Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS: The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS: The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

Geographic disparities in access to liver transplant for advanced cirrhosis: Time to ring the alarm!

Decompensated cirrhosis and hepatocellular cancer are major risk factors for mortality worldwide. Liver transplantation (LT), both live-donor LT or deceased-donor LT, are lifesaving, but there are several barriers toward equitable access. These barriers are exacerbated in the setting of critical illness or acute-on-chronic liver failure. Rates of LT vary widely worldwide but are lowest in lower-income countries owing to lack of resources, infrastructure, late disease presentation, and limited donor awareness. A recent experience by the Chronic Liver Disease Evolution and Registry for Events and Decompensation consortium defined these barriers toward LT as critical in determining overall survival in hospitalized cirrhosis patients. A major focus should be on appropriate, affordable, and early cirrhosis and hepatocellular cancer care to prevent the need for LT. Live-donor LT is predominant across Asian countries, whereas deceased-donor LT is more common in Western countries; both approaches have unique challenges that add to the access disparities. There are many challenges toward equitable access but uniform definitions of acute-on-chronic liver failure, improving transplant expertise, enhancing availability of resources and encouraging knowledge between centers, and preventing disease progression are critical to reduce LT disparities.

A sustainable development goal framework to guide multisectoral action on NAFLD through a societal approach.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition that requires a comprehensive and coordinated response across sectors and disciplines. AIMS: In the absence of a multisectoral framework to tackle this condition, we developed one using the sustainable development goals (SDGs) as the basis for converging thinking about the design and delivery of public health responses. METHODS: A multidisciplinary group identified the SDG targets and indicators for inclusion in the new framework through a two-stage process. Firstly, a core team of three researchers independently reviewed the 169 targets and 231 indicators of the SDGs to select a shortlist. Over two Delphi rounds, a multidisciplinary group of 12 experts selected which of the shortlisted targets and indicators to include. Respondents also provided written feedback on their selection. Targets and indicators with 75% or greater agreement were included in the final framework. RESULTS: The final framework comprises 16 targets-representing 9% of all targets and 62% (16/26) of the shortlisted targets-and seven indicators, accounting for 50% (7/14) of the shortlisted indicators and 3% of all indicators. The selected targets and indicators cover a broad range of factors, from health, food and nutrition to education, the economy, and the built environment. CONCLUSIONS: Addressing the challenge of NAFLD will require a re-envisioning of the liver health landscape, with greater focus on joined-up systems thinking and action. This new framework can help guide this process, including by outlining the stakeholders with whom the liver health community needs to engage.

Antenatal FibroScan® assessment for metabolic-associated fatty liver in pregnant women at risk of gestational diabetes from a multiethnic population: a pilot study.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease with increasingly recognised associations with gestational diabetes (GDM), including within the antenatal period. AIMS: To assess the relationship between MAFLD in pregnancy and development of GDM. METHODS: Fifty pregnant women were enrolled before 24 weeks gestation from a multiethnic obstetrics service in Sydney, Australia. Two FibroScan® assessments were performed, one prior to 24 weeks and one after 30 weeks gestation, to assess hepatic steatosis and stiffness. A control attenuated parameter (CAP) score ≥ 233.5 dB/m signified MAFLD. GDM was determined by an antenatal 75-g oral glucose tolerance testing. RESULTS: Six (12%) women had evidence of FibroScan®-detected MAFLD in early pregnancy, while none had abnormal hepatic stiffness. Sixteen (32%) women developed GDM. No significant difference was observed in GDM rates (50% vs 29.5%; P = 0.37) between those with MAFLD in early pregnancy and those without. At the second scan (completed by 34 women), those who developed GDM had a lower observed mean increase in CAP scores (11.1 ± 23.3 dB/m vs -14.9 ± 26.0 dB/m; P = 0.004) and lower maternal weight gain (0.6 ± 0.2 kg/week vs 0.4 ± 0.2 kg/week; P = 0.04). CONCLUSIONS: There was no statistically significant association between FibroScan®-detected MAFLD in early pregnancy and subsequent development of GDM in this pilot study. Maternal weight gain may be associated with changes in the CAP scores, which reflect steatosis, during pregnancy.

