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Background High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. Methods In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. Results We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. Interpretation Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.

Patients identified as having chronic hepatitis C (CHC) infection can be effectively and rapidly treated using direct-acting antiviral agents. However, there remains a substantial burden of subclinical undetected infection. This study estimates the prevalence and undiagnosed proportion of CHC in British Columbia (BC) and Ontario, Canada using a model-based approach, informed by provincial population-level health administrative data. A two-step approach was used: Step 1) Two population-based retrospective analyses of administrative health data for a cohort of British Columbians and a cohort of Ontarians with CHC were conducted to generate population-level statistics of CHC-related health events; Step 2) using a validated natural history model of hepatitis C virus (HCV) infection and back-calculated the historical prevalence of CHC from the data collected in Step 1. Our retrospective study found that, in BC and Ontario, the number of newly diagnosed CHC cases is declining yearly while the complications of the disease are increasing yearly. BC had a 2014 CHC prevalence of 1.04% (95% CI: 0.84%-1.44%), with 33.3% (95% CI: 25.5%-42.0%) of CHC cases undiagnosed. Ontario had a 2014 CHC prevalence of 0.91% (95% CI: 0.83%-1.02%) with 36.0% (95% CI: 31.2%-38.9%) of CHC cases undiagnosed. Our study offers robust estimates based on the integration of a validated natural history model with population-level health administrative data on HCV-related events, which can provide vital evidence for policy-makers to develop appropriate policies to achieve the elimination targets. Our approach can also be applied and used to produce robust region-specific estimates in other countries.

Introduction: Stigma and discrimination toward obese person are pervasive and have created various consequences for their psychological and physical health. Various studies in American society showed obese person are negatively stereotyped. The aim of the study is to identifying the perceptions of students towards the obesity stigmatisation. Methods: This study used 300 students who will answer a self-administered questionnaire on obese stigmatization. A total of 150 male (50%) and 150 female (50%) are targeted in this research. The study used a convenience sampling method to collect the data using self-administered questionnaires Result: The findings showed that a total of 51% of the students had negative attitude towards obesity. There was a significant correlation between attitude towards obesity stigmatization and eating disorder with (r = 0.201) and between attitude and body image with (r = 0.245) Conclusion: A total of 51% of the students had negative attitude towards obesity. More health promotion and awareness on a balance diet and to understand the perspective view towards obesity stigmatization.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

In Australian prisons approximately 20% of inmates are chronically infected with hepatitis C virus (HCV), providing an important population for targeted treatment and prevention. A dynamic mathematical model of HCV transmission was used to assess the impact of increasing direct-acting antiviral (DAA) treatment uptake on HCV incidence and prevalence in the prisons in New South Wales, Australia, and to assess the cost-effectiveness of alternate treatment strategies. We developed four separate models reflecting different average prison lengths of stay (LOS) of 2, 6, 24, and 36 months. Each model considered four DAA treatment coverage scenarios of 10% (status-quo), 25%, 50%, and 90% over 2016–2045. For each model and scenario, we estimated the lifetime burden of disease, costs and changes in quality-adjusted life years (QALYs) in prison and in the community during 2016–2075. Costs and QALYs were discounted 3.5% annually and adjusted to 2015 Australian dollars. Compared to treating 10% of infected prisoners, increasing DAA coverage to 25%, 50%, and 90% reduced HCV incidence in prisons by 9–33% (2-months LOS), 26–65% (6-months LOS), 37–70% (24-months LOS), and 35–65% (36-months LOS). DAA treatment was highly cost-effective among all LOS models at conservative willingness-to-pay thresholds. DAA therapy became increasingly cost-effective with increasing coverage. Compared to 10% treatment coverage, the incremental cost per QALY ranged from $497-$569 (2-months LOS), -$280–$323 (6-months LOS), -$432–$426 (24-months LOS), and -$245–$477 (36-months LOS). Treating more than 25% of HCV-infected prisoners with DAA therapy is highly cost-effective. This study shows that treating HCV-infected prisoners is highly cost-effective and should be a government priority for the global HCV elimination effort.

Patients with early‐stage hepatocellular carcinoma (HCC) are potential candidates for curative treatments such as radiofrequency ablation (RFA), surgical resection (SR), or liver transplantation (LT), which have demonstrated a significant survival benefit. We aimed to estimate the cost‐effectiveness of curative and combination treatment strategies among patients diagnosed with HCC during 2002–2010. This study used Ontario Cancer Registry‐linked administrative data to estimate effectiveness and costs (2013 USD) of the treatment strategies from the healthcare payer's perspective. Multiple imputation by logistic regression was used to handle missing data. A net benefit regression approach of baseline important covariates and propensity score adjustment were used to calculate incremental net benefit to generate incremental cost‐effectiveness ratio (ICER) and uncertainty measures. Among 2,222 patients diagnosed with HCC, 10.5%, 14.1%, and 10.3% received RFA, SR, and LT monotherapy, respectively; 0.5–3.1% dual treatments; and 0.5% triple treatments. Compared with no treatment (53.2%), transarterial chemoembolization (TACE) + RFA (average $2,465, 95% CI: −$20,000–$36,600/quality‐adjusted life years [QALY]) or RFA monotherapy ($15,553, 95% CI: $3,500–$28,500/QALY) appears to be the most cost‐effective modality with lowest ICER value. The cost‐effectiveness acceptability curve showed that if the relevant threshold was $50,000/QALY, RFA monotherapy and TACE+ RFA would have a cost‐effectiveness probability of 100%. Strategies using LT delivered the most additional QALYs and became cost‐effective at a threshold of $77,000/QALY. Our findings found that TACE+ RFA dual treatment or RFA monotherapy appears to be the most cost‐effective curative treatment for patients with potential early stage of HCC in Ontario. These findings highlight the importance of identifying and measuring differential benefits, costs, and cost‐effectiveness of alternative HCC curative treatments in order to evaluate whether they are providing good value for money in the real world.

Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT).All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival.Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p = 0.02) and tumor burden (p 0.001). The majority of those listed underwent LT (n = 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599-15.464; p = 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660-12.768; p = 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (n = 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p = 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%.Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.

ObjectivesMathematical models are increasingly important in planning for the upcoming chronic hepatitis C (CHC) elimination efforts. Such models require reliable natural history inputs to make accurate predictions on health and economic outcomes. Yet, hepatitis C virus disease progression is known to vary widely in the literature and published inputs are currently outdated. The objectives of this study were to obtain updated estimates of fibrosis progression rates (FPR) in treatment-naïve patients with CHC and to explore sources of heterogeneity.DesignA systematic review was conducted using Ovid-MEDLINE, Ovid-EMBASE and PubMed databases (January 1990 to January 2018) to identify observational studies of hepatic fibrosis in treatment-naïve patients with CHC.OutcomesStage-constant FPRs were estimated for each study given the reported fibrosis scores and duration of infection. Stage-specific FPRs (ie, F0→F1; F1→F2; F2→F3; F3→F4) were estimated using Markov maximum likelihood estimation. Estimates were pooled using random-effects meta-analysis and heterogeneity was evaluated by stratification and random-effects meta-regression.ResultsThe review identified 111 studies involving 131 groups of patients (n=42 693). The pooled stage-constant FPR was 0.094 (95% CI 0.088 to 0.100); stage-specific FPRs were F0→F1: 0.107 (95% CI 0.097 to 0.118); F1→F2: 0.082 (95% CI 0.074 to 0.091); F2→F3: 0.117 (95% CI 0.107 to 0.129); F3→F4: 0.116 (95% CI 0.104 to 0.131). Stratified analysis revealed substantial variation in progression by study population. Meta-regression indicated associations between progression and infection age, duration, source, viral genotype and study population. Findings indicate that FPRs display substantial heterogeneity across study populations and pooled values from more homogenous subpopulations should be considered when estimating prognosis.ConclusionsThis large meta-analysis presents updated prognostic estimates for CHC derived from newer studies using better diagnostic methods and improves estimates for important patient populations in terms of clinical policy (eg, injection drug users, non-clinical populations, liver clinic patients) and should be a valuable resource for patients, clinicians and clinical policymakers.

The Federal Government of Canada established a $1.1 billion compensation programme in 1999 to support individuals who acquired hepatitis C virus (HCV) through blood products between January 1986 and July 1990. We aimed to describe the morbidity and mortality of this unique post-transfusion cohort (n = 4550) followed for over 15 years from 2000 to 2016. The age-standardized mortality rates were compared with that of the Canadian general population and HCV cohorts from other countries. We evaluated all-cause mortality using Kaplan-Meier survival curves and HCV-related and unrelated mortality using competing risk models. The age-standardized all-cause and HCV-related mortality rates per 10 000 person-years were 127 (95% CI: 117-138) and 76 (95% CI: 69-85) for males, and 77 (95% CI: 69-87) and 43 (95% CI: 37-51) for females, respectively. The risk of death of the post-transfusion cohort was almost twice as high as the Canadian general population (rate ratio = 1.8; 95% CI: 1.7-1.9). All-cause, HCV-related and HCV-unrelated mortality were 20%, 12% and 8%, respectively at 15 years of follow-up. By comparison, HCV-related mortality rates per 10 000 person-years for population-based HCV cohorts varied from 18 and 11 in Australia to 65 and 43 in Scotland for males and females, respectively. We reported long-term follow-up data for the largest post-transfusion cohort in the literature. The all-cause mortality rates were markedly higher than that of the Canadian general population. We also showed that HCV-related mortality were greater compared to other HCV cohorts. This suggests that continued efforts to identify and treat post-transfusion HCV are warranted.

Background Esophageal adenocarcinoma (EAC) incidence is increasing rapidly. Esophageal cancer has the second lowest 5-year survival rate of people diagnosed with cancer in Canada. Given the poor survival and the potential for further increases in incidence, phase-specific cost estimates constitute an important input for economic evaluation of prevention, screening, and treatment interventions. The study aims to estimate phase-specific net direct medical costs of care attributable to EAC, costs stratified by cancer stage and treatment, and predictors of total net costs of care for EAC. Methods A population-based retrospective cohort study was conducted using Ontario Cancer Registry-linked administrative health data from 2003 to 2011. The mean net costs of EAC care per 30 patient-days (2016 CAD) were estimated from the payer perspective using phase of care approach and generalized estimating equations. Predictors of net cost by phase of care were based on a generalized estimating equations model with a logarithmic link and gamma distribution adjusting for sociodemographic and clinical factors. Results The mean net costs of EAC care per 30 patient-days were $1016 (95% CI, $955–$1078) in the initial phase, $669 (95% CI, $594–$743) in the continuing care phase, and $8678 (95% CI, $8217–$9139) in the terminal phase. Overall, stage IV at diagnosis and surgery plus radiotherapy for EAC incurred the highest cost, particularly in the terminal phase. Strong predictors of higher net costs were receipt of chemotherapy plus radiotherapy, surgery plus chemotherapy, radiotherapy alone, surgery alone, and chemotherapy alone in the initial and continuing care phases, stage III-IV disease and patients diagnosed with EAC later in a calendar year (2007–2011) in the initial and terminal phases, comorbidity in the continuing care phase, and older age at diagnosis (70–74 years), and geographic region in the terminal phase. Conclusions Costs of care vary by phase of care, stage at diagnosis, and type of treatment for EAC. These cost estimates provide information to guide future resource allocation decisions, and clinical and policy interventions to reduce the burden of EAC. Electronic supplementary material The online version of this article (10.1186/s12885-018-4620-2) contains supplementary material, which is available to authorized users.

