Original ResearchTackling the burden of the hepatitis C virus in the UK: characterizing and assessing the clinical and economic consequences
Introduction
Patients with chronic hepatitis C are at risk of developing long-term, life-threatening sequelae, including decompensated cirrhosis and hepatocellular carcinoma (HCC), precursors to liver transplant, and death.1, 2, 3 While chronic hepatitis C can be successfully diagnosed and treated, significant numbers of patients are unaware of their infection due to the asymptomatic nature of the condition until the development of end-stage liver disease (ESLD); therefore, the expected financial burden of these undiagnosed cases is not well categorized, but is expected to be substantial.4
In the UK, the two major routes of HCV transmission have historically been the sharing of needles and paraphernalia among people who inject drugs (PWID) and transfusion of infected blood or blood products.5, 6 Screening of blood products and heat inactivation of the virus have virtually eliminated the latter as a source of newly acquired HCV infection, and the HCV epidemic in the UK is now largely driven by injecting drug use.5, 6 Latest estimates from UK public health bodies suggest that up to 90% of current HCV infections have occurred as a direct result of injection drug use,6 it is estimated that between 20% and 68% of PWID in the UK are infected with HCV, depending on geographical location and injection practices.4, 7, 8
Recent advances in the therapeutic landscape have led to the introduction of direct-acting antiviral (DAA) regimens with sustained virologic response (SVR) rates consistently >90%.9, 10, 11, 12 These treatments are associated with improved safety profiles and reduced therapy durations compared to historical interferon-based regimens, which provides the potential for improved adherence.9, 10, 11, 12 In principle, these therapies introduce the possibility of eradicating HCV; however, this depends not only on the effectiveness and acceptability of treatments, but on implementation approaches that are both clinically feasible and economically viable. Related research has suggested that concerns around the affordability of treating a large number of patients with chronic hepatitis C may be alleviated by prioritizing treatment in certain patient groups, such as those most likely to transmit infection to others.13 However, assessment of the impact of targeted implementation at a national level has not been undertaken. With this in mind, the principle aims of this research were to derive estimates of the prevalence of chronic hepatitis C in the UK, stratified by disease severity, age and awareness of infection, predict the onward presentation of ESLD and its economic burden, and assess the impact of implementing a targeted approach to treatment, prioritizing patients with advanced disease, on incidence of ESLD at the population level.
Section snippets
Analysis plan
Using a previously published back projection, natural history and cost-effectiveness HCV model14, 15, 16, 17, 18 adapted to a UK setting, a three-stage approach was taken:
Stage 1: The back-projection component of the model was used to predict the UK prevalence of chronic hepatitis C between 1980 and 2014 with constant infection rates applied to extrapolate to years 2015–2035. These prevalence estimates were then stratified by METAVIR fibrosis stage, age at infection and awareness of infection.
Results
The back projection analysis produced a chronic hepatitis C prevalence estimate of 241,487 in 2015 (Fig. 2). The trend indicated that the most rapid period of growth occurred during the 1980s. At 2015, it was estimated that 53,603 (22.20%), 81,422 (33.72%), 41,588 (17.22%), 40,266 (16.67%), and 24,608 (10.19%) of those chronically infected were in METAVIR fibrosis stages F0, F1, F2, F3 and F4, respectively. However, while the overall prevalence of chronic hepatitis C is predicted to decline to
Discussion
This study utilized a contemporary HCV natural history disease progression model to produce estimates of chronic hepatitis C prevalence that are consistent with previously predicted estimates.6, 20 The predicted prevalence of HCC events at 2012 is supported by observational record-linkage data on liver-related sequelae.6 This study has provided further granularity by partitioning according to METAVIR fibrosis stage, age and knowledge of infection status. This information is valuable as fibrosis
Ethical approval
Not required, as the manuscript describes an economic analysis using publicly available data.
Funding
Writing and research was funded by Bristol-Myers Squibb Pharmaceuticals Ltd; however, the publication of study results is not contingent on the sponsor's approval or censorship of the manuscript.