Toward automated assessment of mole similarity on dermoscopic images.

Purpose: Current skin cancer detection relies on dermatologists' visual assessments of moles directly or dermoscopically. Our goal is to show that our similarity assessment algorithm on dermoscopic images can perform as well as a dermatologist's assessment. Approach: Given one target mole and two other moles from the same patient, our model determines which mole is more similar to the target mole. Similarity was quantified as the Euclidean distance in a feature space designed to capture mole properties such as size, shape, and color. We tested our model on 18 patients, each of whom had at least five moles, and compared the model assessments of mole similarity with that of three dermatologists. Fleiss' Kappa agreement coefficients and iteration tests were used to evaluate the agreement in similarity assessment among dermatologists and our model. Results: With the selected features of size, entropy (color variation), and cluster prominence (asymmetry), our algorithm's similarity assessments agreed moderately with the similarity assessments of dermatologists. The mean Kappa of 1000 iteration tests was 0.49 ( confidence interval ( CI ) = [ 0.23 , 0.74 ] ) when comparing three dermatologists and our model, which is comparable to the agreement in similarity assessment among the dermatologists themselves (the mean Kappa of 1000 iteration tests for three dermatologists was 0.48, CI = [ 0.19 , 0.77 ] .) By contrast, the mean Kappa was 0.22 ( CI = [ - 0.00 , 0.43 ] ) when comparing the similarity assessments of three dermatologists and random guesses. Conclusions: Our study showed that our image feature-engineering-based algorithm can effectively assess the similarity of moles as dermatologists do. Such a similarity assessment could serve as the foundation for computer-assisted intra-patient evaluation of moles.

Nonalcoholic fatty liver disease burden: Australia, 2019-2030.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a large and growing proportion of liver disease burden globally. The burden of NAFLD/NASH manifests in increasing levels of advanced liver disease and primary liver cancer in Australia. A Markov model was used to forecast NAFLD burden in Australia through 2030. METHODS: A model was used to estimate fibrosis progression, primary liver cancer, and liver deaths among the Australian NAFLD population, with changes in incident NAFLD cases based on long-term trends for changes in the prevalence of obesity. Published estimates and surveillance data were applied to build and validate the model projections, including surveillance data for the incidence of liver cancer. RESULTS: Prevalent NAFLD cases were projected to increase 25% from the current burden (5 551 000 [4 748 000-6 306 000] cases in 2019) to 7 024 000 [5 838 000-7 886 000] cases in 2030. The projected increase in the number of NASH cases (40%) was greater than that of NAFLD cases. Incident cases of advanced liver disease are projected to increase up to 85% by 2030, and incident NAFLD liver deaths are estimated to increase 85% from 1900 (1100-3300) deaths in 2019 to 3500 (2100-6100) deaths in 2030. CONCLUSIONS: Restraining growth of the obese and diabetic populations, along with potential therapeutic options, will be essential for mitigating disease burden.

The contribution of alcohol use disorder to decompensated cirrhosis among people with hepatitis C: An international study.

BACKGROUND & AIMS: The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings. METHODS: HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995-2011/2012/2013, respectively) were linked to hospital admissions (2001-2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed. RESULTS: Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76-2.10), New South Wales (aHR 3.68; 95% CI 3.38-4.00) and Scotland (aHR 3.88; 95% CI 3.42-4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively. CONCLUSIONS: Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved. LAY SUMMARY: The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.

Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention.

NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.

Stroke volume adjusted to afterload for assessment of cardiac performance in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

