Long-term morbidity and mortality in a Canadian post-transfusion hepatitis C cohort: Over 15 years of follow-up.

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.

Estimating chronic hepatitis C prevalence in British Columbia and Ontario, Canada, using population-based cohort studies.

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, the historical prevalence of CHC was back-calculated 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 policymakers to develop appropriate policies to achieve elimination targets. Our approach can also be applied to produce robust region-specific estimates in other countries.

Estimates and predictors of health care costs of esophageal adenocarcinoma: a population-based cohort study.

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.

Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma.

BACKGROUND: 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). METHODS: 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. RESULTS: 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%. CONCLUSION: Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.

Effect of socioeconomic status on hepatocellular carcinoma incidence and stage at diagnosis, a population-based cohort study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) incidence is increasing worldwide and cirrhosis is the most important risk factor predominantly caused by chronic viral hepatitis infection. We studied the impact of socioeconomic status (SES) on HCC incidence and stage at diagnosis among viral hepatitis cases. METHODS: A population-based retrospective cohort study was conducted through the Ontario Cancer Registry linked data. Incidence rates were calculated using person-time methodology. Association between SES (income quintile) and HCC incidence was assessed using proportional-hazards regression. The impact of SES on HCC stage was investigated using logistic regression. RESULTS: Among 11 350 individuals diagnosed with viral hepatitis between 1991 and 2010, a crude HCC incidence rate of 21.4 cases per 1000 person-years was observed. Adjusting for age, gender, urban/rural residence and year of viral hepatitis diagnosis, a significant association was found between SES and HCC incidence, with an increased risk among individuals in the lowest three income quintiles (incidence rate ratio, IRR = 1.235; 95% CI: 1.074-1.420; IRR = 1.183; 95% CI: 1.026-1.364; IRR = 1.158; 95% CI: 1.000-1.340 respectively). No significant association between SES and HCC incidence was found after additionally adjusting for risk factors associated with HCC. However, HCC risk factors such as cirrhosis and HIV are associated with SES. Furthermore, no association was found between SES and HCC stage. CONCLUSIONS: The association between SES and HCC incidence is likely because of differences in risk factors across income quintiles. Investigating how SES affects HCC incidence facilitates an understanding of which populations are at elevated risk for HCC.

Effectiveness of diagnostic strategies in suspected delayed cerebral ischemia: a decision analysis.

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.

Health care costs associated with hepatocellular carcinoma: a population-based study.

UNLABELLED: 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.

Combining semiquantitative measures of fibrosis and qualitative features of parenchymal remodelling to identify fibrosis regression in hepatitis C: a multiple biopsy study.

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 <2-stage fall in Ishak stage with a rise in QR score (Reg-Qual). Among 159 patients (biopsy interval 5.4 ± 3.1 years), Reg-I was observed in 12 (7.5%) and Reg-Qual in 26 (16.4%) patients. The combined diagnostic criteria increased the diagnosis rate for fibrosis regression (38 patients, 23.9%) compared with use of Reg-I alone (P < 0.001). Combined fibrosis regression was observed in nine patients (50%) who achieved sustained virological response (SVR), and in 29 of 141 (21%) patients despite persistent viraemia. SVR was the only clinical factor associated independently with combined fibrosis regression (odds ratio 3.05). CONCLUSIONS: The combination of semiquantitative measures and qualitative features aids the identification of fibrosis regression in CHC.

Trends in mortality after diagnosis of hepatitis B or C infection: 1992-2006.

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.

Risk factors for hepatocellular carcinoma in a cohort infected with hepatitis B or C.

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.

Health care costs associated with chronic hepatitis C virus infection in Ontario, Canada: a retrospective cohort study.

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.

Hepatitis C treatment strategies in prisons: A cost-effectiveness analysis.

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.

Health status utilities and the impact of pressure ulcers in long-term care residents in Ontario.

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 < 0.001). Factors associated with lower MDS-HSI scores included: older age; being female; having a PU; recent hip fracture; multiple comorbid conditions; bedfast; incontinence; Changes in Health, End-stage disease and Symptoms and Signs; clinically important depression; treated with a turning/repositioning program; taking antipsychotic medications; and use of restraints. CONCLUSIONS: LTC residents with PU had slightly though statistically significantly lower HRQOL than those without PU. Comorbidity contributed substantially to the low HRQOL in these populations. Community-weighted MDS-HSI utilities for LTC residents are useful for cost-effectiveness analyses and help guide health policy development.

Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression.

UNLABELLED: 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.

Health-state utilities in a prisoner population: a cross-sectional survey.