Materials and Methods. Table S1. Fee codes used to define types of treatment for esophageal adenocarcinoma. Table S2. Codes used to define cases of esophageal adenocarcinoma. (DOCX 22 kb)

Table S3. Demographic characteristics of esophageal adenocarcinoma cases and controls, 2003â 2011. (DOCX 21 kb)

Table S5. Mean net costs* of care due to esophageal adenocarcinoma according to service category and phase of care, 2003–2011: Sensitivity analysis. Table S6. Overall and phase of care net cost of health care resources by stage at diagnosis and treatment type for the esophageal adenocarcinoma cohort, 2003–2011: Sensitivity analysis. Table S7. Predictors of total net costs of care in individuals with a diagnosis of esophageal adenocarcinoma according to phase of care, 2003–2011: Multivariate generalized estimation equations with a log link function and gamma distribution – Sensitivity analysis. (DOCX 37 kb)

Table S4. Bootstrap samples for mean net costs* of care due to esophageal adenocarcinoma according to service category and phase of care, 2003â 2011. (DOCX 13 kb)

The incidence of hepatocellular carcinoma (HCC) is increasing and survival rates are poor. Our objectives were to estimate the relative survival over time in patients with HCC in Ontario and to examine potential factors associated with excess mortality risk.We performed a population-based retrospective cohort analysis involving patients with a diagnosis of HCC in Ontario between 1990 and 2009 using data extracted from the Ontario Cancer Registry. Relative survival was estimated by controlling for background mortality using expected mortality from Ontario life tables. A generalized linear model was used to estimate the excess mortality risk for important factors.A total of 5645 patients had HCC diagnosed during the study period; 4412 (78.2%) of these patients were male. Improvements in 1-year relative survival were observed across all age groups over time: the highest was among those patients less than 60 years of age who had a diagnosis of HCC during 2005-2009, with 1-year survival exceeding 50% for both sexes. However, the overall 5-year relative survival did not exceed 28%. The excess mortality risk decreased with increased years of follow-up, recent diagnosis, and curative or noncurative treatments for HCC, whereas excess mortality risk increased with age.Although improving, the prognosis for HCC remains poor. Our findings highlight the importance of effective prevention and treatment for HCC to reduce the burden of disease and improve health care systems.

Background and Purpose— Delayed cerebral ischemia (DCI) is a serious complication after aneurysmal subarachnoid hemorrhage. If DCI is suspected clinically, imaging methods designed to detect angiographic vasospasm or regional hypoperfusion are often used before instituting therapy. Uncertainty in the strength of the relationship between imaged vasospasm or perfusion deficits and DCI-related outcomes raises the question of whether imaging to select patients for therapy improves outcomes in clinical DCI. Methods— Decision analysis was performed using Markov models. Strategies were either to treat all patients immediately or to first undergo diagnostic testing by digital subtraction angiography or computed tomography angiography to assess for angiographic vasospasm, or computed tomography perfusion to assess for perfusion deficits. According to current practice guidelines, treatment consisted of induced hypertension. Outcomes were survival in terms of life-years and quality-adjusted life-years. Results— When treatment was assumed to be ineffective in nonvasospasm patients, Treat All and digital subtraction angiography were equivalent strategies; when a moderate treatment effect was assumed in nonvasospasm patients, Treat All became the superior strategy. Treating all patients was also superior to selecting patients for treatment via computed tomography perfusion. One-way sensitivity analyses demonstrated that the models were robust; 2- and 3-way sensitivity analyses with variation of disease and treatment parameters reinforced dominance of the Treat All strategy. Conclusions— Imaging studies to test for the presence of angiographic vasospasm or perfusion deficits in patients with clinical DCI do not seem helpful in selecting which patients should undergo treatment and may not improve outcomes. Future directions include validating these results in prospective cohort studies.

Summary Among people with hepatitis C virus (HCV) infection, liver disease-related deaths have risen over the last 20 years. Life expectancy has not been estimated in this population. HCV notifications (mandatory notification of anti-HCV-positive serology since 1991) reported to the New South Wales Health Department from 1992 to 2006 were linked to cause of death data. Abridged life tables were constructed from age-specific mortality rates. Life expectancy from ages 18–70 years for non-drug-related mortality causes was estimated using competing risk methods and compared to the general population of Australia. The cohort comprised 81 644 individuals with an HCV notification, with median follow-up of 7.6 years. Median age at notification was 34 years [interquartile range (IQR) 28–42] and 63% were male. Between 1992 and 2006, 4607 deaths occurred. Median age at liver- and drug-related death among males was 51 (IQR 45–66) and 36 (IQR 31–42) years, respectively, and among females was 63 (IQR 49–74) and 36 (IQR 30–41) years, respectively. In each year of follow-up before 2000, 15–21% of deaths were liver- and 30–39% were drug-related. After 2000, liver-related deaths increased to 20–26% of deaths in each year and drug-related deaths decreased to 13–19%. Excluding drug-related causes of death, life expectancy was lowered by an average of 4.2 (SD ± 1.0) and 5.4 (SD ± 0.7) years for males and females, respectively. Among people with an HCV notification, an increasing proportion of deaths are liver-related. Following removal of drug-related mortality, life expectancy in this population remained considerably lower, compared with the general population.