OBJECTIVES: The aim of this study was to evaluate the relationship between valvular resistance and stroke volume (SV) and to assess SV adequacy to afterload in patients with severe aortic stenosis (AS) and normal left ventricular ejection fraction (LVEF). METHODS: We assessed clinical characteristics and echocardiographic parameters in 44 patients with isolated severe AS and preserved LVEF. LV end-diastolic pressure (LVEDP) and LV mean diastolic pressure (LVMDP) were measured by cardiac catheterization. SV values were plotted in relation to valvular resistance. Patients were divided into 2 groups, with an SV that was higher (group 1) or lower (group 2) than the SV calculated by a regression equation using valvular resistance as the dependent variable. RESULTS: At the same degree of valvular stenosis, the patients in group 1 exhibited better contractility as assessed by global longitudinal strain (p < 0.05), higher peak (p < 0.01) and mean gradient (p < 0.05), indexed SV (p < 0.001) and transvalvular flow (p = 0.01) than the patients in group 2, who had a higher heart rate (HR, p < 0.05), shorter ejection time (ET, p < 0.05) and more elevated LVEDP (p < 0.05) and LVMDP (p < 0.05). CONCLUSION: The presence of inappropriately decreased SV relative to afterload in patients with severe AS and normal LVEF was associated with lower contractility, higher HR, shorter ET and elevated LV diastolic pressure, which suggest failed hemodynamic adaptation to afterload.

Community-based prevention of hepatitis-B-related liver cancer: Australian insights.

PROBLEM: Although most primary hepatocellular cancers (HCCs) are attributable to chronic viral hepatitis and largely preventable, such cancers remain a leading cause of cancer-related mortality wherever chronic hepatitis B is endemic. APPROACH: Many HCCs could be prevented by increasing awareness and knowledge of hepatitis B, optimizing the monitoring of chronic hepatitis B and using antiviral treatments - but there are gaps in the implementation of such strategies. LOCAL SETTING: The "B Positive" programme, based in Sydney, Australia, is designed to improve hepatitis-B-related health outcomes among immigrants from countries with endemic hepatitis B. The programme offers information about disease screening, vaccination and treatment options, as well as optimized access to care. RELEVANT CHANGES: The B Positive programme has been informed by economic modelling. The programme offers culturally tailored education on chronic hepatitis B to target communities and their health practitioners and regular follow-up through a population-based registry of cases. LESSONS LEARNT: As the costs of screening for chronic hepatitis B and follow-up are relatively low and less than one in every four cases may require antiviral drugs, optimizing access to treatment seems an appropriate and cost-effective management option. The identification and accurate staging of cases and the judicious use of antiviral medications are predicated upon an informed and educated health workforce. As establishing community trust is a lengthy process, delaying the implementation of programmes against chronic hepatitis B until antiviral drugs become cheaper is unwarranted.

Transient elastography in hepatitis C virus-infected patients with beta-thalassemia for assessment of fibrosis.

AIM: We sought to evaluate the performance of transient elastography (TE) for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients with beta-thalassemia. METHODS: Seventy-six CHC patients with beta-thalassemia underwent TE, liver biopsy, T2 -weighted magnetic resonance imaging (MRI) for the assessment of liver iron content (LIC) and laboratory evaluation. The accuracy of TE and its correlation with the other variables was assessed. RESULTS: TE values increased proportional to fibrosis stage (r = 0.404, P < 0.001), but was independent of T2 -weighted MRI-LIC (r = 0.064, P = 0.581). In multivariate analysis, fibrosis stage was still associated with the log-transformed TE score(standardized ß = 0.42 for F4 stage of METAVIR, P = 0.001). No correlation was noted between LIC and TE score (standardized ß = 0.064, P = 0.512). The area under the receiver operating characteristic curve for prediction of cirrhosis was 80% (95% confidence interval, 59-100%). A cut-off TE score of 11 had a sensitivity of 78% and specificity of 88.1% for diagnosing cirrhosis. The best cut-off values for "TE-FIB-4 cirrhosis score" comprising TE and FIB-4 and "TE-APRI cirrhosis score" combining TE with aspartate aminotransferase-to-platelet ratio index (APRI) both had 87.5% sensitivity and 91.04% specificity for the diagnosis of cirrhosis. CONCLUSION: Regardless of LIC, TE alone or when combined with FIB-4 or APRI, is a diagnostic tool with moderate to high accuracy to evaluate liver fibrosis in CHC patients with beta-thalassemia. However, because splenectomy in a proportion of our subjects might have affected the platelet count, the scores utilizing APRI and FIB-4 should be interpreted cautiously.

Cost of treating chronic hepatitis B: comparison of current treatment guidelines.

