OBJECTIVES: The availability of effective treatment for chronic hepatitis C patients with advanced disease is an area of unmet medical need. The objective of this study was to assess the cost-effectiveness of daclatasvir+sofosbuvir (DCV+SOF) for the treatment of hepatitis C virus (HCV) genotypes (GT) 1, 3 and 4 in patients with advanced disease (METAVIR score ≥ F3) compared to standard of care. METHODS: DCV+SOF was compared to telaprevir+pegylated interferon-alfa+ribavirin (TVR+PR) and no treatment (NT) in GT1, and pegylated interferon-alfa+ribavirin (PR) and NT in GT3 and GT4. A published Markov model (MONARCH) was used to simulate treatment in a cohort (mean age 50 years, 67% male) over a lifetime, using established disease transition rates, costs and health utilities. UK 2013 costs were employed, with costs and benefits discounted at 3.5%. Weekly treatment costs and sustained virologic response (SVR) rates used were: DCV: £2,038.13; SOF: £2,915.24 (DCV+SOF SVR: 100% GT1, GT3 and GT4); TVR: £1,866.50 (SVR: 62%); PR: £191.35 (SVR: 58% GT3; 45% GT4). RESULTS: In GT1, incremental costs were £15,282 and £20,798 and incremental QALYs were 1.95 and 4.88 compared to TVR+PR and NT, respectively.  In GT3, incremental costs were £96,953 and £78,478, with QALY gains of 2.50 and 5.85 for PR and NT, respectively.  In GT4, incremental costs were £26,966 and £18,636, with QALY gains of 3.07 and 5.36 for PR and NT, respectively. Predicted ICERs were: GT1, £7,830 versus TVR+PR, £4,263 versus NT; GT3, £38,815 versus PR, £13,416 versus NT; GT4, £8,782 versus PR, £3,477 versus NT. CONCLUSIONS: At conventional UK cost effectiveness thresholds, treatment with DCV+SOF is estimated to be cost-effective compared to standard of care and no treatment in GT1 and GT4 patients with advanced disease.  In GT3, DCV+SOF is predicted to be cost-effective compared to NT.