Population Health and Cost-Effectiveness Implications of a “Treat All” Recommendation for HCV: A Review of the Model-Based Evidence

Abstract

The World Health Organization HCV Guideline Development Group is considering a “treat all” recommendation for persons infected with hepatitis C virus (HCV). We reviewed the model-based evidence of cost-effectiveness and population health impacts comparing expanded treatment policies to more limited treatment access policies, focusing primarily on evaluations of all-oral directly acting antivirals published after 2012. Searching PubMed, we identified 2,917 unique titles. Sequentially reviewing titles and abstracts identified 226 potentially relevant articles for full-text review. Sixty-nine articles met all inclusion criteria—42 cost-effectiveness analyses and 30 models of population-health impacts, with 3 articles presenting both types of analysis. Cost-effectiveness studies for many countries concluded that expanding treatment to people with mild liver fibrosis, who inject drugs (PWID), or who are incarcerated is generally cost-effective compared to more restrictive treatment access policies at country-specific prices. For certain patient subpopulations in some countries—for example, elderly individuals without fibrosis—treatment is only cost-effective at lower prices. A frequent limitation is the omission of benefits and consequences of HCV transmission (i.e., treatment as prevention; risks of reinfection), which may underestimate or overestimate the cost-effectiveness of a “treat all” policy. Epidemiologic modeling studies project that through a combination of prevention, aggressive screening and diagnosis, and prompt treatment for all fibrosis stages, it may be possible to virtually eliminate HCV in many countries. Studies show that if resources are not available to diagnose and treat all HCV-infected individuals, treatment prioritization may be needed, with alternative prioritization strategies resulting in tradeoffs between reducing mortality or reducing incidence. Notably, because most new HCV infections are among PWID in many settings, HCV elimination requires unrestricted treatment access combined with injection transmission disruption strategies. The model-based evidence suggests that a properly constructed strategy that substantially expands HCV treatment could achieve cost-effective improvements in population health in many countries.

Efficacy and safety of direct‐acting antivirals for hepatitis C in the elderly: A systematic review and meta‐analysis

“…Moreover, some studies also reported higher rates of SAEs and treatment discontinuation in the elderly . These findings have raised concerns whether a ‘treat all’ strategy is justified given the lack of a comprehensive risk‐benefit analysis in this particular patient population …”

“…Our data indicate that DAA treatment for HCV is highly effective and safe in patients aged ≥65 years, thereby supporting current guideline recommendations to treat all patients without age restrictions. However, recent data suggest that treatment in elderly patients without significant fibrosis may only be cost‐effective at lower prices . Moreover, there is still insufficient data to predict the long‐term effects of HCV cure and its impact on overall survival in elderly patients, particularly in the absence of advanced fibrosis or cirrhosis, as the progression to cirrhosis may never occur.…”

“…18,[28][29][30] These findings have raised concerns whether a 'treat all' strategy is justified given the lack of a comprehensive risk-benefit analysis in this particular patient population. 31 This is the first meta-analysis investigating the safety and efficacy of IFN-free DAA therapy for chronic HCV in the elderly, with almost 8000 patients aged ≥65 years included. Our analysis showed that DAA treatment was similarly effective in patients aged ≥65 years when compared with the younger population.…”

“…However, recent data suggest that treatment in elderly patients without significant fibrosis may only be cost-effective at lower prices. 31 Moreover, there is still insufficient data to predict the long-term effects of HCV cure and its impact on overall survival in elderly patients, particularly in the absence of advanced fibrosis or cirrhosis, as the progression to cirrhosis may never occur. In fact several studies have reported only mild disease progression, particularly in women, despite a long history of HCV infection.…”

Economic Evaluation of Hepatitis C Treatment Extension to Acute Infection and Early-Stage Fibrosis Among Patients Who Inject Drugs in Developing Countries: A Case of China

“…Those who failed treatment were not eligible for re-treatment. Previous studies had suggested that broadly expanded treatment could provide substantial health gains due to the reduced the reinfection risks [18]. In this study, due to the lack of data in China, we made a relatively conservative assumption of the expanding treatment's potential for reducing HCV reinfection as 5% (range: 2.5-7.5%) [5], one-way sensitivity analysis would be conducted to determine its impact on cost-effectiveness.…”