AIM: To compare program costs of chronic hepatitis B (CHB) screening and treatment using Australian and other published CHB treatment guidelines. METHODS: Economic modeling demonstrated that in Australia a strategy of hepatocellular cancer (HCC) prevention in patients with CHB is more cost-effective than current standard care, or HCC screening. Based upon this model, we developed the B positive program to optimize CHB management of Australians born in countries of high CHB prevalence. We estimated CHB program costs using the B positive program algorithm and compared them to estimated costs of using the CHB treatment guidelines published by the Asian-Pacific, American and European Associations for the Study of Liver Disease (APASL, AASLD, EASL) and those suggested by an independent United States hepatology panel. We used a Markov model that factored in the costs of CHB screening and treatment, individualized by viral load and alanine aminotransferase levels, and calculated the relative costs of program components. Costs were discounted by 5% and calculated in Australian dollars (AUD). RESULTS: Using the B positive algorithm, total program costs amount to 13,979,224 AUD, or 9634 AUD per patient. The least costly strategy is based upon using the AASLD guidelines, which would cost 34% less than our B positive algorithm. Using the EASL and the United States Expert Group guidelines would increase program costs by 46%. The largest expenditure relates to the cost of drug treatment (66.9% of total program costs). The contribution of CHB surveillance (20.2%) and HCC screening and surveillance (6.6%) is small--and together they represent only approximately a quarter of the total program costs. CONCLUSION: The significant cost variations in CHB screening and treatment using different guidelines are relevant for clinicians and policy makers involved in designing population-based disease control programs.

Pioglitazone and vitamin E for nonalcoholic steatohepatitis: a cost utility analysis.

UNLABELLED: Nonalcoholic steatohepatitis (NASH) is the commonest liver disease in developed countries. However, there are no current data on the cost-effectiveness of therapeutic options such as lifestyle modification, pioglitazone, or vitamin E. We undertook a cost utility analysis to compare these strategies. Using a third-party payer perspective, a deterministic Markov model was developed to compare costs and health benefits of lifestyle modification alone or with pioglitazone or vitamin E in a cohort of patients aged 50 years with biopsy-proven NASH and fibrosis level 3 or greater. We assumed an annual cycle length over a lifetime horizon. Probability and utility estimates were derived from a systematic literature review, and uncertainties in parameter estimates were tested using one- and two-way sensitivity analyses. Our outcome measure was the incremental cost-effectiveness ratio (ICER), with $A50,000 or less considered cost-effective. In comparison with lifestyle modification alone, treatment with either pioglitazone or vitamin E in addition to lifestyle modification was cost-effective, with incremental cost-effectiveness ratios of $A2748 and $A8475 per quality-adjusted life year (QALY) gained, respectively. In a direct comparison, pioglitazone was more cost-effective than vitamin E (ICER $A2,056/QALY gained). Sensitivity analyses indicated that pioglitazone was not cost-effective if either the total drug cost was greater than $A16,000 per annum, or the annual probability of developing cirrhosis in advanced fibrosis was less than 2%. CONCLUSION: Our modeled analyses suggest that in patients with advanced fibrosis due to NASH, pharmacological treatment in addition to standard lifestyle modification is likely to be cost-effective.

Exercise and the liver: implications for therapy in fatty liver disorders.

The increasing recognition that fatty liver plays a direct role in the pathogenesis of cardiovascular and metabolic disease has resulted in significant research enquiry into the efficacy of lifestyle therapy in modulating liver fat. Recently, this has extended to the specific investigation of a possible independent benefit of physical activity/exercise in nonalcoholic fatty liver disease (NAFLD). In this article we review the effect of acute and regular exercise (training) on metabolism, including liver glucose and lipid metabolism, and the available human trials that have compared the benefit of regular exercise versus a nonexercise control on liver fat. The limited human research suggests that exercise can reduce liver fat and that this benefit may be mediated, in part, by a reduction in hepatic lipogenesis. The relative importance of extrahepatic adaptations and acute versus regular exercise in explaining this benefit are discussed. From a clinical perspective, the revelation of a benefit of exercise per se offers a novel approach for liver fat reduction, and highlights the importance of incorporating fitness assessment and prescription in the management of patients with fatty liver disorders. Implementation of exercise therapy in a clinical setting is arguably the biggest challenge because evidence shows that mere provision of information about the benefits of exercise and/or exercise prescription to the patient does not translate to positive outcomes. Rather, the focus should be on implementing strategies to promote behavior change including regular contact and assessment with a health care professional, self-monitoring, and personalization of goals that focus on changing physical activity behavior.