Background: The incidence of hepatocellular carcinoma (HCC) and the complexity of its diagnosis and treatment are increasing. We estimated trends in net health care utilization, costs of care attributable to HCC in Ontario, and rate ratios of resource use at various stages of care. Methods: This population-based retrospective cohort study identified HCC patients and non-cancer control subjects, and health care resource utilization between 2002 and 2009. Generalized estimating equations were then used to estimate net health care utilization (HCC patients vs. the matched control subjects) and net costs of care attributable to HCC. Generalized linear models were used to analyze rate ratios of resource use. Results: We identified 2832 HCC patients and 2808 matched control subjects. In comparison with the control subjects, HCC patients generally used a greater number of health care services. Overall, the mean net cost of care per 30 patient–days (2013 Canadian dollars) attributable to outpatient visits and hospitalizations was highest in the pre-diagnosis (1 year before diagnosis), initial (1st year after diagnosis), and end-of-life (last 6 months before death, short-term survivors) phases. Mean net homecare costs were highest in the end-of-life phase (long-term survivors). In the end-of-life phase (short-term survivors), mean net costs attributable to outpatient visits and total services significantly increased to $14,220 from $1,547 and to $33,121 from $14,450 (2008–2009 and 2002–2003 respectively). Conclusions: In HCC, our study found increasing resource use and net costs of care, particularly in the end-of-life phase among short-term survivors. Our findings offer a basis for resource allocation decisions in the area of cancer prevention and control.

Aim. We conducted a cost-effectiveness analysis of seven hepatitis C virus (HCV) testing strategies in blood donors. Methods. Three of the seven strategies were based on HCV diagnosis and reporting guidelines in Mexico and four were from previous and current recommendations outlined by the CDC. The strategies that were evaluated determine antibody levels according to the signal-to-cut-off (S/CO) ratio and use reflex Immunoblot (IMB) or HCV RNA tests to confirm true positive (TP) cases of chronic HCV infection. Costs were calculated from the perspective of the Mexican Institute of Social Security (IMSS). A decision tree model was developed to estimate the expected number of true positive cases and costs for the base-case scenarios and for the sensitivity analyses. Results. Base-case findings indicate an extended dominance of the CDC-USA2 and CDC-USA4 options by the IMSS Mexico3 and IMSS-Mexico1 alternatives. The probabilistic sensitivity analyses results suggest that for a willingness-to-pay (WTP) range of $0–9,000 USD the IMSS-Mexico1 strategy is the most cost-effective of all strategies ($5,000 USD per TP). The IMSS-Mexico3, IMSS-Mexico2, and CDC-USA3 strategies are also cost-effective strategies that cost between $7,800 and $8,800 USD per TP case detected. The CDC-USA1 strategy was very expensive and not cost-effective. Conclusions. HCV antibody testing strategies based on the classification of two or three levels of the S/CO are cost-effective procedures to identify patients who require reflex IMB or HCV RNA testing to confirm chronic HCV infection.

Aim: Little is known about the patterns of care and the impact of hepatocellular carcinoma (HCC) treatment on health outcomes at a population level. We conducted a population-based cohort study to examine HCC survival trends among people diagnosed with hepatitis B (HBV) or hepatitis C virus (HCV) infection, to determine predictors of receiving potentially curative therapy for HCC, and to examine the impact of HCC treatment on survival in New South Wales, Australia. Methods: The Kaplan–Meier method was used to estimate survival, logistic regression to determine predictors of potentially curative therapy and Cox proportional hazards models to determine the impact of HCC treatment on survival. Years of potential life lost (YPLL) were calculated. Results: During the period 1993–2007, 1081 cases of HCC were diagnosed. Median survival increased from 10.4 months during 1993–1997 to 18.4 months during 1998–2002, with no further improvement thereafter. Younger age at diagnosis (

AIMS: A fall in hepatic fibrosis stage may be observed in patients with chronic hepatitis C (CHC); however, parenchymal architectural changes may also signify hepatic remodelling associated with fibrosis regression. The aim of this study was to utilize semiquantitative and qualitative methods to report the prevalence and factors associated with fibrosis regression in CHC. METHODS AND RESULTS: Paired liver biopsies were scored for fibrosis (Ishak), and for the presence of eight qualitative features of parenchymal remodelling, to derive a qualitative regression score (QR score). Combined fibrosis regression was defined as ≥2-stage fall in Ishak stage (Reg-I) or

Background and Aim: The incidence of hepatocellular carcinoma (HCC) has increased in Australia in recent decades, a large and growing proportion of which occurs among a population chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). However, risk factors for HCC among these high-risk groups require further characterization. Methods: We conducted a population-based cohort study using HBV and HCV cases notified to the New South Wales Health Department between 2000 and 2007. These were linked to cause of death data, HIV/AIDS notifications, and hospital records. Proportional hazards regression was used to identify significant risk factors for developing HCC. Results: A total of 242 and 339 HCC cases were linked to HBV (n = 43 892) and HCV (n = 83 817) notifications, respectively. For both HBV and HCV groups, being male and increasing age were significantly associated with risk of HCC. Increasing comorbidity score indicated high risk, while living outside urban areas was associated with lower risk. Hazard ratios for males were two to three times those of females. For both HBV and HCV groups, cirrhosis, alcoholic liver disease, and the interaction between the two were associated with significantly and considerably elevated risk. Conclusion: This large population-based study confirms known risk factors for HCC. The association with older age highlights the potential impact of HBV and HCV screening of at-risk groups and early clinical assessment. Additional research is required to evaluate the impact of improving antiviral therapy on HCC risk.

