B gene have been identified as important in predicting treatment response and spontaneous clearance of the hepatitis C virus (HCV). In the less than 12 months since the initial genetic discoveries, our knowledge base has rapidly expanded regarding the significance of the IL28B polymorphism in a variety of clinical settings. For genotype 1 HCV infection, it is clear that IL28B genotype has an important role in the prediction of treatment-induced and spontaneous clearance. This association remains important in the HIV/HCV-coinfected population. Host genotype adds further discriminatory information in HCV genotype 2/3 infection. IL28B genotype may remain significant with direct-acting antiviral therapy, although further studies are needed for antiviral agents and novel immunotherapy. Information on IL28B genotype improves treatment prediction with standard of care and will integrate with existing pretreatment clinical factors and measures of on-treatment response. Pretreatment knowledge of sustained viral response may help to reshape treatment regimens of the future with the possibility of reducing therapy duration and improving tolerability, safety, and efficacy.

Objective People with chronic liver disease, particularly those with decompensated cirrhosis, experience several potentially debilitating complications that can have a significant impact on activities of daily living and quality of life. These impairments combined with the associated complex treatment mean that they are faced with specific and high levels of supportive care needs. We aimed to review reported perspectives, experiences and concerns of people with chronic liver disease worldwide. This information is necessary to guide development of policies around supportive needs screening tools and to enable prioritisation of support services for these patients. Design Systematic searches of PubMed, MEDLINE, CINAHL and PsycINFO from the earliest records until 19 September 2014. Data were extracted using standardised forms. A qualitative, descriptive approach was utilised to analyse and synthesise data. Results The initial search yielded 2598 reports: 26 studies reporting supportive care needs among patients with chronic liver disease were included, but few of them were patient-reported needs, none used a validated liver disease-specific supportive care need assessment instrument, and only three included patients with cirrhosis. Five key domains of supportive care needs were identified: informational or educational (eg, educational material, educational sessions), practical (eg, daily living), physical (eg, controlling pruritus and fatigue), patient care and support (eg, support groups), and psychological (eg, anxiety, sadness). Conclusions While several key domains of supportive care needs were identified, most studies included hepatitis patients. There is a paucity of literature describing the supportive care needs of the chronic liver disease population likely to have the most needs—namely those with cirrhosis. Assessing the supportive care needs of people with chronic liver disease have potential utility in clinical practice for facilitating timely referrals to support services.

Background & Aims: Incidence and mortality of hepatocellular carcinoma (HCC) is increasing globally, but varies between countries and regions. To target scarce resources to most need, clinical services must be informed by regional epidemiology. Using population-based data, we sought to document the incidence and mortality of HCC in Queensland, Australia, a state occupying a vast land area with diverse at-risk subpopulations. Methods: Using population-based data from 1996 to 2011, the age-standardised incidence rate (ASR), annual percentage change (APC) and survival of HCC in Queensland were assessed with negative binomial regression, Kaplan-Meier and Cox survival analysis. Spatial patterns of HCC incidence and survival and relevant predictors were mapped. Results: Thousand six hundred and twenty HCCs were diagnosed during this study period, with an overall ASR of 2.00-cases/1000 population. ASR increased by 3.5% per year, (95% CI: 2.1 to 5.0), P < 0.001) among males to 5.6/100,000 in 2011 and a non-significant increase of 2.6% per year, (95% CI = 0.7 to 6.0), P = 0.111) among females to 1.6/100,000 in 2011. Higher incidence was associated with male gender, older age, major city residence and proportionally higher area Indigenous population. Thousand and two hundred and eighty-seven patients died. Median survival was approximately 10 months. Five-year survival improved from 18% in 1996-2000 to 24% in 2006-2011 (P < 0.001). Poorer survival was associated with older age, less recent period of diagnosis, lower hepatitis B prevalence in country of origin and greater area-level social disadvantage. Conclusions: Over this study period, HCC incidence increased significantly. HCC survival improved but remains poor. Social determinants are critical to HCC epidemiology.