Complex non-invasive fibrosis models are more accurate than simple models in non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Significant hepatic fibrosis is prognostic of liver morbidity and mortality in non-alcoholic fatty liver disease (NAFLD); however, it remains unclear whether non-invasive fibrosis models can determine this end-point. We therefore compared the accuracy of simple bedside versus complex fibrosis models across a range of fibrosis in a multi-centre NAFLD cohort. METHODS: Simple (APRI, BARD) and complex (Hepascore, Fibrotest, FIB4) fibrosis models were calculated in 242 NAFLD subjects undergoing liver biopsy. Significant (F2-4) and advanced fibrosis (F3,4) were defined using Kleiner criteria. Models were compared using area under the receiver operator characteristic curves (AUC). Cut-offs were determined by Youden Index or 90% predictive values. RESULTS: For significant fibrosis, non-invasive fibrosis models had modest accuracy (AUC 0.707-0.743) with BARD being least accurate (AUC 0.609, P < 0.05 vs others). Using single cut-offs, sensitivities and predictive values were < 80%; using two cut-offs, > 75% of subjects fell within indeterminate ranges. Simple models had significantly more subjects within indeterminate ranges than complex models (99.1-100% vs 82.1-84.4% respectively, P < 0.05 for all). For advanced fibrosis, complex models were more accurate than BARD (AUC 0.802-0.858 vs 0.701, P < 0.05). Using two cut-offs, complex models had fewer individuals within indeterminate ranges than BARD (11.1-32.3% vs 70.7%, P < 0.01 for all). For cirrhosis, complex models had higher AUC values than simple models. CONCLUSIONS: In NAFLD subjects, non-invasive models have modest accuracy for determining significant fibrosis and have predictive values less than 90% in the majority of subjects. Complex models are more accurate than simple bedside models across a range of fibrosis.

Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed?

UNLABELLED: Screening for hepatocellular carcinoma (HCC) is commonly practiced and recommended in published guidelines, but evidence for its efficacy has been controversial. We tested the feasibility of conducting a randomized controlled trial (RCT) of HCC surveillance in patients with cirrhosis and followed up those offered screening to detect clinical outcomes. Participation was offered to patients with cirrhosis attending liver clinics at three university hospitals. Following discussion, patients received a decision aid (DA) that outlined the risks and benefits of surveillance. The proposed screening program comprised ultrasonography 6-monthly and serum alpha-fetoprotein every 3 months. We envisaged five groups of patients: those who agreed to randomization, those choosing nonrandomized screening, those wanting continuation of usual care, those who were undecided, and those refusing participation. Among 205 patients, 204 (99.5%) declined randomization. Of these, 181 (88%) elected for a nonrandomized screening program, 10% chose usual care (which typically included ad hoc screening), and two were undecided. Among 176 patients fluent in English communication skills, 160 (91%) preferred nonrandomized screening compared with 22/29 (76%) patients needing an interpreter (P < 0.026). Of 173 patients in nonrandomized screening followed up for a mean 13.5 ± 6.04 months, three developed HCC, two died from nonliver-related causes, and one underwent liver transplantation for liver failure. Eighteen of 21 patients in "usual care" received ad hoc screening. A simultaneous survey on the quality of the DA showed that the majority of participants believed that the information provided was unbiased. CONCLUSION: Although an RCT is theoretically ideal for determining the efficacy, efficiency, and cost-effectiveness of HCC screening, informed patients prefer surveillance. A randomized study of HCC screening is not feasible when informed consent is imparted.

Using a population-based approach to prevent hepatocellular cancer in New South Wales, Australia: effects on health services utilisation.

