Estimating chronic hepatitis C prognosis using transient elastography-based liver stiffness: A systematic review and meta-analysis.

Chronic hepatitis C (CHC) is a leading cause of hepatic fibrosis and cirrhosis. The level of fibrosis is traditionally established by histology, and prognosis is estimated using fibrosis progression rates (FPRs; annual probability of progressing across histological stages). However, newer noninvasive alternatives are quickly replacing biopsy. One alternative, transient elastography (TE), quantifies fibrosis by measuring liver stiffness (LSM). Given these developments, the purpose of this study was (i) to estimate prognosis in treatment-naïve CHC patients using TE-based liver stiffness progression rates (LSPR) as an alternative to FPRs and (ii) to compare consistency between LSPRs and FPRs. A systematic literature search was performed using multiple databases (January 1990 to February 2016). LSPRs were calculated using either a direct method (given the difference in serial LSMs and time elapsed) or an indirect method given a single LSM and the estimated duration of infection and pooled using random-effects meta-analyses. For validation purposes, FPRs were also estimated. Heterogeneity was explored by random-effects meta-regression. Twenty-seven studies reporting on 39 groups of patients (N = 5874) were identified with 35 groups allowing for indirect and 8 for direct estimation of LSPR. The majority (~58%) of patients were HIV/HCV-coinfected. The estimated time-to-cirrhosis based on TE vs biopsy was 39 and 38 years, respectively. In univariate meta-regressions, male sex and HIV were positively and age at assessment, negatively associated with LSPRs. Noninvasive prognosis of HCV is consistent with FPRs in predicting time-to-cirrhosis, but more longitudinal studies of liver stiffness are needed to obtain refined estimates.

Cost-effectiveness analysis of universal screening for carbapenemase-producing Enterobacteriaceae in hospital inpatients.

The purpose of this study was to assess the cost-effectiveness of screening all hospital inpatients for carbapenemase-producing Enterobacteriaceae (CPE) at the time of hospital admission, compared to not screening, from a US hospital perspective. We used a linked transmission/Markov model to compare outcomes for a typical hospitalized medical patient, from a community with a colonization prevalence of 0.05%. Outcomes were number of colonized patients, CPE-related clinical infections and deaths, expected quality-adjusted life years (QALYs), cost, and the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to assess the effect of parameter uncertainty, using a willingness-to-pay threshold of $100,000 per QALY gained. Screening prevented six CPE colonization cases per 1000 patients (1/1000 colonized with screening, 7/1000 without screening), over half of all symptomatic CPE infections (2/10,000 symptomatic with screening, 5/10,000 symptomatic without screening), and nearly half of all CPE-related deaths (8/100,000 deaths with screening, 15/100,000 deaths without screening). Screening accrued 0.0009 additional QALYs and cost an additional $24.68, compared to not screening, and was cost-effective (ICER $26,283 per QALY gained). Our results were sensitive to uncertainty in prevalence and the number of secondary colonizations per colonized patient. Screening was not cost-effective at a prevalence below 0.015% or if transmission to fewer than 0.9 new patients occurred for each colonized patient. At prevalence levels above 0.3%, screening was cost-saving compared to not screening. Screening inpatients for CPE carriage is likely cost-effective, and may be cost-saving, depending on the local prevalence of carriage.

Trends in health care utilization and costs attributable to hepatocellular carcinoma, 2002-2009: a population-based cohort study.

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.

Lower life expectancy among people with an HCV notification: a population-based linkage study.

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.

Trends in incidence of hepatocellular carcinoma after diagnosis of hepatitis B or C infection: a population-based cohort study, 1992-2007.

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major risk factors for hepatocellular carcinoma (HCC). We examined trends in the incidence of HCC among a population-based cohort of people infected with HBV or HCV. HBV and HCV cases notified to the New South Wales Health Department between 1992 and 2007 were linked to the Central Cancer Registry, Registry of Births, Deaths and Marriages, and National HIV/AIDS Registries. Crude HCC incidence rates were estimated using person-time methodology. Age-standardized incidence rates were calculated using the 2001 Australian population. Trends in incidence were examined using join point regression models. Between 1992 and 2007, 1201 people had a linked HCC record: 556 of those with HBV; 592 with HCV; 45 with HBV/HCV co-infection; and 8 with HIV co-infection. The overall age-standardized HCC incidence rates declined non-significantly from 148.0 (95% confidence intervals (CI) 63.7, 287.4) per 100,000 population in 1995 to 101.2 (95% CI 67.3, 144.6) in 2007 among the HBV monoinfected group and significantly from 151.8 (95% CI 62.4, 299.8) per 100,000 population to 75.3 (95% CI 50.8, 105.5) among the HCV monoinfected group. However, incidence rates in the HCV monoinfected group progressively increased from the period 1992-1997 to 2004-2007 when adjusted for age, sex, and birth cohort, and the total number of cases per annum continued to increase. Despite declines in the age-adjusted incidence rates of HCC over time, the absolute number of cases increased likely due to the ageing cohort and an increasing prevalence of both hepatitis B and C in Australia.

Prognosis of hepatitis C virus-infected Canadian post-transfusion compensation claimant cohort.

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.

Experience of hepatitis C testing among injecting drug users in Sydney, Australia.

Testing injecting drug users (IDUs) for HIV and hepatitis C virus (HCV) provides a useful opportunity for health promotion, risk-reduction assessment and counselling, and increases opportunities for treatment assessment, yet little is known about IDUs' experience of testing. This study aimed to examine the experiences of testing among IDUs recruited through primary healthcare and drug treatment services. Almost all the 229 participants recruited had been previously tested for HIV (96%) and HCV (97%), a median of five and four times respectively. Reasons for seeking testing were similar for both HIV and HCV, the most common being to protect others (72 and 74%, respectively), blood/needle exposure (66 and 70%, respectively) and to receive early treatment (66%, both). The most common locations for testing were general medical practices (GPs) (53%), specialised clinics (45%) and methadone clinics (43%). Preferred locations were similar for HIV and HCV testing: methadone clinics (47 and 48%, respectively), GPs (42%, both), specialised clinics (32%, both). The most common reasons for delaying testing were being anxious about waiting for results (66%), scared or afraid of finding out results (65%) and having trouble keeping appointments (64%). The majority of participants (HIV 62%; HCV 59%) reported that they would prefer pre-test counselling to be delivered in person rather than receiving written information and would prefer test results to be delivered face-to-face (HIV 83%; HCV 80%). High prevalence of testing suggests good uptake and high acceptability among this population in Australia. Specialised services for drug users such as methadone clinics and primary healthcare are suitable locations to provide access to testing.

Improved cognitive function as a consequence of hepatitis C virus treatment.

OBJECTIVE: The aim of the study was to investigate the impact of treatment-related clearance of hepatitis C virus (HCV) on cognitive function. METHODS: A prospective study was conducted in 19 HCV-monoinfected and 15 HIV/HCV-coinfected individuals undergoing pegylated interferon alpha-2a and ribavirin therapy between April 2003 and August 2005. Neuropsychological, mood, and health-related quality of life (HRQOL) effects were assessed using computer-based battery, Trail Making Tests, Depression Anxiety Stress Scales and the Short Form-36 health survey. RESULTS: Pretreatment cognitive function, mood status, and HRQOL were similar between the HCV patient groups. Sustained virological response (SVR) rates were similar between HCV-monoinfected (68%) and HIV/HCV-coinfected (73%) groups. SVR was associated with significant improvements in some measures of cognitive function, independent of HRQOL improvement. CONCLUSIONS: Our findings provide evidence to support cognitive effects of HCV independent of mood status and HRQOL profiles.