Background & Aims Chronic hepatitis B (HBV) or C (HCV) virus infection has been associated with increased risk of death, particularly from liver- and drug-related causes. We examined specific causes of death among a population-based cohort of people infected with HBV or HCV to identify areas of excess risk and examine trends in mortality. Methods HBV and HCV cases notified to the New South Wales (NSW) Health Department between 1992 and 2006 were linked to cause of death data and HIV/AIDS notifications. Mortality rates and standardised mortality ratios (SMRs) were calculated using person time methodology, with NSW population rates used as a comparison. Results The study cohort comprised 42,480 individuals with HBV mono-infection and 82,034 with HCV mono-infection. HIV co-infection increased the overall mortality rate three to 10-fold compared to mono-infected groups. Liver-related deaths were associated with high excess risk of mortality in both HBV and HCV groups (SMR 10.0, 95% CI 9.0–11.1; 15.8, 95% CI 14.8–16.8). Drug-related deaths among the HCV group also represented an elevated excess risk (SMR 15.4, 95% CI 14.5–16.3). Rates of hepatocellular carcinoma (HCC)-related death remained steady in both groups. A decrease in non-HCC liver-related deaths was seen in the HBV group between 1997 and 2006, but not in the HCV group. After a sharp decrease between 1999 and 2002, drug-related mortality rates in the HCV group have been stable. Conclusions Improvements in HBV treatment and uptake have most likely reduced non-HCC liver-related mortality. Encouragingly, HCV drug-related mortality remained low compared to pre-2002 levels, likely due to changes in opiate supply, and maintenance or improvement in harm reduction strategies.

Purpose To estimate health status utilities in long-term care (LTC) residents in Ontario, both with and without pressure ulcers (PUs), and to determine the impact of PU on health-related quality of life (HRQOL). Methods A retrospective population-based study was carried out using Minimum Data Set (MDS) health assessment data among all residents in 89 LTC homes in Ontario who had a full MDS assessment between May 2004 and November 2007. The Minimum Data Set-Health Status Index (MDS-HSI) was used to measure HRQOL. A stepwise regression was used to determine the impact of PU on MDS-HSI scores. Results A total of 1,498 (9%) of 16,531 LTC residents had at least one stage II PU or higher. The mean ± SD MDS-HSI scores of LTC residents without PU and those with PU were 0.36 ± 0.17 and 0.26 ± 0.13, respectively (p

Objective: To evaluate the potential impact of the current global economic crisis (GEC) on the spread of HIV. Design: To evaluate the impact of the economic downturn we studied two distinct HIV epidemics in Southeast Asia: the generalized epidemic in Cambodia where incidence is declining and the epidemic in Papua New Guinea (PNG) which is in an expansion phase. Methods: Major HIV-related risk factors that may change due to the GEC were identified and a dynamic mathematical transmission model was developed and used to forecast HIV prevalence, diagnoses, and incidence in Cambodia and PNG over the next 3 years. Results: In Cambodia, the total numbers of HIV diagnoses are not expected to be largely affected. However, an estimated increase of up to 10% in incident cases of HIV, due to potential changes in behavior, may not be observed by the surveillance system. In PNG, HIV incidence and diagnoses could be more affected by the GEC, resulting in respective increases of up to 17% and 11% over the next 3 years. Decreases in VCT and education programs are the factors that may be of greatest concern in both settings. A reduction in the rollout of antiretroviral therapy could increase the number of AIDS-related deaths (by up to 7.5% after 3 years). Conclusions: The GEC is likely to have a modest impact on HIV epidemics. However, there are plausible conditions under which the economic downturns can noticeably influence epidemic trends. This study highlights the high importance of maintaining funding for HIV programs.

Accurate prognostic estimates were required to ensure the sufficiency of the $1.1 billion compensation fund established in 1998 to compensate Canadians who acquired hepatitis C virus (HCV) infection through blood transfusion between 1986 and 1990. This article reports the application of Markov modelling and epidemiological methods to estimate the prognosis of individuals who have claimed compensation. Clinical characteristics of the claimant cohort (n = 5004) were used to define the starting distribution. Annual stage-specific transition probabilities (F0-->F1, . . ., F3-->F4) were derived from the claimants, using the Markov maximum likelihood estimation method. HCV treatment efficacy was derived from the literature and practice patterns were estimated from a national survey. The estimated stage-specific transition probabilities of the cohort between F0-->F1, F1-->F2, F2-->F3 and F3-->F4 were 0.032, 0.137, 0.150 and 0.097 respectively. At 20 years after the index transfusion, approximately 10% of all living claimants (n = 3773) had cirrhosis and 0.5% developed hepatocellular carcinoma (HCC). For nonhaemophilic patients, the predicted 20-year (2030) risk of HCV-related cirrhosis was 23%, and the risk of HCC and liver-related death was 7% and 11% respectively. Haemophilic patients who are younger and are frequently co-infected with human immunodeficiency virus would have higher 20-year risks of cirrhosis (37%), HCC (12%) and liver-related death (19%). Our results indicate that rates of progression to advanced liver disease in post-transfusion cohorts may be lower than previously reported. The Canadian post-transfusion cohort offers new and relevant prognostic information for post-transfusion HCV patients in Canada and is an invaluable resource to study the natural history and resource utilization of HCV-infected individuals in future studies.

