Hepatitis: Krahn MD

Thein HH, Yi Q, Dore GJ, Krahn MD. · University Health Network, Division of Clinical Decision-Making and Healthcare Research, Toronto, Canada. · AIDS. · Pubmed #18784461 No free full text.

Abstract: 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.

Thein HH, Yi Q, Dore GJ, Krahn MD. · University Health Network, Division of Clinical Decision-Making and Health Care Research, Toronto, Ontario, Canada. · Hepatology. · Pubmed #18563841 No free full text.

Abstract: 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.

Hsu PC, Krajden M, Yoshida EM, Anderson FH, Tomlinson GA, Krahn MD. · British Columbia Centre for Disease Control, Vancouver, BC, Canada. · Liver Int. · Pubmed #19267865 No free full text.

Abstract: BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and is associated with impairments in health-related quality of life. AIMS: To evaluate quality of life (QOL) in cirrhotic (compensated and decompensated) and non-cirrhotic patients with chronic HCV infection, using preference-based (utilities) and non-preference-based methods of evaluating QOL. METHODS: In a tertiary care setting, 271 patients completed a self-administered time trade-off utility instrument, the Health Utility Index Mark 2 and Mark 3, and the Hepatitis Quality of Life Questionnaire Version 2. Mean QOL scores were compared across HCV disease stages and sociodemographical categories. We examined the association between QOL and disease stage using linear regression adjusting for age, education, marital status, log income and Charlson comorbidity scores. Mean utility scores were compared across disease stages using a propensity score method. RESULTS: Mean utilities were lower than general population norms (0.81-0.92) and ranged from 0.62 to 0.82 in non-cirrhotic patients (n=197), 0.56-0.84 in compensated cirrhotic patients (n=17) and 0.55-0.76 for decompensated cirrhotic patients (n=57). No significant association found was between disease stage and utility for current health status. Higher income, fewer comorbidities and living in a married or common-law relationship were significantly associated with higher utilities and better QOL. No significant difference in utilities was found between disease stages using propensity score matching. CONCLUSIONS: Our study confirms that changes in HCV disease stage explain only small changes in QOL and suggests that factors such as underlying comorbidities, income and marital status have a greater effect on QOL than disease stage.

Bauch CT, Anonychuk AM, Pham BZ, Gilca V, Duval B, Krahn MD. · University of Guelph, Department of Mathematics and Statistics, Guelph, Ontario, Canada. · Vaccine. · Pubmed #17996339 No free full text.

Abstract: Hepatitis A (HA) vaccination in Canada is currently targeted toward high-risk groups. The cost-effectiveness and expected health outcomes of universal vaccination relative to targeted vaccination in low-incidence countries such as Canada are currently unknown. Here, we conducted a cost-utility analysis for this situation, with Canada as the study population. We included vaccine costs, time costs, infection costs, and public health costs. We assessed a range of possible universal vaccination strategies over an 80-year time horizon using multiple cost perspectives. A dynamic model was used to account for herd immunity. Aggregate health gains from switching to universal vaccination are modest (10-30 QALYs per year). However, a "9+9" strategy that replaces two doses of monovalent hepatitis B (HB) vaccine at 9/10 years (universally administered in most provinces) with two doses of bivalent HA/HB vaccine is cost-saving from the societal perspective. At a willingness to pay threshold of $50,000/QALY, mean net benefit is +49.4 QALYs (S.D. 12.6) from the societal perspective and +3.8 QALYS (S.D. 3.0) from the payer perspective for the "9+9" strategy. Net benefit from the payer perspective is sensitive to the marginal cost of HA/HB vaccine relative to HB vaccine. Similar conclusions may apply in other countries with low incidence and a targeted vaccination policy.

Thein HH, Maruff P, Krahn MD, Kaldor JM, Koorey DJ, Brew BJ, Dore GJ. · National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, NSW, Australia. · HIV Med. · Pubmed #17944685 No free full text.

Abstract: 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.