BACKGROUND: Health-state utilities for prisoners have not been described. METHODS: We used data from a 1996 cross-sectional survey of Australian prisoners (n = 734). Respondent-level SF-36 data was transformed into utility scores by both the SF-6D and Nichol's method. Socio-demographic and clinical predictors of SF-6D utility were assessed in univariate analyses and a multivariate general linear model. RESULTS: The overall mean SF-6D utility was 0.725 (SD 0.119). When subdivided by various medical conditions, prisoner SF-6D utilities ranged from 0.620 for angina to 0.764 for those with none/mild depressive symptoms. Utilities derived by the Nichol's method were higher than SF-6D scores, often by more than 0.1. In multivariate analysis, significant independent predictors of worse utility included female gender, increasing age, increasing number of comorbidities and more severe depressive symptoms. CONCLUSION: The utilities presented may prove useful for future economic and decision models evaluating prison-based health programs.

Estimation of fibrosis progression rates for chronic hepatitis C: a systematic review and meta-analysis update.

OBJECTIVES: Mathematical 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. DESIGN: A 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. OUTCOMES: Stage-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. RESULTS: The 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. CONCLUSIONS: This 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.

Acceptability of hepatitis C virus testing methods among injecting drug users.

INTRODUCTION AND AIMS: The acceptability of testing methods and procedures has implications for uptake of blood-borne virus screening in sentinel samples of injecting drug users (IDUs) likely to participate in surveillance. The aim of the current study was to determine the acceptability of three methods of hepatitis C virus (HCV) testing among injecting drug users (IDUs): oral fluid, capillary blood and venous blood sampling. DESIGN AND METHODS: A cross-sectional survey of IDUs was conducted in inner-city Sydney in 2005 for a laboratory validation study of HCV antibody testing. Participants were tested using the three different specimen collection methods and asked about the acceptability of each method and a particular preference documented. RESULTS: Two-hundred and twenty-nine IDUs participated in the study. Before and after specimen collection, the acceptability of all three collection methods for HCV testing was high (> 85%). Oral fluid remained the preferred method after sample collection, with females (65%) significantly more likely than males (49%) to report a preference (unadjusted odds ratio 2.0; 95% confidence interval 1.1-3.5, p = 0.03) for that method. DISCUSSION AND CONCLUSIONS: Findings suggest that oral fluid testing is an acceptable and preferred alternative for HCV testing among IDUs. However, concerns reported by participants in the study indicate that information and education regarding the nature and diagnostic value of oral fluid testing is necessary prior to its implementation for surveillance purposes among this population.

Modelling the hepatitis C virus epidemic in Australia.

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.

Effects of socioeconomic status on esophageal adenocarcinoma stage at diagnosis, receipt of treatment, and survival: A population-based cohort study.

The incidence of esophageal adenocarcinoma (EAC) is increasing worldwide and has overtaken squamous histology in occurrence. We studied the impact of socioeconomic status (SES) on EAC stage at diagnosis, receipt of treatment, and survival. A population-based retrospective cohort study was conducted using Ontario Cancer Registry-linked administrative health data. Multinomial logistic regression was used to examine the association between SES (income quintile) and stage at EAC diagnosis and EAC treatment. Survival times following EAC diagnosis were estimated using Kaplan-Meier method. Cox proportional-hazards regression analysis was used to examine the association between SES and EAC survival. Between 2003-2012, 2,125 EAC cases were diagnosed. Median survival for the lowest-SES group was 10.9 months compared to 11.6 months for the highest-SES group; the 5-year survival was 9.8% vs. 15.0%. Compared to individuals in the highest-SES group, individuals in the lowest-SES category experienced no significant difference in EAC treatment (91.6% vs. 93.3%, P = 0.314) and deaths (78.9% vs. 75.6%, P = 0.727). After controlling for covariates, no significant associations were found between SES and cancer stage at diagnosis and EAC treatment. Additionally, after controlling for age, gender, urban/rural residence, birth country, health region, aggregated diagnosis groups, cancer stage, treatment, and year of diagnosis, no significant association was found between SES and EAC survival. Moreover, increased mortality risk was observed among those with older age (P = 0.001), advanced-stage of EAC at diagnosis (P < 0.001), and those receiving chemotherapy alone, radiotherapy alone, or surgery plus chemotherapy (P < 0.001). Adjusted proportional-hazards model findings suggest that there is no association between SES and EAC survival. While the unadjusted model suggests reduced survival among individuals in lower income quintiles, this is no longer significant after adjusting for any covariate. Additionally, there is an apparent association between SES and survival when considering only those individuals diagnosed with stage 0-III EAC. These analyses suggest that the observed direct relationship between SES and survival is explained by patient-level factors including receipt of treatment, something that is potentially modifiable.

Cost-effectiveness analysis of potentially curative and combination treatments for hepatocellular carcinoma with person-level data in a Canadian setting.

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.