OBJECTIVES To estimate stage-specific transition probabilities in individuals coinfected with HIV and hepatitis C virus (HCV), to examine the effect of covariates on these rates, and to investigate the effect of HIV on HCV-related cirrhosis in the era of highly active antiretroviral therapy (HAART). DESIGN Systematic review of natural history studies among HCV-infected individuals. METHODS Markov maximum likelihood estimation method was used to estimate stage-specific transition probabilities. A meta-analysis was performed to obtain pooled transition probabilities, and a meta-regression to investigate the impact of covariates on these rates. Risk of cirrhosis between individuals monoinfected with HCV and coinfected with HIV/HCV were compared by HAART status. RESULTS The estimated mean (95% confidence intervals) annual transition probabilities of 3567 individuals coinfected with HIV/HCV (n = 17 studies) were as follows: fibrosis stage (F) F0 --> F1 0.122 (0.098-0.153); F1 --> F2 0.115 (0.095-0.140); F2 --> F3 0.124 (0.097-0.159); and F3 --> F4 0.115 (0.098-0.135) units/year. The prevalence of cirrhosis after 20 and 30 years of HCV infection was 21% (16-28%) and 49% (40-59%), respectively. Longer duration of HCV infection was significantly associated with slower rate of fibrosis progression. The overall rate ratio of cirrhosis between individuals coinfected with HIV/HCV and monoinfected with HCV (n = 27 studies) was 2.1 (1.5-3.0), 2.5 (1.8-3.4) in the non-HAART group, and 1.7 (1.1-2.8) in the HAART group. CONCLUSION The rate of fibrosis progression among individuals coinfected with HIV/HCV appears constant. Our results confirm that chronic hepatitis C outcomes are worse among coinfected individuals. Over the period studied, HAART did not appear to fully correct the adverse effect of HIV infection on HCV prognosis.

Published estimates of liver fibrosis progression in individuals with chronic hepatitis C virus (HCV) infection are heterogeneous. We aimed to estimate stage-specific fibrosis progression rates and their determinants in these individuals. A systematic review of published prognostic studies was undertaken. Study inclusion criteria were as follows: (1) presence of HCV infection determined by serological assays; (2) available information about age at assessment of liver disease or HCV acquisition; (3) duration of HCV infection; and (4) histological and/or clinical diagnosis of cirrhosis. Annual stage-specific transition probabilities (F0→F1, … , F3→F4) were derived using the Markov maximum likelihood estimation method and a meta-analysis was performed. The impact of potential covariates was evaluated using meta-regression. A total of 111 studies of individuals with chronic HCV infection (n = 33,121) were included. Based on the random effects model, the estimated annual mean (95% confidence interval) stage-specific transition probabilities were: F0→F1 0.117 (0.104–0.130); F1→F2 0.085 (0.075–0.096); F2→F3 0.120 (0.109–0.133); and F3→F4 0.116 (0.104–0.129). The estimated prevalence of cirrhosis at 20 years after the infection was 16% (14%–19%) for all studies, 18% (15%–21%) for cross-sectional/retrospective studies, 7% (4%–14%) for retrospective-prospective studies, 18% (16%–21%) for studies conducted in clinical settings, and 7% (4%–12%) for studies conducted in nonclinical settings. Duration of infection was the most consistent factor significantly associated with progression of fibrosis. Conclusion: Our large systematic review provides increased precision in estimating fibrosis progression in chronic HCV infection and supports nonlinear disease progression. Estimates of progression to cirrhosis from studies conducted in clinical settings were lower than previous estimates. (HEPATOLOGY 2008.)

Background Hepatitis C virus (HCV) infection in Australia is predominantly transmitted through injecting drug use. A reduction in the heroin supply in Australia in late 2000 and early 2001 may have impacted the number of injecting drug users (IDUs) and consequently the number of new hepatitis C infections in Australia. This paper updates estimates of HCV incidence and prevalence between 1960 and 2005. Methods Simple mathematical models were used to estimate HCV incidence among IDUs, migrants to Australia from high HCV-prevalence countries, and other HCV exposure groups. Recent trends in numbers of IDUs were based on indicators of injecting drug use. A natural history of HCV model was applied to estimate the prevalence of HCV in the population. Results The modelled best estimate of past HCV incidence showed a consistent increasing rate of HCV infections to a peak of 14,000 new seroconversions in 1999, followed by a decline in 2001–2002 coincident with the decline in heroin availability. HCV incidence was estimated to be 9700 (lower and upper limits of 6600 and 13,200) in 2005. Of these, 88.7% were estimated to be through injecting drug use, 7.2% among migrants and 4.1% through other transmission routes. An estimated 264,000 (lower and upper limits of 206,000 and 318,000) people were HCV antibody positive in 2005. Conclusions Mathematical models suggest that HCV incidence in Australia decreased from a peak of 14,000 new infections in 1999 to 9700 new infections in 2005, largely attributable to a reduction in injecting drug use. The numbers of people living with HCV in Australia is, however, estimated to continue to increase.

The optimal schedule for ultrasonographic surveillance of patients with viral hepatitis for the detection of hepatocellular carcinoma (HCC) remains unclear owing to a lack of reliable studies. We examined the timing of ultrasonography in patients with viral hepatitis-induced HCC and its impact on survival and mortality risk while determining predictors of receiving surveillance before HCC diagnosis. A population-based retrospective cohort analysis of patients with viral hepatitis-induced HCC in Ontario between 2000 and 2010 was performed using data from the Ontario Cancer Registry linked health administrative data. HCC surveillance for 2 years preceding diagnosis was assigned as: i) ≥ 2 abdominal ultrasound screens annually; ii) 1 screen annually; iii) inconsistent screening; and iv) no screening. Survival rates were estimated using the Kaplan-Meier method and parametric models to correct for lead-time bias. Associations between HCC surveillance and the risk of mortality after diagnosis were examined using proportional-hazards regression adjusting for confounding factors. Overall, 1,483 patients with viral hepatitis-induced HCC were identified during the study period; 20.2% received ≥ 1 ultrasound screen annually (routine surveillance) for the 2 years preceding diagnosis. The 5-year survival of those receiving routine surveillance was 31.93% (95% CI: 25.77-38.24%) and 31.84% (95% CI: 25.69-38.14%) when corrected for lead-time bias (HCC sojourn time 70 days and 140 days, respectively). This is contrasted with 20.67% (95% CI: 16.86-24.74%) 5-year survival in those who did not undergo screening. In the fully adjusted model, compared to unscreened patients, routine surveillance was associated with a lower mortality risk and a hazard ratio of 0.76 (95% CI: 0.64-0.91) and 0.81 (95% CI: 0.68-0.97), corrected for the respective lead-time bias. Our findings suggest that routine ultrasonography in patients with viral hepatitis is associated with improved survival and reduced mortality risk in a population-based setting. The data emphasizes the importance of surveillance for timely intervention in HCC-diagnosed patients.