The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people. Current therapy relies upon a combination of pegylated interferon-alpha and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus. The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC ) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log10 reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors.

In 2009, genome-wide association studies identified key roles for IL28B and ITPA polymorphisms in predicting HCV treatment outcomes using pegylated interferon-α and ribavirin therapy. The IL28B polymorphism is strongly associated with antiviral efficacy of interferon-based HCV therapy, as well as with the spontaneous clearance of acute HCV infection. Very recently, it was proposed that IL28B polymorphisms actually tag a functional variant that affects the novel IFNL4 gene. Two functional ITPA variants determine the risk of ribavirin-induced hemolytic anemia. Personalized medicine is now a reality for chronic HCV patients, and IL28B genotyping has been incorporated into the clinical algorithm for individuals considering antiviral therapy.

IntroductionPharmacogenomic testing is important in developing individualized therapeutic approaches. In the phase 3 IDEAL (Individualized Dosing to Assess Optimal Pegylated Interferon Therapy) clinical trial, a subset of patients receiving peginterferon and ribavirin for treatment of chronic hepatitis C agreed to provide blood samples for genetic testing. Genome-wide association studies subsequently identified associations between IL28B polymorphism and sustained virologic response, and ITPA polymorphism and ribavirin-associated anemia.ObjectiveTo characterize the groups of patients who accepted or declined pharmacogenomic testing in the IDEAL study.MethodsClinical and demographic factors and treatment outcomes were compared at all sites that had approved pharmacogenomic testing. Differences between patients who consented to and declined pharmacogenomic testing were analyzed using Student's t-test and (2)-test.ResultsIn total, 109 of 118 sites participated in the pharmacogenomic substudy, and 1674 of 2949 (57%) patients enrolled at these sites consented to pharmacogenomic testing. More patients treated in academic medical centers than in community centers (60 vs. 52%, P

To control the growing burden of HCV disease, new infrastructure and models of care to enable assessment and treatment outside tertiary referral liver clinics need to be developed...

Anaemia frequently complicates peginterferon/ribavirin therapy for chronic hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase (ITPA) genetic variants are associated with ribavirin-induced anaemia and dose reduction; however, their impact in real-life clinic patient cohorts remains to be defined. We studied 193 clinic patients with chronic hepatitis C infection of mixed viral genotype (genotype 1/4 n = 123, genotype 2/3, n = 70) treated with peginterferon/ribavirin. Patients were genotyped for ITPA polymorphisms rs1127354 and rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present. Estimated ITPA deficiency was graded on severity (0-3, no deficiency/mild/moderate/severe, n = 126/40/24/3, respectively). Multivariable models tested the association with anaemia at 4 weeks of treatment [including decline in haemoglobin (g/dL); haemoglobin10 g/dL and haemoglobin decline3 g/dL]; ribavirin dose reduction and EPO use and explored sustained viral response (SVR) to peginterferon/ribavirin. More severe ITPA deficiency was associated with less reduction in haemoglobin level (P0.001; R(2) = 0.34), less ribavirin dose reduction (OR 0.42; (95% CI = 0.23-0.77); P = 0.005) and less EPO use [OR 0.53; (0.30-0.94); P = 0.029]. ITPA deficiency was associated with SVR [OR: 1.70; (1.02-2.83); P = 0.041] independently of clinical covariates (adjusted R(2) = 0.31). In this clinical cohort, ITPA deficiency helped predict the risk of on-treatment anaemia, ribavirin dose reduction, need for EPO support and was associated with SVR. For patients on HCV regimens including peginterferon/ribavirin, testing for ITPA deficiency may have clinical utility.

Scientific and therapeutic advances related to hepatitis C virus (HCV) are cause for optimism about the care of HCV-infected patients, but the true rate-limiting step in achieving better outcomes may turn out to be access to diagnosis and treatment.