Competing interests
Thomas Ward, Phil McEwan, Jason Gordon, Hayley Bennett Wilton, Beverley Jones, Daniel Sugrue and Samantha Webster are employees of Health Economics and Outcomes Research Ltd, who received funding from
References (49)
- et al.
Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study
Lancet
(2014) - et al.
Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial
Lancet
(2014) - et al.
Estimating the long-term clinical and economic outcomes of Daclatasvir plus Asunaprevir in difficult-to-treat Japanese patients chronically infected with hepatitis C genotype 1b
Value Health Regional Issues
(2014) - et al.
Modelling the hepatitis C virus epidemic in Australia
Drug Alcohol Depend
(2007) - et al.
Can antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user populations? A modeling analysis of its prevention utility
J Hepatol
(2011) - et al.
Structural frameworks and key model parameters in cost-effectiveness analyses for current and future treatments of chronic hepatitis C
Value Health
(2011) - et al.
The natural history of hepatitis C virus (HCV) infection
Int J Med Sci
(2006) - et al.
Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection
Gastroenterology
(2011) Clinical practice guidelines: EASL recommendations on treatment of hepatitis C 2015
J Hepatol
(2015)Data tables of the unlinked anonymous monitoring survey of HIV and hepatitis in people who inject drugs
(2013)
Who is at risk and how do we identify them?
J Viral Hepat
Health Protection Scotland, Public Health Wales, Public Health Agency. Hepatitis C in the UK: 2015 report
Hepatitis C virus infection epidemiology among people who inject drugs in Europe: a systematic review of data for scaling up treatment and prevention
PloS One
HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact
J Viral Hepat
Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection
N Engl J Med
Sofosbuvir for previously untreated chronic hepatitis C infection
N Engl J Med
Strategies for the treatment of Hepatitis C in an era of interferon-free therapies: what public health outcomes do we value most?
Gut
The impact of timing and prioritization on the cost-effectiveness of birth cohort testing and treatment for hepatitis C virus in the United States
Hepatology
Estimating the incidence and prevalence of chronic hepatitis C infection in Taiwan using back projection
Value Health Regional Issues
Assessing the cost utility of response-guided therapy in patients with chronic hepatitis C genotype 1 in the UK using the MONARCH model
Appl Health Econ Health Policy
Estimating the clinical and economic benefit associated with incremental improvements in sustained virologic response in chronic hepatitis C
PLoS One
Backcalculation of HIV infection rates
Stat Sci
The burden of hepatitis C in England
J Viral Hepat
Modeling the hepatitis C virus epidemic in France
Hepatology
Cited by (11)
How Does Treating Chronic Hepatitis C Affect Individuals in Need of Organ Transplants in the United Kingdom?
2019, Value in HealthCitation Excerpt :We then made assumptions on how inputs would vary on the basis of the policy change, and estimated the model again to understand how the long-run performance metrics would change as a result. In particular, we simulated the effects of universally treating HCV-infected individuals and allowing them to donate organs in the following way: (1) the rate of organ arrivals would increase proportionally to the prevalence of HCV-positive individuals who are not co-infected with HIV (∼0.035%4,33–35) and (2) the arrival rate of patients needing a liver transplant would reduce proportionally by the fraction of patients who currently join the waitlist because of CHC (5%).36 Note that this specification implicitly assumes that all HCV-infected individuals will be treated, and that all treated individuals will be cured, given that newly released DAAs have cure rates of up to 100% in clinical trials.37
Epidemiology: Modeling of natural history
2021, Hepatitis C: Epidemiology, Prevention and Elimination: Volume 1Improving the detection and treatment of hepatitis C
2021, PractitionerEffectiveness of generic direct-acting agents for the treatment of hepatitis C: Systematic review and meta-analysis
2020, Bulletin of the World Health OrganizationCost-effectiveness of diagnostic and therapeutic interventions for chronic hepatitis C: A systematic review of model-based analyses
2018, BMC Medical Research Methodology