Srinivasa Rao AS, Chen MH, Pham BZ, Tricco AC, Gilca V, Duval B, Krahn MD, Bauch CT. · Department of Mathematics and Statistics, University of Guelph, Guelph, Canada. <> · BMC Infect Dis. · Pubmed #17147828 links to  free full text

Abstract: BACKGROUND: Infection rates for many infectious diseases have declined over the past century. This has created a cohort effect, whereby older individuals experienced a higher infection rate in their past than younger individuals do now. As a result, age-stratified seroprevalence profiles often differ from what would be expected from constant infection rates. METHODS: Here, we account for the cohort effect by fitting an age-structured compartmental model with declining transmission rates to Hepatitis A seroprevalence data for Canadian-born individuals. We compare the predicted impact of universal vaccination with and without including the cohort effect in the dynamic model. RESULTS: We find that Hepatitis A transmissibility has declined by a factor of 2.8 since the early twentieth century. When the cohort effect is not included in the model, incidence and mortality both with and without vaccination are significantly over-predicted. Incidence (respectively mortality) over a 20 year period of universal vaccination is 34% (respectively 90%) higher than if the cohort effect is included. The percentage reduction in incidence and mortality due to vaccination are also over-predicted when the cohort effect is not included. Similar effects are likely for many other infectious diseases where infection rates have declined significantly over past decades and where immunity is lifelong. CONCLUSION: Failure to account for cohort effects has implications for interpreting seroprevalence data and predicting the impact of vaccination programmes with dynamic models. Cohort effects should be included in dynamic modelling studies whenever applicable.

Witkos M, Yi QL, Heathcote J, Kapral MK, Krahn MD. · Department of Health Policy, Management and Evaluation, University of Toronto, Toronto General Hospital, Ontario, Canada. · Can J Gastroenterol. · Pubmed #16482237 links to  free full text

Abstract: INTRODUCTION: In the past, antiviral therapy has been given to 15% to 30% of patients infected with hepatitis C virus (HCV). The efficacy of therapy has recently improved with the addition of ribavirin and pegylated interferon. The aim of the present study was to identify the clinical, socioeconomic and health-system predictors of antiviral treatment for HCV. METHODS: A retrospective analysis of compensation claims data of patients who acquired HCV through blood transfusions between 1986 and 1990 was performed. The patients consisted of 2456 Canadian HCV-positive individuals. The authors reviewed narrative comments from physicians, and constructed univariate and multivariate logistic regression models, using receipt of antiviral therapy with interferon or interferon/ribavirin as the primary outcome. RESULTS: Of the 2456 patients, approximately 30% appeared to be eligible, but only 16% received treatment. Univariate analyses suggested that the disease severity, age, HIV status and province of residence were associated with the likelihood of receiving treatment (P<0.01). The final, multivariable model indicated that in patients with HCV: intermediate disease severity (eg, fibrosis, P<0.0001); middle age (P<0.0001); HIV-negative status (P<0.0001); and province of residence (Quebec, P<0.0001; and Saskatchewan, P<0.0001) were independent predictors of treatment. Narrative comments of physicians emphasized the importance of age, HIV status and patient preferences in clinical decision-making. DISCUSSION: Given the efficacy and cost-effectiveness of current antiviral therapy, treatment rates of HCV patients may be suboptimal. Further work is required to understand barriers to treatment related to geography, organization of medical care, age, medical provider and patient preferences.

Krahn MD, John-Baptiste A, Yi Q, Doria A, Remis RS, Ritvo P, Friedman S. · Department of Medicine, University Health Network, Department of Health Policy, Management and Evaluation, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 1C4. · Vaccine. · Pubmed #15694507 No free full text.

Abstract: Hepatitis C virus (HCV) vaccine development remains at an early stage. We explored the economic and health consequences of potential HCV vaccines by comparing universal vaccination with a hepatitis C vaccine to no vaccination in two groups: (1) injecting drug users (IDU); (2) all 12 year olds, using a Markov cohort simulation. Among IDUs, vaccination would avert 248 cases of HCV infection and 89 HCV-related deaths per 1000 individuals, and reduce costs. In average risk cohorts, vaccination did not reduce costs but was reasonably cost effective. These results provide encouragement to vaccine developers that a vaccine that is moderately effective and reasonably priced should not face economic barriers to implementation and will be attractive to third party payers.