BACKGROUND: Australians born in countries where hepatitis B infection is endemic are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. However, a program of screening, surveillance and treatment of chronic hepatitis B (CHB) in high risk populations could significantly reduce disease progression and death related to end-stage liver disease and HCC. Consequently we are implementing the B Positive pilot project, aiming to optimise the management of CHB in at-risk populations in south-west Sydney. Program participants receive routine care, enhanced disease surveillance or specialist referral, according to their stage of CHB infection, level of viral load and extent of liver injury. In this paper we examine the program's potential impact on health services utilisation in the study area. METHODS: Estimated numbers of CHB infections were derived from Australian Bureau of Statistics data and applying estimates of HBV prevalence rates from migrants' countries of birth. These figures were entered into a Markov model of disease progression, constructing a hypothetical cohort of Asian-born adults with CHB infection. We calculated the number of participants in different CHB disease states and estimated the numbers of GP and specialist consultations and liver ultrasound examinations the cohort would require annually over the life of the program. RESULTS: Assuming a 25% participation rate among the 5,800 local residents estimated to have chronic hepatitis B infection, approximately 750 people would require routine follow up, 260 enhanced disease surveillance and 210 specialist care during the first year after recruitment is completed. This translates into 5 additional appointments per year for each local GP, 25 for each specialist and 420 additional liver ultrasound examinations. CONCLUSIONS: While the program will not greatly affect the volume of local GP consultations, it will lead to a significant increase in demand for specialist services. New models of CHB care may be required to aid program implementation and up scaling the program will need to factor in additional demands on health care utilisation in areas of high hepatitis B sero-prevalence.

Costs of managing conditions associated with obesity among Australian teenagers.

AIM: To determine the health-care charges associated with monitoring and managing, over 1 year, the cases of elevated insulin concentration, elevated alanine aminotransferase concentration and dyslipidaemia due to overweight or obesity among 15-19-year-old Australian males and females. METHODS: Fasting blood samples (n= 500) were collected in 2004 from a representative population sample of adolescents (n= 496; mean age 15.3 years) attending schools in Sydney, Australia. Full service charges and Medicare expenditures for specialist medical and dietary consultations, pathology tests and radiological investigations, over 1 year, under efficient and inefficient health-care delivery models, including and excluding participants in the healthy body mass index (BMI) category. RESULTS: Under an inefficient delivery model and including all participants with elevated risk factors, the Medicare expenditure was $A305.1 million per annum (M pa). Exclusion of participants in the healthy BMI category resulted in an annual Medicare expenditure of $A170.0M pa. Under an efficient delivery model and including all participants with elevated risk factors, the Medicare expenditure was $A295.5M pa. Exclusion of participants in the healthy BMI category reduced annual Medicare expenditure to $A164.8M pa. Medicare expenditure for 15-19-year-olds would increase by 48% if only cases among overweight and obese adolescents were treated and by 85% if all cases were identified and treated. CONCLUSIONS: Short-term management of the health consequences of overweight and obesity among adolescents will increase Medicare expenditure on this group by at least 48%. Failure to treat will delay, but compound, health-care expenditure.

Antiviral therapy for hepatitis B-related liver cancer prevention is more cost-effective than cancer screening.

BACKGROUND/AIMS: In Australia, Asian-born populations are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. We therefore, modelled the consequences of different management strategies for chronic hepatitis B (CHB) in Asian-born adults aged > or = 35 years. METHODS: A Markov model compared (1) enhanced surveillance for HCC alone (HCC surveillance), or (2) enhanced HCC surveillance coupled with CHB treatment (HCC prevention) to the current practice, of low CHB treatment uptake. Patients were stratified and managed according to risk categories, based upon hepatitis B virus (HBV) viral load and alanine aminotransferase (ALT) levels. We measured costs, health outcomes [cases of HCC and deaths averted, quality-adjusted life-years (QALYs) gained] and incremental cost-effectiveness ratios (ICERs). RESULTS: HCC surveillance would cost on average AU$8479 per person, compared to AU$2632 with current clinical practice and result in a gain of 0.014 QALYs (AU$401,516/QALY gained). A HCC prevention strategy would cost on average AU$14,600 per person, result in 0.923 QALYs gained (AU$12,956/QALY gained), reduce cases of cirrhosis by 52%, HCC diagnoses by 47% and CHB-related deaths by 56%, compared to current practice. CONCLUSIONS: HCC prevention appears to be a cost-effective public health strategy in at-risk populations in Australia and is preferable to HCC surveillance as a cancer control strategy.