Objective: To describe public opinion towards supervised injecting centres (SICs) and the Sydney Medically Supervised Injecting Centre (MSIC) before and after the opening of the MSIC. Methods: In 2000 and 2002, telephone interviews were conducted with 515 and 540 residents and 209 and 207 businesses in Kings Cross, Australia, 7 months before and 17 months after the MSIC opened in Kings Cross. Information was obtained on respondents' characteristics, knowledge of the MSIC, and agreement with SICs. Differences in public opinion before and after the MSIC opened were assessed using the chi-square statistical test. Results: Two-thirds of the businesses and half the residents knew the correct location of the Sydney MSIC in 2002. The level of support for establishment of a MSIC in Kings Cross (68–78%, p p =0.003) increased significantly among residents between 2000 and 2002. Both groups were more likely to disagree than agree that SICs would encourage illicit drug injection. Conclusion: Public opinion towards SICs and the establishment of the MSIC generally was supportive in the short-term. Assessing whether this level of support is sustained over time will involve further research that demonstrates the benefits and effectiveness of such facilities.

Objective : To compare demographic and injecting characteristics of clients collecting needle syringes from needle syringe programmes (NSPs) and pharmacies. Methods : Clients obtaining needle syringes from three NSPs and one pharmacy in the same geographic area during one and four weeks, respectively were asked to complete a self-administered questionnaire. Results : Approximately half the 336 NSP (56%) and 63 pharmacy (49%) respondents reported using both NSPs and pharmacies in the past month. NSP and pharmacy respondents were similar on many characteristics: male gender (60 and 62%, respectively); median age (30 years for both groups); median age at first injection (18 years both groups); history of methadone treatment (62 and 53%); and heroin as the last drug injected (60 and 59%). NSP respondents were more likely than pharmacy respondents to report imprisonment in the previous year (20% versus 8%, P =0.05), daily injection (67% versus 56%, P =0.09) and re-use of more than one other person's needle syringe in the previous month (27% versus 7% of 52 and 15 reporting needle syringe re-use). Pharmacy respondents were more likely than NSP respondents to report amphetamine use (32% versus 10%, P P =0.01), spoons (43% versus 32%, P =0.09), filters (22% versus 15%, P =0.1), or drug mix (16% versus 9%, P =0.1), and difficulty finding a vein (73% versus 26%, P Conclusion : The risk profile of IDUs (Injecting Drug Users) recruited at various sites provides important information for behavioural surveillance and health promotion efforts. Increased convenience of needle syringe access enhances HIV prevention efforts, however, appropriate education is required for people obtaining needle syringes at pharmacies to reduce sharing of injecting equipment other than needle syringes.

Background Given the increasing burden of hepatitis C (HCV) related liver disease, innovative health care models are required to extend the reach of HCV care and treatment. Opioid substitution treatment (OST) clinics are places of high HCV prevalence. The OST clinic is a complex environment, quite distinct to other health care settings, with punitive regulations and practices, and a client population likely to be mistrustful of systems of authority. Nonetheless, trust is widely documented as essential to effective therapeutic encounters. This paper examines what is required to develop a trustworthy service in a place, the OST clinic, described by some critics as a site of "social control". Methods In-depth interviews were conducted with 57 clients and 19 staff from four NSW pilot clinics participating in the Australian ETHOS study. Results Interview data were examined using Hall's framework of trust, involving five principle domains: fidelity, competence, honest, confidentiality and global trust. ‘Honesty' was found to be key to participants' establishing trust in the co-located service and its staff. However, the clinic site was also found to be a place of rationed trust, in which the themes of OST as "ruling peoples' lives" and the fear of repercussions resulting from perceived transgressions against clinic rules, threatened to over-ride or undermine the development of trust in HCV services. Client participants described trusting health workers "to a point". They expressed concerns about the fidelity of co-located HCV and OST services and described fears of "institutionalised lies" and breaches of confidentiality. Anxieties around the latter revealed a sense of "us and them" held by some clients, one in which health workers were perceived to "stick together" by putting their own interests before those of the clients. Discussion Although the co-location of HCV and opioid treatments makes intuitive policy sense, HCV health workers in the OST space may be seen as representatives of a deeply mistrusted system. For the effective development of a trustworthy HCV care service, policy and practice activities are required to engender trust through clearly articulated explanations of service boundaries and the promotion of "success stories" through trusted peer networks.

Introduction : It is increasingly important to prioritize the most cost-effective HIV interventions. We sought to summarize the evidence on which types of interventions provide the best value for money in regions with concentrated HIV epidemics. Methods : We conducted a systematic review of peer-reviewed and grey literature reporting measurements of cost-effectiveness or cost-benefit for HIV/AIDS interventions in Asia and Eastern Europe. We also collated HIV/AIDS spending assessment data from case-study countries in the region. Results : We identified 91 studies for inclusion, 47 of which were from peer-reviewed journals. Generally, in concentrated settings, prevention of mother-to-child transmission programmes and prevention programmes targeting people who inject drugs and sex workers had lower incremental cost-effectiveness ratios than programmes aimed at the general population. The few studies evaluating programmes targeting men who have sex with men indicate moderate cost-effectiveness. Collation of prevention programme spending data from 12 countries in the region (none of which had generalized epidemics) indicated that resources for the general population/non-targeted was greater than 30% for eight countries and greater than 50% for five countries. Conclusions : There is a misalignment between national spending on HIV/AIDS responses and the most affected populations across the region. In concentrated epidemics, scarce funding should be directed more towards most-at-risk populations. Reaching consensus on general principles of cost-effectiveness of programmes by epidemic settings is difficult due to inconsistent evaluation approaches. Adopting a standard costing, impact evaluation, benefits calculation, analysis and reporting framework would enable cross comparisons and improve HIV resource prioritization and allocation. Keywords: HIV; cost-benefit analyses; programme evaluation; systematic review; concentrated epidemics; Asia; Eastern Europe; cost-effectiveness. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 25 February 2014) Citation: Craig AP et al. Journal of the International AIDS Society 2014, 17 :18822 http://www.jiasociety.org/index.php/jias/article/view/18822 | http://dx.doi.org/10.7448/IAS.17.1.18822

Objective To evaluate the impact and cost-effectiveness of needle-syringe programs (NSPs) with respect to HIV and hepatitis C virus (HCV) infections among Australian injecting drug users (IDUs). Design/methods A health economic analysis was conducted incorporating a mathematical model of HIV and HCV transmission among IDUs. An empirical relationship between syringe availability and receptive syringe sharing (RSS) was assessed. We compared the epidemiological outcomes and costs of NSP coverage (status quo RSS of 15-17%) with scenarios that had no NSPs (RSS of 25-50%). Outcomes included numbers of HIV and HCV infections averted, lifetime health sector costs, and cost per quality-adjusted life year (QALY) gained. Discounting was applied at 3% (sensitivity: 0%, 5%) per annum. Results We estimated that NSPs reduced incidence of HIV by 34-70% (192-873 cases) and HCV by 15-43% (19 000-77 000 cases) during 2000-2010, leading to 20 000-66 000 QALYs gained. Economic analysis showed that NSP coverage saved A$70-220 million in healthcare costs during 2000-2010 and will save an additional A$340-950 million in future healthcare costs. With NSPs costing A$245 million, the programs are very cost-effective at A$416-8750 per QALY gained. Financial investment in NSPs over 2000-2010 is estimated to be entirely recovered in healthcare cost savings by 2032 with a total future return on investment of $1.3-5.5 for every $1 invested. Conclusion Australia's early introduction and high coverage of NSPs has significantly reduced the prevalence of HIV and HCV among IDUs. NSPs are a cost-effective public health strategy and will result in substantial net cost savings in the future.

Although the burden of hepatocellular carcinoma (HCC) is an escalating public health problem, it has not been rigorously estimated within a Canadian context. We conducted a population-based study using Ontario Cancer Registry linked administrative data. The mean net costs of care due to HCC were estimated using a phase of care approach and generalized estimating equations. Using an incidence approach, the mean net costs of care were applied to survival probabilities of HCC patients to estimate 5-year net costs of care and extrapolated to the Canadian population of newly diagnosed HCC patients in 2009. During 2002-2008, 2,341 HCC cases were identified in Ontario. The mean (95% confidence interval [CI]) net costs of HCC care per 30 patient-days (2010 US dollars) were $3,204 ($2,863-$3,545) in the initial phase, $2,055 ($1,734-$2,375) in the continuing care phase, and $7,776 ($5,889-$9,663) in the terminal phase. The mean (95% CI) 5-year net cost of care was $77,509 ($60,410-$94,607) and the 5-year aggregate net cost of care was $106 million ($83-$130 million) (undiscounted). The net costs of patients receiving liver transplantation only and those undergoing surgical resection only were highest in the terminal phase. The net cost of patients receiving radiofrequency ablation as the only treatment was relatively low in the initial phase, and there were no significant differences in the continuing and terminal phases. Conclusion: Our findings suggest that costs attributable to HCC are significant in Canada and expected to increase. Our findings of phase-specific cost estimates by resource categories and type of treatment provide information for future cost-effectiveness analysis of potential innovative interventions, resource allocation, and health care budgeting, and public health policy to improve the health of the population. (Hepatology 2013;58:1375–1384)

BackgroundResearch has shown that people from higher socioeconomic status (SES) have better hepatocellular carcinoma (HCC) survival outcomes, although no such research has been carried out in Canada. We aimed to assess if an association between SES and HCC survival existed in the Canadian context.Methodology/principal findingsWe conducted a population-based cohort study linking HCC cases identified in the Ontario Cancer Registry between 1990 and 2009 to administrative and hospital data. Logistic regression and chi-squared tests were used to evaluate associations between SES (income quintile) and covariates. The Kaplan-Meier method was used to estimate survival. Sequential analysis of the proportional-hazards models were used to determine the association between SES and HCC survival controlling for potential prognostic covariates. During the period 1990-2009, 5,481 cases of HCC were identified. A significant association was found between SES and curative treatment (p = 0.0003), but no association was found between SES and non-curative treatment (p = 0.064), palliative treatment (p = 0.680), or ultrasound screening (p = 0.615). The median survival for the lowest SES was 8.5 months, compared to 8.8 months for the highest SES group. The age- and sex-adjusted proportional-hazards model showed statistically significant difference in HCC survival among the SES groups, with hazard ratio 0.905 (95% confidence intervals 0.821, 0.998) when comparing highest to lowest SES group. Further adjustments indicated that potentially curative treatment was the likely explanation for the association between SES and HCC survival.Conclusions/significanceOur findings suggest that a 10% HCC survival advantage exists for the higher SES groups. This association between SES and HCC survival is most likely a reflection of lack of access to care for low SES groups, revealing inequities in the Canadian healthcare system.